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Vicario-Feliciano R, Zil-E-Ali A, Aziz F. Beta Blockers are Associated with Increased Mortality Without a Decrease in Reinterventions After Endovascular Abdominal Aortic Repair (EVAR). Ann Vasc Surg 2025; 110:395-404. [PMID: 39103012 DOI: 10.1016/j.avsg.2024.07.104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 07/10/2024] [Accepted: 07/10/2024] [Indexed: 08/07/2024]
Abstract
INTRODUCTION Predictors of sac behavior after endovascular aortic aneurysm repair (EVAR) and the impact of sac behavior on long-term survival are not well known. There are limited multicenter trials studying the impact of beta blockers (BBs) on sac behavior. BBs have consistently failed to show a benefit on abdominal aortic aneurysm sac regression in patients with connective tissue disorders and the general population. This study aims to assess the association between BBs and sac behavior after EVAR. METHODS Patients undergoing EVAR registered in Vascular Quality Initiative (2003-2021) stratified by BB and no BB on discharged after an index procedure were assessed at follow-up of 30 days and 1 year. The primary outcomes included mortality and reintervention at 30 days and 1 year. The causes of reintervention were also studied at the defined time endpoints. Categorical and continuous variables were analyzed separately for association between the 2 groups. A P value of <0.05 was considered statistically significant. RESULTS A total of 50,411 patients, stratified by BB (28,866; 57.3%), and no BB (21,545; 42.7%) were studied. Patients with hypertension, diabetes, chronic obstructive pulmonary disease, coronary artery disease, prior history of coronary artery bypass graft or percutaneous coronary intervention, prior angioplasty or stent, lower extremity bypass, carotid surgery, major amputation, and smokers were more likely to be on a BB at the time of discharge (P < 0.05). There was no significant difference in reinterventions when comparing patients with and without BB (P = 0.061). At 30-day follow-up, there was no significant difference between the 2 groups for any cause of reintervention. At 1-year follow-up, patients on BB were less likely to need reintervention for graft occlusion (no BB 18.70%, BB 11.77%, P = 0.002). There was no significant difference in reintervention for all other causes at 1-year follow-up. There was an increase in 30-day (no BB 0.20%, BB 0.33%, P = 0.007) and 1-year mortality (no BB 2.35%, BB 3.19%, P < 0.001) in patients on BBs. A time to event adjusted analysis based on Cox proportional hazard model revealed a 26% higher risk of 1-year mortality for patients on BB (hazard ratio: 1.26 [1.10-1.41] P < 0.001). CONCLUSIONS Despite theoretical benefits of BBs on aneurysm behavior, review of the largest national vascular surgery database shows that patients on BBs do not have lower incidence of endovascular reinterventions after EVAR while additionally showing a higher mortality in this patient population.
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Affiliation(s)
- Raquel Vicario-Feliciano
- Division of Vascular Surgery, Heart and Vascular Institute, Pennsylvania State Milton S. Hershey Medical Center, Hershey, PA
| | - Ahsan Zil-E-Ali
- Division of Vascular Surgery, Heart and Vascular Institute, Pennsylvania State Milton S. Hershey Medical Center, Hershey, PA.
| | - Faisal Aziz
- Division of Vascular Surgery, Heart and Vascular Institute, Pennsylvania State Milton S. Hershey Medical Center, Hershey, PA
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Herrera Hernández D, Abreu B, Xiao TS, Rojas A, Romero KL, Contreras V, Nogueyra SV, Sosa Z, Alvarez SM, Sánchez Cruz C, Calderón Martinez E. Beta-Blocker Use in Patients Undergoing Non-Cardiac Surgery: A Systematic Review and Meta-Analysis. Med Sci (Basel) 2024; 12:64. [PMID: 39584914 PMCID: PMC11587062 DOI: 10.3390/medsci12040064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 10/15/2024] [Accepted: 10/30/2024] [Indexed: 11/26/2024] Open
Abstract
BACKGROUND The use of beta-blockers in the perioperative period has been widely investigated due to their potential to reduce the risk of major adverse cardiovascular and cerebrovascular events (MACCE) and mortality; yet their overall impact on various postoperative outcomes remains debated. This study constitutes a systematic review and meta-analysis of the impact of beta-blockers on mortality, MI, stroke, and other adverse effects such as hypotension and bradycardia in patients undergoing non-cardiac surgery. METHODS A comprehensive systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. Searches were performed across PubMed, Cochrane, Web of Science, Scopus, EMBASE, and CINAHL databases; we included randomized controlled trials and cohort and case-control studies published from 1999 to 2024. RESULTS This meta-analysis included data from 28 studies encompassing 1,342,430 patients. Perioperative beta-blockers were associated with a significant increase in stroke risk (RR 1.42, 95% CI: 1.03 to 1.97, p = 0.03, I2 = 62%). However, no statistically significant association was found between beta-blocker use and mortality (RR 0.62, 95% CI: 0.38 to 1.01, p = 0.05, I2 = 100%). Subgroup analyses revealed a protective effect on mortality for patients with high risks, such as patients with a history of atrial fibrillation, chronic heart failure, and other arrhythmias. For myocardial infarction (RR 0.82, 95% CI: 0.53 to 1.28, p = 0.36, I2 = 86%), a reduction in events was observed in the subgroup of randomized controlled trials. Beta-blockers significantly increased the risk of hypotension (RR 1.46, 95% CI: 1.26 to 1.70, p < 0.01, I2 = 25%) and bradycardia (RR 2.26, 95% CI: 1.37 to 3.74, p < 0.01, I2 = 64%). CONCLUSIONS Perioperative beta-blockers show increasing rates of stroke events following non-cardiac surgery but do not significantly impact the incidence of MI or mortality. The increased risks of hypotension and bradycardia necessitate careful patient selection and monitoring. Future research should aim to refine patient selection criteria and optimize perioperative management to balance the benefits and risks of beta-blocker use in surgical settings.
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Affiliation(s)
| | - Bárbara Abreu
- Facultad de Medicina, Universidad de Carabobo, Valencia 2005, Venezuela
| | - Tania Siu Xiao
- Radiology Department, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Andreina Rojas
- Facultad de Medicina, Universidad de Oriente, Núcleo Anzoátegui, Barcelona 6001, Venezuela
| | - Kevin López Romero
- Facultad de Medicina, Universidad del Salvador, San Salvador 1101, El Salvador
| | - Valentina Contreras
- Department of Lymphoma and Myeloma, MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Sol Villa Nogueyra
- Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1053ABK, Argentina
| | - Zulma Sosa
- Facultad de medicina, Universidad Evangélica de El Salvador, San Salvador 1101, El Salvador
| | | | - Camila Sánchez Cruz
- Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico;
| | - Ernesto Calderón Martinez
- Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico;
- Department of Internal Medicine, The University of Texas Health Science Medical Center, Houston, TX 77030, USA
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Glarner N, Puelacher C, Gualandro DM, Pargger M, Huré G, Maiorano S, Strebel I, Fried S, Bolliger D, Steiner LA, Lampart A, Lurati Buse G, Mujagic E, Lardinois D, Kindler C, Guerke L, Schaeren S, Mueller A, Clauss M, Buser A, Hammerer-Lercher A, Mueller C. Association of preoperative beta-blocker use and cardiac complications after major noncardiac surgery: a prospective cohort study. Br J Anaesth 2024; 132:1194-1203. [PMID: 38627137 DOI: 10.1016/j.bja.2024.02.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 02/13/2024] [Accepted: 02/27/2024] [Indexed: 05/12/2024] Open
Abstract
INTRODUCTION Cardiac complications after major noncardiac surgery are common and associated with high morbidity and mortality. How preoperative use of beta-blockers may impact perioperative cardiac complications remains unclear. METHODS In a multicentre prospective cohort study, preoperative beta-blocker use was ascertained in consecutive patients at elevated cardiovascular risk undergoing major noncardiac surgery. Cardiac complications were prospectively monitored and centrally adjudicated by two independent experts. The primary endpoint was perioperative myocardial infarction or injury attributable to a cardiac cause (cardiac PMI) within the first three postoperative days. The secondary endpoints were major adverse cardiac events (MACE), defined as a composite of myocardial infarction, acute heart failure, life-threatening arrhythmia, and cardiovascular death and all-cause death after 365 days. We used inverse probability of treatment weighting to account for differences between patients receiving beta-blockers and those who did not. RESULTS A total of 3839/10 272 (37.4%) patients (mean age 74 yr; 44.8% female) received beta-blockers before surgery. Patients on beta-blockers were older, and more likely to be male with established cardiorespiratory and chronic kidney disease. Cardiac PMI occurred in 1077 patients, with a weighted odds ratio of 1.03 (95% confidence interval [CI] 0.94-1.12, P=0.55) for patients on beta-blockers. Within 365 days of surgery, 971/10 272 (9.5%) MACE had occurred, with a weighted hazard ratio of 0.99 (95% CI 0.83-1.18, P=0.90) for patients on beta-blockers. CONCLUSION Preoperative use of beta-blockers was not associated with decreased cardiac complications including cardiac perioperative myocardial infarction or injury and major adverse cardiac event. Additionally, preoperative use of beta-blockers was not associated with increased all-cause death within 30 and 365 days. CLINICAL TRIAL REGISTRATION NCT02573532.
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Affiliation(s)
- Noemi Glarner
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Christian Puelacher
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland.
| | - Danielle M Gualandro
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Mirjam Pargger
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Gabrielle Huré
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Silvia Maiorano
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Ivo Strebel
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Simona Fried
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Daniel Bolliger
- Department of Anaesthesiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Luzius A Steiner
- Department of Anaesthesiology, University Hospital Basel, University of Basel, Basel, Switzerland; Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Andreas Lampart
- Department of Anaesthesiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Giovanna Lurati Buse
- Department of Anaesthesiology, University Hospital Dusseldorf, Dusseldorf, Germany
| | - Edin Mujagic
- Department of Vascular Surgery, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Didier Lardinois
- Department of Thoracic Surgery, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Christoph Kindler
- Department of Anaesthesiology, Cantonal Hospital Aarau, Aarau, Switzerland
| | - Lorenz Guerke
- Department of Vascular Surgery, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Stefan Schaeren
- Department of Spinal Surgery, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Andreas Mueller
- Department of Orthopaedics and Traumatology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Martin Clauss
- Department of Orthopaedics and Centre of Musculoskeletal Infections, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Andreas Buser
- Department of Haematology and Blood Bank, University Hospital Basel, University of Basel, Basel, Switzerland
| | | | - Christian Mueller
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland
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Morgan H, Ezad SM, Rahman H, De Silva K, Partridge JSL, Perera D. Assessment and Management of Ischaemic Heart Disease in Non-Cardiac Surgery. Heart Int 2023; 17:19-26. [PMID: 38419719 PMCID: PMC10898586 DOI: 10.17925/hi.2023.17.2.19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Accepted: 10/18/2023] [Indexed: 03/02/2024] Open
Abstract
In the setting of non-cardiac surgery, cardiac complications contribute to over a third of perioperative deaths. With over 230 million major surgeries performed annually, and an increasing prevalence of cardiovascular risk factors and ischaemic heart disease, the incidence of perioperative myocardial infarction is also rising. The recent European Society of Cardiology guidelines on cardiovascular risk in noncardiac surgery elevated practices aiming to identify those at most risk, including biomarker monitoring and stress testing. However the current evidence base on if, and how, the risk of cardiac events can be modified is lacking. This review focuses on patient, surgical and cardiac risk assessment, as well as exploring the data on perioperative revascularization and other risk-reduction strategies.
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Affiliation(s)
- Holly Morgan
- British Heart Foundation Centre of Research Excellence at the School of Cardiovascular and Metabolic Medicine and Sciences, King's College, London, UK
| | - Saad M Ezad
- British Heart Foundation Centre of Research Excellence at the School of Cardiovascular and Metabolic Medicine and Sciences, King's College, London, UK
| | - Haseeb Rahman
- British Heart Foundation Centre of Research Excellence at the School of Cardiovascular and Metabolic Medicine and Sciences, King's College, London, UK
| | - Kalpa De Silva
- British Heart Foundation Centre of Research Excellence at the School of Cardiovascular and Metabolic Medicine and Sciences, King's College, London, UK
| | - Judith S L Partridge
- British Heart Foundation Centre of Research Excellence at the School of Cardiovascular and Metabolic Medicine and Sciences, King's College, London, UK
- Guy’s and St Thomas’ NHS Foundation Trust, London, UK
| | - Divaka Perera
- British Heart Foundation Centre of Research Excellence at the School of Cardiovascular and Metabolic Medicine and Sciences, King's College, London, UK
- Guy’s and St Thomas’ NHS Foundation Trust, London, UK
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Binu AJ, Kapoor N, Bhattacharya S, Kishor K, Kalra S. Sarcopenic Obesity as a Risk Factor for Cardiovascular Disease: An Underrecognized Clinical Entity. Heart Int 2023; 17:6-11. [PMID: 38419720 PMCID: PMC10897945 DOI: 10.17925/hi.2023.17.2.6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 09/15/2023] [Indexed: 03/02/2024] Open
Abstract
Sarcopenic obesity (SO) is a chronic condition and an emerging health challenge, in view of the growing elderly population and the obesity epidemic. Due to a lack of awareness among treating doctors and the non-specific nauture of the associated symptoms, SO remains grossly underdiagnosed. There is no consensus yet on a standard definition or diagnostic criteria for SO, which limits the estimation of the global prevalence of this condition. It has been linked to numerous metabolic derangements, cardiovascular disease (CVD) and mortality. The treatment of SO is multimodal and requires expertise across multiple specialties. While dietary modifications and exercise regimens have shown a potential therapeutic benefit, there is currently no proven pharmacological management for SO. However, numerous drugs and the role of bariatric surgery are still under trial, and have great scope for further research. This article covers the available literature regarding the definition, diagnostic criteria, and prevalence of SO, with available evidence linking it to CVD, metabolic disease and mortality, and an overview of current directives on management.
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Affiliation(s)
- Aditya John Binu
- Department of Cardiology, Christian Medical College, Vellore, India
| | - Nitin Kapoor
- Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India
- Non-communicable Disease Unit, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
| | | | - Kamal Kishor
- Department of Cardiology, Rama Hospital, Karnal, India
| | - Sanjay Kalra
- Department of Endocrinology, Bharti Hospital, Karnal, India
- University Center for Research & Development, Chandigarh University, Mohali, India
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Mol KHJM, Liem VGB, van Lier F, Stolker RJ, Hoeks SE. Intraoperative hypotension in noncardiac surgery patients with chronic beta-blocker therapy: A matched cohort analysis. J Clin Anesth 2023; 89:111143. [PMID: 37216803 DOI: 10.1016/j.jclinane.2023.111143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 04/19/2023] [Accepted: 05/01/2023] [Indexed: 05/24/2023]
Abstract
STUDY OBJECTIVE To explore the incidence of intraoperative hypotension in patients with chronic beta-blocker therapy, expressed as time spent, area and time-weighted average under predefined mean arterial pressure thresholds. DESIGN Retrospective analysis of a prospective observational cohort registry. SETTING Patients ≥60 years undergoing intermediate- to high-risk noncardiac surgery with routine postoperative troponin measurements on the first three days after surgery. PATIENTS 1468 matched sets of patients (1:1 ratio with replacement) with and without chronic beta-blocker treatment. INTERVENTIONS None. MEASUREMENTS The primary outcome was the exposure to intraoperative hypotension in beta-blocker users vs. non-users. Time spent, area and time-weighted average under predefined mean arterial pressure thresholds (55-75 mmHg) were calculated to express the duration and severity of exposure. Secondary outcomes included incidence of postoperative myocardial injury and thirty-day mortality, myocardial infarction (MI) and stroke. Furthermore, analyses for patient subgroup and beta-blocker subtype were conducted. MAIN RESULTS In patients with chronic beta-blocker therapy, no increased exposure to intraoperative hypotension was observed for all characteristics and thresholds calculated (all P > .05). Beta-blocker users had lower heart rate before, during and after surgery (70 vs. 74, 61 vs. 65 and 68 vs. 74 bpm, all P < .001, respectively). Postoperative myocardial injury (13.6% vs. 11.6%, P = .269) and thirty-day mortality (2.5% vs. 1.4%, P = .055), MI (1.4% vs. 1.5%, P = .944) and stroke (1.0% vs 0.7%, P = .474) rates were comparable. The results were consistent in subtype and subgroup analyses. CONCLUSIONS In this matched cohort analysis, chronic beta-blocker therapy was not associated with increased exposure to intraoperative hypotension in patients undergoing intermediate- to high-risk noncardiac surgery. Furthermore, differences in patient subgroups and postoperative adverse cardiovascular events as a function of treatment regimen could not be demonstrated.
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Affiliation(s)
- Kristin H J M Mol
- Department of Anesthesia, Erasmus University Medical Center, Rotterdam, the Netherlands.
| | - Victor G B Liem
- Department of Anesthesia, Erasmus University Medical Center, Rotterdam, the Netherlands.
| | - Felix van Lier
- Department of Anesthesia, Erasmus University Medical Center, Rotterdam, the Netherlands.
| | - Robert Jan Stolker
- Department of Anesthesia, Erasmus University Medical Center, Rotterdam, the Netherlands.
| | - Sanne E Hoeks
- Department of Anesthesia, Erasmus University Medical Center, Rotterdam, the Netherlands.
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Apaydin EA, Woo K, Rollison J, Baxi S, Motala A, Hempel S. Enhanced recovery after surgery (ERAS) for vascular surgery: an evidence map and scoping review. Syst Rev 2023; 12:162. [PMID: 37710325 PMCID: PMC10500918 DOI: 10.1186/s13643-023-02324-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 08/15/2023] [Indexed: 09/16/2023] Open
Abstract
BACKGROUND Enhanced recovery after surgery (ERAS) interventions aim to improve patient outcomes. Vascular surgery patients have unique requirements and it is unclear which ERAS interventions are supported by an evidence base. METHODS We conducted a scoping review to identify ERAS randomized controlled trials (RCTs) published in the biomedical or nursing literature. We assessed interventions for applicability to vascular surgery and differentiated interventions given at preadmission, preoperative, intraoperative, and postoperative surgery stages. We documented the research in an evidence map. RESULTS We identified 76 relevant RCTs. Interventions were mostly administered in preoperative (23 RCTs; 30%) or intraoperative surgery stages (35 RCTs; 46%). The majority of studies reported mortality outcomes (44 RCTs; 58%), but hospital (27 RCTs; 35%) and intensive care unit (9 RCTs; 12%) length of stay outcomes were less consistently described. CONCLUSION The ERAS evidence base is growing but contains gaps. Research on preadmission interventions and more consistent reporting of key outcomes is needed.
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Affiliation(s)
- Eric A Apaydin
- Southern California Evidence Review Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
- RAND Health Care, RAND Corporation, Santa Monica, CA, USA.
- Center for the Study of Healthcare Innovation, Implementation, and Policy, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
| | - Karen Woo
- Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
| | | | - Sangita Baxi
- RAND Health Care, RAND Corporation, Santa Monica, CA, USA
| | - Aneesa Motala
- Southern California Evidence Review Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- RAND Health Care, RAND Corporation, Santa Monica, CA, USA
| | - Susanne Hempel
- Southern California Evidence Review Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- RAND Health Care, RAND Corporation, Santa Monica, CA, USA
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Khan O, Patel M, Tomdio AN, Beall J, Jovin IS. Beta-Blockers in the Prevention and Treatment of Ischemic Heart Disease: Evidence and Clinical Practice. Heart Views 2023; 24:41-49. [PMID: 37124437 PMCID: PMC10144413 DOI: 10.4103/heartviews.heartviews_75_22] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 10/02/2022] [Indexed: 02/25/2023] Open
Abstract
Coronary artery disease (CAD) is the most prevalent cardiovascular disease characterized by atherosclerotic plaque buildup that can lead to partial or full obstruction of blood flow in the coronary arteries. Treatment for CAD involves a combination of lifestyle changes, pharmacologic therapy, and modern revascularization procedures. Beta-adrenoceptor antagonists (or beta-blockers) have been widely used for decades as a key therapy for CAD. In this review, prior studies are examined to better understand beta-adrenoceptor antagonist use in patients with acute coronary syndrome, stable coronary heart disease, and in the perioperative setting. The evidence for the benefit of beta-blocker therapy is well established for patients with acute myocardial infarction, but it diminishes as the time from the index cardiac event elapses. The evidence for benefit in the perioperative setting is not strong.
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Affiliation(s)
- Omer Khan
- Department of Medicine, Hunter Holmes McGuire VA Medical Center, Richmond, Virginia, USA
| | - Murti Patel
- Department of Medicine, Hunter Holmes McGuire VA Medical Center, Richmond, Virginia, USA
- Department of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Anna N. Tomdio
- Department of Medicine, Hunter Holmes McGuire VA Medical Center, Richmond, Virginia, USA
- Department of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Jeffrey Beall
- Department of Medicine, Hunter Holmes McGuire VA Medical Center, Richmond, Virginia, USA
| | - Ion S. Jovin
- Department of Medicine, Hunter Holmes McGuire VA Medical Center, Richmond, Virginia, USA
- Department of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
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Chang H, Rockman CB, Ramkhelawon B, Maldonado TS, Cayne NS, Veith FJ, Jacobowitz GR, Patel VI, Laskowski I, Garg K. Beta-blocker Use After Thoracic Endovascular Aortic Repair in Patients with Type B Aortic Dissection Is Associated with Improved Early Aortic Remodeling. J Vasc Surg 2022; 76:1477-1485.e2. [PMID: 35868420 DOI: 10.1016/j.jvs.2022.06.100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Revised: 06/11/2022] [Accepted: 06/28/2022] [Indexed: 11/29/2022]
Abstract
OBJECTIVE Beta-blockers are first-line anti-impulse therapy in patients presenting with acute type B aortic dissection (TBAD). However, little is understood about their impact after aortic repair. The aim of this study was to evaluate the role of postoperative beta-blocker use on outcomes of thoracic endovascular aortic repair (TEVAR) in TBAD. METHODS The Vascular Quality Initiative database was queried for all patients undergoing TEVAR for TBAD from 2012 to 2020. Aortic-related reintervention, all-cause mortality and effect of TEVAR on false lumen thrombosis of the treated aortic segment were assessed and compared between patients treated with and without beta-blocker postoperatively. Cox proportional hazards models were used to estimate the effect of beta-blocker therapies on outcomes. RESULTS 1,114 patients undergoing TEVAR for TBAD were identified with a mean follow-up of 18±12 months. The mean age was 61.1±11.9 years, and 791 (71%) were male. 935 (84%) patients were maintained on beta-blocker at discharge and follow-up. Patients on beta-blocker were more likely to have an entry tear originating in zones 1-2 (22% vs 13%; P=.022). The prevalence of acute, elective and symptomatic AD, concurrent aneurysm, number of endografts used, distribution of the proximal and distal zones of dissection and operative time were comparable between the two cohorts. At 18-months, significantly more complete false lumen thrombosis (58 vs 47%; log-rank P=.018) was observed in patients on beta-blocker while the rates of aortic-related reinterventions (13% vs 9%; log-rank P=.396) and mortality (0.2% vs 0.7%; log-rank P=.401) were similar in patients with and without beta-blocker, respectively. Even after adjusting for clinical and anatomic factors, postoperative beta-blocker use was associated with increased complete false lumen thrombosis (HR 1.56; 95% CI: 1.10-2.21; P=.012) but did not affect mortality or aortic-related reintervention. A secondary analysis of beta-blocker use in acute versus chronic TBAD showed a higher rate of complete false lumen thrombosis in patients on beta-blocker in chronic TBAD (59% vs 38%; log-rank P=.038). In contrast, there was no difference in the rate of complete false lumen thrombosis in acute TBAD between the two cohorts (58% vs 51%; log-rank P=.158). When analyzed separately, postoperative ACE inhibitor use did not affect the rates of complete false lumen thrombosis, mortality and aortic-related reintervention. CONCLUSIONS Beta-blocker use was associated with promotion of complete false lumen in patients undergoing TEVAR for TBAD. In addition to its role in acute setting, anti-impulse control with beta-blocker appears to confer favorable aortic remodeling and may improve outcomes after TEVAR, particularly for chronic TBAD.
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Affiliation(s)
- Heepeel Chang
- Division of Vascular and Endovascular Surgery, Department of Surgery, Westchester Medical Center, New York Medical College, Valhalla, NY, 10959
| | - Caron B Rockman
- Division of Vascular and Endovascular Surgery, Department of Surgery, New York University Langone Medical Center, New York, NY, 10016
| | - Bhama Ramkhelawon
- Division of Vascular and Endovascular Surgery, Department of Surgery, New York University Langone Medical Center, New York, NY, 10016
| | - Thomas S Maldonado
- Division of Vascular and Endovascular Surgery, Department of Surgery, New York University Langone Medical Center, New York, NY, 10016
| | - Neal S Cayne
- Division of Vascular and Endovascular Surgery, Department of Surgery, New York University Langone Medical Center, New York, NY, 10016
| | - Frank J Veith
- Division of Vascular and Endovascular Surgery, Department of Surgery, New York University Langone Medical Center, New York, NY, 10016
| | - Glenn R Jacobowitz
- Division of Vascular and Endovascular Surgery, Department of Surgery, New York University Langone Medical Center, New York, NY, 10016
| | - Virendra I Patel
- Division of Cardiac, Thoracic, and Vascular Surgery, New York Presbyterian / Columbia University Irving Medical Center / Columbia University College of Physicians and Surgeons, New York, NY 10032
| | - Igor Laskowski
- Division of Vascular and Endovascular Surgery, Department of Surgery, Westchester Medical Center, New York Medical College, Valhalla, NY, 10959
| | - Karan Garg
- New York University Langone Medical Center, 530 First Avenue, 11(th) floor, New York, NY, 10016.
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Kraft WK. Clinical Pharmacology and the Best Use of Public Research Investment. Clin Pharmacol Ther 2022; 111:1185-1188. [PMID: 35586960 DOI: 10.1002/cpt.2590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 03/25/2022] [Indexed: 11/11/2022]
Affiliation(s)
- Walter K Kraft
- Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
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12
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Liu M, Yuan L, Zhu C, Pan C, Gao Q, Wang H, Cheng Z, Epstein IR. Peptide-modulated pH rhythms. Chemphyschem 2022; 23:e202200103. [PMID: 35648769 DOI: 10.1002/cphc.202200103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 05/31/2022] [Indexed: 11/11/2022]
Abstract
Many drugs adjust and/or control the spatiotemporal dynamics of periodic processes such as heartbeat, neuronal signaling and metabolism, often by interacting with proteins or oligopeptides. Here we use a quasi-biocompatible, non-equilibrium pH oscillatory system as a biomimetic biological clock to study the effect of pH-responsive peptides on rhythm dynamics. The added peptides generate a feedback that can lengthen or shorten the oscillatory period during which the peptides alternate between random coil and coiled-coil conformations. This modulation of a chemical clock supports the notion that short peptide reagents may have utility as drugs to regulate human body clocks.
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Affiliation(s)
- Mengfei Liu
- China University of Mining and Technology, Chemical Engineering, CHINA
| | - Ling Yuan
- China University of Mining and Technology, Chemical Engineering, CHINA
| | - Chenghao Zhu
- China University of Mining and Technology, Chemical Engineering, CHINA
| | - Changwei Pan
- China University of Mining and Technology, Chemical Engineering, CHINA
| | - Qingyu Gao
- China University of Mining and Technology, Chemical Engineering, CHINA
| | - Hongzhang Wang
- China University of Mining and Technology, Chemical Engineering, CHINA
| | - Zhenfang Cheng
- China University of Mining and Technology, Chemical Engineering, CHINA
| | - Irving R Epstein
- Brandeis University, Chemistry Department, 415 South Street, MS 015, 02454, Waltham, UNITED STATES
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13
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Chrysant SG, Chrysant GS. Antihypertensive and cardioprotective effects of three generations of beta-adrenergic blockers: an historical perspective. Hosp Pract (1995) 2022; 50:196-202. [PMID: 35157531 DOI: 10.1080/21548331.2022.2040920] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
There are currently, 3 generations of beta-adrenergic blockers for the treatment of hypertension and cardiovascular diseases. The 1st generation caused vasoconstriction and bronchoconstriction due to β1 + β2 receptor blockade and unopposed α1 receptors. The 2nd generation of beta-blockers has lesser adverse effects than the 1st generation with the 3rd generation beta-blockers having much lesser effects than the other two generations. Current US and International guideline do not recommend beta-blockers as first line therapy of hypertension, but only in the presence of coronary artery disease or heart failure due to their lesser antihypertensive effect. These recommendations are disputed by several older and recent studies which have shown that the beta-blockers are effective and safe for the treatment of hypertension and could be used as first line therapy. To clarify this issue a Medline search of the English language literature was conducted between 2012 and 2021 and 30 pertinent papers were selected. The data from these studies show that the beta-blockers have inferior antihypertensive and stroke protective effect compared with the other classes of antihypertensive drugs and should be used as first line therapy only in patients with hypertension associated with coronary artery disease or heart failure. The information from these papers and collateral literature will be discussed in this perspective.
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Affiliation(s)
- Steven G Chrysant
- Department of Cardiology University of Oklahoma Health Sciences Center, Oklahoma, OK, USA
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14
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Méndez-Bailón M, Sobrino JLB, Marco-Martínez J, Elola-Somoza J, Márquez MG, Fernández-Pérez C, Azana-Gómez J, García-Klepzig JL, Andrès E, Zapatero-Gaviria A, Barba-Martin R, Canora-Lebrato J, Lorenzo-Villalba N. Heart failure and in-hospital mortality in elderly patients after elective noncardiac surgery in Spain. Med Clin (Barc) 2022; 159:307-312. [DOI: 10.1016/j.medcli.2021.11.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 11/18/2021] [Accepted: 11/21/2021] [Indexed: 10/19/2022]
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15
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El-Menyar A, Asim M, Bahey AAA, Chughtai T, Alyafai A, Abdelrahman H, Rizoli S, Peralta R, Al-Thani H. Beta blocker use in traumatic brain injury based on the high-sensitive troponin status (BBTBBT): methodology and protocol implementation of a double-blind randomized controlled clinical trial. Trials 2021; 22:890. [PMID: 34876207 PMCID: PMC8650244 DOI: 10.1186/s13063-021-05872-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 11/24/2021] [Indexed: 11/21/2022] Open
Abstract
Background Beta-adrenergic receptor blockers (BB) play an important role in the protection of organs that are susceptible for secondary injury due to stress-induced adrenergic surge. However, the use of BB in traumatic brain injury (TBI) patients is not yet the standard of care which necessitates clear scientific evidence to be used. The BBTBBT study aims to determine whether early administration of propranolol based on the high-sensitive troponin T(HsTnT) status will improve the outcome of TBI patients. We hypothesized that early propranolol use is effective in reducing 10- and 30-day mortality in TBI patients. Secondary outcomes will include correlation between serum biomarkers (troponin, epinephrine, cytokines, enolase, S100 calcium binding protein B) and the severity of injury and the impact of BB use on the duration of hospital stay and functional status at a 3-month period. Methods The BBTBBT study is a prospective, randomized, double-blinded, placebo-controlled three-arm trial of BB use in mild-to-severe TBI patients based on the HsTnT status. All enrolled patients will be tested for HsTnT at the first 4 and 6 h post-injury. Patients with positive HsTnT will receive BB if there is no contraindication (group 1). Patients with negative HsTnT will be randomized to receive either propranolol (group 2) or placebo (group 3). The time widow for receiving the study treatment is the first 24 h post-injury. Discussion Early BB use may reduce the catecholamine storm and subsequently the cascade of immune and inflammatory changes associated with TBI. HsTnT could be a useful fast diagnostic and prognostic tool in TBI patients. This study will be of great clinical interest to improve survival and functional outcomes of TBI patients. Trial registration ClinicalTrials.gov NCT04508244. Registered on 7 August 2020. Recruitment started on 29 December 2020 and is ongoing. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05872-8.
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Affiliation(s)
- Ayman El-Menyar
- Clinical Research, Trauma & Vascular Surgery Section, Hamad General Hospital (HGH), PO Box 3050, Doha, Qatar. .,Clinical Medicine, Weill Cornell Medical College, Doha, Qatar.
| | - Mohammad Asim
- Clinical Research, Trauma & Vascular Surgery Section, Hamad General Hospital (HGH), PO Box 3050, Doha, Qatar
| | | | - Talat Chughtai
- Department of Surgery, Trauma Surgery Section, HGH, Doha, Qatar.,Department of Surgery, Qatar University, Doha, Qatar
| | | | | | - Sandro Rizoli
- Department of Surgery, Trauma Surgery Section, HGH, Doha, Qatar
| | - Ruben Peralta
- Department of Surgery, Trauma Surgery Section, HGH, Doha, Qatar
| | - Hassan Al-Thani
- Department of Surgery, Trauma Surgery Section, HGH, Doha, Qatar
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16
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A systematic review and meta-analysis of real-world studies evaluating the association between beta-blocker use and postoperative adverse events of carotid endarterectomy (CEA). J Vasc Surg 2021; 75:1456-1465.e5. [PMID: 34788650 DOI: 10.1016/j.jvs.2021.10.052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Accepted: 10/27/2021] [Indexed: 11/22/2022]
Abstract
OBJECTIVE To estimate the association of beta-blocker use with postoperative adverse events of CEA based on real-world data. METHODS Electronic bibliographic sources (MEDLINE, EMBASE, and CENTRAL) were searched up to Apr. 2021 using a combination of thesaurus and free-text terms to identify the studies about the effect of beta-blockers on outcomes of CEA. The systematic review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. All observational studies and randomized controlled trials investigating the effect of preoperative beta-blockers on the outcomes of CEA were included. Independent extraction of articles by two authors using predefined data fields, including study quality indicators. All pooled analyses were based on a random-effects model. RESULTS A total of seven observational studies (six case-control studies and one cohort study) were included. Of the three case-control studies that examine the association of beta-blockers with composite postoperative adverse events, two studies including three datasets totaled 24161 participants were included in the quantitative synthesis and the overall results showed a statistically significant association between beta-blocker use and composite postoperative adverse events of CEA (OR 1.35, 95%CI 1.15- 1.59, p = .0003; I2 = 13%). Publication bias was not present in the meta-analysis (Egger's test showed non-significant results: p = .453). Two of the included studies utilized indirect measures of cerebral ischemia: intraoperative EEG, intraoperative hemodynamic indicators; and found a significant association between beta-blockers and intraoperative cerebral ischemia. Another two studies were included for meta-analysis on the association between beta-blockers and 30-day strokes or death of CEA (OR 1.61, 95%CI 0.98-2.65, p = .06; I2=0%). Of all included studies, there is only one cohort study that reported the association of beta-blockers with postoperative MI by chi-squared analysis (OR 1.96, 95%CI 1.86-2.07). CONCLUSION This systematic review suggested that there was an increased risk of postoperative adverse outcomes of CEA among beta-blocker users compared to non-users in the real world.
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17
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Effects of short-term bisoprolol on perioperative myocardial injury in patients undergoing non-cardiac surgery: a randomized control study. Sci Rep 2021; 11:22006. [PMID: 34759287 PMCID: PMC8581026 DOI: 10.1038/s41598-021-01365-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 10/27/2021] [Indexed: 11/09/2022] Open
Abstract
The protective role of preoperative beta-blocker in patients undergoing non-cardiac surgery is unknown. We aimed to evaluate the effects of beta-blocker on perioperative myocardial injury in patients undergoing non-cardiac surgery. We consecutively enrolled 112 patients undergoing non-cardiac surgery. They were randomly allocated to receive bisoprolol or placebo given at least 2 days preoperatively and continued until 30 days after surgery. The primary outcome was incidence of perioperative myocardial injury defined by a rise of high-sensitive troponin-T (hs-TnT) more than 99th percentile of upper reference limit or a rise of hs-TnT more than 20% if baseline level is abnormal. Baseline characteristics were comparable between bisoprolol and placebo in randomized cohort Mean age was 62.5 ± 11.8 years and 76 (67.8%) of 112 patients were male. Among 112 patients, 49 (43.8%) underwent vascular surgery and 63 (56.2%) underwent thoracic surgery. The median duration of assigned treatment prior to surgery was 4 days (2-6 days). We did not demonstrate the significant difference in the incidence of perioperative myocardial injury [52.6% (30 of 57 patients) vs. 49.1% (27 of 55 patients), P = 0.706]. In addition, the incidence of intraoperative hypotension was higher in bisoprolol group than placebo group in patients undergoing non-cardiac surgery [70.2% (40 of 57 patients) vs. 47.3% (26 of 55 patients), P = 0.017]. We demonstrated that there was no statistically significant difference in perioperative myocardial injury observed between patients receiving bisoprolol and placebo who had undergone non-cardiac surgery.
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18
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The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019). Hypertens Res 2020; 42:1235-1481. [PMID: 31375757 DOI: 10.1038/s41440-019-0284-9] [Citation(s) in RCA: 1262] [Impact Index Per Article: 252.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Wang J, Liu J, Xie L, Cai X, Ma X, Gong J. Bisoprolol, a β 1 antagonist, protects myocardial cells from ischemia-reperfusion injury via PI3K/AKT/GSK3β pathway. Fundam Clin Pharmacol 2020; 34:708-720. [PMID: 32363697 DOI: 10.1111/fcp.12562] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 04/23/2020] [Accepted: 04/29/2020] [Indexed: 12/30/2022]
Abstract
The aim of this work was to explore whether bisoprolol plays a protective role in cardiomyocytes against ischemia-reperfusion injury via PI3K/AKT/ GSK3β pathway. We pretreated male Sprague Dawley (SD) rats with bisoprolol by oral administration prior to 0.5 h ischemia/4 h reperfusion. Myocardial infarct size and serum levels of cTnI and CK-MB were measured. In vitro, H9c2 cells were treated with hypoxia and reoxygenation, followed by measurement of cell viability, apoptosis, ROS production, cytometry, activities of AKT, GSK3β, and p-38 in the presence and absence of GSK3β siRNA. We found that bisoprolol reduced infarct size from 44% in I/R group to 31% in treated group (P < 0.05). The levels of cTnI and CK-MB were decreased from 286 ± 7 pg/mL and 32.2 ± 2 ng/mL in I/R group to 196 ± 2 pg/mL and 19.6 ± 0.9 ng/mL in the treated group, respectively (P < 0.05). Bisoprolol also increased cell viability while decreased apoptosis and ROS production in the treatment of hypoxia/ reoxygenation. Furthermore, bisoprolol increased AKT and GSK3β phosphorylation, an effect that was immediately eliminated by LY294002. GSK3β-specific siRNA experiment further confirmed that bisoprolol protected the myocardium against hypoxia/reoxygenation-induced injury via suppressing GSK3β activity. In conclusion, bisoprolol protected myocardium against ischemia-reperfusion injury via the PI3K/AKT/ GSK3β pathway.
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Affiliation(s)
- Jing Wang
- Department of Cardiology, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Rd., Nanjing, 210002, Jiangsu, China
| | - Jing Liu
- Department of Cardiology, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Rd., Nanjing, 210002, Jiangsu, China
| | - Liang Xie
- Department of Cardiology, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Rd., Nanjing, 210002, Jiangsu, China
| | - Xiaomin Cai
- Department of Cardiology, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Rd., Nanjing, 210002, Jiangsu, China
| | - Xiaohua Ma
- Department of Cardiology, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Rd., Nanjing, 210002, Jiangsu, China
| | - Jianbin Gong
- Department of Cardiology, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Rd., Nanjing, 210002, Jiangsu, China
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20
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Abstract
The cardiovascular effects of beta blockers are widespread, so their use in the perioperative period ought to be beneficial, although this is not clear cut. This article discusses the evidence for and against the use of beta blockers perioperatively and gives guidance for best practice.
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Affiliation(s)
- Mark Prince
- Department of Anaesthesia, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
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21
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Alegria S, Costa J, Vaz-Carneiro A, Caldeira D. Cochrane Corner: Perioperative beta-blockers for preventing surgery-related mortality and morbidity. Rev Port Cardiol 2020; 38:691-694. [PMID: 31928792 DOI: 10.1016/j.repc.2018.10.014] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Accepted: 10/28/2018] [Indexed: 10/25/2022] Open
Abstract
Randomized controlled trials have yielded conflicting results regarding the impact of beta-blockers on perioperative cardiovascular morbidity and mortality. This Cochrane systematic review assessed the impact of this intervention on mortality and cardiovascular events. Eighty-eight randomized controlled trials with 19 161 participants were included (53 trials on cardiac surgery and 35 trials on non-cardiac surgery). In cardiac surgery perioperative beta-blockers had a protective effect against supraventricular and ventricular arrhythmias but had no significant effect on mortality or on the occurrence of acute myocardial infarction (AMI), stroke, heart failure, hypotension or bradycardia. In non-cardiac surgery, beta-blockers had a protective effect against AMI and arrhythmias, but this was counterbalanced by an increased risk of death and stroke. In conclusion, perioperative use of beta-blockers appears overall to be beneficial in cardiac surgery. However, in non-cardiac surgery the substantial reduction in rhythm disturbances and AMI appears to be offset by an increase in mortality and stroke, and so the systematic use of beta-blockers in this setting is not recommended.
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Affiliation(s)
- Sofia Alegria
- Serviço de Cardiologia, Hospital Garcia de Orta, Almada, Portugal
| | - João Costa
- Centro de Estudos de Medicina Baseada na Evidência, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Centro Colaborador Português da Rede Cochrane Iberoamericana, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Laboratório de Farmacologia Clínica e Terapêutica, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal
| | - António Vaz-Carneiro
- Centro de Estudos de Medicina Baseada na Evidência, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Centro Colaborador Português da Rede Cochrane Iberoamericana, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
| | - Daniel Caldeira
- Laboratório de Farmacologia Clínica e Terapêutica, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal; Serviço de Cardiologia, Hospital Universitário de Santa Maria (CHLN), CAML, Centro Cardiovascular da Universidade de Lisboa - CCUL, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal.
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22
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Kotlovskiy MY, Udut EV, Kairov GT, Fisenko VP, Udut VV. Effects of Simvastatin on the Metabolism of Fatty Acids in Combined Secondary Prevention of Coronary Heart Disease: Dosage and Gender Differences between the Effects. Cardiovasc Hematol Disord Drug Targets 2020; 20:93-107. [PMID: 31916523 DOI: 10.2174/1871529x20666200109144353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2018] [Revised: 11/12/2019] [Accepted: 11/26/2019] [Indexed: 11/22/2022]
Abstract
BACKGROUND Statins are currently used for secondary prevention of Coronary Heart Disease (CHD), as the lipid-lowering therapy with them is proven safe and effective. OBJECTIVE The purpose of this research is to investigate the dose-dependent effect of statins used for secondary prevention of coronary heart disease, as well as mechanisms of quantitative and qualitative changes in lipoproteins, fatty acids and cholesterol in the blood and tissues of people of both sexes. METHODS In a clinical trial (n=125, of which 89 patients belong to group 1 and 36 to group 2) and an experiment on laboratory animals (n = 100), simvastatin reduced the total level of fatty acids in blood plasma, when given in the amount that was within the therapeutic dose range. RESULTS This effect was achieved through a drug-induced improvement in the capacity of hepatic cells to absorb Low-density (LDL) and Very-low-density (VLDL) lipoproteins. CONCLUSION Considering the formation of saturated fatty acids, statin performed better in males. With Omega-3 polyunsaturated fatty acids involved, changes in lipoproteins, cholesterol and fatty acids (liver and myocardium) were similar to those caused by small doses of a statin drug. Effects of the combination of bisoprolol and acetylsalicylic acid were completely different from those caused by the use of statin.
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Affiliation(s)
- Mikhail Y Kotlovskiy
- Laboratory of Drug Toxicology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center of the Russian Academy of Science, Tomsk, Russian Federation.,Laboratory of Drug Toxicology, National Research Tomsk State University, Tomsk, Russian Federation
| | - Elena V Udut
- Central Research Laboratory, Siberian State Medical University, Tomsk, Russian Federation
| | - Gaisa T Kairov
- Central Research Laboratory, Siberian State Medical University, Tomsk, Russian Federation
| | - Vladimir P Fisenko
- Department Pharmacology, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation
| | - Vladimir V Udut
- Laboratory of Drug Toxicology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center of the Russian Academy of Science, Tomsk, Russian Federation.,Laboratory of Drug Toxicology, National Research Tomsk State University, Tomsk, Russian Federation
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23
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Magoon R, Makhija N, Das D. Perioperative myocardial injury and infarction following non-cardiac surgery: A review of the eclipsed epidemic. Saudi J Anaesth 2020; 14:91-99. [PMID: 31998026 PMCID: PMC6970380 DOI: 10.4103/sja.sja_499_19] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 09/02/2019] [Indexed: 12/23/2022] Open
Abstract
The perioperative period induces unpredictable and significant alterations in coronary plaque characteristics which may culminate as adverse cardiovascular events in background of a compromised myocardial oxygen supply and demand balance. This “ischemic-imbalance” provides a substrate for perioperative cardiac adversities which incur a considerable morbidity and mortality. The propensity of myocardial injury is dictated by the conglomeration of various factors like pre-existing medical condition, high-risk surgical interventions, intraoperative hemodynamic management, and the postoperative care. Perioperative myocardial infarction (PMI) differs from myocardial infarction (MI) in a non-operative setting. PMI can often be notoriously “silent” demonstrating a conspicuous absence of the classic clinical symptoms. Moreover, myocardial injury following non-cardiac surgery (MINS) characterized by an elevation of the cardiac insult biomarkers has demonstrated an independent prognostic significance in the perioperative scenario despite the lack of a formal categorization as PMI. This has evoked interest in the meticulous characterization of MINS as a discrete clinical entity. Multifactorial etiology, varying symptomatology, close differential diagnosis, and a debatable management regime makes perioperative myocardial injury-infarction, a subject of detailed discussion.
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Affiliation(s)
- Rohan Magoon
- Department of Cardiac Anaesthesia, Cardiothoracic Centre, CNC, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
| | - Neeti Makhija
- Department of Cardiac Anaesthesia, Cardiothoracic Centre, CNC, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
| | - Devishree Das
- Department of Cardiac Anaesthesia, Cardiothoracic Centre, CNC, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
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24
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Peterson CY, Blank J, Ludwig K. Colorectal Cancer in Elderly Patients: Considerations in Treatment and Management. PRINCIPLES AND PRACTICE OF GERIATRIC SURGERY 2020:903-929. [DOI: 10.1007/978-3-319-47771-8_59] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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25
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Preoperative β-blocker use correlates with worse outcomes in patients undergoing aortic valve replacement. J Thorac Cardiovasc Surg 2019; 158:1589-1597.e3. [DOI: 10.1016/j.jtcvs.2018.12.108] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Revised: 12/17/2018] [Accepted: 12/20/2018] [Indexed: 01/26/2023]
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26
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Koutsaki M, Patoulias D, Tsinivizov P, Doumas M, Kallistratos M, Thomopoulos C, Poulimenos L, Agnelli G, Mancia G, Manolis A. Evaluation, risk stratification and management of hypertensive patients in the perioperative period. Eur J Intern Med 2019; 69:1-7. [PMID: 31606306 DOI: 10.1016/j.ejim.2019.09.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 08/18/2019] [Accepted: 09/15/2019] [Indexed: 12/19/2022]
Abstract
Uncontrolled hypertension represents an important cause for postponing a non-cardiac surgery. Perioperative management of hypertensive patients should focus on cardiovascular risk stratification, evaluation of blood pressure levels and hypertension control, registration of the ongoing antihypertensive regimen and counseling about clinical decisions related to the expected perioperative blood pressure fluctuations. To date, there is a lack of evidence on how hypertensive patients should be perioperatively treated, while an empirical clinical approach is usually pursued in the usual practice. The present review appraises the gaps in the evidence and illustrates the current empirical approach of perioperative management of hypertension in non-cardiac surgery.
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Affiliation(s)
- Maria Koutsaki
- Department of Cardiology, Asklepeion General Hospital, Athens, Greece
| | - Dimitrios Patoulias
- Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Pavlos Tsinivizov
- Department of Cardiology, Asklepeion General Hospital, Athens, Greece
| | - Michael Doumas
- Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
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27
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Contemporary personalized β-blocker management in the perioperative setting. J Anesth 2019; 34:115-133. [PMID: 31637510 DOI: 10.1007/s00540-019-02691-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Accepted: 09/26/2019] [Indexed: 10/25/2022]
Abstract
Beta-adrenergic blockers (β-blockers) are clearly indicated for the long-term treatment of patients with systolic heart failure and post-acute myocardial infarction. Early small-scale studies reported their potential benefits for perioperative use; subsequent randomized controlled trials, however, failed to reproduce earlier findings. Furthermore, their role in reducing major postoperative cardiac events following noncardiac and cardiac surgery remains controversial. This case-based review presents an overview of contemporary literature on perioperative β-blocker use with a focus on data available since 2008 when the PreOperative ISchemic Evaluation (POISE) trial was published. Our review suggests that studies should determine the effects of situational-based guidelines on perioperative β-blocker use on the risk of cardiac adverse events and mortality in the perioperative period.
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28
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Alegria S, Costa J, Vaz-Carneiro A, Caldeira D. Cochrane Corner: Perioperative beta-blockers for preventing surgery-related mortality and morbidity. REVISTA PORTUGUESA DE CARDIOLOGIA (ENGLISH EDITION) 2019. [DOI: 10.1016/j.repce.2020.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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Blessberger H, Lewis SR, Pritchard MW, Fawcett LJ, Domanovits H, Schlager O, Wildner B, Kammler J, Steinwender C, Cochrane Anaesthesia Group. Perioperative beta-blockers for preventing surgery-related mortality and morbidity in adults undergoing non-cardiac surgery. Cochrane Database Syst Rev 2019; 9:CD013438. [PMID: 31556094 PMCID: PMC6761481 DOI: 10.1002/14651858.cd013438] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Randomized controlled trials (RCTs) have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and mortality. Thus routine prescription of these drugs in an unselected population remains a controversial issue. A previous version of this review assessing the effectiveness of perioperative beta-blockers in cardiac and non-cardiac surgery was last published in 2018. The previous review has now been split into two reviews according to type of surgery. This is an update, and assesses the evidence in non-cardiac surgery only. OBJECTIVES To assess the effectiveness of perioperatively administered beta-blockers for the prevention of surgery-related mortality and morbidity in adults undergoing non-cardiac surgery. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, CINAHL, Biosis Previews and Conference Proceedings Citation Index-Science on 28 June 2019. We searched clinical trials registers and grey literature, and conducted backward- and forward-citation searching of relevant articles. SELECTION CRITERIA We included RCTs and quasi-randomized studies comparing beta-blockers with a control (placebo or standard care) administered during the perioperative period to adults undergoing non-cardiac surgery. If studies included surgery with different types of anaesthesia, we included them if 70% participants, or at least 100 participants, received general anaesthesia. We excluded studies in which all participants in the standard care control group were given a pharmacological agent that was not given to participants in the intervention group, studies in which all participants in the control group were given a beta-blocker, and studies in which beta-blockers were given with an additional agent (e.g. magnesium). We excluded studies that did not measure or report review outcomes. DATA COLLECTION AND ANALYSIS Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We assessed the certainty of evidence with GRADE. MAIN RESULTS We included 83 RCTs with 14,967 participants; we found no quasi-randomized studies. All participants were undergoing non-cardiac surgery, and types of surgery ranged from low to high risk. Types of beta-blockers were: propranolol, metoprolol, esmolol, landiolol, nadolol, atenolol, labetalol, oxprenolol, and pindolol. In nine studies, beta-blockers were titrated according to heart rate or blood pressure. Duration of administration varied between studies, as did the time at which drugs were administered; in most studies, it was intraoperatively, but in 18 studies it was before surgery, in six postoperatively, one multi-arm study included groups of different timings, and one study did not report timing of drug administration. Overall, we found that more than half of the studies did not sufficiently report methods used for randomization. All studies in which the control was standard care were at high risk of performance bias because of the open-label study design. Only two studies were prospectively registered with clinical trials registers, which limited the assessment of reporting bias. In six studies, participants in the control group were given beta-blockers as rescue therapy during the study period.The evidence for all-cause mortality at 30 days was uncertain; based on the risk of death in the control group of 25 per 1000, the effect with beta-blockers was between two fewer and 13 more per 1000 (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.89 to 1.54; 16 studies, 11,446 participants; low-certainty evidence). Beta-blockers may reduce the incidence of myocardial infarction by 13 fewer incidences per 1000 (RR 0.72, 95% CI 0.60 to 0.87; 12 studies, 10,520 participants; low-certainty evidence). We found no evidence of a difference in cerebrovascular events (RR 1.65, 95% CI 0.97 to 2.81; 6 studies, 9460 participants; low-certainty evidence), or in ventricular arrhythmias (RR 0.72, 95% CI 0.35 to 1.47; 5 studies, 476 participants; very low-certainty evidence). Beta-blockers may reduce atrial fibrillation or flutter by 26 fewer incidences per 1000 (RR 0.41, 95% CI 0.21 to 0.79; 9 studies, 9080 participants; low-certainty evidence). However, beta-blockers may increase bradycardia by 55 more incidences per 1000 (RR 2.49, 95% CI 1.74 to 3.56; 49 studies, 12,239 participants; low-certainty evidence), and hypotension by 44 more per 1000 (RR 1.40, 95% CI 1.29 to 1.51; 49 studies, 12,304 participants; moderate-certainty evidence).We downgraded the certainty of the evidence owing to study limitations; some studies had high risks of bias, and the effects were sometimes altered when we excluded studies with a standard care control group (including only placebo-controlled trials showed an increase in early mortality and cerebrovascular events with beta-blockers). We also downgraded for inconsistency; one large, well-conducted, international study found a reduction in myocardial infarction, and an increase in cerebrovascular events and all-cause mortality, when beta-blockers were used, but other studies showed no evidence of a difference. We could not explain the reason for the inconsistency in the evidence for ventricular arrhythmias, and we also downgraded this outcome for imprecision because we found few studies with few participants. AUTHORS' CONCLUSIONS The evidence for early all-cause mortality with perioperative beta-blockers was uncertain. We found no evidence of a difference in cerebrovascular events or ventricular arrhythmias, and the certainty of the evidence for these outcomes was low and very low. We found low-certainty evidence that beta-blockers may reduce atrial fibrillation and myocardial infarctions. However, beta-blockers may increase bradycardia (low-certainty evidence) and probably increase hypotension (moderate-certainty evidence). Further evidence from large placebo-controlled trials is likely to increase the certainty of these findings, and we recommend the assessment of impact on quality of life. We found 18 studies awaiting classification; inclusion of these studies in future updates may also increase the certainty of the evidence.
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Affiliation(s)
- Hermann Blessberger
- Kepler University Hospital, Medical Faculty of the Johannes Kepler University LinzDepartment of Cardiology, Med Campus IIIKrankenhausstraße 9LinzAustria4020
| | - Sharon R Lewis
- Royal Lancaster InfirmaryLancaster Patient Safety Research UnitPointer Court 1, Ashton RoadLancasterUKLA1 4RP
| | - Michael W Pritchard
- Royal Lancaster InfirmaryLancaster Patient Safety Research UnitPointer Court 1, Ashton RoadLancasterUKLA1 4RP
| | - Lizzy J Fawcett
- Royal Lancaster InfirmaryLancaster Patient Safety Research UnitPointer Court 1, Ashton RoadLancasterUKLA1 4RP
| | - Hans Domanovits
- Vienna General Hospital, Medical University of ViennaDepartment of Emergency MedicineWähringer Gürtel 18‐20ViennaAustria1090
| | - Oliver Schlager
- Vienna General Hospital, Medical University of ViennaDepartment of Internal Medicine II, Division of AngiologyWähringer Gürtel 18‐20ViennaAustria1090
| | - Brigitte Wildner
- University Library of the Medical University of ViennaInformation Retrieval OfficeWähringer Gürtel 18‐20ViennaAustria1090
| | - Juergen Kammler
- Kepler University Hospital, Medical Faculty of the Johannes Kepler University LinzDepartment of Cardiology, Med Campus IIIKrankenhausstraße 9LinzAustria4020
| | - Clemens Steinwender
- Kepler University Hospital, Medical Faculty of the Johannes Kepler University LinzDepartment of Cardiology, Med Campus IIIKrankenhausstraße 9LinzAustria4020
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Eldrup-Jorgensen J. The role of cardiac risk stratification in preoperative beta blockade. J Vasc Surg 2019; 70:1021. [PMID: 31445645 DOI: 10.1016/j.jvs.2019.05.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Accepted: 05/18/2019] [Indexed: 10/26/2022]
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Beattie WS, Yang H. Perioperative beta-adrenergic antagonism: panacea or poison? Br J Anaesth 2019; 123:97-100. [PMID: 31248641 PMCID: PMC6676158 DOI: 10.1016/j.bja.2019.05.039] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Revised: 05/16/2019] [Accepted: 05/26/2019] [Indexed: 01/24/2023] Open
Affiliation(s)
- W Scott Beattie
- University Health Network Department of Anesthesia and Pain Medicine, University of Toronto Department of Anesthesia, Toronto, ON, Canada.
| | - Homer Yang
- Department of Anesthesia and Perioperative Medicine, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada
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Kertai MD, Cooter M, Pollard RJ, Buhrman W, Aronson S, Mathew JP, Stafford-Smith M. Is Compliance With Surgical Care Improvement Project Cardiac (SCIP-Card-2) Measures for Perioperative β-Blockers Associated With Reduced Incidence of Mortality and Cardiovascular-Related Critical Quality Indicators After Noncardiac Surgery? Anesth Analg 2019; 126:1829-1838. [PMID: 29200062 DOI: 10.1213/ane.0000000000002577] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND While continuation of β-blockers (BBs) perioperatively has become a national quality improvement measure, the relationship between BB withdrawal and mortality and cardiovascular-related critical quality indicators has not been studied in a contemporary cohort of patients undergoing noncardiac surgery. METHODS For this retrospective study, the quality assurance database of a large community-based anesthesiology group practice was used to identify 410,288 surgical cases, 18 years of age or older, who underwent elective or emergent noncardiac surgical procedures between January 1, 2009, and December 31, 2014. Each surgical case that was withdrawn from BBs perioperatively was propensity matched by clinical and surgical characteristics to 4 cases that continued BBs perioperatively. Subsequently, multivariable conditional logistic regression analyses were performed in the matched cohort to determine the extent to which withdrawal of perioperative BBs was independently associated with mortality as the primary outcome and cardiovascular-related critical quality indicators as the secondary outcome (need for vasopressor, electrocardiographic changes requiring treatment, unplanned admission to intensive care unit, postanesthesia care unit stay >2 hours, and a combination of cardiac arrest and myocardial infarction) within 48 hours postoperatively. RESULTS Of the 66,755 (16%) cases in the cohort admitted on BB therapy, BBs were withdrawn in 3829 (6%) and continued in 62,926 (94%). Propensity score matching resulted in an analysis cohort of 19,145 cases. Withdrawal of perioperative BBs in the multivariable conditional logistic regression analysis was significantly associated with an increased risk for mortality (odds ratio [OR], 3.61; 95% confidence interval [CI], 1.75-7.35; P = .0003), but a significantly decreased risk for need of blood pressure support requiring vasopressor initiation (OR, 0.84; 95% CI, 0.76-0.92; P = .0003) and extended postanesthesia care unit stay (OR, 0.69; 95% CI, 0.54-0.88; P = .004) within 48 hours after noncardiac surgery. CONCLUSIONS Perioperative withdrawal of BBs was associated with increased risk for mortality within 48 hours after noncardiac surgery and with decreased risk for need of vasopressor during the early postoperative period and a shorter stay in the postanesthesia care unit.
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Affiliation(s)
- Miklos D Kertai
- From the Division of Cardiothoracic Anesthesiology and Critical Care Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina
| | - Mary Cooter
- From the Division of Cardiothoracic Anesthesiology and Critical Care Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina
| | | | | | - Solomon Aronson
- From the Division of Cardiothoracic Anesthesiology and Critical Care Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina
| | - Joseph P Mathew
- From the Division of Cardiothoracic Anesthesiology and Critical Care Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina
| | - Mark Stafford-Smith
- From the Division of Cardiothoracic Anesthesiology and Critical Care Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina
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Jacka MJ, Guyatt G, Mizera R, Van Vlymen J, Ponce de Leon D, Schricker T, Bahari MY, Lv B, Afzal L, Plou García MP, Wu X, Nigro Maia L, Arrieta M, Rao-Melacini P, Devereaux PJ. Age Does Not Affect Metoprolol's Effect on Perioperative Outcomes (From the POISE Database). Anesth Analg 2019; 126:1150-1157. [PMID: 29369093 PMCID: PMC5882297 DOI: 10.1213/ane.0000000000002804] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
BACKGROUND: Perioperative β-blockade reduces the incidence of myocardial infarction but increases that of death, stroke, and hypotension. The elderly may experience few benefits but more harms associated with β-blockade due to a normal effect of aging, that of a reduced resting heart rate. The tested hypothesis was that the effect of perioperative β-blockade is more significant with increasing age. METHODS: To determine whether the effect of perioperative β-blockade on the primary composite event, clinically significant hypotension, myocardial infarction, stroke, and death varies with age, we interrogated data from the perioperative ischemia evaluation (POISE) study. The POISE study randomly assigned 8351 patients, aged ≥45 years, in 23 countries, undergoing major noncardiac surgery to either 200 mg metoprolol CR daily or placebo for 30 days. Odds ratios or hazard ratios for time to events, when available, for each of the adverse effects were measured according to decile of age, and interaction term between age and treatment was calculated. No adjustment was made for multiple outcomes. RESULTS: Age was associated with higher incidences of the major outcomes of clinically significant hypotension, myocardial infarction, and death. Age was associated with a minimal reduction in resting heart rate from 84.2 (standard error, 0.63; ages 45–54 years) to 80.9 (standard error, 0.70; ages >85 years; P < .0001). We found no evidence of any interaction between age and study group regarding any of the major outcomes, although the limited sample size does not exclude any but large interactions. CONCLUSIONS: The effect of perioperative β-blockade on the major outcomes studied did not vary with age. Resting heart rate decreases slightly with age. Our data do not support a recommendation for the use of perioperative β-blockade in any age subgroup to achieve benefits but avoid harms. Therefore, current recommendations against the use of β-blockers in high-risk patients undergoing noncardiac surgery apply across all age groups.
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Affiliation(s)
- Michael J Jacka
- From the Department of Anesthesiology and Critical Care, University of Alberta, Edmonton, Alberta, Canada
| | - Gordon Guyatt
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Richard Mizera
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Janet Van Vlymen
- Department of Anesthesiology, Queen's University, Kingston, Ontario, Canada
| | | | - Thomas Schricker
- Department of Anesthesiology, McGill University, Montreal, Quebec, Canada
| | - Mohd Yani Bahari
- Department of Medicine, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia
| | - Bonan Lv
- Department of Surgery, Heibei People's Hospital, Shijiazhuang, China
| | - Lalitha Afzal
- Department of Medicine, Christian Medical College, Ludhiana, India
| | | | - Xinmin Wu
- Department of Surgery, First Hospital, Beijing University, Beijing, China
| | - Lília Nigro Maia
- Hospital de Base Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, Brazil
| | - Maribel Arrieta
- Department of Medicine, Hospital Militar Central, Bogota, Columbia
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Walter S, Guyatt G, Bassler D, Briel M, Ramsay T, Han H. Randomised trials with provision for early stopping for benefit (or harm): The impact on the estimated treatment effect. Stat Med 2019; 38:2524-2543. [DOI: 10.1002/sim.8142] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Revised: 01/26/2019] [Accepted: 02/20/2019] [Indexed: 11/08/2022]
Affiliation(s)
- S.D. Walter
- Department of Health Research Methods, Evidence, and ImpactMcMaster University Hamilton Canada
| | - G.H. Guyatt
- Department of Health Research Methods, Evidence, and ImpactMcMaster University Hamilton Canada
| | - D. Bassler
- Department of Neonatology, University Hospital ZurichUniversity of Zurich Zürich Switzerland
| | - M. Briel
- Department of Health Research Methods, Evidence, and ImpactMcMaster University Hamilton Canada
- Basel Institute for Clinical Epidemiology and BiostatisticsUniversity Hospital Basel Basel Switzerland
| | - T. Ramsay
- Ottawa Hospital Research InstituteUniversity of Ottawa Ottawa Canada
| | - H.D. Han
- Mount Sinai Hospital Toronto Canada
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Abstract
The aim of our study was to describe the knowledge and practice of New Zealand anaesthetists in relation to perioperative beta-adrenergic blockade, and to define barriers to implementation of perioperative beta-blockade in surgical patients at risk of myocardial ischaemia. A survey was sent to 400 New Zealand specialist anaesthetists. Information was sought on their knowledge and current practice relating to perioperative beta-blockade, and the barriers encountered to implementing therapy. The response rate was 59%. Perioperative beta-blockade was seen as beneficial in at risk patients by 95% of responding anaesthetists, but practice varied widely. Only 45% of anaesthetists always or usually commenced a beta blocker perioperatively, a department protocol was available to only 20%, and understanding of indications and contraindications to beta-blockade varied. There were logistical difficulties when initiating and monitoring perioperative beta-blocker regimens, and where treatment required multidisciplinary commitment. The lack of clarity of the guidelines was also a barrier to more widespread use. Difficulties were encountered relating general guidelines to individual patients, when co-morbidities, concurrent treatment and the influence of regional or general anaesthesia may influence the risk/benefit ratio. This study has identified variations in practice and reasons why New Zealand anaesthetists use of perioperative beta-blockers is at odds with published guidelines. Deficiencies in the guidelines are part of the problem. However, even with consensus on guidelines, effective multidisciplinary strategies will be required to optimize treatment of patients at risk of perioperative cardiac events.
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Affiliation(s)
- J Weller
- Department of Anaesthesiology, Wellington School of Medicine, University of Otago, New Zealand
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Shannon AH, Mehaffey JH, Cullen JM, Hawkins RB, Roy R, Upchurch GR, Robinson WP. Preoperative beta blockade is associated with increased rates of 30-day major adverse cardiac events in critical limb ischemia patients undergoing infrainguinal revascularization. J Vasc Surg 2018; 69:1167-1172.e1. [PMID: 30598355 DOI: 10.1016/j.jvs.2018.07.077] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Accepted: 07/22/2018] [Indexed: 11/15/2022]
Abstract
OBJECTIVE The association between beta blockers and cardiovascular or limb-related outcomes after revascularization for critical limb ischemia (CLI) remains unclear. The objective of this study was to assess the impact of preoperative beta blockade on 30-day major adverse cardiac events (MACEs) and major adverse limb events (MALEs) in patients undergoing infrainguinal revascularization for CLI. We hypothesized that rates of MALEs and MACEs will be higher in patients not receiving preoperative beta blockade. METHODS The National Surgical Quality Improvement Program vascular targeted file for 2011 to 2014 identified patients receiving beta blockade and undergoing infrainguinal endovascular intervention and open bypass for CLI. Primary outcomes including 30-day MACE (stroke, myocardial infarction [MI], or death) and MALE (untreated loss of patency, reintervention, or amputation) were compared between patients taking and not taking preoperative beta blockers. Multivariate logistic regression identified independent predictors of MACEs and MALEs. RESULTS A total of 11,785 revascularizations were performed for CLI during the study period (7408 bypasses vs 4377 endovascular interventions). Preoperative beta blockers were used by 7365 patients, including 4541 (61.7%) in the open bypass cohort and 2824 (64.5%) in the endovascular group (P < .01). MACEs and MI were significantly higher in patients with preoperative beta blockers (MACEs, 5.8% vs 3.4% [P < .0001]; MI, 3.1% vs 1.8% [P < .0001]). After controlling for cardiac risk factors, beta blockers independently predicted MACEs (odds ratio [OR], 1.27; P = .03) and MI (OR, 1.36; P = .03) but not stroke (OR, 1.17; P = .58) or 30-day mortality (OR, 1.22; P = .19). Beta-blocker use did not have an effect on MALEs (OR, 0.99; P = .88). CONCLUSIONS In patients with CLI, preoperative beta blockade was an independent predictor of 30-day MI and MACEs after controlling for other cardiovascular risk factors. Beta blockers did not have an impact on short-term limb-related outcomes. The association between beta blockade and revascularization for CLI deserves further investigation.
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Affiliation(s)
| | | | - J Michael Cullen
- Department of Surgery, University of Virginia, Charlottesville, Va
| | - Robert B Hawkins
- Department of Surgery, University of Virginia, Charlottesville, Va
| | - Rishi Roy
- Department of Surgery, University of Virginia, Charlottesville, Va
| | | | - William P Robinson
- Division of Vascular and Endovascular Surgery, University of Virginia, Charlottesville, Va.
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Early Resumption of β Blockers Is Associated with Decreased Atrial Fibrillation after Noncardiothoracic and Nonvascular Surgery. Anesthesiology 2018; 129:1101-1110. [DOI: 10.1097/aln.0000000000002457] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Abstract
Editor’s Perspective
What We Already Know about This Topic
What This Article Tells Us That Is New
Background
Beta (β) blockers reduce the risk of postoperative atrial fibrillation and should be restarted after surgery, but it remains unclear when best to resume β blockers postoperatively. The authors thus evaluated the relationship between timing of resumption of β blockers and atrial fibrillation in patients recovering from noncardiothoracic and nonvascular surgery.
Methods
The authors evaluated 8,201 adult β-blocker users with no previous history of atrial fibrillation who stayed at least two nights after noncardiothoracic and nonvascular surgery as a retrospective observational cohort. After propensity score matching on baseline and intraoperative variables, 1,924 patients who did resume β blockers by the end of postoperative day 1 were compared with 973 patients who had not resumed by that time on postoperative atrial fibrillation using logistic regression. A secondary matched analysis compared 3,198 patients who resumed β blockers on the day of surgery with 3,198 who resumed thereafter.
Results
Of propensity score–matched patients who resumed β blockers by end of postoperative day 1, 4.9% (94 of 1,924) developed atrial fibrillation, compared with 7.0% (68 of 973) of those who resumed thereafter (adjusted odds ratio, 0.69; 95% CI, 0.50–0.95; P = 0.026). Patients who resumed β blockers on day of surgery had an atrial fibrillation incidence of 4.9% versus 5.8% for those who started thereafter (odds ratio, 0.84; 95% CI, 0.67–1.04; P = 0.104).
Conclusions
Resuming β blockers in chronic users by the end of the first postoperative day may be associated with lower odds of in-hospital atrial fibrillation. However, there seems to be little advantage to restarting on the day of surgery itself.
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Lomivorotov VV, Efremov SM, Abubakirov MN, Belletti A, Karaskov AM. Perioperative Management of Cardiovascular Medications. J Cardiothorac Vasc Anesth 2018; 32:2289-2302. [DOI: 10.1053/j.jvca.2018.01.018] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Indexed: 12/28/2022]
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Ahl R, Matthiessen P, Fang X, Cao Y, Sjolin G, Lindgren R, Ljungqvist O, Mohseni S. Effect of beta-blocker therapy on early mortality after emergency colonic cancer surgery. Br J Surg 2018; 106:477-483. [DOI: 10.1002/bjs.10988] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Revised: 06/18/2018] [Accepted: 07/28/2018] [Indexed: 11/07/2022]
Abstract
Abstract
Background
Emergency colorectal cancer surgery is associated with significant mortality. Induced adrenergic hyperactivity is thought to be an important contributor. Downregulating the effects of circulating catecholamines may reduce the risk of adverse outcomes. This study assessed whether regular preoperative beta-blockade reduced mortality after emergency colonic cancer surgery.
Methods
This cohort study used the prospectively collected Swedish Colorectal Cancer Registry to recruit all adult patients requiring emergency colonic cancer surgery between 2011 and 2016. Patients were subdivided into those receiving regular beta-blocker therapy before surgery and those who were not (control). Demographics and clinical outcomes were compared. Risk factors for 30-day mortality were evaluated using Poisson regression analysis.
Results
A total of 3187 patients were included, of whom 685 (21·5 per cent) used regular beta-blocker therapy before surgery. The overall 30-day mortality rate was significantly reduced in the beta-blocker group compared with controls: 3·1 (95 per cent c.i. 1·9 to 4·7) versus 8·6 (7·6 to 9·8) per cent respectively (P < 0·001). Beta-blocker therapy was the only modifiable protective factor identified in multivariable analysis of 30-day all-cause mortality (incidence rate ratio 0·31, 95 per cent c.i. 0·20 to 0·47; P < 0·001) and was associated with a significant reduction in death of cardiovascular, respiratory, sepsis and multiple organ failure origin.
Conclusion
Preoperative beta-blocker therapy may be associated with a reduction in 30-day mortality following emergency colonic cancer surgery.
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Affiliation(s)
- R Ahl
- Department of Surgery, Karolinska University Hospital, Stockholm, Sweden
- School of Medical Sciences, Orebro University, Orebro, Sweden
| | - P Matthiessen
- School of Medical Sciences, Orebro University, Orebro, Sweden
- Department of Surgery, Orebro University Hospital, Orebro, Sweden
| | - X Fang
- Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Y Cao
- Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
- Clinical Epidemiology and Biostatistics, School of Medical Sciences, Orebro University, Orebro, Sweden
| | - G Sjolin
- School of Medical Sciences, Orebro University, Orebro, Sweden
- Department of Surgery, Orebro University Hospital, Orebro, Sweden
| | - R Lindgren
- Department of Surgery, Orebro University Hospital, Orebro, Sweden
| | - O Ljungqvist
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- School of Medical Sciences, Orebro University, Orebro, Sweden
| | - S Mohseni
- School of Medical Sciences, Orebro University, Orebro, Sweden
- Department of Surgery, Orebro University Hospital, Orebro, Sweden
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Miarons M, Tomsen N, Nascimento W, Espín À, López-Faixó D, Clavé P, Rofes L. Increased levels of substance P in patients taking beta-blockers are linked with a protective effect on oropharyngeal dysphagia. Neurogastroenterol Motil 2018; 30:e13397. [PMID: 30043538 DOI: 10.1111/nmo.13397] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2018] [Accepted: 05/23/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND We have recently found a potential protective effect of beta-blockers on oropharyngeal dysphagia (OD). The action mechanism by which beta-blockers could wield this protective effect is unknown, but the neurotransmitter substance P (SP) could play a key role. The aim of this study was to analyze serum and saliva SP levels in patients taking beta-blockers (TBB), and to explore its relationship with OD. METHODS Adult (>50 year) patients TBB were randomly recruited from the primary care setting and 1:1 matched by age, sex, and Barthel Index (BI) with patients not taking beta-blockers (NTBB). Serum and saliva samples were taken and analyzed for their SP levels using an enzyme-linked immunosorbent assay (ELISA). Socio-demographic and clinical variables were collected. Dysphagia was evaluated in all patients using the clinical volume-viscosity swallow test (V-VST). KEY RESULTS We studied 28 patients TBB (64.96 ± 7.31 years, 57.1% women, BI 99.6 ± 1.31, carvedilol-equivalent dose 24.11 ± 18.12 mg) and 28 patients NTBB (65.61 ± 6.43 years, 57.1% women, BI 99.6 ± 1.31). SP serum levels were significantly higher in patients TBB (260.68 ± 144.27 vs 175.46 ± 108.36 pg/mL, P = .009) as were SP saliva levels (170.34 ± 146.48 vs 102.73 ± 52.28 pg/mL, P < .001) compared with patients NTBB. The prevalence of OD was 32.1% in patients TBB and 67.9% in patients NTBB (P = .015). Moreover, patients with OD had significantly lower SP saliva levels in comparison with patients without clinical signs of OD (98.39 ± 43.25 vs 174.69 ± 147.21 pg/mL) P < .001. CONCLUSIONS & INFERENCES We have found that serum and saliva SP levels are greater in patients TBB. This increase in SP levels could be the action mechanism by which beta-blockers protect patients from OD.
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Affiliation(s)
- M Miarons
- Department of Pharmacy, Hospital de Mataró, Mataró, Spain
| | - N Tomsen
- Unitat d'Exploracions Funcionals Digestives, Department of Surgery, Hospital de Mataró, Universitat Autònoma de Barcelona, Mataró, Spain
| | - W Nascimento
- Unitat d'Exploracions Funcionals Digestives, Department of Surgery, Hospital de Mataró, Universitat Autònoma de Barcelona, Mataró, Spain
| | - À Espín
- Unitat d'Exploracions Funcionals Digestives, Department of Surgery, Hospital de Mataró, Universitat Autònoma de Barcelona, Mataró, Spain
| | - D López-Faixó
- Department of Pharmacy, Hospital de Mataró, Mataró, Spain
| | - P Clavé
- Unitat d'Exploracions Funcionals Digestives, Department of Surgery, Hospital de Mataró, Universitat Autònoma de Barcelona, Mataró, Spain.,Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Instituto de Salud Carlos III, Barcelona, Spain
| | - L Rofes
- Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Instituto de Salud Carlos III, Barcelona, Spain
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Association between perioperative β-blocker use and clinical outcome of non-cardiac surgery in coronary revascularized patients without severe ventricular dysfunction or heart failure. PLoS One 2018; 13:e0201311. [PMID: 30067841 PMCID: PMC6070245 DOI: 10.1371/journal.pone.0201311] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Accepted: 07/12/2018] [Indexed: 01/06/2023] Open
Abstract
Perioperative use of β-blocker has been encouraged in patients undergoing non-cardiac surgery despite weak evidence, especially in patients without left ventricular systolic dysfunction (LVSD) or heart failure (HF). This study evaluated the effects of perioperative β-blocker on clinical outcomes after non-cardiac surgery among coronary revascularized patients without LVSD or HF. Among a total of 503 patients with a history of coronary revascularization (either by percutaneous coronary intervention or coronary arterial bypass grafts) undergoing non-cardiac surgery, those without severe LVSD defined by ejection fraction over 30% or HF were evaluated. The primary outcome was a composite of death, myocardial infarction, repeat revascularization, and stroke during 1-year follow-up. Perioperative β-blocker was used in 271 (53.9%) patients. During 1-year follow-up, we found no significant difference in primary outcome between the two groups on multivariate analysis (hazard ratio [HR], 1.01; confidence interval [CI] 95%, 0.56–1.82; P = 0.963). The same result was shown in propensity-matched population (HR, 1.25; CI 95%, 0.65–2.38; P = 0.504). In coronary revascularized patients without severe LVSD or HF, perioperative β-blocker use may not be associated with postoperative clinical outcome of non-cardiac surgery. Larger registry data is needed to support this finding.
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Ostroumova OD, Kochetkov AI, Starodubova AV, Guseva ТF. NOVEL COMBINATION OF THE ANGIOTENSIN CONVERTING ENZYME INHIBITOR PERINDOPRIL AND HIGHLY SELECTIVE β-ADRENOBLOCKER BISOPROLOL: PRIME AMONG THE EQUAL. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2018. [DOI: 10.15829/1728-8800-2018-3-85-95] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
The article is focused on a broad evidence of antihypertension efficacy of perindopril and bisoprolol. The issues considered, of the drugs usage in patients with arterial hypertension, ischemic heart disease and chronic heart failure according to the international and local clinical guidelines. Special attention is paid for the influence of perindopril and bisoprolol on prognosis — the risk of cardiovascular complications from the evidence based medicine perspective. The data provided on a novel unique combination of these medications, and the benefits are accounted, as the mechanism of complimentary interaction; the results of randomized trials, clinical trials provided, that point on the high potential of this sort of combinational treatment.
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Affiliation(s)
- O. D. Ostroumova
- A. I. Evdokimov Moscow State University of Medicine and Dentistry of the Ministry of Health; I.M. Sechenov First Moscow State Medical University of the Ministry of Health
| | - A. I. Kochetkov
- A. I. Evdokimov Moscow State University of Medicine and Dentistry of the Ministry of Health. Moscow
| | - A. V. Starodubova
- Federal Research Cneter of Food, Biotechnologies and Food Safety; N. I. Pirogov Russian National Research Medical University of the Ministry of Health
| | - Т. F. Guseva
- A. I. Evdokimov Moscow State University of Medicine and Dentistry of the Ministry of Health. Moscow
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43
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Affiliation(s)
- Pierre Foëx
- From the Nuffield Division of Anaesthetics, University of Oxford, Oxford, United Kingdom
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Oprea AD, Lombard FW, Kertai MD. Perioperative β-Adrenergic Blockade in Noncardiac and Cardiac Surgery: A Clinical Update. J Cardiothorac Vasc Anesth 2018; 33:817-832. [PMID: 29934209 DOI: 10.1053/j.jvca.2018.04.045] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Indexed: 01/17/2023]
Affiliation(s)
- Adriana D Oprea
- Department of Anesthesiology, Yale School of Medicine, New Haven, CT
| | - Frederick W Lombard
- Division of Cardiothoracic Anesthesiology, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN
| | - Miklos D Kertai
- Division of Cardiothoracic Anesthesiology, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN.
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Jørgensen ME, Andersson C, Venkatesan S, Sanders RD. Beta-blockers in noncardiac surgery: Did observational studies put us back on safe ground? Br J Anaesth 2018; 121:16-25. [PMID: 29935568 DOI: 10.1016/j.bja.2018.02.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Revised: 01/10/2018] [Accepted: 02/07/2018] [Indexed: 01/10/2023] Open
Abstract
Based on landmark trials, international guidelines had for years promoted the use of beta-blockers in the setting of non-cardiac surgery. In 2011, concerns were raised regarding the integrity of some of the landmark trials, as the Dutch Erasmus Medical Center found some of them to be scientifically incorrect. Based on the remaining studies that were to be trusted, investigations showed that, in contrast to prior beliefs, the widespread use of perioperative beta-blockers might be harmful. A call for further investigations into the matter ushered in several observational studies evaluating the safety of perioperative beta-blocker therapy in specific patient subgroups. Within this review, we discuss important aspects for making these decisions, and compare the major observational studies and specific estimates of risk in subgroups of interest. We conclude that patients at high risk with heavy co-morbidities, such as heart failure, may benefit from beta-blocker therapy, whereas low-risk patients, such as patients with uncomplicated hypertension, may be at increased risk with beta-blocker therapy. We provide a critical review of current perioperative guidelines in view of the new observational data, suggesting that the recommended schematics, such as the Revised Cardiac Risk Index, for risk stratification of patients in this setting may be suboptimal. Further, we provide discussions of other aspects, including risk of sepsis, type of beta-blocker, and the potential of perioperative beta-blocker withdrawal, which may be important in guiding future studies. Summarising the current evidence, we argue that, after a precarious decade, we may just now, be back on safe ground.
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Affiliation(s)
- M E Jørgensen
- The Cardiovascular Research Center, Herlev-Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
| | - C Andersson
- The Cardiovascular Research Center, Herlev-Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - S Venkatesan
- Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK
| | - R D Sanders
- Anesthesiology & Critical Care Trials & Interdisciplinary Outcome Network, Department of Anesthesiology, University of Wisconsin, Madison, WI, USA
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Blessberger H, Kammler J, Domanovits H, Schlager O, Wildner B, Azar D, Schillinger M, Wiesbauer F, Steinwender C, Cochrane Anaesthesia Group. Perioperative beta-blockers for preventing surgery-related mortality and morbidity. Cochrane Database Syst Rev 2018; 2018:CD004476. [PMID: 29533470 PMCID: PMC6494407 DOI: 10.1002/14651858.cd004476.pub3] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
BACKGROUND Randomized controlled trials have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and mortality. Thus routine prescription of these drugs in unselected patients remains a controversial issue. OBJECTIVES The objective of this review was to systematically analyse the effects of perioperatively administered beta-blockers for prevention of surgery-related mortality and morbidity in patients undergoing any type of surgery while under general anaesthesia. SEARCH METHODS We identified trials by searching the following databases from the date of their inception until June 2013: MEDLINE, Embase , the Cochrane Central Register of Controlled Trials (CENTRAL), Biosis Previews, CAB Abstracts, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Derwent Drug File, Science Citation Index Expanded, Life Sciences Collection, Global Health and PASCAL. In addition, we searched online resources to identify grey literature. SELECTION CRITERIA We included randomized controlled trials if participants were randomly assigned to a beta-blocker group or a control group (standard care or placebo). Surgery (any type) had to be performed with all or at least a significant proportion of participants under general anaesthesia. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data from all studies. In cases of disagreement, we reassessed the respective studies to reach consensus. We computed summary estimates in the absence of significant clinical heterogeneity. Risk ratios (RRs) were used for dichotomous outcomes, and mean differences (MDs) were used for continuous outcomes. We performed subgroup analyses for various potential effect modifiers. MAIN RESULTS We included 88 randomized controlled trials with 19,161 participants. Six studies (7%) met the highest methodological quality criteria (studies with overall low risk of bias: adequate sequence generation, adequate allocation concealment, double/triple-blinded design with a placebo group, intention-to-treat analysis), whereas in the remaining trials, some form of bias was present or could not be definitively excluded (studies with overall unclear or high risk of bias). Outcomes were evaluated separately for cardiac and non-cardiac surgery.CARDIAC SURGERY (53 trials)We found no clear evidence of an effect of beta-blockers on the following outcomes.• All-cause mortality: RR 0.73, 95% CI 0.35 to 1.52, 3783 participants, moderate quality evidence.• Acute myocardial infarction (AMI): RR 1.04, 95% CI 0.71 to 1.51, 3553 participants, moderate quality evidence.• Myocardial ischaemia: RR 0.51, 95% CI 0.25 to 1.05, 166 participants, low quality evidence.• Cerebrovascular events: RR 1.52, 95% CI 0.58 to 4.02, 1400 participants, low quality evidence.• Hypotension: RR 1.54, 95% CI 0.67 to 3.51, 558 participants, low quality evidence.• Bradycardia: RR 1.61, 95% CI 0.97 to 2.66, 660 participants, low quality evidence.• Congestive heart failure: RR 0.22, 95% CI 0.04 to 1.34, 311 participants, low quality evidence.Beta-blockers significantly reduced the occurrence of the following endpoints.• Ventricular arrhythmias: RR 0.37, 95% CI 0.24 to 0.58, number needed to treat for an additional beneficial outcome (NNTB) 29, 2292 participants, moderate quality evidence.• Supraventricular arrhythmias: RR 0.44, 95% CI 0.36 to 0.53, NNTB five, 6420 participants, high quality evidence.• On average, beta-blockers reduced length of hospital stay by 0.54 days (95% CI -0.90 to -0.19, 2450 participants, low quality evidence).NON-CARDIAC SURGERY (35 trials)Beta-blockers significantly increased the occurrence of the following adverse events.• All-cause mortality: RR 1.25, 95% CI 1.00 to 1.57, 11,413 participants, low quality of evidence, number needed to treat for an additional harmful outcome (NNTH) 167.• Hypotension: RR 1.50, 95% CI 1.38 to 1.64, NNTH 16, 10,947 participants, high quality evidence.• Bradycardia: RR 2.23, 95% CI 1.48 to 3.36, NNTH 21, 11,033 participants, moderate quality evidence.We found a potential increase in the occurrence of the following outcomes with the use of beta-blockers.• Cerebrovascular events: RR 1.59, 95% CI 0.93 to 2.71, 9150 participants, low quality evidence.Whereas no clear evidence of an effect was found when all studies were analysed, restricting the meta-analysis to low risk of bias studies revealed a significant increase in cerebrovascular events with the use of beta-blockers: RR 2.09, 95% CI 1.14 to 3.82, NNTH 265, 8648 participants.Beta-blockers significantly reduced the occurrence of the following endpoints.• AMI: RR 0.73, 95% CI 0.61 to 0.87, NNTB 76, 10,958 participants, high quality evidence.• Myocardial ischaemia: RR 0.51, 95% CI 0.34 to 0.77, NNTB nine, 978 participants, moderate quality evidence.• Supraventricular arrhythmias: RR 0.73, 95% CI 0.57 to 0.94, NNTB 112, 8744 participants, high quality evidence.We found no clear evidence of an effect of beta-blockers on the following outcomes.• Ventricular arrhythmias: RR 0.68, 95% CI 0.31 to 1.49, 476 participants, moderate quality evidence.• Congestive heart failure: RR 1.18, 95% CI 0.94 to 1.48, 9173 participants, moderate quality evidence.• Length of hospital stay: mean difference -0.45 days, 95% CI -1.75 to 0.84, 551 participants, low quality evidence. AUTHORS' CONCLUSIONS According to our findings, perioperative application of beta-blockers still plays a pivotal role in cardiac surgery, as they can substantially reduce the high burden of supraventricular and ventricular arrhythmias in the aftermath of surgery. Their influence on mortality, AMI, stroke, congestive heart failure, hypotension and bradycardia in this setting remains unclear.In non-cardiac surgery, evidence shows an association of beta-blockers with increased all-cause mortality. Data from low risk of bias trials further suggests an increase in stroke rate with the use of beta-blockers. As the quality of evidence is still low to moderate, more evidence is needed before a definitive conclusion can be drawn. The substantial reduction in supraventricular arrhythmias and AMI in this setting seems to be offset by the potential increase in mortality and stroke.
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Affiliation(s)
- Hermann Blessberger
- Kepler University Hospital, Medical Faculty of the Johannes Kepler University LinzDepartment of Cardiology, Med Campus IIIKrankenhausstraße 9LinzAustria4020
| | - Juergen Kammler
- Kepler University Hospital, Medical Faculty of the Johannes Kepler University LinzDepartment of Cardiology, Med Campus IIIKrankenhausstraße 9LinzAustria4020
| | - Hans Domanovits
- Vienna General Hospital, Medical University of ViennaDepartment of Emergency MedicineWähringer Gürtel 18‐20ViennaAustria1090
| | - Oliver Schlager
- Vienna General Hospital, Medical University of ViennaDepartment of Internal Medicine II, Division of AngiologyWähringer Gürtel 18‐20ViennaAustria1090
| | - Brigitte Wildner
- University Library of the Medical University of ViennaInformation Retrieval OfficeWähringer Gürtel 18‐20ViennaAustria1090
| | - Danyel Azar
- Landesklinikum Thermenregion BadenDepartment of General SurgeryWimmergasse 19BadenAustria2500
| | - Martin Schillinger
- Vienna General Hospital, Medical University of ViennaDepartment of Internal Medicine II, Division of AngiologyWähringer Gürtel 18‐20ViennaAustria1090
| | - Franz Wiesbauer
- Division of Cardiology, Vienna General Hospital, Medical University of ViennaDepartment of Internal Medicine IIWähringerstrasse 18‐20ViennaAustria1090
| | - Clemens Steinwender
- Kepler University Hospital, Medical Faculty of the Johannes Kepler University LinzDepartment of Cardiology, Med Campus IIIKrankenhausstraße 9LinzAustria4020
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Abstract
New-onset atrial fibrillation (NOAF) is the most common perioperative complication of heart surgery, typically occurring in the perioperative period. NOAF commonly occurs in patients who are elderly, or have left atrial enlargement, or left ventricular hypertrophy. Various factors have been identified as being involved in the development of NOAF, and numerous approaches have been proposed for its prevention and treatment. Risk factors include diabetes, obesity, and metabolic syndrome. For prevention of NOAF, β-blockers and amiodarone are particularly effective and are recommended by guidelines. NOAF can be treated by rhythm/rate control, and antithrombotic therapy. Treatment is required in patients with decreased cardiac function, a heart rate exceeding 130 beats/min, or persistent NOAF lasting for ≥ 48 h. It is anticipated that anticoagulant therapies, as well as hemodynamic management, will also play a major role in the management of NOAF. When using warfarin as an anticoagulant, its dose should be adjusted based on PT-INR. PT-INR should be controlled between 2.0 and 3.0 in patients aged < 70 years and between 1.6 and 2.6 in those aged ≥ 70 years. Rate control combined with antithrombotic therapies for NOAF is expected to contribute to further advances in treatment and improvement of survival.
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Affiliation(s)
- Takeshi Omae
- Department of Anesthesiology and Pain Clinic, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni, Shizuoka, 410-2295, Japan. .,Department of Anesthesiology and Pain Medicine, School of Medicine, Juntendo University, Tokyo, Japan.
| | - Eiichi Inada
- Department of Anesthesiology and Pain Medicine, School of Medicine, Juntendo University, Tokyo, Japan
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Howell S. Abdominal aortic aneurysm repair in the United Kingdom: an exemplar for the role of anaesthetists in perioperative medicine. Br J Anaesth 2017; 119:i15-i22. [DOI: 10.1093/bja/aex360] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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49
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Affiliation(s)
- Karl Swedberg
- Department of Clinical and Molecular Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,National Heart and Lung Institute, Imperial College, London, UK
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50
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Bemenderfer TB, Rozario NL, Moore CG, Karunakar MA. Morbidity and Mortality in Elective Total Hip Arthroplasty Following Surgical Care Improvement Project Guidelines. J Arthroplasty 2017; 32:2359-2362. [PMID: 28366317 DOI: 10.1016/j.arth.2017.02.080] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2016] [Revised: 02/19/2017] [Accepted: 02/28/2017] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Following evidence questioning the safety and efficacy of perioperative beta-blocker therapy in noncardiac surgery, the Surgical Care Improvement Project (SCIP) guidelines were retired in 2015. However, perioperative myocardial infarctions and cardiac complications remain leading causes of mortality following noncardiac surgery. The impact of the SCIP guidelines on reducing cardiac complications in patients undergoing elective total hip arthroplasty (THA) has not been evaluated. METHODS The Nationwide Inpatient Sample was queried for 345,875 elective THA performed from 2003 to 2011. Patient demographics and morbidity as well as the incidence of nonfatal and fatal cardiac complications and overall mortality associated with cardiac complications were determined before and following SCIP implementation. RESULTS Following the institution of the SCIP guidelines, the overall mortality following cardiac complications decreased by 41%. Although the incidence of nonfatal cardiac events after THA did increase 5% (primarily secondary to an increased incidence of nonfatal hypotension), the incidence of postoperative inpatient mortality, stroke, fatal hypotension, fatal myocardial infarction, and nonfatal and fatal cardiac arrest significantly decreased. CONCLUSION Following the implementation of SCIP guidelines, there was a 41% reduction in mortality and a significant decrease in fatal cardiac complications, postoperative hypotension, myocardial infarction, and cardiac arrest. Despite SCIP guidelines being retired in 2015, evidence supports continuation of perioperative beta-blockade in primary elective total adult hip and knee arthroplasty.
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Affiliation(s)
- Thomas B Bemenderfer
- Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, North Carolina
| | - Nigel L Rozario
- Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, North Carolina; Dickson Advanced Analysis Group (DA(2)), Carolinas HealthCare System, Charlotte, North Carolina
| | - Charity G Moore
- Dickson Advanced Analysis Group (DA(2)), Carolinas HealthCare System, Charlotte, North Carolina
| | - Madhav A Karunakar
- Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, North Carolina
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