• aspirin resistance
• congenital heart disease
• thromboembolic events
• transcatheter pulmonary heart valve

• Humans
• Female
• Male
• Aspirin/therapeutic use
• Aspirin/adverse effects
• Retrospective Studies
• Drug Resistance
• Platelet Aggregation Inhibitors/therapeutic use
• Platelet Aggregation Inhibitors/adverse effects
• Prevalence
• Adult
• Middle Aged
• Young Adult
• Adolescent
• Treatment Outcome
• Cardiac Catheterization/adverse effects
• Heart Defects, Congenital/surgery
• Child
• Risk Factors
• Aged
• Child, Preschool
• Pulmonary Valve/surgery
• Pulmonary Valve/physiopathology
• Pulmonary Valve/diagnostic imaging
• Infant
• Heart Valve Prosthesis Implantation/adverse effects
• Heart Valve Prosthesis Implantation/instrumentation
• Pulmonary Valve Insufficiency/physiopathology
• Pulmonary Valve Insufficiency/surgery
• Pulmonary Valve Insufficiency/diagnostic imaging
• Thromboembolism/prevention & control
• Thromboembolism/etiology
• Thromboembolism/epidemiology
• Time Factors
• Platelet Function Tests
• Risk Assessment
• Platelet Aggregation/drug effects
• Sex Factors

• The authors thank Patrick Ten Eyck for the statistical analysis of the study data.

• Coagulation
• Collagen
• Piper retrofractum
• Piperine
• Thrombosis

• NEWTREE CO., LTD

• ASA
• craniotomy
• hemorrhage
• meningioma

• NSAIDs
• antiplatelet
• diclofenac
• drugs
• ibuprofen
• ketoprofen
• naproxen
• paracetamol
• platelet
• platelet aggregation

• megakaryocyte
• platelet
• ploidy
• therapeutics
• thrombosis

• Antiplatelet therapy
• Aspirin
• CVA
• Intracranial hemorrhage
• Ischemic stroke

• Acute coronary syndrome (ACS)
• P2Y12 inhibitor
• antiplatelet
• cardiovascular disease
• chronic kidney disease (CKD)
• end stage kidney disease (ESKD)
• ischaemic heart disease (IHD)
• renal replacement therapy (RRT)

• Humans
• Platelet Aggregation Inhibitors/pharmacology
• Platelet Aggregation Inhibitors/therapeutic use
• Vacuum
• Renal Insufficiency, Chronic/complications
• Renal Insufficiency, Chronic/drug therapy
• Hemorrhage/complications
• Coronary Artery Disease/complications
• Myocardial Ischemia/complications
• Myocardial Ischemia/drug therapy
• Myocardial Ischemia/chemically induced

• FS/18/49/33752 British Heart Foundation

• Humans
• Cross-Sectional Studies
• Inpatients
• Antiphospholipid Syndrome/complications
• Antiphospholipid Syndrome/drug therapy
• Antiphospholipid Syndrome/epidemiology
• Risk Factors
• Cardiovascular Diseases/epidemiology

Antiplatelet agents, with aspirin and P2Y₁₂ receptor antagonists as major key molecules, are currently the cornerstone of pharmacological treatment of atherothrombotic events including a variety of cardio- and cerebro-vascular as well as peripheral artery diseases. Over the last decades, significant changes have been made to antiplatelet therapeutic and prophylactic strategies. The shift from a population-based approach to patient-centered precision medicine requires greater awareness of individual risks and benefits associated with the different antiplatelet strategies, so that the right patient gets the right therapy at the right time. In this review, we present the currently available antiplatelet agents, outline different management strategies, particularly in case of bleeding or in perioperative setting, and develop the concept of high on-treatment platelet reactivity and the steps toward person-centered precision medicine aiming to optimize patient care.

• P2Y12 receptor antagonists
• acute coronary syndrome
• aspirin
• atherothrombosis
• bleeding
• cardiovascular disease
• dual antiplatelet therapy
• platelets

• Cardiovascular Diseases/drug therapy
• Humans
• Platelet Aggregation Inhibitors/adverse effects
• Platelet Aggregation Inhibitors/pharmacology
• Platelet Aggregation Inhibitors/therapeutic use

• Cardiovascular disease
• Lipidomics
• Mechanical circulatory support
• Mechanobiology
• Platelets
• Shear activation

• T32 HL007955 NHLBI NIH HHS
• U01 HL131052 NHLBI NIH HHS
• Arizona Biomedical Research Commission
• Foundation for the National Institutes of Health

Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of drugs which are widely used globally for the treatment of pain and inflammation, and in the case of aspirin, for secondary prevention of cardiovascular disease. Chronic non-steroidal anti-inflammatory drug use is associated with potentially serious upper gastrointestinal adverse drug reactions (ADRs) including peptic ulcer disease and gastrointestinal bleeding. A few clinical and genetic predisposing factors have been identified; however, genetic data are contradictory. Further research is needed to identify clinically relevant genetic and non-genetic markers predisposing to NSAID-induced peptic ulceration.

• NSAID (non-steroidal anti-inflammatory drug)
• adverse drug reaction
• aspirin
• gastrointestinal toxicities
• pharmacogenomic

• antiplatelets
• flow diverter
• intracranial aneurysm

There has been an increase in the use of acetylsalicylic acid (ASA, Aspirin®) among patients with stroke and heart disease as well as in aging populations as a means of primary prevention. The potentially life-threatening consequences of a postoperative hemorrhagic complication after neurosurgical operative procedures are well known. In the present study, we evaluate the risk of continued ASA use as it relates to postoperative hemorrhage and cardiopulmonary complications in patients undergoing cerebral aneurysm surgery. We retrospectively analyzed 200 consecutive clipping procedures performed between 2008 and 2018. Two different statistical models were applied. The first model consisted of two groups: (1) group with No ASA impact - patients who either did not use ASA at all as well as those who had stopped their use of the ASA medication in time (> = 7 days prior to operation); (2) group with ASA impact - all patients whose ASA use was not stopped in time. The second model consisted of three groups: (1) No ASA use; (2) Stopped ASA use (> = 7 days prior to operation); (3) Continued ASA use (did not stop or did not stop in time, <7 days prior to operation). Data collection included demographic information, surgical parameters, aneurysm characteristics, and all hemorrhagic/thromboembolic complications. A postoperative hemorrhage was defined as relevant if a consecutive operation for hematoma removal was necessary. An ASA effect has been assumed in 32 out of 200 performed operations. A postoperative hemorrhage occurred in one out these 32 patients (3.1%). A postoperative hemorrhage in patients without ASA impact was detected and treated in 5 out of 168 patients (3.0%). The difference was statistically not significant in either model (ASA impact group vs. No ASA impact group: OR = 1.0516 [0.1187; 9.3132], p = 1.000; RR = 1.0015 [0.9360; 1.0716]). Cardiopulmonary complications were significantly more frequent in the group with ASA impact than in the group without ASA impact (p = 0.030). In this study continued ASA use was not associated with an increased risk of a postoperative hemorrhage. However, cardiopulmonary complications were significantly more frequent in the ASA impact group than in the No ASA impact group. Thus, ASA might relatively safely be continued in patients with increased cardiovascular risk and cases of emergency cerebrovascular surgery.

• Acetylsalicylic acid
• Aneurysm surgery
• Clipping
• Postoperative hemorrhage

• PFO
• cryptogenic stroke
• network meta-analysis
• patent foramen ovale
• treatment strategies

To estimate the incidence of major adverse cardiovascular events (MACE) with genotype test-guided antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome.

Patients who had undergone PCI for acute coronary syndrome as well as stable coronary artery disease were recruited. Salivary samples were obtained from these patients and genotyped for CYP2C19∗2, CYP2C19∗3 variations by sequencing method (GAAP x method). Patients were categorized as normal (GG, GG) (29%), intermediate (AG) (52%) or poor metabolizes (homozygous variant AA) (19%). Dual antiplatelets were given based on the genotyping data. Poor metabolizes received newer agent (ticagrelor), intermediate metabolizes received double-dose of clopidogrel and normal metabolizes received therapeutic doses of clopidogrel. All subjects were followed-up for six months.

Based on the genotyping data of CYP2C19∗2 and CYP2C19∗3 variations, it was found that most patients were categorized as ‘intermediate’ (78, 51.65%), followed by ‘normal’ (43, 28.48%) and ‘poor’ metabolizes (30, 19.87%). Only 3 (1.5%) of 151 patients reported MACE at follow-up.

Genotyping for CYP2C19 variations to assess clopidogrel resistance in patients undergoing PCI and subsequent drug selection helps reduce MACE after coronary intervention.

• Antiplatelet
• Clopidogrel
• Coronary intervention
• Genotyping

• CD40L
• DAPT
• amyloid precursor protein
• angina pectoris
• biomarker
• cardiovascular disease
• heart failure
• ischemia
• plasma
• platelet
• shedding

• Rapid (4 Hour) protocol
• allergy
• alternative medication
• clopidogrel desensitization
• drug desensitization
• hypersensitivity reaction.

• ADP
• Antiplatelet therapy
• Atherosclerosis
• Inflammation
• Platelet-activating factor
• Thrombin
• Thromboxane

• Animals
• Atherosclerosis/drug therapy
• Atherosclerosis/etiology
• Atherosclerosis/metabolism
• Atherosclerosis/pathology
• Biomarkers
• Blood Coagulation
• Blood Coagulation Factors/metabolism
• Blood Platelets/metabolism
• Disease Management
• Disease Susceptibility
• Humans
• Inflammation/drug therapy
• Inflammation/etiology
• Inflammation/metabolism
• Inflammation/pathology
• Inflammation Mediators/metabolism
• Platelet Activation
• Platelet Aggregation Inhibitors/pharmacology
• Platelet Aggregation Inhibitors/therapeutic use

• Anticoagulation
• Antiplatelet
• Atrial fibrillation
• Myocardial infarction
• Perioperative complications hemorrhage
• Pulmonary embolism
• Radical cystectomy
• Stroke
• Venous thromboembolism

• Anticoagulants/pharmacology
• Anticoagulants/therapeutic use
• Cystectomy/methods
• Female
• Humans
• Male
• Platelet Aggregation Inhibitors/pharmacology
• Platelet Aggregation Inhibitors/therapeutic use
• Urinary Bladder Neoplasms/drug therapy

• Aspirin resistance (AR)
• aspirin
• obesity

The p48 is a low-profile, intermediate-porosity flow diverter. phenox GmbH-trademarked hydrophilic polymer coating (pHPC) is a hydrophilic coating that has been shown in vitro to reduce the thrombogenicity of nitinol device surfaces. We performed the present study to determine whether the p48_HPC can be implanted using prasugrel alone.

We retrospectively identified all patients who were treated with the p48_HPC from January 2017 to December 2018 (n = 5) and underwent single antiplatelet therapy (SAPT) with prasugrel. P2Y12 inhibition was confirmed by the VerifyNow assay. The occurrence of thromboembolic and haemorrhagic complications was recorded alongside the occlusion rates of the treated aneurysms.

All patients achieved adequate occlusion (Raymond–Roy Occlusion Classification I or II) during the follow-up period. No thromboembolic complications occurred. One patient developed a contained haematoma within the Sylvian fissure from the treated aneurysm 2 weeks postoperatively without clinical sequelae.

In this small series, no thromboembolic complications occurred in patients treated with the surface modified p48_HPC flow diverter and SAPT. Further studies with longer follow-up periods and larger cohorts should be performed.

• Aneurysm
• flow diverter
• hydrophilic polymer coating
• p48_HPC
• single antiplatelet therapy
• surface modification

• Adult
• Aged
• Aged, 80 and over
• Aneurysm/diagnostic imaging
• Angiography
• Embolization, Therapeutic/adverse effects
• Embolization, Therapeutic/instrumentation
• Female
• Follow-Up Studies
• Humans
• Middle Aged
• Platelet Aggregation Inhibitors/adverse effects
• Platelet Aggregation Inhibitors/therapeutic use
• Thrombosis/diagnostic imaging
• Thrombosis/drug therapy

The prevalence of cardiovascular disease (CVD) and its mortality continues to increase. Various studies have shown aspirin can reduce CVD mortality but has adverse side effects. Research on a comparison between aspirin and honey has not been done, but both have antiplatelet effects.

This study is aimed to prove the antiplatelet effects on honey and compare the antiplatelet effects of aspirin with honey based on the bleeding time in mice.

This study is a true experimental design with a post-test only control group using 32 male mice, Double Ditsch Webster, ± 3 months old, the weight of 20-30 g, divided into 4 groups. Consisting of a negative control group (placebo), aspirin and honey. The suspension has given orally for 12 days using the probe. The research was conducted at the Laboratory of Pharmacology Department of Pharmacology and Therapeutics Faculty of Medicine, the University of North Sumatra in September until December 2015. The data collected was bleeding time in mice. Data analysed by Shapiro Wilk test, Kruskal Wallis and Mann Whitney.

The mean bleeding time was a placebo (102.88 seconds), aspirin (369.38 seconds) and honey (304.63 seconds). Mann Whitney test showed significant results in the aspirin and honey groups against the control group (placebo) with p = 0.001. There were no significant differences in the aspirin group against honey (p = 0.172). Honey has an antiplatelet effect in mice. The mean bleeding time in mice given honey is longer or closer to the mean bleeding time in the aspirin group.

The results could be used as a basis for further research to determine its use in humans with cardiovascular disease.

• Antiplatelet
• Bleeding time
• Honey

• Cardiac surgery
• bleeding.
• patient blood management
• transfusion

Cardiovascular diseases (CVD) are the number one cause of morbidity and death worldwide. As estimated by the WHO, the global death rate from CVD is 31% wherein, a staggering 85% results from stroke and myocardial infarction. Platelets, one of the key components of thrombi, have been well-investigated over decades for their pivotal role in thrombus development in healthy as well as diseased blood vessels. In hemostasis, when a vascular injury occurs, circulating platelets are arrested at the site of damage, where they are activated and aggregate to form hemostatic thrombi, thus preventing further bleeding. However, in thrombosis, pathological activation of platelets occurs, leading to uncontrolled growth of a thrombus, which in turn can occlude the blood vessel or embolize, causing downstream ischemic events. The molecular processes causing pathological thrombus development are in large similar to the processes controlling physiological thrombus formation. The biggest challenge of anti-thrombotics and anti-platelet therapeutics has been to decouple the pathological platelet response from the physiological one. Currently, marketed anti-platelet drugs are associated with major bleeding complications for this exact reason; they are not effective in targeting pathological thrombi without interfering with normal hemostasis. Recent studies have emphasized the importance of shear forces generated from blood flow, that primarily drive platelet activation and aggregation in thrombosis. Local shear stresses in obstructed blood vessels can be higher by up to two orders of magnitude as compared to healthy vessels. Leveraging abnormal shear forces in the thrombus microenvironment may allow to differentiate between thrombosis and hemostasis and develop shear-selective anti-platelet therapies. In this review, we discuss the influence of shear forces on thrombosis and the underlying mechanisms of shear-induced platelet activation. Later, we summarize the therapeutic approaches to target shear-sensitive platelet activation and pathological thrombus growth, with a particular focus on the shear-sensitive protein von Willebrand Factor (VWF). Inhibition of shear-specific platelet aggregation and targeted drug delivery may prove to be much safer and efficacious approaches over current state-of-the-art antithrombotic drugs in the treatment of cardiovascular diseases.

• VWF
• aggregation
• platelets
• shear
• thrombosis

The degree of antiplatelet response to P2Y12 inhibitors has been associated with clinical outcomes. The aim of this study was to test the variability of platelet reactivity over time among patients treated with clopidogrel or ticagrelor.

A single-center cohort of acute coronary syndrome patients that underwent percutaneous coronary intervention (PCI) was analyzed. Platelet reactivity was measured at baseline, 48 hours after PCI, 1 month, and 6 months after clopidogrel (n=79) or ticagrelor (n=93) treatment. High on-treatment platelet reactivity (HPR) was defined as ≥47 U, assessed by multiple electrode platelet aggregometry.

Platelet reactivity in the clopidogrel group increased over time, 38.2±21.7 U at 48 hours, 41.4±22.3 U at 1 month, and 44.7±25.5 U at 6 months (p=0.018, 48 hours to 6 months). However, platelet reactivity in the ticagrelor group was not significantly changed, 21.4±12.6 U at 48 hours, 20.0±12.2 U at 1 month, and 22.8±13.8 U at 6 months (p=0.392). A platelet reactivity change over time of more than 20U was found in 67.1% of the patients with clopidogrel group and 34.4% of ticagrelor group (p<0.001). Between 48 hours and 6 months, 43% of patients changed their responder status in the clopidogrel group, and 13% in the ticagrelor group (p<0.001).

Although ticagrelor treatment resulted in less temporal variability of platelet reactivity than clopidogrel treatment in terms of HPR, platelet reactivity varied over time in a significant proportion of patients.

• Clopidogrel
• Platelet function tests
• Ticagrelor

• Acute coronary syndrome
• Cardiovascular disease
• Platelet surface receptors
• Polymorphism

• body mass index
• obesity
• platelet aggregation
• preeclampsia thromboxane B2

• Biomarkers
• Cancer
• Immunity
• Inflammation
• Microparticles
• Platelets

• Blood-biomaterial interactions
• Hemocompatibility
• Platelets
• Vascular implants

• adenosine diphosphate receptor inhibitor
• allogenic blood
• antiplatelet medications management
• aspirin
• autologous blood
• blood conservation
• blood salvage
• blood transfusion
• clopidogrel
• erythropoietin
• hemotinics
• irreversible cyclooxygenase inhibitors
• postoperative anemia
• tranexamic acid

• Adult
• Aspirin/administration & dosage
• Blood Platelets/drug effects
• Coronary Artery Disease/blood
• Coronary Artery Disease/etiology
• Coronary Artery Disease/prevention & control
• Diabetes Mellitus, Type 2/blood
• Diabetes Mellitus, Type 2/complications
• Diabetes Mellitus, Type 2/urine
• Dose-Response Relationship, Drug
• Female
• Humans
• Male
• Middle Aged
• Platelet Activation/drug effects
• Platelet Aggregation/drug effects
• Platelet Aggregation Inhibitors/administration & dosage
• Platelet Function Tests
• Thromboxane B2/urine
• Treatment Outcome

• M01 RR000052 NCRR NIH HHS
• U01 HL072518 NHLBI NIH HHS

• Brain tumors
• CLEC-2
• Cancer-associated VTE
• Platelet aggregation
• Podoplanin
• Thrombosis

• Humans
• Membrane Glycoproteins/adverse effects
• Membrane Glycoproteins/metabolism
• Neoplasms/complications
• Thrombosis/etiology

• arterial thrombosis
• bevacizumab
• non-small
• non-squamous lung cancer

• Aged
• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Aortic Diseases/chemically induced
• Aortic Diseases/drug therapy
• Bevacizumab/adverse effects
• Bevacizumab/therapeutic use
• Carcinoma, Non-Small-Cell Lung/drug therapy
• Cisplatin/administration & dosage
• Cisplatin/adverse effects
• Cisplatin/therapeutic use
• Heparin/therapeutic use
• Humans
• Lung Neoplasms/drug therapy
• Male
• Pemetrexed/adverse effects
• Pemetrexed/therapeutic use
• Thrombosis/chemically induced
• Thrombosis/drug therapy
• Treatment Outcome
• Warfarin/therapeutic use

The current guidelines dispose recommendations to manage antiplatelet agents in the perioperative period; however, the daily medical practices lack standardization.

To asses factors associated with inadequate management of antiplatelet agents in the perioperative period of non-cardiac surgeries.

Cross-sectional Study conducted in hospital from October 2014 to October 2016. The study dependent variable was a therapy that did not comply with the recommendations in the Brazilian Association of Cardiology (SBC) guidelines. The independent variables included some characteristics, the people in charge of the management and causes of lack of adherence to those guidelines. Variables were included in the multivariate model. Analysis was based on the odds ratio (OR) value and its respective 95% confidence interval (CI) estimated by means of logistic regression with 5% significance level.

The sample was composed of adult patients submitted to non-cardiac surgeries and who would use acetylsalicylic acid (aspirin) or clopidogrel (n = 161). The management failed to comply with the recommendations in the guidelines in 80.75% of the sample. Surgeons had the highest number of noncomplying orientations (n = 63). After multivariate analysis it was observed that patients with a higher level of schooling (OR = 0.24; CI95% 0.07-0.78) and those with a previous episode of acute myocardial infarction (AMI) (OR = 0.18; CI95% 0.04-0.95) had a higher probability of using a therapy complying with the guidelines.

Positive association between patients’ schooling level, or those with a history of previous AMI, with management of the use of aspirin and clopidogrel in the perioperative period of non-cardiac surgeries. However, diverging conducts stress the need of having internal protocol defined.

To examine the comparative safety of individual NSAIDs when given concomitantly with clopidogrel.

We conducted a retrospective cohort study using Medicaid claims from five US states during 1999–2010, supplemented with Medicare claims for dual-enrollees. The exposure of interest was the first concomitant use of clopidogrel and one of the 10 selected NSAIDs after a 1-year baseline period. The outcomes were: all-cause mortality; acute myocardial infarction (AMI)/ischemic stroke; and gastrointestinal bleeding (GIB)/intracranial hemorrhage (ICH). We calculated the hazard ratio of each NSAID for each outcome, with ibuprofen as the reference drug, using high-dimensional propensity score-adjusted proportional-hazards regression models.

Of 1,060,412 clopidogrel users, 268,114 concomitant NSAID users met inclusion/exclusion criteria, contributing 48,483 person-years. We observed 2,463 deaths, 2,822 AMI/ischemic stroke outcomes, and 2,620 GIB/ICH outcomes, for unadjusted incidence rates of 50.8, 58.6, and 54.3 per 1,000 person-years, respectively. Compared with ibuprofen and controlling for potential confounders, rofecoxib (hazard ratio [HR] = 1.22; 95% confidence interval [CI]: 1.04, 1.43) and valdecoxib (HR = 0.66; 95% CI: 0.48, 0.92) showed higher and lower hazards of mortality, respectively. Indomethacin showed an increased AMI/ischemic stroke hazard (HR = 1.38; 95% CI: 1.09, 1.74). For GIB/ICH, indomethacin (HR = 2.18; 95% CI: 1.74, 2.73), diclofenac (HR = 1.65; 95% CI: 1.39, 1.97), naproxen (HR = 1.47; 95% CI: 1.28, 1.70), and rofecoxib (HR = 1.26; 95% CI: 1.08, 1.48) showed higher hazards, and valdecoxib (HR = 0.73; 95% CI: 0.55, 0.98) showed a lower hazard.

The bleeding risks of individual NSAIDs varied more markedly than thrombotic risks when used concomitantly with clopidogrel. Moreover, bleeding risk and thrombotic risk among individual NSAIDs did not appear to be inversely related to each other in the presence of clopidogrel. Further studies are needed to elucidate underlying biological mechanisms and help clinical decision-making for a better NSAID choice in clopidogrel users.

• Aspirin
• Drug-drug interaction
• Panax notoginseng saponins
• Pharmacokinetic
• Transport

• Aggregation
• Aggregometry
• Impedance
• Thromboembolism

• Animals
• Aspirin/pharmacology
• Blood Platelets/drug effects
• Clopidogrel
• Dogs
• Double-Blind Method
• Drug Therapy, Combination/veterinary
• Female
• Male
• Platelet Aggregation/drug effects
• Platelet Count/veterinary
• Platelet Function Tests/instrumentation
• Platelet Function Tests/methods
• Platelet Function Tests/veterinary
• Ticlopidine/analogs & derivatives
• Ticlopidine/pharmacology