Non-vitamin K oral anticoagulants are recommended over vitamin K antagonists in patients with nonvalvular atrial fibrillation (AF). However, the risk of gastrointestinal bleeding may be higher with non-vitamin K oral anticoagulants versus vitamin K antagonists. Patients after successful transcatheter aortic valve replacement (TAVR) who are elderly and frail have worse outcomes with major gastrointestinal bleeding (MGIB), including death. This study evaluated incidence, predictors, and impact of MGIB among patients with AF after successful TAVR.

This on-treatment analysis of ENVISAGE-TAVI AF (Edoxaban Compared to Standard Care After Heart Valve Replacement Using a Catheter in Patients With Atrial Fibrillation) included patients who received ≥1 dose of the study drug. Demographic, clinical, and procedural characteristics were compared between patients with versus without an MGIB event. Cox multivariable regression analysis identified predictors of MGIB.

Of 1377 patients in this analysis, 83 (6.0%) experienced MGIB, with 56 (67.5%) of these patients receiving edoxaban. Patients with versus without MGIB were more likely to have undergone percutaneous coronary intervention ≤30 days before TAVR (9.6% versus 4.2%; P=0.03), a higher ejection fraction (mean±SD, 58.0±10.4 versus 55.3±11.5; P=0.04), and carotid artery disease (13.3% versus 6.6%; P=0.04). Edoxaban without dose adjustment versus vitamin K antagonist use (P=0.003), smoking (P=0.01), low hemoglobin levels (P<0.0001), and percutaneous coronary intervention ≤30 days before TAVR (P=0.01) emerged as predictors of MGIB.

In this ENVISAGE-TAVI AF subanalysis, MGIB occurred in 6.0% of patients with prevalent or incident AF undergoing TAVR, and those receiving edoxaban versus vitamin K antagonists had a higher risk of MGIB. A priori identification of risk factors for MGIB may help optimize outcomes for patients with AF undergoing TAVR.

URL: https://www.clinicaltrials.gov; unique identifier: NCT02943785.

P2Y12 inhibitor selection involves numerous factors, including CYP2C19 genetics, since evidence demonstrates reduced clopidogrel efficacy in patients with decreased or no function CYP2C19 variants. In 2020, Indiana University health embedded interruptive clinical decision support (CDS) alerts in the electronic health record (EHR) to recommend alternative P2Y12 inhibitors for patients with decreased CYP2C19 function who had undergone percutaneous coronary intervention (PCI). The objective of this study was to evaluate prescriber response to these CDS alerts. Utilizing alert response data and P2Y12 inhibitor prescriptions from October 2020 to December 2023, we evaluated prescriber response for 362 patients who had a mean of 2.2 (SD: 1.7) CYP2C19-clopidogrel alerts fire post-PCI. Alert recommendations were accepted 24.5% ± 36.8% (mean ± SD) of the time. Alternative (i.e., non-clopidogrel) P2Y12 inhibitors were prescribed for 22.4% ± 36.8% of days during the year following PCI. Alerts were accepted more for CYP2C19 poor metabolizers than for intermediate metabolizers (P = 0.03). Each year after 2020 was associated with a 4.6% increase in the days prescribed alternative P2Y12 inhibitors. In contrast, increasing age was associated with decreased alert acceptance and decreased percentage of days prescribed alternatives, and concomitant oral anticoagulant use was associated with decreased percentage of days prescribed alternatives. Provider clinical judgment was the most common alert override reason, accounting for 68% of clinician responses. Our findings demonstrate that CYP2C19-clopidogrel CDS alerts promoted genotype-guided P2Y12 inhibitor prescribing in some cases (~22% of study days). Future research should better determine prescriber reasons for rejecting alert recommendations and establish best implementation practices to complement CDS alerts.

The role of medication adherence trajectories in the clinical outcomes in patients with cardiovascular diseases (CVDs) remains unclear. We aimed to analyse the impact of different medication adherence trajectories on mortality and other key clinical outcomes in patients with CVDs.

We identified longitudinal cohort studies that reported the association between medication adherence trajectories and clinical outcomes in patients with CVDs by conducting a comprehensive search of the Cochrane Library, PubMed, Embase, CINAHL, and Web of Science databases, without applying language restrictions in August 2024. We pooled the published hazard ratios and 95% confidence intervals using random effects models and assessed potential bias through Egger regression analysis.

In this meta-analysis, we included nine cohorts with 226 203 patients with a mean age of 66.1 years and a maximum follow-up of five years. Eight of the nine studies used the proportion of days covered to assess medication adherence. We identified four distinct medication adherence trajectories: persistent adherence, persistent nonadherence, gradually increasing adherence, and gradually declining adherence. Compared to persistent adherence, persistent nonadherence was associated with significantly higher risks of all-cause mortality, major adverse cardiovascular events (MACE), and recurrent venous thromboembolism, with risk increases ranging from 32% to nearly three times higher. Gradually increasing adherence was associated with a 26% higher risk of mortality and a 22% increased risk of MACE. In the group with gradually declining adherence, the risk of MACE increased by 24%, while the risk of major bleeding decreased by 43%. The overall risk of bias was low. Sensitivity analyses confirmed the consistency and robustness of these findings.

This study underscores the substantial benefits of maintaining persistent adherence to prescribed medication regimens for patients with CVDs. Conversely, persistent nonadherence significantly elevates the risk of adverse clinical outcomes.

PROSPERO: CRD42023456395.

Arterial and venous thromboses are the leading causes of morbidity and mortality worldwide. Numerous antithrombotic agents are currently available with antiplatelet, thrombolytic/fibrinolytic, and anticoagulant activity. However, all the currently available antithrombotic agents carry a risk of bleeding that often prevents their use. This unfavorable risk-benefit profile is particularly challenging for patients with cancer-associated venous thromboembolism, patients with atrial fibrillation at a high risk of bleeding, and patients with end-stage renal disease. Patients with ischemic stroke and acute coronary syndromes have not yet found a favorable risk-benefit profile with anticoagulant therapy to help reduce the residual thromboembolic risk that remains after antiplatelet and lipid therapy. Two emerging classes of antithrombotic agents, factor (F)XI or activated factor Ⅺ (FⅪa) inhibitors and glycoprotein VI inhibitors, have shown promise in their ability to prevent pathologic thrombosis without increasing the risk of hemostatic-related bleeding in phase 2 studies. Among the FⅪ/FXIa inhibitors of coagulation, a parenterally administered monoclonal antibody (abelacimab) and 2 orally administered small molecule inhibitors (asundexian, milvexian) are collectively being studied in patients with atrial fibrillation, cancer-associated venous thromboembolism, acute coronary syndrome, and ischemic stroke. One parenterally administered glycoprotein VI antiplatelet agent (glenzocimab) is currently being studied in patients with ischemic stroke. If shown to be efficacious and safe in ongoing phase 3 studies, both classes of emerging antithrombotic agents have the potential to greatly improve outcomes for patients with challenging thrombotic conditions.

Triple antithrombotic therapy (TAT), combining dual antiplatelet therapy (DAPT) with oral anticoagulants, is commonly used in patients requiring long-term anticoagulation following acute coronary syndrome or percutaneous coronary intervention. However, TAT may increase the risk of hemorrhage. There is a dearth of data regarding the risks of bleeding with various oral anticoagulants in TAT in comparison with DAPT and individual anticoagulants and antiplatelets due to which we carried out the present study examining the real-world pharmacovigilance data.

Data were extracted from the USFDA Adverse Event Reporting System (AERS) from March 2004 to June 2024 using the Standardized MedDRA Query (SMQ) code for "haemorrhages." We employed the "case-non-case" approach in disproportionality analysis to detect safety signals for hemorrhage among anticoagulant, antiplatelet, dual antiplatelet and triple antithrombotic combinations. Reports including combinations of DAPT (acetylsalicylic acid and clopidogrel) with oral anticoagulants (acenocoumarol, apixaban, dabigatran, edoxaban, rivaroxaban, and warfarin) were analyzed. Signal detection used both frequentist (reporting odds ratio [ROR], proportional reporting ratio and Bayesian (Bayesian Confidence Propagation Neural Network, Multi-Item Gamma Poisson Shrinker algorithms. The lower limit of 95% confidence interval of ROR above 1 indicates higher reporting risk of bleeding. Following outcomes were evaluated for each TAT: death, disability and hospitalization.

Of 20,626 unique reports, 812 involved TAT, 3,820 DAPT, and 15,995 individual antiplatelets. Most cases occurred in elderly patients (age ≥ 65 years) with a predominance of male patients. Rivaroxaban combined with DAPT presented the highest hemorrhage signal (ROR: 82.84; 95% CI, 60.77-112.92), while apixaban showed the lowest (ROR: 13.11; 95% CI, 9.39-18.3) and the other anticoagulants are as follows: warfarin (ROR: 15.96; 95% CI: 18.36), dabigatran (ROR: 27.32; 95% CI: 20.03-37.26) and acenocoumarol (ROR: 43.98; 95% CI: 17.21-112.4). Mortality and hospitalization rates varied significantly among treatments, with rivaroxaban linked to the highest mortality.

This study highlights the elevated hemorrhage risk associated with TAT, particularly with rivaroxaban, while apixaban appears safer in terms of bleeding and mortality. These findings underscore the need for cautious monitoring of bleeding outcomes with anticoagulant regimens, particularly rivaroxaban combinations for optimizing patient outcomes. However, the signals obtained in this study need to be validated in future trials.

The self-controlled case-series (SCCS) research design is increasingly used in pharmacoepidemiologic studies of drug-drug interactions (DDIs), with the target of inference being the incidence rate ratio (IRR) associated with concomitant exposure to the object plus precipitant drug vs the object drug alone. While day-level drug exposure can be inferred from dispensing claims, these inferences may be inaccurate, leading to biased IRRs. Grace periods (periods assuming continued treatment impact after days' supply exhaustion) are frequently used by researchers, but the impact of grace period decisions on bias from exposure misclassification remains unclear. Motivated by an SCCS study examining the potential DDI between clopidogrel (object) and warfarin (precipitant), we investigated bias due to precipitant or object exposure misclassification using simulations. We show that misclassified precipitant treatment always biases the estimated IRR toward the null, whereas misclassified object treatment may lead to bias in either direction or no bias, depending on the scenario. Further, including a grace period for each object dispensing may unintentionally increase the risk of misclassification bias. To minimize such bias, we recommend (1) avoiding the use of grace periods when specifying object drug exposure episodes and (2) including a washout period following each precipitant exposed period. This article is part of a Special Collection on Pharmacoepidemiology.

Guidelines for managing left ventricular thrombus remain limited, particularly when incorporating oral anticoagulants into dual antiplatelet therapy for acute myocardial infarction. This study aims to assess the safety and efficacy of direct oral anticoagulants (DOACs) vs vitamin K antagonists (VKAs) in managing left ventricular thrombus among patients with and without recent myocardial infarction.

This retrospective observational study used data from the TriNetX research network. Patients with left ventricular thrombus treated with either DOACs or VKAs between December 1, 2013 and December 1, 2023, were included. Subgroup analyses were conducted for patients with or without recent acute coronary syndrome (<1 month). Risk and Kaplan-Meier survival analysis were conducted at 90 days after the indexed event.

A total of 39,770 patients were included. DOACs treatment had lower rates of stroke (11.8% vs 13.7%; relative risk [RR] 0.859; 95% confidence interval [CI], 0.816-0.905; P < .001), major bleeding (4.8% vs 5.3%; RR 0.902; 95% CI, 0.829-0.982; P = .018), and systemic embolism (3.5% vs 4.2%; RR 0.841; 95% CI, 0.762-0.928; P = .001) compared with VKAs in overall cohort. Within the acute coronary syndrome group (n = 14,302), DOACs had lower stroke (12.3% vs 14.4%, RR 0.860; 95% CI, 0.791-0.935; P < .0001) and systemic embolism (3.1% vs 4%; RR 0.774; 95% CI, 0.651-0.919; P = .003) risks. For non-acute coronary syndrome group (n = 24,162), DOACs had lower stroke (11.4% vs 13.1%; RR 0.868; 95% CI, 0.811-0.929; P < .001) and major bleeding (4.8% vs 5.5%; RR 0.877; 95% CI, 0.787-0.977; P = .017) risks. No significant differences in all-cause mortality were observed across groups.

DOACs demonstrated better safety and efficacy outcomes when compared with VKAs in left ventricular thrombus treatment, with or without recent acute coronary syndrome.

Literature shows that atrial fibrillation (AF) patients with a history of cancer have a higher risk of thromboembolism (TE) and major bleeding (MB) compared to patients without. However, cancer type and time between cancer and AF diagnosis is often lacking in such analyses.

To examine MB and TE rates of AF patients with a prior cancer diagnosis, stratified by cancer type and interval between cancer and AF diagnosis.

This Danish population-based cohort study included all patients aged ≥50 years with incident AF between January 1, 1995, and December 31, 2016, and identified those who had cancer before the AF diagnosis. From hospital and drug prescription databases, data on cancer type, time interval between cancer and AF diagnosis (ie, <1, 1-3, or >3 years), outcomes, and antithrombotic exposure were collected. Follow-up started from the AF diagnosis until the occurrence of an outcome or the end of the 2-year follow-up. Incidence rates (IRs) per 100 patient-years and adjusted hazard ratios (aHRs) with corresponding 95% CIs were calculated using Cox regression.

We identified 39,178 patients with incident AF and a prior cancer diagnosis. These patients demonstrated higher MB (IR, 3.35 [3.25-3.45] vs 2.23 [2.29-2.35]) and TE rates (IR, 3.21 [3.11-3.31] vs 2.53 [2.50-2.56]) than those without prior cancer. The higher MB risk in AF patients with a prior cancer diagnosis was observed in all examined time intervals, while a higher TE risk was only observed in those with a cancer diagnosis <1 year prior (aHR, 1.27 [1.16-1.40]). Prior respiratory cancer was associated with increased MB (aHR, 1.37 [1.26-1.48]) and TE risks (aHR, 1.26 [1.15-1.38]).

A prior cancer diagnosis confers additional MB and, to a lesser extent and in certain conditions, thromboembolic risks in patients with AF. The type and timing of the prior cancer diagnosis determines the degree of risk.

Anticoagulant management of patients with atrial fibrillation with active cancer is complex because cancer increases the risk of thrombosis as well as bleeding. Previous studies have investigated the impact of any type of cancer, while outcomes may differ per specific type. We performed the present study to provide more insight into the impact of specific types of cancer on clinical outcomes.

We examined major bleeding (MB) and thromboembolism (TE) rates associated with antithrombotic treatment in patients with atrial fibrillation/flutter (AF) who develop cancer and examined whether cancer type affected MB and TE risks.

This Danish population-based cohort study included all patients aged ≥ 50 years discharged with incident AF between January 1, 1995, and December 31, 2016, and identified those who subsequently developed cancer. Data on cancer type, outcomes, and antithrombotic exposure were obtained from hospital and drug prescription databases. Follow-up continued from the time of cancer diagnosis until the occurrence of an outcome or the end of the 2-year follow-up. Incidence rates (IRs) per 100 patient-years and adjusted hazard ratios with corresponding 95% CIs were calculated using Cox regression.

A total of 22,996 patients with AF with subsequent incident cancer were identified. These patients had higher MB (IR, 5.36 [95% CI, 5.09-5.64] vs 2.27 [95% CI, 2.22-2.32]) and TE (IR, 3.91 [95% CI, 3.68-4.15] vs 2.71 [95% CI, 2.66-2.76]) rates than those without cancer. The higher MB rate was observed across all antithrombotic exposure categories. Urogenital (IR, 6.43 [95% CI, 5.94-6.95]) and intracranial cancer (IR, 6.36 [95% CI, 3.85-9.76]) demonstrated the highest MB rates; hematologic (IR, 4.92 [95% CI, 4.12-5.82]) and gastrointestinal cancer (IR, 4.82 [95% CI, 4.31-5.36]) had the highest TE rates. A particularly high MB rate was observed in patients with AF with gastrointestinal cancer and triple antithrombotic therapy (IR, 39.0 [95% CI, 15.5-79.1]).

Patients with AF with certain incident cancer types experienced higher rates of MB and TE than those without cancer. Dual/triple antithrombotic therapy in patients with AF with incident cancer was associated with high bleeding rates, particularly with gastrointestinal cancer.

Posterior cerebral artery (PCA) aneurysms are rare but clinically significant due to their critical location and complex management. The risk factor of the PCA aneurysms rupture remains unclear. This study aimed to investigate the associated factor of PCA aneurysms rupture in a large Chinese cohort.

We conducted a cross-sectional study including patients diagnosed with PCA aneurysms between January 2017 and December 2020. The study population comprised 143 patients, with 95 in the ruptured group and 48 in the unruptured group. Data on demographic characteristics, aneurysm features, medical history, and treatment outcomes were collected and analyzed using SPSS 27.0. Univariate and multivariate logistic regression analyses were performed to identify associated factors for PCA aneurysm rupture.

The presence of coexisting internal carotid artery occlusion (ICAO) was identified as an independent associated factor for PCA aneurysm rupture (odds ratio [OR] = 4.74, 95% confidence interval [CI] 1.22-18.42, P = 0.03). Ischemic stroke (OR=0.44, 95% CI: 0.20-0.97, P = 0.02) and multiple aneurysms (OR=0.41, 95% CI: 0.19-0.87, P = 0.04) were found to be potential protective factors against rupture. The study also revealed a higher incidence of ICAO in the ruptured group (18.9%) compared to the unruptured group (6.3%), indicating a significant association with aneurysm rupture.

This is the first multicenter study to highlight the coexistence of ICAO as a major associated factor for PCA aneurysm rupture in the Chinese population.

Patients with comorbid coronary artery disease and valvular heart disease usually undergo coronary artery bypass grafting alongside valve replacement or ring repair surgeries. Following these procedures, they typically receive a combination of anticoagulation and antiplatelet therapy, which notably heightens their bleeding risk. However, Current scoring systems provide limited predictive capability.

A total of 500 adult patients treated with anticoagulation plus antiplatelet therapy after cardiac surgery were randomly divided into the training set and the validation set at a ratio of 7:3. Predictive factors were identified using univariate logistic regression, LASSO regression and multivariable analysis. Various models were developed, validated and evaluated by using methods including ROC curves, calibration curves, the Hosmer-Lemeshow test, net reclassification improvement (NRI), integrated discrimination improvement (IDI) index, decision curve analysis (DCA) and clinical impact curves (CIC).

Mod2 showed the best performance (AUC of validation set = 0.863) which consists of 8 independent predictive factors (gender, age > 65 years, diabetes, anemia, atrial fibrillation, cardiopulmonary bypass time, intraoperative bleeding and postoperative drainage), with a significantly higher AUC compared to Mod1 (only preoperative factors) and Mod3 (the HAS-BLED scoring model). NRI and IDI analyses further confirmed the superior predictive ability of Mod2 (NRI < 0.05, IDI < 0.05). Both DCA and CIC indicated that Mod2 exhibited good clinical applicability.

This research established and validated a nomogram model incorporating eight predictive factors to evaluate the bleeding risk in patients who receive anticoagulation combined with antiplatelet therapy following cardiac surgery. The model holds significant potential for clinical applications in bleeding risk assessment, decision-making and personalized treatment strategies.

Patients with atrial fibrillation (AF) often develop acute coronary syndrome and undergo percutaneous coronary intervention (PCI), and vice versa. Acute coronary syndrome and PCI mandate the use of dual antiplatelet therapy, while oral anticoagulation is recommended in patients with AF to mitigate thromboembolic risks. Clinical evidence concerning antithrombotic treatment in patients with AF and PCI has been accumulated, but when combined, the therapeutic strategy becomes complex. Although triple therapy, a combination of oral anticoagulation with dual antiplatelet therapy, has been used for patients with AF undergoing PCI as an initial antithrombotic strategy, less intensive regimens may be associated with a lower rate of bleeding without an increased risk in thrombotic events. This narrative review article summarizes currently available evidence of antithrombotic therapy in patients with AF undergoing PCI.

All foreign bodies inserted in the circulatory system are thrombogenic and require temporary or lifelong antithrombotic therapies to prevent thrombosis. The adequate level of anticoagulation during the first few months determines the long-term durability, particularly for mechanical prostheses, and also for biological valves. Suboptimal anticoagulation is the most frequent source of mechanical valve thrombosis (MVT). The patient's clinical presentation decides how mechanical prosthetic valve obstruction is managed. If the mechanical valve thrombosis is obstructive and the patient is in a critical condition with hemodynamic instability, an immediate surgical intervention should be performed. The thrombolytic treatment is an option for left mechanical valve thrombosis in patients who have high surgical risk and no contraindications and also for right heart valve thrombosis. In non-obstructive thrombosis on the mechanical valve, patients can be asymptomatic, requiring optimization of the anticoagulant treatment. Both obstructive and non-obstructive thrombus formed on the mechanical prosthesis can result in embolic events. If the thrombus persists following anticoagulant treatment, the recommended options include thrombolytic treatment or redo surgery. Pannus can also cause obstruction of the prosthesis for which surgical treatment is the only option. While these clinical scenarios may initially appear to have straightforward solutions in terms of surgery, thrombolysis, or effective anticoagulation, real-world clinical experience often proves more complex. For instance, a patient with some usual comorbidities and non-obstructive mechanical valve thrombosis, experiencing symptoms solely by repeated systemic embolizations, might undergo all three therapeutic options due to the unpredictable nature of MVT. Therefore, treatment indications can intersect both on the time axis and depending on the patient's clinical status and the expertise of the center where he is hospitalized. Moreover, the European and American guidelines show subtle but important differences. The aim of this review was to compare these differences, comment on recent studies and evidence gaps, propose a more pragmatic algorithm combining all current recommendations, and highlight important research directions for this disease that has dominated the cardiovascular landscape for more than five decades, but for which there have been no significant recent changes in management.

Premature peripheral artery disease (PAD), defined by lower extremity revascularization (LER) at age ≤ 50 years, is associated with poor major adverse limb events. The early onset of disease is thought to be influenced by genetic factors that regulate homeostasis of the vascular wall and coagulation. The aim of this study is to investigate the effect of anticoagulation as an adjunct to antiplatelet therapy on the outcomes of LER in patients with premature PAD.

There were 8,804 patients with premature PAD on preoperative and postoperative antiplatelet therapy only and 1,236 patients on preoperative and postoperative anticoagulation plus antiplatelet therapy in the Vascular Quality Initiative peripheral vascular intervention, infrainguinal, and suprainguinal files. Propensity score matching (2:1) was performed between patients with premature PAD who were on antiplatelet therapy and those on anticoagulation plus antiplatelet therapy. Perioperative and 1-year outcomes were analyzed including reintervention, major amputation, and mortality.

Patients on anticoagulation were more likely to have coronary artery disease (48.7% vs. 41.2%, P < 0.001), congestive heart failure (20.2% vs. 13.1%, P < 0.001), and have undergone prior LER (73.9% vs. 49.2%, P < 0.001) compared to patients on antiplatelet therapy only. They were also less likely to be independently ambulatory (74.2% vs. 81.8%, P < 0.001) and be on a statin medication (66.8% vs. 74.3%, P < 0.001) compared to patients on antiplatelet therapy only. Patients on anticoagulation were also less likely to be treated for claudication (38.1% vs. 48.6%, P < 0.001), and less likely to be treated with an endovascular procedure (64.8% vs. 73.8%, P < 0.001). After matching for baseline characteristics, there were 1,256 patients on antiplatelet therapy only and 628 patients on anticoagulation. Patients on anticoagulation were more likely to require a return to the operating room (3.7% vs. 1.6%, P < 0.001) and had higher perioperative mortality (1.1% vs. 0.3%, P = 0.032), but major amputation was not significantly different (1.8% vs. 1.6%, P = 0.798) compared to patients on antiplatelet therapy alone. At 1 year, amputation-free survival was higher in patients on antiplatelets only compared to patients on anticoagulation and antiplatelet medications (87.5% vs. 80.9%, log-rank P = 0.001).

Anticoagulation in addition to antiplatelet therapy in patients with premature PAD undergoing LER is associated with increased reintervention and mortality at 1 year.

The optimal antithrombotic management of atrial fibrillation (AF) patients who require oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) remains unclear. Current guidelines recommend dual antithrombotic therapy (DAT; OAC plus P2Y12 inhibitor - preferably clopidogrel) after a short course of triple antithrombotic therapy (TAT; DAT plus aspirin). Although DAT reduces bleeding risk compared to TAT, this is counterbalanced by an increase in ischaemic events. Aspirin provides early ischaemic benefit, but TAT is associated with an increased haemorrhagic burden; therefore, we propose a 30-day dual antiplatelet therapy (DAPT; aspirin plus P2Y12 inhibitor) strategy post-PCI, temporarily omitting OAC. The study aims to compare bleeding and ischaemic risk between a 30-day DAPT strategy following PCI and a guideline-directed therapy in AF patients requiring OAC. WOEST-3 (ClinicalTrials.gov: NCT04436978) is an investigator-initiated, international, open-label, randomised controlled trial (RCT). AF patients requiring OAC who have undergone successful PCI will be randomised within 72 hours after PCI to guideline-directed therapy (edoxaban plus P2Y12 inhibitor plus limited duration of aspirin) or a 30-day DAPT strategy (P2Y12 inhibitor plus aspirin, immediately discontinuing OAC) followed by DAT (edoxaban plus P2Y12 inhibitor). With a sample size of 2,000 patients, this trial is powered to assess both superiority for major or clinically relevant non-major bleeding and non-inferiority for a composite of all-cause death, myocardial infarction, stroke, systemic embolism or stent thrombosis. In summary, the WOEST-3 trial is the first RCT temporarily omitting OAC in AF patients, comparing a 30-day DAPT strategy with guideline-directed therapy post-PCI to reduce bleeding events without hampering efficacy.

To provide a comprehensive summary of relevant studies and evidence concerning the utilization of different pharmacotherapeutic and revascularization strategies in managing coronary artery disease and acute coronary syndrome specifically in the older adult population.

Approximately 30% to 40% of hospitalized patients with acute coronary syndrome are older adults, among whom the majority of cardiovascular-related deaths occur. When compared to younger patients, these individuals generally experience inferior clinical outcomes. Most clinical trials assessing the efficacy and safety of various therapeutics have primarily enrolled patients under the age of 75, in addition to excluding those with geriatric complexities. In this review, we emphasize the need for a personalized and comprehensive approach to pharmacotherapy for coronary heart disease and acute coronary syndrome in older adults, considering concomitant geriatric syndromes and age-related factors to optimize treatment outcomes while minimizing potential risks and complications. In the realm of clinical practice, cardiovascular and geriatric risks are closely intertwined, with both being significant factors in determining treatments aimed at reducing negative outcomes and attaining health conditions most valued by older adults.

Currently, non-vitamin K-antagonist oral anticoagulant (NOAC) monotherapy has been suggested as the optimal antithrombotic therapy for atrial fibrillation (AF) beyond one year after coronary revascularization. The aim of this study was to compare the outcomes between NOAC monotherapy and NOAC plus antiplatelet combination therapy using real-world data.

Between 2015 and 2020, patients with AF who had received NOACs beyond one year after coronary revascularization were enrolled from Korean national insurance data. We emulated a pragmatic sequence of trials between the NOAC monotherapy and the antiplatelet combination therapy followed by propensity score matching. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, and stroke.

Among 206,407 person-trials from 4,465 individuals, we compared 3,275 pairs of the monotherapy and the matched combination therapy. During a median follow-up of 1.24 years, the incidence rate of MACCE was 19.4% and 20.0% per patient-year in the monotherapy group and the antiplatelet combination group, respectively (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.88-1.05; P = 0.422). Compared with the antiplatelet combination group, the monotherapy group had a significantly lower incidence rate of major bleeding, defined as intracranial bleeding or gastrointestinal bleeding requiring hospitalization (2.8% vs. 3.6% per patient-year; HR, 0.78; 95% CI, 0.62-0.97; P = 0.024).

As an antithrombotic therapy for AF beyond one year after coronary revascularization, NOAC monotherapy was associated with a similar risk of MACCE and a lower risk of major bleeding compared to NOAC plus antiplatelet combination therapy.

Duplicate prescribing clinical decision support alerts can prevent important prescribing errors but are frequently the cause of much alert fatigue. Stat dose prescriptions are a known reason for overriding these alerts. This study aimed to evaluate the effect of excluding stat dose prescriptions from duplicate prescribing alerts for antithrombotic medicines on alert burden, prescriber adherence, and prescribing.

A before (January 1st, 2017 to August 31st, 2022) and after (October 5th, 2022 to September 30th, 2023) study was undertaken of antithrombotic duplicate prescribing alerts and prescribing following a change in alert settings. Alert and prescribing data for antithrombotic medicines were joined, processed, and analysed to compare alert rates, adherence, and prescribing. Alert burden was assessed as alerts per 100 prescriptions. Adherence was measured at the point of the alert as whether the prescriber accepted the alert and following the alert as whether a relevant prescription was ceased within an hour. Co-prescribing of antithrombotic stat dose prescriptions was assessed pre- and post-alert reconfiguration.

Reconfiguration of the alerts reduced the alert rate by 29 % (p < 0.001). The proportion of alerts associated with cessation of antithrombotic duplication significantly increased (32.8 % to 44.5 %, p < 0.001). Adherence at the point of the alert increased 1.2 % (4.8 % to 6.0 %, p = 0.012) and 11.5 % (29.4 % to 40.9 %, p < 0.001) within one hour of the alert. When ceased after the alert over 80 % of duplicate prescriptions were ceased within 2 min of overriding. Antithrombotic stat dose co-prescribing was unchanged for 4 out of 5 antithrombotic duplication alert rules.

By reconfiguring our antithrombotic duplicate prescribing alerts, we reduced alert burden and increased alert adherence. Many prescribers ceased duplicate prescribing within 2 min of alert override highlighting the importance of incorporating post-alert measures in accurately determining prescriber alert adherence.

Concomitant presence of atrial fibrillation and coronary artery disease requiring percutaneous coronary intervention is a frequent occurrence. The choice of optimal antithrombotic therapy, in this context, is still challenging. To offer the best protection both in terms of stroke and stent thrombosis, triple therapy with oral anticoagulation and dual antiplatelet therapy would be required. Several drug combinations have been tested in recent years, including direct oral anticoagulants, with the aim of balancing ischemic and bleeding risk. Both pharmacokinetic aspects of the molecules and patient's characteristics should be analyzed in choosing oral anticoagulation. Then, as suggested by guidelines, triple therapy should start with a seven-day duration and the aim to prolong to thirty days in high thrombotic risk patients. Dual therapy should follow to reach twelve months after coronary intervention. Even not fully discussed by the guidelines, in order to balance ischemic and bleeding risk it should also be considered: 1) integrated assessment of coronary artery disease and procedural complexity of coronary intervention; 2) appropriateness to maintain the anticoagulant drug dosage indicated in technical data sheet; the lack of data on the suspension of antiplatelet drugs one year after percutaneous intervention; 3) the possibility of combination therapy with ticagrelor; and 4) the need to treat the occurrence of paroxysmal atrial fibrillation during acute coronary syndrome. With data provided clinician should pursue a therapy as personalized as possible, both in terms of drug choice and treatment duration, in order to balance ischemic and bleeding risk.

Aspirin (ASA), the mainstay antiplatelet treatment in patients with cardiovascular disease (CVD), has been received by a considerable number of AF patients. This study sought to examine the association between ASA monotherapy and the risk of major adverse cardiac and cerebrovascular events (MACCE) in patients with atrial fibrillation (AF).

A total of 850 patients with AF were identified from a community-based Kailuan study. All patients were assigned to two groups according to their medicine history: an aspirin therapy group (ASA group) (n = 174), and a non-aspirin therapy group (non-ASA group) (n = 676). The clinical endpoints are MACCE, including myocardial infarction (MI), ischemic stroke (IS), and hemorrhagic stroke (HS). Incidence curves for MACCE were plotted using the Kaplan-Meier method, and the Log rank test was used to assess the differences in incidence rates. The hazard ratios (HR) and 95% confidence intervals (CI) for MACCE were analyzed using Cox proportional-hazards analysis regression models.

During the 7.2-year follow-up, 30 MACCE occurred in the ASA group, and 101 in the non-ASA group, with a cumulative incidence of 19.88% vs 17.27%, P = 0.511; 3 cases of MI occurred in the ASA group, and 18 cases in the non-ASA group, with a cumulative incidence of 1.78% vs 2.90%, P = 0.305. Twenty-seven cases of IS occurred in the ASA group, and 84 cases in the non-ASA group, with a cumulative incidence of 1.78% vs 2.90%, P = 0.305. Eight cases of HS occurred in the ASA group, and 13 cases in the non-ASA group, with a cumulative incidence of 5.01% vs 2.34%, P = 0.045. Multivariate regression analysis showed that ASA therapy was not associated with MACCE (HR: 1.130, 95% CI: 0.747-1.710, P = 0.562). In addition, ASA therapy was not associated with IS (HR: 1.309, 95% CI: 0.843-2.034, P = 0.231). However, ASA therapy was significantly associated with HS (HR: 2.563, 95% CI: 1.024-6.418, P = 0.044).

ASA monotherapy is not associated with a lower risk of ischemic events, while significantly associated with a higher risk of bleeding events. Patients with AF are unlikely to benefit from aspirin monotherapy.

Upper gastrointestinal (GI) hemorrhage presents a substantial clinical challenge. Initial management typically involves resuscitation and endoscopy within 24 h, although the benefit of very early endoscopy (< 12 h) for high-risk patients is debated. Treatment goals include stopping acute bleeding, preventing rebleeding, and using a multimodal approach encompassing endoscopic, pharmacological, angiographic, and surgical methods. Pharmacological agents such as vasopressin, prostaglandins, and proton pump inhibitors are effective, but the increase in antithrombotic use has increased GI bleeding morbidity. Endoscopic hemostasis, particularly for nonvariceal bleeding, employs techniques such as electrocoagulation and heater probes, with concerns over tissue injury from monopolar electrocoagulation. Novel methods such as Hemospray and Endoclot show promise in creating mechanical tamponades but have limitations. Currently, the first-line therapy includes thermal probes and hemoclips, with over-the-scope clips emerging for larger ulcer bleeding. The gold probe, combining bipolar electrocoagulation and injection, offers targeted coagulation but has faced device-related issues. Future advancements involve combining techniques and improving endoscopic imaging, with studies exploring combined approaches showing promise. Ongoing research is crucial for developing standardized and effective hemorrhage management strategies.

Ischemic stroke and transient ischemic attack (TIA) are the most prevalent cerebrovascular diseases. The conventional antiplatelet drugs are associated with an inherent bleeding risk, while indobufen is a new antiplatelet drug and has the similar mechanism of antiplatelet aggregation as aspirin with more safety profile. However, there have been no studies evaluating the combination therapy of indobufen and clopidogrel for antiplatelet therapy in cerebrovascular diseases.

The CARMIA study aims to investigate the effectiveness and safety of a new dual antiplatelet therapy consisting of indobufen and clopidogrel comparing with the conventional dual antiplatelet therapy consisting of aspirin and clopidogrel in patients with minor ischemic stroke or high-risk TIA.

An open-label randomized controlled clinical trial was conducted at a clinical center. We randomly assigned patients who had experienced a minor stroke or transient ischemic attack (TIA) within 72 h of onset, or within 1 month if they had intracranial stenosis (IS), to receive either indobufen 100 mg twice daily or aspirin 100 mg once daily for 21 days. For patients with IS, the treatment duration was extended to 3 months. All patients received a loading dose of 300 mg clopidogrel orally on the first day, followed by 75 mg once daily from the second day to 1 year. We collected prospective data using paper-based case report forms, and followed up on enrolled patients was conducted to assess the incidence of recurrent ischemic stroke or TIA, mRS score, NIHSS (National Institutes of Health Stroke Scale) score, and any bleeding events occurring within 3 month after onset.

We enrolled 202 patients diagnosed with ischemic stroke or transient ischemic attack. After applying the criteria, 182 patients were eligible for data analysis. Endpoint events (recurrence of ischemic stroke/TIA, myocardial infarction, or death) were observed in 6 patients (6.5%) receiving aspirin and clopidogrel, including 4 (4.3%) with stroke recurrence, 1 (1.1%) with TIA recurrence, and 1 (1%) with death. In contrast, no endpoint events were reported in the indobufen and clopidogrel group (P = 0.029). The group of patients receiving indobufen and clopidogrel exhibited significantly lower modified Rankin Scale (mRS) score. (scores range from 0 to 6, with higher scores indicating more severe disability) compared to the aspirin and clopidogrel group (common odds ratio 3.629, 95% CI 1.874-7.036, P < 0.0001). Although the improvement rate of NIHSS score in the indobufen and clopidogrel group was higher than that in the aspirin and clopidogrel group, the difference was not statistically significant (P > 0.05). Bleeding events were observed in 8 patients (8.6%) receiving aspirin and clopidogrel, including 4 (4.3%) with skin bleeding, 2 (2.2%) with gingival bleeding, 1 (1.1%) with gastrointestinal bleeding, and 1 (1.1%) with urinary system bleeding. On the other hand, only 1 patient (1.1%) in the indobufen and clopidogrel group experienced skin bleeding (P = 0.035).

The combination of indobufen and clopidogrel has shown non-inferior and potentially superior effectiveness and safety compared to aspirin combined with clopidogrel in patients with minor ischemic stroke and high-risk TIA in the CARMIA study (registered under chictr.org.cn with registration number ChiCTR2100043087 in 01/02/2021).

Combined anticoagulant-antiplatelet therapy is often indicated in adults with cardiovascular disease and atrial fibrillation or venous thromboembolism. The study aim was to assess the comparative risk of bleeding between rivaroxaban and apixaban when combined with clopidogrel.

We conducted a retrospective cohort study of commercially insured US adults newly treated with a combination of rivaroxaban+clopidogrel or apixaban+clopidogrel (2015-2018) using Merative™ Marketscan Research Databases. We used propensity score-based inverse probability of treatment weighting (IPTW) to balance the treatment groups. Weighted Cox proportional hazards regression was used to estimate the risk of major bleeding.

The study cohort included 2895 rivaroxaban+clopidogrel users and 3628 apixaban+clopidogrel users. The median (range) duration of follow up was 61 (73) days. Rivaroxaban+clopidogrel users had a similar risk of major bleeding compared with apixaban+clopidogrel users (IPTW incidence rate per 100 person-years 7.96 vs 7.38; IPTW hazard ratio [HR] 1.13 [95% CI 0.78-1.63]). In the subcohort of adults who were treated with DOAC or clopidogrel monotherapy prior to the combined therapy, the risk of major bleeding did not differ by the drug of monotherapy (IPTW HR for rivaroxaban+clopidogrel group: 0.66 [95% CI 0.33-1.32]; IPTW HR for apixaban+clopidogrel group: 1.10 [95% CI 0.55-2.23]) CONCLUSIONS: In our study of commercially insured US adults, the concomitant use of rivaroxaban+clopidogrel and apixaban+clopidogrel conferred a similar risk of major bleeding. DOAC versus clopidogrel monotherapy prior to the concomitant therapy did not influence the risk of major bleeding.

Platelet-rich thrombi occlude arteries causing fatal infarcts like heart attacks and strokes. Prevention of thrombi by current antiplatelet agents can cause major bleeding. Instead, we propose using N-acetyl cysteine (NAC) to act against the protein VWF (von Willebrand factor), and not platelets, to prevent arterial thrombi from forming.

NAC was assessed for its ability to prevent arterial thrombosis by measuring platelet accumulation rate and occlusion time using a microfluidic model of arterial thrombosis with human blood. Acute clot formation, clot stability, and tail bleeding were measured in vivo with the murine modified Folts model. The effect of NAC in the murine model after 6 hours was also measured to determine any persistent effects of NAC after it has been cleared from the blood.

We demonstrate reduction of thrombi formation following treatment with NAC in vitro and in vivo. Human whole blood treated with 3 or 5 mmol/L NAC showed delayed thrombus formation 2.0× and 3.7× longer than control, respectively (P<0.001). Blood treated with 10 mmol/L NAC did not form an occlusive clot, and no macroscopic platelet aggregation was visible (P<0.001). In vivo, a 400-mg/kg dose of NAC prevented occlusive clots from forming in mice without significantly affecting tail bleeding times. A lower dose of NAC significantly reduced clot stability. Mice given multiple injections showed that NAC has a lasting and cumulative effect on clot stability, even after being cleared from the blood (P<0.001).

Both preclinical models demonstrate that NAC prevents thrombus formation in a dose-dependent manner without significantly affecting bleeding time. This work highlights a new pathway for preventing arterial thrombosis, different from antiplatelet agents, using an amino acid derivative as an antithrombotic therapeutic.

Balancing antithrombotic therapy for atrial fibrillation (AF) patients undergoing percutaneous coronary intervention (PCI) remains a clinical challenge due to coexisting thrombogenic risks. This review emphasizes the delicate balance required to prevent ischemic events while minimizing bleeding complications, particularly in the context of risk assessment.

This review spans from 2010 to October 2023, exploring the complexities of antithrombotic management for AF patients undergoing PCI. It stresses the need for personalized treatment decisions to optimize antithrombotic therapies effectively.

The evolving evidence supports double antithrombotic therapy (DAT) over triple antithrombotic therapy (TAT) for these patients, showcasing a more favorable safety profile without compromising efficacy. Non-vitamin K antagonist oral anticoagulant (NOAC)-based DAT strategies exhibit superiority in reducing major bleeding events while effectively preventing ischemic events. Recommendations from the 2023 European Society of Cardiology (ESC) Guidelines advocate for NOAC-based DAT post-PCI, endorsing safer antithrombotic profiles.Challenges persist for specific patient categories requiring both oral anticoagulants and antiplatelets, necessitating personalized approaches. Future advances in intravascular imaging and novel coronary stent technologies offer promising avenues to optimize outcomes and influence antithrombotic strategies in AF-PCI patients.

Venous thromboembolism (VTE) is a prevalent medical condition with high morbidity, mortality, and associated costs. Anticoagulation remains the main treatment for VTE, though the decision on when, how, and for how long to administer anticoagulants is increasingly complex. This review highlights the different phases of VTE management, with special circumstances for consideration such as antiphospholipid syndrome, coronary artery disease, cancer-associated thrombus, COVID-19, and future anticoagulation options. Anticoagulation management will continue to be a complex decision, applying evidence-based medicine to individual patients with the hope of maximizing effectiveness while minimizing risks.

Background  Atrial fibrillation (AF) prevalence is rising; however, data on the bleeding risks associated with the detection of subclinical AF are needed. Objective  Our objective was to determine the bleeding increment associated with implantable loop recorder (ILR) screening for subclinical AF and subsequent anticoagulation initiation compared with usual care. Methods  This post hoc study utilized LOOP trial data from 6,004 elderly patients with stroke risks randomized to either ILR ( n  = 1,503) or usual care ( n  = 4,503). The mean follow-up time was 64.5 months, and none were lost to follow-up. The primary exposure was the initiation of oral anticoagulation, and the main outcome was the risk of major bleeding events following initiation of oral anticoagulants (OACs), determined by time-dependent cox regression. Second, we investigated antithrombotic prescription patterns and major bleeding events after antiplatelet treatment and in subgroups. Results  OAC was initiated in 1,019 participants with a mean age (years) of 78.8 (± 4.67) in control versus 77.0 (± 4.84) in ILR, p  < 0.0001. Altogether did 202 participants end or pause OAC treatment. Among AF patients (n = 910) had 40 (28%) completely ended OAC and 105 (72%) temporarily paused OAC during follow-up. Major bleeding events totaled 221 (3.7%). Forty-seven major bleeding events followed an OAC initiation in 1,019 participants (4.6%); 26 versus 21 events in the control and ILR groups, respectively. The hazard ratio (HR) for major bleeding after OAC initiation compared with before initiation was 2.08 (1.50-2.90) p  < 0.0001 overall, 2.81 (1.82-4.34) p  < 0.0001 for control and 1.32 (0.78-2.23) p  = 0.31 for the ILR group ( p  = 0.07 for interaction). Antiplatelet treatment resulted in an overall adjusted HR of 1.3 (0.96-1.75) p  = 0.09. For OAC users aged ≥75 years in the ILR group, the rate of major bleeding was 1.73 (0.92-2.96) compared with 0.84 (0.36-1.66) for an age <75 years, and the rate of the corresponding control subgroup aged ≥75 years was 2.20 (1.23-3.63) compared with 1.64 (0.82-2.93) for an age <75 years. Conclusion  The individual risk of major bleeding increased twofold after initiation of oral anticoagulation for all patients in this study. However, the patients screened for subclinical AF did not have a higher bleeding risk after initiation of anticoagulation compared with those in usual care. Trial Registration:  The LOOP study is registered at ClinicalTrials.gov, identifier: NCT020364 50.

The efficacy and safety of ticagrelor or prasugrel vs. clopidogrel in patients with atrial fibrillation (AF) on oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) for myocardial infarction (MI) have not been established.

This was a nationwide cohort study of patients on OAC for AF who underwent PCI for MI from 2011 through 2019 and were prescribed a P2Y12 inhibitor at discharge. The primary efficacy outcome was major adverse cardiovascular events (MACE), defined as a composite of death from any cause, stroke, recurrent MI, or repeat revascularization. The primary safety outcome was cerebral, gastrointestinal, or urogenital bleeding requiring hospitalization. Absolute and relative risks for outcomes at 1 year were calculated through multivariable logistic regression with average treatment effect modelling. Outcomes were standardized for the individual components of the CHA2DS2-VASc and HAS-BLED scores as well as type of OAC, aspirin, and proton pump inhibitor use. We included 2259 patients of whom 1918 (84.9%) were prescribed clopidogrel and 341 (15.1%) ticagrelor or prasugrel. The standardized risk of MACE was significantly lower in the ticagrelor or prasugrel group compared with the clopidogrel group (standardized absolute risk, 16.3% vs. 19.4%; relative risk, 0.84, 95% confidence interval, 0.70-0.98; P = 0.02), while the risk of bleeding did not differ (standardized absolute risk, 5.5% vs. 5.1%; relative risk, 1.07, 95% confidence interval, 0.73-1.41; P = 0.69).

In patients with AF on OAC who underwent PCI for MI, treatment with ticagrelor or prasugrel vs. clopidogrel was associated with reduced ischaemic risk, without a concomitantly increased bleeding risk.

The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients on long-term oral anticoagulation (OAC) therapy is still uncertain.

The aim of this analysis was to assess the effects of 1- vs 3-month DAPT in patients with and those without concomitant OAC included in the XIENCE Short DAPT program.

The XIENCE Short DAPT program enrolled patients with high bleeding risk who underwent successful PCI with a cobalt-chromium everolimus-eluting stent. DAPT was discontinued at 1 or 3 months in patients free from ischemic events and adherent to treatment. The effect of 1- vs 3-month DAPT was compared in patients with and those without OAC using propensity score stratification. The primary endpoint was all-cause death or any myocardial infarction (MI). The key secondary endpoint was Bleeding Academic Research Consortium (BARC) types 2 to 5 bleeding. Outcomes were assessed from 1 to 12 months after index PCI.

Among 3,364 event-free patients, 1,462 (43%) were on OAC. Among OAC patients, the risk for death or MI was similar between 1- and 3-month DAPT (7.4% vs 8.8%; adjusted HR: 0.74; 95% CI: 0.49-1.11; P = 0.139), whereas BARC types 2 to 5 bleeding was lower with 1-month DAPT (adjusted HR: 0.71; 95% CI: 0.51-0.99; P = 0.046). These effects were consistent in patients with and those without OAC (P for interaction = NS).

Between 1 and 12 months after PCI, 1-month compared with 3-month DAPT was associated with similar rates of all-cause death or MI and a reduced rate of BARC types 2 to 5 bleeding, irrespective of OAC treatment.

Patients with impaired left ventricular (LV) function can develop LV thrombus, a potentially life-threatening condition due to risk of stroke and embolization. Conventional treatment with vitamin K antagonists (VKAs; e.g., warfarin) puts patients at risk of bleeding, and the use of direct oral anticoagulants (DOACs) appears promising, although data are scant. We searched the published English language literature for randomized controlled trials (RCTs) comparing DOACs with VKAs in LV thrombus. End points were failure to resolve, thromboembolic events (stroke, embolism), bleeding, or any adverse event (composite of thromboembolism or bleeding), or all-cause death. Data were pooled and analyzed in hierarchical Bayesian models. In three eligible RCTs, 141 patients were studied during an average of 4.6 months (53.8 patient-years; n = 71 assigned to DOAC, n = 70 assigned to VKA). A similar number of patients in each treatment arm demonstrated failure to resolve (DOAC: 14/71 vs. VKA: 15/70) and death events (3/71 vs. 4/70). However, patients on DOACs suffered fewer strokes/thromboembolic events (1/71 vs. 7/70; log odds ratio [OR], -2.02 [95% credible interval (CI95 ), -4.53 to -0.31]) and fewer bleeding events (2/71 vs. 9/70; log OR, -1.62 [CI95 , -3.43 to -0.26]), leading to fewer patients on DOACs with any adverse event versus VKAs (3/71 vs. 16/70; log OR, -1.93 [CI95 , -3.33 to -0.75]). In conclusion, pooled analysis of RCT data favors DOACs over VKAs in patients with LV thrombus in terms of both efficacy and safety.

Coronary artery disease (CAD) is highly prevalent in older adults, yet its management remains challenging. Treatment choices are made complex by the frailty burden of older patients, a high prevalence of comorbidities and body composition abnormalities (e.g., sarcopenia), the complexity of coronary anatomy, and the frequent presence of multivessel disease, as well as the coexistence of major ischemic and bleeding risk factors. Recent randomized clinical trials and epidemiological studies have provided new data on optimal management of complex patients with CAD. However, frail older adults are still underrepresented in the literature. This narrative review aims to highlight the importance of assessing frailty as an aid to guide therapeutic decision-making and tailor CAD management to the specific needs of older adults, taking into account age-related pharmacokinetic and pharmacodynamic changes, polypharmacy, and potential drug interactions. We also discuss gaps in the evidence and offer perspectives on how best in the future to optimize the global strategy of CAD management in older adults.

To evaluate the postoperative incidence of bleeding, incidence of thromboembolic complications, and all-cause mortality in patients with valvular heart disease and ischemic heart disease (IHD) associated with various regimens of the antithrombotic treatment during one year after surgery.

This study included 271 patients with valvular heart disease and IHD after heart valve replacement and myocardial revascularization from 2009 through 2018. However, during the follow-up period (12 months), contact with 12 patients was lost, and therefore these patients were excluded from the study. Further analysis included 259 patients. Coronary artery bypass grafting (CABG) in combination with heart valve intervention was performed in 217 (83.8 %) patients, and percutaneous coronary interventions (PCIs) were performed in 42 (16.2 %) patients. There were 197 (72.7 %) male participants; median age was 64.0 [58.0; 67.5] years. The patients were divided into two groups. Group 1 consisted of 113 patients who received postoperative dual antithrombotic therapy (DAT) with acetylsalicylic acid (ASA)/clopidogrel+vitamin K antagonist (VKA). Group 2 included 146 patients receiving postoperative triple antithrombotic therapy (TAT) with ASA+clopidogrel+VKA. Follow-up duration was 12 months after surgery. Due to significant intergroup differences in major clinical anamnestic data, the data were adjusted using pseudo-randomization (Propensity Score Matching, PSM). In result, 109 patients were selected for each group.

The incidence of adverse hemorrhagic outcomes was significantly higher in the group treated with TAT than with DAT. Minor bleedings were observed in 19 (17.4 %) vs. 8 (7.3 %) cases; moderate, clinically significant bleedings in 16 (14.7 %) vs. 6 (5.5 %) cases; and the total number of bleedings was 35 (32.1 %) vs. 14 (12.8 %; p=0.02, p=0.02, and р=0.001, respectively). Comparing the incidence of major bleedings did not show and significant intergroup differences (p=1.000). The incidence rate of any bleeding during the follow-up period was 32.1 % in patients treated with TAT (n=109) and 12.8 % in patients treated with DAT (n=109; p=0.005). The incidence of no bleeding during one year after surgery was 87 % in the DAT treatment group and 67 % in the TAT treatment group (p=0.005). The incidence of secondary endpoints, including ischemic stroke, myocardial infarction, prosthetic valve thrombosis, and death, was statistically non-significant.

Administration of DAT vs. TAT after heart valve replacement and myocardial revascularization significantly decreases the incidence of any bleedings in the absence of significant differences in the incidence of thromboembolic events and mortality.

Percutaneous left atrial appendage closure (LAAC) has shown non-inferiority compared to oral anticoagulation (OAC) in preventing atrial fibrillation (AF)-related stroke. The objective of this study was to assess whether LAAC reduces the incidence of gastrointestinal bleeding (GIB) and/or chronic anaemia associated with OAC, as well as the consumption of healthcare resources.

Prospective, single-center study from 2016 to 2022, LAAC was performed. Clinical, analytical and healthcare resource consumption data were collected (endoscopies, blood transfusions, hospital admissions) prior and 6 months after LAAC.

43 patients were included, with an average age of 77.6 years. LAAC indication was upper, low and obscure GIB in 7 (16%), 8 (19%) and 28 patients (65%) respectively. GIB source was intestinal angiodysplasias in 27 patients (63%), occult origin in 12 (28%), and others (antral vascular ectasia, portal hypertension gastropathy, etc.) in 4 patients (9%). The mean number of packed red blood cells per patient before LAAC was (mean ± SD) 7.29 ± 5 vs 0.42 ± 1.3 (p < 0.001); endoscopic procedures were 4.34 ± 2.85 vs 0.27 ± 0.76 (p < 0.001); and hospitalizations 2.67 ± 2.14 vs 0.03 ± 0.17 (p < 0.001), with a hospital stay of 21.5 ± 17.3 vs 0.09 ± 0.5 days (p < 0.001) at 6 months post-intervention. Haemoglobin value increased from 8.1 ± 1.2g/dl to 12.4 ± 2.2g/dl (p < 0.001) at 6 months. No thromboembolic events were registered during a median follow-up of 16.6 months (range 6-65).

LAAC could be a safe and effective alternative to OAC in patients with non-valvular AF presenting significant, recurrent or potentially unresolvable GIB. This intervention also leads to important savings in the consumption of healthcare resources.

The prevalence of AF in patients with coronary artery disease is high. The guidelines from many professional groups, including the European Society of Cardiology, American College of Cardiology/American Heart Association and Heart Rhythm Society, recommend a maximum duration of 12 months of combination single antiplatelet and anticoagulation therapy in patients who undergo percutaneous coronary intervention and who have concurrent AF, followed by anticoagulation alone beyond 1 year. However, the evidence that anticoagulation alone without antiplatelet therapy adequately reduces the well-documented attritional risk of stent thrombosis after coronary stent implantation is relatively sparse, particularly given that very late stent thrombosis (>1 year from stent implantation) is the commonest type. By contrast, the elevated risk of bleeding from combined anticoagulation and antiplatelet therapy is clinically important. The aim of this review is to assess the evidence for long-term anticoagulation alone without antiplatelet therapy 1 year post-percutaneous coronary intervention in patients with AF.

Antiplatelet and/or anticoagulant agents (collectively known as antithrombotic agents) are used to reduce the risk of thromboembolic events in patients with conditions such as atrial fibrillation, acute coronary syndrome, recurrent stroke prevention, deep vein thrombosis, hypercoagulable states and endoprostheses. Antithrombotic-associated gastrointestinal (GI) bleeding is an increasing burden due to the growing population of advanced age with multiple comorbidities and the expanding indications for the use of antiplatelet agents and anticoagulants. GI bleeding in antithrombotic users is associated with an increase in short-term and long-term mortality. In addition, in recent decades, there has been an exponential increase in the use of diagnostic and therapeutic GI endoscopic procedures. Since endoscopic procedures hold an inherent risk of bleeding that depends on the type of endoscopy and patients' comorbidities, in patients already on antithrombotic therapies, the risk of procedure-related bleeding is further increased. Interrupting or modifying doses of these agents prior to any invasive procedures put these patients at increased risk of thromboembolic events. Although many international GI societies have published guidelines for the management of antithrombotic agents during an event of GI bleeding and during urgent and elective endoscopic procedures, no Indian guidelines exist that cater to Indian gastroenterologists and their patients. In this regard, the Indian Society of Gastroenterology (ISG), in association with the Cardiological Society of India (CSI), Indian Academy of Neurology (IAN) and Vascular Society of India (VSI), have developed a "Guidance Document" for the management of antithrombotic agents during an event of GI bleeding and during urgent and elective endoscopic procedures.