RESUMEN
The recent study by Kaiwen Wang et al., titled "Early postoperative acetylsalicylic acid administration does not increase the risk of postoperative intracranial bleeding in patients with spontaneous intracerebral hemorrhage," explores the association between postoperative intracranial bleeding (PIB) and various risk factors, including smoking, pre-hemorrhagic antiplatelet therapy, and dyslipidemia. While the study highlights that smoker, particularly women, are at increased risk for subarachnoid hemorrhage and acknowledges the risks of pre-hemorrhagic antiplatelet use, it overlooks the potential risk of PIB associated with early postoperative aspirin administration. This critique underscores the need to approach the study's findings with caution, given the broader context of aspirin's risk profile. Specifically, aspirin has been associated with a 37% higher relative risk of any intracranial hemorrhage, as indicated by other randomized trials. Additionally, the study's implications regarding the benefits of aspirin in stroke prevention must be critically evaluated, as the increased risk of intracranial bleeding may outweigh the potential benefits. This abstract emphasizes the importance of careful consideration of aspirin's adverse effects in the context of postoperative care.
Asunto(s)
Aspirina , Hemorragia Cerebral , Inhibidores de Agregación Plaquetaria , Humanos , Aspirina/efectos adversos , Aspirina/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Factores de Riesgo , Hemorragias Intracraneales , Femenino , Complicaciones Posoperatorias , Hemorragia Posoperatoria , MasculinoRESUMEN
Patients with peripheral artery disease (PAD) who undergo lower extremity revascularization (LER) are at high risk for cardiovascular and limb-related ischemic events. The role of antithrombotic therapy is to prevent thrombotic complications, but this requires balancing increased risk of bleeding events. The dual pathway inhibition (DPI) strategy including aspirin and low-dose rivaroxaban after LER has been shown to reduce major adverse cardiovascular and limb-related events without significant differences in major bleeding. There is now a need to implement the broad adoption of DPI therapy in PAD patients who have undergone LER in routine practice.
Asunto(s)
Fibrinolíticos , Enfermedad Arterial Periférica , Humanos , Enfermedad Arterial Periférica/cirugía , Fibrinolíticos/uso terapéutico , Trombosis/prevención & control , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Extremidad Inferior/irrigación sanguínea , Extremidad Inferior/cirugía , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Rivaroxabán/uso terapéutico , Rivaroxabán/administración & dosificaciónRESUMEN
Importance: Prior trials showed that dual antiplatelet therapy could reduce the risk of early new stroke in patients with acute mild ischemic stroke or transient ischemic attack (TIA) within 24 hours of symptom onset. However, it is currently uncertain whether dual antiplatelet therapy can reduce the risk of early new stroke in patients with a more delayed initiation time window. Objective: To evaluate the efficacy and safety of clopidogrel and aspirin among patients with mild ischemic stroke or TIA when initiated within 24 hours, from more than 24 hours to 48 hours, and from more than 48 hours to 72 hours. Design, Setting, and Participants: The Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis randomized clinical trial was a double-blind, placebo-controlled, multicenter, 2-by-2 factorial randomized clinical trial conducted at 222 hospitals in China from September 17, 2018, to October 15, 2022. All patients with acute mild ischemic stroke and TIA were included in this subgroup analysis and categorized into 3 groups according to time from symptom onset to randomization (group 1: ≤24 hours; group 2: >24 to ≤48 hours; and group 3: >48 to 72 hours). Patients were followed up for 90 days. Interventions: All patients received clopidogrel combined with aspirin (clopidogrel 300 mg loading dose on day 1, followed by 75 mg daily on days 2 to 90, and aspirin 100 to 300 mg on the first day and then 100 mg daily for days 2 to 90) or aspirin alone (100 to 300 mg on day 1 and then 100 mg daily for days 2 to 90) within 72 hours after symptom onset. Main Outcomes and Measures: The primary outcome was new stroke (ischemic or hemorrhagic) within 90 days. The primary safety outcome was moderate-to-severe bleeding, according to Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria. Results: This analysis included a total of 6100 patients (3050 in the clopidogrel-aspirin group and 3050 in the aspirin group). The median age was 65 years (IQR, 57-71 years), and 3915 patients (64.2%) were male. In the population with time to randomization of 24 hours or less, stroke occurred in the next 90 days in 97 of 783 patients (12.4%); among those randomized from more than 24 hours to 48 hours, in 211 of 2552 patients (8.3%) among those randomized from more than 24 hours to 48 hours, and in 193 of 2765 patients (7.0%). The clopidogrel-aspirin group had a lower risk of new stroke within 90 days compared with the aspirin alone group both in patients with time to randomization of from 48 to 72 hours (5.8% vs 8.2%; hazard ratio [HR], 0.70 [95% CI, 0.53-0.94]), of more than 24 to 48 hours (7.6% vs 8.9%; HR, 0.85 [95% CI, 0.65-1.12]), and of 24 hours or less (11.5% vs 13.4%; HR, 0.83 [95% CI, 0.55-1.25]) (P = .38 for interaction). Among those with time to randomization of more than 48 to 72 hours, moderate-to-severe bleeding occurred in 12 patients (0.9%) in the clopidogrel-aspirin group and in 6 patients (0.4%) in the aspirin-alone group (HR, 2.00 [95% CI, 0.73-5.43]), while moderate-to-severe bleeding in those with time to randomization of more than 24 hours to 48 hours occurred in 9 patients (0.7%) in the clopidogrel-aspirin group and in 4 patients (0.3%) in the aspirin-alone group (HR, 2.25 [95% CI, 0.68-7.39]) and in those with time to randomization of within 24 hours, occurred in 6 patients (1.5%) in the clopidogrel-aspirin group and in 3 patients (0.8%) in the aspirin-alone group (HR, 1.57 [95% CI, 0.36-6.83]) (P = .92 for interaction). Conclusions and Relevance: In this randomized clinical trial of antiplatelet therapy in China, patients with mild ischemic stroke or TIA had consistent benefit from dual antiplatelet therapy with clopidogrel and aspirin vs aspirin alone when initiated within 72 hours after symptom onset, with a similar increase in the risk of moderate-to-severe bleeding. Patients should receive dual antiplatelet therapy with clopidogrel and aspirin within 72 hours after symptom onset. Trial Registration: ClinicalTrials.gov Identifier: NCT03635749.
Asunto(s)
Aspirina , Clopidogrel , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Humanos , Clopidogrel/uso terapéutico , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Masculino , Femenino , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/prevención & control , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anciano , Método Doble Ciego , Ataque Isquémico Transitorio/tratamiento farmacológico , China/epidemiología , Tiempo de Tratamiento/estadística & datos numéricos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Understanding the cost-effectiveness of aspirin-clopidogrel combination therapy is crucial in determining its influence on coagulation parameters, specifically prothrombin time (PT) and activated partial thromboplastin time (APTT). The aim of this study was to assess the cost-effectiveness and clinical impact of using the aspirin-clopidogrel combination compared to aspirin alone in managing ischemic stroke. Employing an observational research design, inpatient ischemic stroke cases receiving the aspirin-clopidogrel combination were compared to those treated with aspirin alone. Focusing on the hospital's perspective on costs, the research specifically analyzed medical expenses without discounting costs or effects. The analysis involved comparing the direct medical costs and coagulation parameters between the two treatment groups. Our data revealed that the aspirin-clopidogrel combination demonstrated superior cost-effectiveness over aspirin alone, indicated by the incremental cost-effectiveness ratio (ICER) values for PT (IDR -246,930/second) and APTT (IDR -119,270/second). This indicated that the combination therapy was associated with lower costs while yielding better clinical parameter values. The ICER analysis placed the aspirin-clopidogrel combination in the southeast quadrant, marking its dominance over aspirin monotherapy by demonstrating higher effectiveness at lower costs. These results suggest that combination therapy might be a favorable alternative for managing ischemic stroke, presenting a viable option for consideration in clinical practice. The findings underscore the potential economic and clinical advantages of employing the aspirin-clopidogrel combination in routine stroke management protocols.
Asunto(s)
Aspirina , Clopidogrel , Análisis Costo-Beneficio , Quimioterapia Combinada , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Humanos , Clopidogrel/uso terapéutico , Clopidogrel/administración & dosificación , Aspirina/uso terapéutico , Aspirina/economía , Aspirina/administración & dosificación , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/economía , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/economía , Inhibidores de Agregación Plaquetaria/administración & dosificación , Femenino , Masculino , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/economíaRESUMEN
BACKGROUND: We conducted a post hoc analysis of the ATAMIS (Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke) trial to investigate whether the priority of clopidogrel plus aspirin to aspirin alone was consistent between patients with and without stroke pathogenesis of large-artery atherosclerosis (LAA). METHODS AND RESULTS: Patients with stroke classification randomized to a clopidogrel-plus-aspirin group and aspirin-alone group in a modified intention-to-treat analysis set of ATAMIS were classified into LAA and non-LAA subtypes. The primary outcome was early neurologic deterioration at 7 days, defined as a >2-point increase in National Institutes of Health Stroke Scale score compared with baseline, and safety outcomes were bleeding events and intracranial hemorrhage. We compared treatment effects in each stroke subtype and investigated the interaction. Among 2910 patients, 225 were assigned into the LAA subtype (119 in the clopidogrel-plus-aspirin group and 106 in the aspirin-alone group) and 2685 into the non-LAA subtype (1380 in the clopidogrel-plus-aspirin group and 1305 in the aspirin-alone group). Median age was 66 years, and 35% were women. A lower proportion of early neurologic deterioration was found to be associated with dual antiplatelet therapy in the LAA subtype (adjusted risk difference, -10.4% [95% CI, -16.2% to -4.7%]; P=0.001) but not in the non-LAA subtype (adjusted risk difference, -1.4% [95% CI, -2.6% to 0.1%]; P=0.06). No significant interaction was found (P=0.11). CONCLUSIONS: Compared with the non-LAA subtype, patients with stroke of the LAA subtype may get more benefit from dual antiplatelet therapy with clopidogrel plus aspirin with respect to early neurologic deterioration at 7 days. REGISTRATION: URL: clinicaltrials.gov; UnIque identifier: NCT02869009.
Asunto(s)
Aspirina , Clopidogrel , Terapia Antiplaquetaria Doble , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Humanos , Femenino , Masculino , Anciano , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Aspirina/efectos adversos , Clopidogrel/uso terapéutico , Clopidogrel/administración & dosificación , Clopidogrel/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Terapia Antiplaquetaria Doble/métodos , Terapia Antiplaquetaria Doble/efectos adversos , Persona de Mediana Edad , Resultado del Tratamiento , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/prevención & control , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/etiología , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/diagnóstico , Aterosclerosis/complicaciones , Índice de Severidad de la Enfermedad , Quimioterapia CombinadaRESUMEN
BACKGROUND: Clopidogrel monotherapy improved clinical outcomes compared with aspirin monotherapy during a chronic maintenance period in patients who underwent coronary stenting in the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) trial. However, it is uncertain whether the beneficial effect of clopidogrel over aspirin is different according to the renal function. METHODS AND RESULTS: We conducted a post hoc analysis of the HOST-EXAM trial. Chronic kidney disease (CKD) was defined as baseline estimated glomerular filtration rate <60 mL/min per 1.73 m2. The primary end point was a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium bleeding type ≥3, during the 2-year follow up. Among the 5438 patients enrolled in the HOST-EXAM trial, 4844 patients (mean age, 63.3±10.6 years; 74.9% men) with a baseline creatinine value were analyzed in this study. A total of 508 (10.5%) patients had CKD, who were at higher risk of the primary end point compared with those without CKD (hazard ratio [HR], 2.01 [95% CI, 1.51-2.67]). Clopidogrel monotherapy was associated with a lower rate of the primary end point in both patients with CKD (HR, 0.74 [95% CI, 0.44-1.25]) and patients without CKD (HR, 0.71 [95% CI, 0.56-0.91]). No significant interaction was observed between the treatment effect and CKD status (P for interaction=0.889). CONCLUSIONS: During the chronic maintenance period after coronary stenting, the risk of thrombotic and bleeding events was significantly higher in patients with CKD compared with those without CKD. There was no statistical difference in the treatment effect of clopidogrel monotherapy in those with versus without CKD.
Asunto(s)
Aspirina , Clopidogrel , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Insuficiencia Renal Crónica , Humanos , Clopidogrel/uso terapéutico , Clopidogrel/efectos adversos , Clopidogrel/administración & dosificación , Masculino , Femenino , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/terapia , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Aspirina/efectos adversos , Anciano , Hemorragia/inducido químicamente , Resultado del Tratamiento , Tasa de Filtración Glomerular , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/mortalidad , Stents , Factores de TiempoRESUMEN
BACKGROUND AND OBJECTIVES: Clopidogrel-aspirin initiated within 72 hours of symptom onset is effective in patients with mild ischemic stroke or transient ischemic attack (TIA) in the Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial. Uncertainties remain about the duration of the treatment effect. This study aimed to assess duration of benefit and risk of clopidogrel-aspirin in these patients. METHODS: The INSPIRES trial was a 2*2 factorial placebo-controlled randomized trial conducted in 222 hospitals in China. The 2 treatments did not interact and were evaluated separately. In this study, we performed secondary analyses based on antiplatelet treatment. All patients with mild stroke or TIA of presumed atherosclerotic cause within 72 hours of symptom onset enrolled in the trial were included. Patients were randomly assigned to receive clopidogrel-aspirin on days 1-21 followed by clopidogrel on days 22-90 or aspirin alone for 90 days. The primary efficacy outcome was major ischemic event which included the composite of ischemic stroke and nonhemorrhagic death. The primary safety outcome was moderate-to-severe bleeding. We estimated the risk difference between the 2 treatments for each stratified week. RESULTS: All 6,100 patients in the trial were included (3,050 in each group). The mean age was 65 years, and 3,915 patients (64.2%) were men. Compared with aspirin alone, the reduction of major ischemic events by clopidogrel-aspirin mainly occurred in the first week (absolute risk reduction [ARR] 1.42%, 95% CI 0.53%-2.32%) and remained in the second week (ARR 0.49%, 95% CI 0.09%-0.90%) and the third week (ARR 0.29%, 95% CI -0.05% to 0.62%). Numerical higher risk of moderate-to-severe bleedings in the clopidogrel-aspirin group was observed in the first 3 weeks (absolute risk increase 0.05% [95% CI -0.10% to 0.20%], 0.10% [95% CI -0.09% to 0.29%], and 0.18% [95% CI -0.03% to 0.40%] in the first, second, and third weeks, respectively). CONCLUSIONS: Among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, the net benefit of clopidogrel-aspirin initiated within 72 hours of symptom onset was pronounced in the first week and continued to a lesser degree in the following 2 weeks, outweighing the low, but ongoing hemorrhagic risk. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03635749. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, the net benefit of clopidogrel-aspirin initiated within 72 hours of symptom onset was pronounced in the first week and continued to a lesser degree in the following 2 weeks, outweighing the low but ongoing hemorrhagic risk.
Asunto(s)
Aspirina , Clopidogrel , Terapia Antiplaquetaria Doble , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Humanos , Ataque Isquémico Transitorio/tratamiento farmacológico , Masculino , Femenino , Clopidogrel/uso terapéutico , Clopidogrel/administración & dosificación , Persona de Mediana Edad , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Anciano , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Terapia Antiplaquetaria Doble/métodos , Factores de Tiempo , Quimioterapia Combinada , Resultado del TratamientoRESUMEN
Recently, in Hepatocellular carcinoma (HCC) setting, the use of metformin has been associated to a trend toward worse response rate, overall survival and progression free survival in patients who received immunotherapy. The study population included individuals from both Eastern and Western regions with a confirmed diagnosis of HCC and receiving first line treatment with Atezolizumab plus bevacizumab or Lenvatinib. Univariate and multivariate analyses were performed by Cox proportional. For the analysis, patients were stratified based on their use of concomitant medication or not. At the time of database lock, 319 deaths were observed: 209 in the Lenvatinib cohort, 110 in the Atezolizumab plus bevacizumab cohort. In the Atezolizumab plus Bevacizumab arm, 50 (16.5%) patients were on chronic metformin use. At the univariate analysis for OS, patients who used metformin showed significantly shorter OS compared to patients who did not use metformin (HR 1.9, 95% CI 1.1-3.2). Multivariate analysis confirmed that patients in metformin group had significantly shorter OS compared to patients in no-metformin group (HR 1.9; 95% CI 1.1-3.1). At the univariate analysis for PFS, patients in metformin group had significantly shorter PFS compared to patients in no-metformin group (HR 1.6, 95% CI 1.0-2.6). Multivariate analysis confirmed that patients in metformin group had significantly shorter PFS compared to patients in no-metformin group (HR 1.7; 95% CI 1.1-2.7; p = 0.0147). No differences were reported in terms of ORR and DCR between patients in metformin group and those in no-metformin group. In the Lenvatinib cohort, 65 (15%) patients were recorded to chronically use metformin. No statistically significant differences in terms of both OS and PFS were found between patients in metformin group and patients in no-metformin group. This analysis unveils a negative prognostic role associated with metformin use specifically within the Atezolizumab plus Bevacizumab group.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Aspirina , Bevacizumab , Carcinoma Hepatocelular , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Insulina , Neoplasias Hepáticas , Metformina , Compuestos de Fenilurea , Quinolinas , Humanos , Metformina/uso terapéutico , Metformina/administración & dosificación , Masculino , Femenino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Bevacizumab/uso terapéutico , Bevacizumab/administración & dosificación , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Anciano , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Persona de Mediana Edad , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/mortalidad , Pronóstico , Insulina/uso terapéutico , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Anciano de 80 o más AñosRESUMEN
ABSTRACT: The dual pathway inhibition (DPI) with low-dose rivaroxaban and aspirin in patients with stable atherosclerotic vascular disease reduces the occurrence of cardiovascular events, with no significant increase of intracranial or other critical organ bleedings. Our observational study aimed to describe the clinical performance, adherence, and persistence of DPI therapy among a real-world setting of patients with an established diagnosis of coronary artery (CAD) and/or peripheral artery disease (PAD). We prospectively included all consecutive patients with an established diagnosis of CAD and/or PAD treated with aspirin (ASA) 100 mg once daily and rivaroxaban 2.5 mg twice daily. Clinical evaluation was performed at baseline, before starting treatment, at 1 month, and every 6 months after the study drug administration. A total of 202 consecutive patients (mean age 66 ± 10 years; male 80%) eligible to DPI therapy were included. During a mean follow-up of 664 ± 177 days, the incidence rate of major bleedings and of major adverse cardiovascular events was 0.8 and 1.1 per 100 patients/year, respectively. The adherence to pharmacological treatment was 99%. Additionally, 13.4% of patients suspended the DPI therapy during the follow-up. Minor bleedings resulted the most common cause of both temporary and permanent DPI therapy discontinuation. This observational study supports the safety of DPI with low-dose rivaroxaban and aspirin among patients with CAD and PAD in a real-world setting, showing high persistence and maximum adherence to medical treatment.
Asunto(s)
Aspirina , Enfermedad de la Arteria Coronaria , Inhibidores del Factor Xa , Hemorragia , Cumplimiento de la Medicación , Enfermedad Arterial Periférica , Inhibidores de Agregación Plaquetaria , Rivaroxabán , Humanos , Rivaroxabán/efectos adversos , Rivaroxabán/administración & dosificación , Aspirina/efectos adversos , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Masculino , Anciano , Femenino , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/administración & dosificación , Enfermedad Arterial Periférica/tratamiento farmacológico , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/epidemiología , Estudios Prospectivos , Persona de Mediana Edad , Hemorragia/inducido químicamente , Resultado del Tratamiento , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Factores de Tiempo , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/diagnóstico , Factores de RiesgoRESUMEN
INTRODUCTION: Venous thromboembolism (VTE) is a major concern following total knee arthroplasty (TKA). The optimal pharmacological prophylaxis remains, however, controversial. The present investigation compared several non-vitamin K antagonist oral anticoagulants commonly employed as VTE prophylaxis following TKA. A Bayesian network meta-analysis was conducted to compare apixaban, aspirin, dabigatran, edoxaban, enoxaparin, fondaparinux, and rivaroxaban. The outcomes of interest were to compare the rate of deep venous thrombosis (DVT), pulmonary embolism (PE), and major and minor haemorrhages. METHODS: This study was conducted according to the PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-Analyses of Health Care Interventions. In March 2024, PubMed, Web of Science, and Google Scholar were accessed with no time constraints. All randomised controlled trials (RCTs) comparing two or more drugs for the prevention of VTE following TKA were considered for inclusion. RESULTS: Data from 29,678 patients were collected. Of them, 67% (19,884 of 29,678 patients) were women. The mean age of the patients was 66.8 ± 2.8 years, and the mean BMI was 29.2 ± 1.5 kg/m2. There was comparability in age, sex, and BMI at baseline. Apixaban 5 mg, dabigatran 220 mg, and rivaroxaban 10 mg were the most effective in reducing the rate of DVT. Apixaban 5 mg, enoxaparin 60 mg, and rivaroxaban 40 mg were the most effective in reducing the rate of PE. Apixaban 5 mg, rivaroxaban 10 mg, and apixaban 10 mg were associated with the lowest rate of major haemorrhages. Apixaban 5 mg and 20 mg, and dabigatran 220 mg were associated with the lowest rate of minor haemorrhages. CONCLUSION: Administration of apixaban 5 mg demonstrated the best balance between VTE prevention and haemorrhage control following TKA. LEVEL OF EVIDENCE: Level I, network meta-analysis of RCTs.
Asunto(s)
Artroplastia de Reemplazo de Rodilla , Teorema de Bayes , Metaanálisis en Red , Tromboembolia Venosa , Humanos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/etiología , Rivaroxabán/uso terapéutico , Rivaroxabán/administración & dosificación , Piridonas/administración & dosificación , Piridonas/uso terapéutico , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Dabigatrán/uso terapéutico , Dabigatrán/administración & dosificación , Pirazoles/uso terapéutico , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Embolia Pulmonar/prevención & control , Embolia Pulmonar/etiología , Enoxaparina/administración & dosificación , Enoxaparina/uso terapéutico , Hemorragia/inducido químicamente , Femenino , Fondaparinux/uso terapéutico , Piridinas , TiazolesRESUMEN
SOURCE CITATION: Ge Z, Kan J, Gao X, et al; ULTIMATE-DAPT investigators. Ticagrelor alone versus ticagrelor plus aspirin from month 1 to month 12 after percutaneous coronary intervention in patients with acute coronary syndromes (ULTIMATE-DAPT): a randomised, placebo-controlled, double-blind clinical trial. Lancet. 2024;403:1866-1878. 38599220.
Asunto(s)
Síndrome Coronario Agudo , Aspirina , Terapia Antiplaquetaria Doble , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Ticagrelor , Ticagrelor/uso terapéutico , Ticagrelor/administración & dosificación , Humanos , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/terapia , Método Doble Ciego , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Hemorragia/inducido químicamenteRESUMEN
Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is indicated after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Approximately 30% of the US population has a CYP2C19 no-function allele that reduces the effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI. We have shown improved outcomes with the integration of CYP2C19 genotyping into clinical care to guide the selection of prasugrel or ticagrelor in CYP2C19 no-function allele carriers. However, the influence of patient-specific demographic, clinical, and other genetic factors on outcomes with genotype-guided DAPT has not been defined. In addition, the impact of genotype-guided de-escalation from prasugrel or ticagrelor to clopidogrel in patients without a CYP2C19 no-function allele has not been investigated in a diverse, real-world clinical setting. The Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry is a multicenter US registry of patients who underwent PCI and clinical CYP2C19 testing. The registry is enrolling a diverse population, assessing atherothrombotic and bleeding events over 12 months, collecting DNA samples, and conducting platelet function testing in a subset of patients. The registry aims to define the influence of African ancestry and other patient-specific factors on clinical outcomes with CYP2C19-guided DAPT, evaluate the safety and effectiveness of CYP2C19-guided DAPT de-escalation following PCI in a real-world setting, and identify additional genetic influences of clopidogrel response after PCI, with the ultimate goal of establishing optimal strategies for individualized antiplatelet therapy that improves outcomes in a diverse, real-world population.
Asunto(s)
Clopidogrel , Citocromo P-450 CYP2C19 , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Clorhidrato de Prasugrel , Medicina de Precisión , Sistema de Registros , Ticagrelor , Humanos , Intervención Coronaria Percutánea/efectos adversos , Citocromo P-450 CYP2C19/genética , Medicina de Precisión/métodos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Clopidogrel/administración & dosificación , Clopidogrel/efectos adversos , Ticagrelor/administración & dosificación , Ticagrelor/uso terapéutico , Clorhidrato de Prasugrel/administración & dosificación , Clorhidrato de Prasugrel/uso terapéutico , Clorhidrato de Prasugrel/efectos adversos , Terapia Antiplaquetaria Doble/métodos , Aspirina/administración & dosificación , Aspirina/efectos adversos , Aspirina/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/prevención & controlRESUMEN
BACKGROUND: Treatment of isolated and non-obstructive atherosclerotic coronary artery ectasia (CAE) is still controversial. AIM: To assess the efficacy and safety of vitamin-K antagonist (VKA) versus dual antiplatelet (DAPT) therapy in management of patients with isolated and non-obstructive atherosclerotic CAE. METHODS: We prospectively enrolled 79 patients diagnosed on elective coronary angiography to have either isolated CAE or non-obstructive atherosclerotic CAE. Patients were assigned in 1:1 pattern to receive either VKA (warfarin) or DAPT (aspirin plus clopidogrel). Patients were followed-up for nine-months. The primary endpoint was the cumulative events rate including acute coronary event, target vessel intervention, or cardiac death. Analysis of cumulative events at different time intervals, its individual components, and bleeding were considered secondary endpoints. RESULTS: Cumulative events rate was 33%, with mortality rate of 2.5%. Both treatment groups showed comparable cumulative events during the nine-months follow-up duration. Nevertheless, Kaplan-Meier analysis beyond the first 3-months of follow-up showed significantly higher event-free survival among the VKA-group. Recurrent events (≥2) were significantly higher among the DAPT-group. Both groups showed no major bleeding events. Multivariable cox-regression analysis showed that presence of significant coronary tortuosity, use of DAPT in reference to VKA, and lower percent time in therapeutic range (%TTR) among those receiving VKA were significant independent predictors of clinical adverse events beyond the first 3-months of follow-up. CONCLUSION: Cumulative adverse events were comparable among both treatment groups for isolated non-obstructive CAE. However, adverse events were significantly more frequent in the DAPT-group beyond the first three months.
Asunto(s)
Enfermedad de la Arteria Coronaria , Terapia Antiplaquetaria Doble , Inhibidores de Agregación Plaquetaria , Vitamina K , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Vitamina K/antagonistas & inhibidores , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Estudios de Seguimiento , Terapia Antiplaquetaria Doble/métodos , Resultado del Tratamiento , Angiografía Coronaria , Dilatación Patológica , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Clopidogrel/uso terapéutico , Clopidogrel/administración & dosificación , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Manejo de la Enfermedad , Warfarina/uso terapéutico , Warfarina/administración & dosificación , Warfarina/efectos adversosRESUMEN
AIM: To evaluate the prognostic value of GDF-15 in relation the development of bleeding and events in stable CAD patients, receiving combined antithrombotic therapy. MATERIALS AND METHODS: The data was obtained from the prospective registry REGATA, 343 CAD patients (249 males), median age 68 [IQR 62; 75] years) were enrolled. Patients with sinus rhythm and concomitant PAD received acetylsalicylic acid in combination with rivaroxaban 2.5 mg bid (31.8%) or clopidogrel (24.8%). Other 43.4% with concomitant atrial fibrillation (AF) received direct oral anticoagulants in combination with antiplatelet therapy after elective percutaneous coronary interventions. Median follow-up was 12 months [IQR 9.0; 18.0]. The safety end point was major and clinically relevant bleedings (type 2-5) according to the BARC classification. Plasma samples for GDF-15 identification were taken at the inclusion and analyzed using ELISA assay. RESULTS: Frequency of BARC 2-5 bleedings was 16% (BARC 2 - 46; BARC 3 - 9; BARC 4-5 - 0), median GDF-15 level was 1185.0 pg/ml [850.0; 1680.0]. In patients with AF and concomitant MFA, the level of GDF-15 was significantly higher than in the subgroups of patients with only AF or MFA (p=0.0022). According to the quintile analysis, GDF-15 values in the top three quintiles of distribution (cut-off value >943 pg/ml) were associated with higher frequency of bleeding events: 23.2% versus 5.1%; p=0.0001. The multivariable logistic regression model demonstrated that bleeding events were independently associated with GDF-15 level>943 pg/ml (OR 2.65, 95% CI 1.11-6.30; p=0.0275), AF (OR 2.61, 95% CI 1.41-4.83; p=0.0023) and chronic kidney disease (OR 1.92, 95% CI 1.03-3.60; p=0.0401). Clinical factors determining the risk of bleeding events also determined a GDF-15 elevation. CONCLUSION: Assessment of GDF-15 level may improve bleeding risk stratification in CAD patients with concomitant AF and/or PAD receiving combined antithrombotic therapy.
Asunto(s)
Factor 15 de Diferenciación de Crecimiento , Hemorragia , Sistema de Registros , Humanos , Masculino , Femenino , Anciano , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Hemorragia/etiología , Persona de Mediana Edad , Factor 15 de Diferenciación de Crecimiento/sangre , Estudios Prospectivos , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/sangre , Quimioterapia Combinada , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Aspirina/administración & dosificación , Aspirina/efectos adversos , Clopidogrel/administración & dosificación , Clopidogrel/efectos adversos , Pronóstico , Federación de Rusia/epidemiología , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Rivaroxabán/administración & dosificación , Rivaroxabán/efectos adversos , Intervención Coronaria Percutánea/métodos , Intervención Coronaria Percutánea/efectos adversosRESUMEN
PURPOSE: Antiplatelet therapy is used for the primary and secondary prevention of thrombotic diseases such as acute coronary syndrome (ACS). These patients are more vulnerable to infections, as such, strategies are required to mitigate these risks. METHODS: We conducted a retrospective cohort study using TriNetX, a global federated health research network that includes both inpatient and outpatient electronic medical records from health care organizations worldwide. Patients ≥18 years old, after ACS, who were placed on aspirin and ticagrelor were compared with patients placed on aspirin and clopidogrel or prasugrel. Patients were identified using International Statistical Classification of Diseases and Related Health Problems terminology codes. After propensity score matching (1:1), a total of 239,358 patients were identified in each cohort. The primary outcomes of interest investigated were rates of (1) acute and subacute infective endocarditis, (2) sepsis of unknown origin, (3) staphylococcus arthritis, (4) cellulitis and acute lymphangitis, (5) Staphylococcus aureus bacteremia, and (6) staphylococcal pneumonia after initiation of treatment. Outcomes were analyzed at 1, 3, and 5 years. FINDINGS: At 5 years, a combination of aspirin and ticagrelor, compared with a combination of aspirin and clopidogrel or prasugrel, was associated with significantly reduced rates of (1) acute and subacute endocarditis (hazard ratio [HR] plus 95% CI) (HR = 0.85; 0.77-0.945; P = 0.030), (2) sepsis of unknown origin (HR = 0.89; 95% CI, 0.86-0.91; P < 0.0001), (3) cellulitis and acute lymphangitis (HR = 0.89; 95% CI, 0.87-0.92; P < 0.0001, and (4) Staphylococcus aureus bacteremia (HR = 0.72; 95% CI, 0.61-0.85; P = 0.0007). However, a combination of aspirin and clopidogrel was associated with a marinally lower risk of staphylococcal pneumonia (HR = 1.04; 95% CI, 1.01-1.062; P < 0.0001). IMPLICATIONS: A combination of aspirin and ticagrelor is associated with a lower rate of a variety of bacterial infections. This combination warrants further investigation in in-vitro studies to tease out mechanisms and through clinical randomized trials in groups who have ACS and are at high infection risk.
Asunto(s)
Aspirina , Clopidogrel , Inhibidores de Agregación Plaquetaria , Clorhidrato de Prasugrel , Infecciones Estafilocócicas , Ticagrelor , Humanos , Ticagrelor/uso terapéutico , Ticagrelor/administración & dosificación , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Femenino , Masculino , Estudios Retrospectivos , Clopidogrel/uso terapéutico , Clopidogrel/administración & dosificación , Clorhidrato de Prasugrel/uso terapéutico , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Anciano , Infecciones Estafilocócicas/tratamiento farmacológico , Síndrome Coronario Agudo/tratamiento farmacológico , Quimioterapia CombinadaRESUMEN
BACKGROUND: The combination of rivaroxaban plus aspirin compared with aspirin alone reduces the risk of major adverse cardiovascular and limb events for high-risk patients with peripheral artery disease. It is unknown whether rivaroxaban plus aspirin improves intermittent claudication for adults with lower-risk peripheral arterial disease. METHODS: In this randomized, open-label, multicenter, 24-week clinical trial, we randomly assigned patients with peripheral artery disease and intermittent claudication to receive either 2.5 mg of rivaroxaban twice daily plus 100 mg of aspirin once daily or 100 mg of aspirin once daily. The primary outcome was a 24-week change in total walking distance, measured by the 6-minute walking test. The primary safety outcome was the incidence of major bleeding or clinically relevant nonmajor bleeding. RESULTS: Eighty-eight patients were randomly assigned to either rivaroxaban plus aspirin (n=46) or aspirin alone (n=42). The mean age was 67 years, and 54% were female. The total walking distance measured by 6-minute walk test improved by 89 ± 18 m (mean±standard error) in the rivaroxaban-plus-aspirin group versus 21 ± 16 m in the aspirin-alone group. This corresponded to an absolute difference of 68 ± 24 m (95% confidence interval [CI], 19 to 116 m; P=0.007) and a relative improvement over the aspirin-alone group of 327% (95% CI, 94 to 560%). No major bleeding events were observed in either group. CONCLUSIONS: In patients with peripheral artery disease and intermittent claudication, 2.5 mg of rivaroxaban twice daily plus 100 mg of aspirin daily improved the total walking distance by a 6-minute walking test compared with 100 mg of aspirin daily alone. (Funded by Bayer S.A.; Clinicaltrials.gov number, NCT04853719.).
Asunto(s)
Aspirina , Inhibidores del Factor Xa , Claudicación Intermitente , Enfermedad Arterial Periférica , Rivaroxabán , Humanos , Rivaroxabán/uso terapéutico , Rivaroxabán/administración & dosificación , Rivaroxabán/efectos adversos , Claudicación Intermitente/tratamiento farmacológico , Femenino , Masculino , Anciano , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Aspirina/efectos adversos , Persona de Mediana Edad , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/farmacología , Enfermedad Arterial Periférica/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Quimioterapia Combinada , Resultado del Tratamiento , Hemorragia/inducido químicamenteRESUMEN
BACKGROUND: The prevalence of and outcomes associated with different antithrombotic strategies after left atrial appendage occlusion (LAAO) are not well described. OBJECTIVES: This study sought to evaluate patterns of antithrombotic medication strategies at discharge following LAAO with the Watchman FLX device in real-world practice and to compare the risk of adverse events among the different antithrombotic regimens. METHODS: The authors evaluated patients in the NCDR (National Cardiovascular Data Registry) LAAO Registry who underwent LAAO with the second-generation LAA closure device between 2020 and 2022. They grouped patients by mutually exclusive discharge antithrombotic strategies and compared the rates of adverse events at 45 days and 6 months using multivariable Cox proportional hazards regression. RESULTS: Among 53,878 patients undergoing successful LAAO with the second-generation LAA closure device, the most common antithrombotic discharge regimens were direct oral anticoagulant (DOAC) plus aspirin (48.3%), DOAC alone (22.6%), dual antiplatelet therapy (8.1%), warfarin plus aspirin (7.7%), and DOAC plus P2Y12 inhibitor (4.9%). In multivariate analysis, DOAC alone had a lower rate of major adverse events and major bleeding at 45 days of follow-up compared with DOAC plus aspirin (major adverse events: HR: 0.78; 95% CI: 0.68-0.91; major bleeding: HR: 0.69; 95% CI: 0.60-0.80). These differences persisted at 6 months. Warfarin without aspirin also showed lower rates of major bleeding at both time points. No differences were seen in stroke/transient ischemic attack or device-related thrombus. CONCLUSIONS: In real-world U.S. practice, discharge on DOAC alone or warfarin alone was associated with a lower rate of adverse events compared with DOAC plus aspirin.
Asunto(s)
Anticoagulantes , Aspirina , Apéndice Atrial , Fibrilación Atrial , Inhibidores de Agregación Plaquetaria , Humanos , Apéndice Atrial/cirugía , Masculino , Femenino , Aspirina/administración & dosificación , Aspirina/efectos adversos , Aspirina/uso terapéutico , Anciano , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Sistema de Registros , Anciano de 80 o más Años , Terapia Antiplaquetaria Doble/métodos , Quimioterapia Combinada , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/epidemiología , Persona de Mediana EdadRESUMEN
Background A transfeminine patient is a 79-year-old with past medical history significant for type 2 diabetes mellitus, hypertension, gender dysphoria, chronic kidney disease, dyslipidemia, total left hip replacement, and recent provoked deep venous thromboembolism (DVT). She was seen by a pharmacist in a primary care clinic after her discharge from a skilled nursing facility. The patient was experiencing symptoms of gender dysphoria after discontinuation of her estradiol in setting of her DVT. Assessment Her renal function was calculated to ensure she was on appropriate dosing of her medications. Because her DVT was provoked, providers determined she would require only 3 months of anticoagulation. Her laboratory test results showed a subtherapeutic estradiol level and her estradiol was restarted. Additionally, aspirin was being prescribed for primary prevention of atherosclerotic cardiovascular disease and was discontinued. Outcome She has significant improvement in her gender dysphoria symptoms with resuming her estradiol and now has a therapeutic estradiol level. She is tolerating her direct oral coagulant well and reports good quality of life. Conclusion When reviewing medications for patients it is important to take several factors into account, including dose, appropriate indication, and patient preference. Pharmacists play a key role, through collaboration with providers, in assessing these medication-specific factors. Estradiol was stopped in this patient because of her DVT, but given her DVT was provoked after a recent surgery, it was unlikely that estradiol was the cause of her clot. Weighing the risks and benefits for any patient is important when determining what medications are appropriate to continue. Additionally, calculating renal function appropriately in a gender-non-conforming patients ensures appropriate and safe dosing.
Asunto(s)
Anticoagulantes , Humanos , Anciano , Femenino , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Disforia de Género/tratamiento farmacológico , Estradiol/uso terapéutico , Estradiol/sangre , Estradiol/administración & dosificación , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/tratamiento farmacológico , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Calidad de Vida , Atención de Afirmación de GéneroRESUMEN
BACKGROUND: Rivaroxaban 2.5 mg plus aspirin reduced limb and cardiovascular events and increased bleeding in patients with symptomatic peripheral artery disease (PAD) after lower extremity revascularization in the VOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) study. Fragile patients are at heightened risk for ischemic and bleeding events. OBJECTIVES: The purpose of this study was to investigate the safety and efficacy of rivaroxaban 2.5 mg in fragile patients from VOYAGER PAD. METHODS: Patients were categorized as fragile based on prespecified criteria (age >75 years, weight ≤50 kg, or baseline estimated glomerular filtration rate <50 mL/min/1.73 m2). The primary efficacy outcome was the composite of acute limb ischemia, major amputation of a vascular etiology, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was TIMI major bleeding. RESULTS: Of 6,564 randomized patients, a total of 1,674 subjects were categorized as fragile at baseline. In the placebo arm, fragile patients were at higher risk of the primary outcome (HR: 1.34; 95% CI: 1.12-1.61) and TIMI major bleeding (HR: 1.57; 95% CI: 0.83-2.96), compared with nonfragile patients. The effect of rivaroxaban on the primary endpoint was not modified by frailty status (fragile HR: 0.93; 95% CI: 0.75-1.15; nonfragile HR: 0.83; 95% CI: 0.72-0.97; P interaction = 0.37). Rivaroxaban increased TIMI major bleeding in fragile (HR: 1.54; 95% CI: 0.82-2.91) and nonfragile patients (HR: 1.37; 95% CI: 0.84-2.23; P interaction = 0.65). CONCLUSIONS: Patients with PAD after lower extremity revascularization meeting fragile criteria are at higher risk of ischemic complications and bleeding. Rivaroxaban reduces ischemic risk and increases bleeding regardless of frailty status. These data may assist in personalization of antithrombotic therapy in fragile population.