RESUMO
Background and Purpose- The role of aspirin plus clopidogrel (A+C) therapy compared with aspirin monotherapy in patients presenting with acute ischemic stroke (IS) or transient ischemic attack remains uncertain. We conducted this study to determine the optimal period of efficacy and safety of A+C compared with aspirin monotherapy. Methods- Ten randomized controlled trials (15 434 patients) were selected using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) (inception June 2018) comparing A+C with aspirin monotherapy in patients with transient ischemic attack or IS. The primary efficacy outcome was recurrent IS, and the primary safety outcome was major bleeding. The secondary outcomes were major adverse cardiovascular events (composite of stroke, myocardial infarction, and cardiovascular mortality) and all-cause mortality. We stratified analysis based on the short- (≤1 month), intermediate- (≤3 month), and long-term (>3 month) A+C therapy. Effects were estimated as relative risk (RR) with 95% CI. Results- A+C significantly reduced the risk of recurrent IS at short-term (RR, 0.53; 95% CI, 0.37-0.78) and intermediate-term (RR, 0.72; 95% CI, 0.58-0.90) durations. Similarly, major adverse cardiovascular event was significantly reduced by short-term (RR, 0.68; 95% CI, 0.60-0.78) and intermediate-term (RR, 0.76; 95% CI, 0.61-0.94) A+C therapy. However, long-term A+C did not yield beneficial effect in terms of recurrent IS (RR, 0.81; 95% CI, 0.63-1.04) and major adverse cardiovascular events (RR, 0.87; 95% CI, 0.71-1.07). Intermediate-term (RR, 2.58; 95% CI, 1.19-5.60) and long-term (RR, 1.87; 95% CI, 1.36-2.56) A+C regimens significantly increased the risk of major bleeding as opposed to short-term A+C (RR, 1.82; 95% CI, 0.91-3.62). Excessive all-cause mortality was limited to long-term A+C (RR, 1.45; 95% CI, 1.10-1.93). Conclusions- Short-term A+C is more effective and equally safe in comparison to aspirin alone in patients with acute IS or transient ischemic attack.
Assuntos
Aspirina/administração & dosagem , Isquemia Encefálica/tratamento farmacológico , Clopidogrel/administração & dosagem , Ataque Isquêmico Transitório/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Aspirina/uso terapêutico , Isquemia Encefálica/prevenção & controle , Clopidogrel/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Humanos , Ataque Isquêmico Transitório/prevenção & controle , Prevenção Secundária , Acidente Vascular Cerebral/prevenção & controleRESUMO
BACKGROUND: The ideal oral anticoagulant agent during catheter ablation (CA) for atrial fibrillation (AF) remained unclear. HYPOTHESIS: Novel oral anticoagulants (NOACs) are safer and effective compared to uninterrupted vitamin K antagonists (U-VKA) among patients requiring CA for AF. METHODS: Four randomized controlled trials (RCTs) and 9 observational studies (OS) were selected using PubMed/Medline, EMBASE and the CENTRAL data bases (Inception-December-2017). Estimates were reported as random effects risk ratio (RR) with 95% confidence interval (CI). The primary safety outcome was major bleeding and main efficacy endpoint was thromboembolism. RESULTS: In RCTs restricted analysis, NOACs significantly reduced the relative risk of major bleeding by 72% compared to U-VKA (RR, 0.28, 95% CI, 0.14-0.58, Pâ¯<â¯0.001). This significant effect was not achieved in OS based analysis (RR, 0.86, 95% CI, 0.42-1.78, Pâ¯=â¯0.68). In terms of thromboembolism, both anticoagulation strategies were equally effective in analysis of RCTs (RR, 0.28, 95% CI, 0.05-1.70, Pâ¯=â¯0.17) or OS (RR, 1.43, 95% CI, 0.46-4.39, Pâ¯=â¯0.54). In sensitivity analysis, there was no difference among uninterrupted NOACs (U-NOACs) and U-VKA in terms of major bleeding [(RCTs: RR, 0.33, 95% CI, 0.10-1.06, Pâ¯=â¯0.06); (OS: RR, 0.70, 95% CI, 0.28-1.78, Pâ¯=â¯0.46)] or thromboembolism [(RCTs: RR, 0.25, 95% CI, 0.03-2.29, Pâ¯=â¯0.22); (OS: RR, 0.68, 95% CI, 0.08-5.53, Pâ¯=â¯0.72)]. CONCLUSION: NOACs, either interrupted or un-interrupted, are safer and equally effective drugs compared to U-VKA in AF patients requiring CA.