Beatrice Mainoli1,2, Gonçalo S Duarte1,2,3, João Costa1,2,3, Joaquim Ferreira1,2,4, Daniel Caldeira5,6,7. 1. Laboratório de Farmacologia Clínica E Terapêutica, Faculdade de Medicina, Universidade de Lisboa. Avenida Professor Egas Moniz, 1649-028, Lisbon, Portugal. 2. IMM, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisbon, Portugal. 3. Centro de Estudos de Medicina Baseada Na Evidência, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal. 4. CNS, Campus Neurológico Sénior, Torres Vedras, Portugal. 5. Laboratório de Farmacologia Clínica E Terapêutica, Faculdade de Medicina, Universidade de Lisboa. Avenida Professor Egas Moniz, 1649-028, Lisbon, Portugal. dgcaldeira@hotmail.com. 6. IMM, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisbon, Portugal. dgcaldeira@hotmail.com. 7. Serviço de Cardiologia, Faculdade de Medicina, Hospital Universitário de Santa Maria (CHULN), CAML, Centro Cardiovascular da Universidade de Lisboa, CCUL, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisbon, Portugal. dgcaldeira@hotmail.com.
Abstract
BACKGROUND: Acetylsalicylic acid (ASA) is a frequently used antiplatelet agent, although some individuals have reduced antiplatelet responses on ASA, with recurrent ischemic events. It has been proposed that shortening the ASA dosing interval may overcome the time-dependent renewal of the drug target, leading to a greater antiplatelet effect. We conducted a systematic review of randomized controlled trials (RCTs) to determine the efficacy of once- versus twice-daily ASA in conditions with increased platelet turnover. METHODS: We conducted a systematic review and meta-analysis by searching the CENTRAL, MEDLINE, and Embase databases for RCTs assessing once- versus twice-daily ASA. Data were screened, extracted, and appraised by two independent reviewers, and were pooled using a random-effects model. The primary outcomes were major adverse cardiovascular events (MACEs) and serum thromboxane B2 (TxB2). Other pharmacodynamic measures were retrieved as secondary outcomes. Results were reported as mean differences with corresponding 95% confidence intervals (CIs). We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Seven RCTs were included, enrolling 379 participants overall. None of the studies reported clinical outcomes. Pooled results showed that compared with once-daily ASA, twice-daily ASA was associated with a decrease in mean TxB2 of 1.42 ng/mL (95% CI - 2.71 to - 0.13; I2 = 66%). We found no differences in subgroup analyses based on disease subtype, trial blinding, or trial design. A greater antiplatelet activity of the twice-daily regimen was also found when using PFA-100-ADP methods, although not when using the VerifyNow, LTA-AA, and multiplate methods. CONCLUSIONS: Twice-daily ASA was associated with a greater antiplatelet effect compared with standard once-daily ASA.
BACKGROUND:Acetylsalicylic acid (ASA) is a frequently used antiplatelet agent, although some individuals have reduced antiplatelet responses on ASA, with recurrent ischemic events. It has been proposed that shortening the ASA dosing interval may overcome the time-dependent renewal of the drug target, leading to a greater antiplatelet effect. We conducted a systematic review of randomized controlled trials (RCTs) to determine the efficacy of once- versus twice-daily ASA in conditions with increased platelet turnover. METHODS: We conducted a systematic review and meta-analysis by searching the CENTRAL, MEDLINE, and Embase databases for RCTs assessing once- versus twice-daily ASA. Data were screened, extracted, and appraised by two independent reviewers, and were pooled using a random-effects model. The primary outcomes were major adverse cardiovascular events (MACEs) and serum thromboxane B2 (TxB2). Other pharmacodynamic measures were retrieved as secondary outcomes. Results were reported as mean differences with corresponding 95% confidence intervals (CIs). We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Seven RCTs were included, enrolling 379 participants overall. None of the studies reported clinical outcomes. Pooled results showed that compared with once-daily ASA, twice-daily ASA was associated with a decrease in mean TxB2 of 1.42 ng/mL (95% CI - 2.71 to - 0.13; I2 = 66%). We found no differences in subgroup analyses based on disease subtype, trial blinding, or trial design. A greater antiplatelet activity of the twice-daily regimen was also found when using PFA-100-ADP methods, although not when using the VerifyNow, LTA-AA, and multiplate methods. CONCLUSIONS: Twice-daily ASA was associated with a greater antiplatelet effect compared with standard once-daily ASA.
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