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Once- versus Twice-Daily Aspirin in Patients at High Risk of Thrombotic Events: Systematic Review and Meta-Analysis

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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.

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Authors and Affiliations

  1. Laboratório de Farmacologia Clínica E Terapêutica, Faculdade de Medicina, Universidade de Lisboa. Avenida Professor Egas Moniz, 1649-028, Lisbon, Portugal

    Beatrice Mainoli, Gonçalo S. Duarte, João Costa, Joaquim Ferreira & Daniel Caldeira

  2. IMM, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisbon, Portugal

    Beatrice Mainoli, Gonçalo S. Duarte, João Costa, Joaquim Ferreira & Daniel Caldeira

  3. Centro de Estudos de Medicina Baseada Na Evidência, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal

    Gonçalo S. Duarte & João Costa

  4. CNS, Campus Neurológico Sénior, Torres Vedras, Portugal

    Joaquim Ferreira

  5. 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

    Daniel Caldeira

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  1. Beatrice Mainoli
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Correspondence to Daniel Caldeira.

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Funding

This review was an academic project and was not supported by any form of funding.

Conflict of Interest

Daniel Caldeira has participated in educational meetings and/or attended conferences or symposia (including travel, accommodation and/or hospitality) for Bristol-Myers Squibb, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Merck Serono, Ferrer, Pfizer, Novartis and Roche. Joaquim Ferreira reports grants from GlaxoSmithKline, Grunenthal, Fundação MSD (Portugal), TEVA, MSD, Allergan, Novartis and Medtronic, and also reports consultancy fees from GlaxoSmithKline, Novartis, TEVA, Lundbeck, Solvay, BIAL, Merck-Serono, Merz, Ipsen, Biogen, Acadia, Allergan, Abbvie and Sunovion Pharmaceuticals. In addition, he received personal fees from Faculdade de Medicina de Lisboa and CNS – Campus Neurológico Sénior, personal fees from Advisory Boards from BIAL, and expert testimony from Novartis.

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Mainoli, B., Duarte, G.S., Costa, J. et al. Once- versus Twice-Daily Aspirin in Patients at High Risk of Thrombotic Events: Systematic Review and Meta-Analysis. Am J Cardiovasc Drugs 21, 63–71 (2021). https://doi.org/10.1007/s40256-020-00409-x

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