Clopidogrel Bests Aspirin for Secondary Prevention of ASCVD

In the chronic phase of secondary prevention (i.e., after the guideline-recommended duration of dual antiplatelet therapy is completed), P2Y12 inhibitors are often discontinued, and aspirin monotherapy is continued for long-term prevention of cardiovascular events. This preferential use of aspirin stems at least partly from insufficient evidence about the risks and benefits of P2Y12 inhibitor monotherapy compared with aspirin monotherapy. Therefore, Dr Arman Qamar and his team conducted a study to compare the efficacy and safety of P2Y12 inhibitor or aspirin monotherapy for secondary prevention in patients with atherosclerotic cardiovascular disease (ASCVD).

In a meta-analysis, the researchers searched Medline, Embase, and Cochrane Central databases to identify randomized trials comparing monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention in patients with ASCVD (cardiovascular, cerebrovascular, or peripheral artery disease). The major outcome was major adverse cardiac events (MACE). They also assessed for myocardial infarction (MI), stroke, all-cause mortality, and major bleeding. They used a random-effects model to calculate risk ratios (RR) and the corresponding 95% confidence interval (CI) and heterogeneity among studies were assessed using the Higgins I2 value.

Key findings of the study:

• The researchers included a total of 9 eligible trials (5 with clopidogrel & 4 with ticagrelor) with 61,623 patients.
• They found that monotherapy with P2Y12 inhibitors significantly reduced the risk of MACE by 11% (0.89; I2 = 0%), and MI by 19% (0.81; I2 = 0%) compared with aspirin monotherapy.
• However, they observed no significant difference in the risk of stroke (0.85) or all-cause mortality (1.01).
• They also observed no significant difference in the risk of major bleeding with P2Y12 inhibitor monotherapy compared with aspirin (0.94).
• They noted that the results were consistent irrespective of the P2Y12 inhibitor.

The authors concluded, "P2Y12 inhibitor monotherapy for secondary prevention is associated with a significant reduction in atherothrombotic events compared with aspirin alone without an increased risk of major bleeding."

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DOI: https://doi.org/10.1093/ehjopen/oeac019