P2Y12 inhibitor monotherapy better than aspirin for secondary prevention in CAD patients, finds Meta-analysis

The patient-level meta-analysis of seven randomized trials, called PANTHER, showed that P2Y12 inhibitor monotherapy, such as ticagrelor or clopidogrel, was associated with a lower risk of stroke, myocardial infarction, and cardiovascular death than aspirin monotherapy in CAD patients. Therefore, the authors suggest preferring P2Y12 inhibitor monotherapy over aspirin monotherapy for long-term secondary prevention in patients with established CAD.

For long-term prevention of cardiovascular (CV) events, aspirin is the only antiplatelet agent with a Class I recommendation in patients with coronary artery disease. Data is inconsistent in its comparison with other alternative antiplatelet agents. Therefore, Felice Gragnano, University of Campania Luigi Vanvitelli, Naples, Italy, and colleagues compared P2Y12 inhibitor monotherapy versus aspirin in patients with CAD.

For this purpose, the researchers conducted a patient-level meta-analysis of randomized trials comparing P2Y12 inhibitor monotherapy versus aspirin monotherapy for the prevention of CV events in patients with established CAD.

This comprehensive individual patient data meta-analysis of randomized controlled trials (RCTs) included 24,325 participants with established CAD, of whom a large proportion received modern pharmaco-invasive treatments.

The primary outcome was the composite of stroke, myocardial infarction, and cardiovascular death. Prespecified key secondary outcomes included major bleeding and net adverse clinical events (the composite of the primary outcome and major bleeding). Data pooling was done in a 1-step meta-analysis.

The study led to the following findings:

• Patient-level data were obtained from 7 trials. Overall, 24,325 participants were available for analysis, including 12,178 patients assigned to receive P2Y12 inhibitor monotherapy (clopidogrel in 62.0%, ticagrelo in 38.0%) and 12,147 assigned to receive aspirin.
• The risk of the primary outcome was lower with P2Y12 inhibitor monotherapy compared with aspirin over 2 years (HR: 0.88), mainly owing to less myocardial infarction (HR: 0.77).
• Major bleeding was similar (HR: 0.87) and net adverse clinical events were lower (HR: 0.89) with P2Y12 inhibitors.
• The treatment effect was consistent across prespecified subgroups and types of P2Y12 inhibitors.

"The meta-analysis provides evidence of a significant reduction of ischemic events with P2Y12 inhibitor monotherapy compared with aspirin monotherapy for secondary cardiovascular prevention, with no increased bleeding risk," the researchers wrote.

"Given its similar overall safety and superior efficacy, P2Y12 inhibitor monotherapy might be preferred over aspirin monotherapy for long-term secondary prevention in CAD patients," they concluded.

Reference:

Gragnano, F., Cao, D., Pirondini, L., Franzone, A., Kim, H., von Scheidt, M., Pettersen, A. R., Zhao, Q., Woodward, M., Chiarito, M., McFadden, E. P., Park, K. W., Kastrati, A., Seljeflot, I., Zhu, Y., Windecker, S., Kang, J., Schunkert, H., Arnesen, H., . . . Valgimigli, M. (2023). P2Y12 Inhibitor or Aspirin Monotherapy for Secondary Prevention of Coronary Events. Journal of the American College of Cardiology, 82(2), 89-105. https://doi.org/10.1016/j.jacc.2023.04.051