Clinical question: In patients with coronary artery disease (CAD), what is the difference in risk and benefit between secondary prevention with aspirin (ASA) versus a P2Y12 inhibitor?
Background: Lifelong ASA is the mainstay of care for patients with CAD who require secondary prevention. This is predicated on studies from several decades ago. Subsequent studies examining P2Y12 monotherapy versus ASA have had inconsistent results.
Study design: Systematic review and meta-analysis
Setting: Seven randomized clinical trials from 1996 to 2021 were found to meet the criteria for analysis.
Synopsis: 24,325 patients were included in the analysis, mostly older men from Europe who had risk factors for CAD. Many also presented with acute myocardial infarction (MI) or had percutaneous coronary intervention. Of these patients, 12,178 received P2Y12 monotherapy (62% clopidogrel, 38% ticagrelor) and 12,147 received ASA monotherapy. The primary outcome was a composite of cardiovascular death, MI, and stroke. Secondary outcomes included major bleeding and net adverse clinical events (NACE) which was a composite of primary outcome plus major bleeding. Primary outcome was assessed at a median time of 493 days with the risk of primary outcome lower in the P2Y12 group compared to ASA monotherapy (hazard ratio [HR], 0.88; 95% CI, 0.79 to 0.97, P=0.012). NACE risk was lower in the P2Y12 arm compared with ASA (HR 0.89; 95% CI, 0.81 to 0.98, P=0.020). Furthermore, P2Y12 monotherapy was associated with a lower risk of myocardial infarction, any gastrointestinal bleeding, stent thrombosis, and hemorrhagic stroke (HRs, 0.77 0.75, 0.42, and 0.43 respectively). Effects were probably underestimated due to limited follow-up time. Limitations include no patients on prasugrel, open-label design in four of the seven included trials, and variable study definitions.
Bottom line: In patients with established CAD, the use of P2Y12 monotherapy reduced the risk of the primary composite outcome, though this was mainly driven by a reduction in MI. It also was associated with a reduction in gastrointestinal bleeding and hemorrhagic strokes when compared to ASA. In select patients, it is reasonable to consider P2Y12 monotherapy for secondary prevention of CAD.
Citation: Gragnano F, et al. P2Y12 inhibitor or aspirin monotherapy for secondary prevention of coronary events. J Am Coll Cardiol. 2023;82(2):89-105.
Dr. Dang
Dr. Dang is a hospitalist at Atrium Health in Charlotte, N.C.