Secondary Prevention with P2Y12 Inhibitors: How Consolidated Is This Long Term Alternative vs. Aspirin?

Secondary prevention with P2Y12 inhibitors vs aspirin monotherapy in CAD patients

Antiaggregation therapy plays a central role at long term to prevent new cardiovascular events in atherosclerosis patients.  After repeat myocardial infarction (MI) or stroke, prognosis can vary considerably. Even though the current guidelines prefer aspirin as the first choice for secondary prevention over P2Y12 inhibitors, this strategy is based on dated studies and reviews with inconsistent outcomes including heterogeneous studies. 

Prevención secundaria con Inhibidores P2Y12 ¿Cuan consolidada está la alternativa a largo plazo respecto a la aspirina?

The aim of this study carried out by Gragnano et al. (Panther Group) was to assess the effect of P2Y12 inhibitor monotherapy (Clopidogrel, Prasugrel or ticagrelor) vs. aspirin monotherapy in ischemic and bleeding events in patients with established CAD. 

Researchers carried out a systematic review and meta-analysis at individual patient level, using randomized studies, including studies with an initial phase of tolerated dual antiplatelet therapy (DAPT), while studies with chronic anticoagulation treatments were excluded. 

Efficacy primary end point was a composite of cardiovascular death, MI and stroke. Other pre-specified secondary events were major bleeding (BARC 3 or 5) and net clinical adverse events (NACE).

7 randomized studies met inclusion criteria (ASCET, CADET, CAPRIE, DACAB, GLASSY, HOST-EXAM and TiCAB). Data from 24,325 patients were obtained, 12,178 were assigned a P2Y12 inhibitor (mainly clopidogrel [62%]) and 12,147 aspirin, with mean treatment duration of 557 days.

Mean age was 64.3 years, 21.7% were women, 25% had diabetes and 11% chronic kidney disease. All participants presented established CAD (60.6% as acute coronary syndrome).

There was lower risk of efficacy end point with P2Y12 inhibitor monotherapy vs aspirin monotherapy (HR: 0.88; CI 95%: 0.79-0.97; P=0.012), which translated into a number necessary to treat of 121 in 2 years. The risk of major bleeding was similar between strategies (HR: 0.87; CI 95%: 0.70-1.09; P=0.23). Also, NACE risk resulted lower vs. aspirin (HR: 0.89; CI 95%: 0.81-0.98; P=0.020).

As regards pre-specified points, there was reduced AMI rate (HR: 0.77; CI  95%: 0.66-0.90; P<0.001), with number necessary to treat 136. There were no significant differences in cardiovascular mortality (P=0.82) or all-cause mortality (P=0.56).

In terms of safety, there was lower risk of gastrointestinal bleeding (HR: 0.75; CI 95%: 0.57-0.97; P=0.027), stent thrombosis (HR: 0.42; CI 95%: 0.19-0.97; P=0.041) and hemorrhagic stroke (HR: 0.43; CI  95%: 0.23-0.83; P=0.012) with P2Y12 inhibitors. 

Efficacy and key secondary outcomes were consistent across predefined subgroups, such as chosen P2Y12 inhibitor (clopidogrel or ticagrelor), and there was a greater benefit vs lower doses of aspirin. 


This meta-analysis of individual data from randomized studies has shown that P2Y12 inhibitor monotherapy significantly reduces ischemic events vs. aspirin in the secondary prevention of cardiovascular events, without increased bleeding risk. 

Dr. Omar Tupayachi

Dr. Omar Tupayachi.
Member of the Editorial Board of

Original Title: P2Y12 Inhibitor or Aspirin Monotherapy for Secondary Prevention of Coronary Events.

Reference: Gragnano, Felice et al. “P2Y12 Inhibitor or Aspirin Monotherapy for Secondary Prevention of Coronary Events.” Journal of the American College of Cardiology vol. 82,2 (2023): 89-105. doi:10.1016/j.jacc.2023.04.051.

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