Novel Antiplatelet Agents: Clarifying Roles in ACS

Acute coronary syndrome can take a variety of forms.

For example, unstable angina and non-ST-segment elevation myocardial infarction are classified as non-ST-elevation acute coronary syndromes (NSTE-ACS), which differ from ST-segment elevation myocardial infarction (STEMI).

Although they occur less frequently, prognoses for NSTE-ACS are less promising, most likely because the conditions tend to develop in older people who have more comorbidities.

The newer, direct-acting oral P2Y₁₂ inhibitors, prasugrel and ticagrelor, have been tested in STEMI, but researchers weren’t able to discern differences in the drugs’ mortality, safety, and efficacy profiles from those of clopidogrel in patients with NSTE-ACS. Essentially, the clinical studies lacked statistical power to tease out that information.

Interest in comparative effectiveness of oral P2Y₁₂ inhibitors is rooted in that fact that the newest drugs are more potent and have faster onset of action than clopidogrel.

A team of cardiologists recently completed a meta-analysis published in the American Journal of Cardiology that indicated P2Y₁₂ inhibitors decrease major cardiovascular events and myocardial infarction (MI) in NSTE-ACS, but tend to significantly increase bleeding risk.

This meta-analysis included data from 31,470 patients with NSTE-ACS enrolled in 4 randomized, controlled trials. Approximately half of patients received either prasugrel or ticagrelor, while the remaining patients took clopidogrel.

For every 1000 patients treated with prasugrel or ticagrelor, 16 major cardiac events and 13 MIs were prevented. However, 6 more major bleeding events occurred with the newer oral P2Y₁₂ inhibitors than clopidogrel.

Results were similar regardless of which P2Y₁₂ inhibitor patients received, with 1 exception: prasugrel was associated with increased Thrombolysis in Myocardial Infarction (TIMI) major and minor bleeding compared with ticagrelor.

Previous trials have shown that prasugrel or ticagrelor tend to have advantages over clopidogrel, particularly in patients with STEMI and those treated with percutaneous coronary infusion. This meta-analysis indicated that the newer P2Y₁₂ inhibitors similarly reduce cardiovascular risk in NSTE-ACS, but to a lesser degree than in STEMI.