Prasugrel or Clopidogrel in ACS: A Head-to-Head Study

A recent study examines the comparative efficacy of prasugrel and clopidogrel in the treatment of patients who underwent percutaneous coronary intervention.

Acute coronary syndrome (ACS) is a killer—it’s the leading cause of death in the United States. Patients who experience ACS are whisked into the cardiac catheterization lab to undergo percutaneous coronary intervention (PCI). After PCI, dual antiplatelet therapy with aspirin and a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) is the standard of care to prevent thrombotic complications. A retrospective, observational, pilot study published ahead of print in the American Journal of Therapeutics examines the comparative efficacy of prasugrel, the drug previously identified as most effective in a landmark study, and clopidogrel at a loading dose higher than that employed in said study.

The newer study enrolled patients with ACS who underwent PCI and received a 600-mg loading dose of clopidogrel or a 60-mg loading dose of prasugrel followed by daily maintenance doses of 75 mg and 10 mg, respectively, for 2 years. The study period was between July 1, 2009, and June 30, 2011, and 221 patients participated.

Loading doses of clopidogrel and prasugrel are often given to achieve maximal platelet inhibition quickly (although prasugrel’s onset of action is faster than clopidogrel’s). A higher loading dose of clopidogrel (600 mg in this study vs 300 mg in a previous study) was used because this drug has a slow onset of action requiring activation by P450 isoenzymes. A higher clopidogrel loading dose (600 mg) has also been associated with lower rates of ischemic complication and death.

The primary efficacy end point was composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke occurring through 1 year. When patients died during the study, investigators attempted to identify cause of death using medical records or death certificates.

Primary efficacy end point was similar in the 2 treatment groups, as were bleeding events. The previous study had identified higher rates of adverse events with prasugrel, and this study did not replicate those findings.

The authors conclude that prasugrel is at least as effective and safe as clopidogrel in patients with ACS undergoing early invasive management.