MUNICH, Germany—In patients with unstable angina or non-ST-segment myocardial infarction (NSTEMI) who do not undergo revascularization, prasugrel does not reduce the frequency of ischemic events compared with clopidogrel, according to results presented on August 26, 2012, at the European Society of Cardiology (ESC) Congress. The findings, simultaneously published in the New England Journal of Medicine, also showed similar bleeding risks.

For the TRILOGY ACS (Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes) trial, Matthew T. Roe, MD, MHS, of Duke University Medical Center (Durham, NC), and colleagues randomized 9,326 patients with unstable angina or NSTEMI on aspirin to either prasugrel (30 mg loading dose) or clopidogrel (300 mg loading dose followed my 75 mg daily). Maintenance doses of 10 mg prasugrel daily were given to patients under the age of 75 (primary cohort; n = 7,243) and 5 mg prasugrel daily to those aged 75 and older. Patients were enrolled in 52 countries from June 2008 to September 2011.

Similar Adverse Event Rates

The median follow-up duration was 17.1 months, during which 7.9% of patients younger than 75 underwent revascularization (427 PCI, 170 CABG, and 26 both), with a median time from randomization to first revascularization of 113 days.

After 30 months, there was no difference in the primary composite endpoint (cardiovascular death, MI, or stroke) in the younger patient cohort (table 1). Results were also similar in the overall population.

Table 1. Thirty-Month Efficacy Outcomes in Patients Younger than 75

After 12 months, there was a divergence of treatment effect between the drugs with a weak trend toward a reduced risk for the composite and its components with prasugrel in patients under 75 years (P = P=0.07 for interaction). Prasugrel treatment was associated with higher frequency of the primary endpoint in recent smokers, those who underwent angiography before randomization, and those taking a proton-pump inhibitor at randomization.

In terms of bleeding, GUSTO non-CABG-related severe or life-threatening events and TIMI major bleeding were similar in the younger patient group at 30 months (table 2). Similar rates were also observed in the overall population.

Table 2. Thirty-Month Safety Outcomes in Patients Younger than 75

The frequency of new non-benign neoplasms in the overall population did not differ between the prasugrel and clopidogrel groups (1.9% vs. 1.8%; P = 0.79).

Guideline Changes Not Needed

“The optimal treatment duration and intensity of P2Y12 inhibition after a coronary event for patients who do not undergo revascularization remain uncertain,” the authors write. “However, our findings highlight the need for further study of the differences in the response to intensified platelet inhibition for patients receiving medical therapy without revascularization, as compared with those undergoing revascularization, for treatment of an index cardiac event.”

After the presentation, commentator Raffaele de Caterina, MD, PhD, of Università degli Studi “G. D’Annunzio” (Chieti, Italy), said this trial was needed because “despite recommendations for moderate/high-risk patients with non-ST-elevation ACS, about half of them do not undergo early revascularization. As such, medically treated patients usually have more comorbidities, a higher risk of bleeding, and a worse global outcome than invasively treated patients, and here the benefit-risk balance changing clopidogrel with a more potent platelet inhibitor is uncertain.”

In addition, he said, theTRITON-TIMI 38 trial was conducted exclusively in patients treated invasively.

Dr. de Caterina praised the study for its large population, geographic diversity, and long follow-up, but recommended no change to the current guidelines for the management of ACS in patients without persistent ST-segment elevation.

Related Stories:

• Guidelines Elevate Ticagrelor to First-line Antiplatelet Status in Unstable Angina
• Ticagrelor Provides More Potent Platelet Inhibition Than Prasugrel
• Platelet Function Recovery Longer After Stopping Prasugrel Than Clopidogrel