Vorapaxar in Patients With Diabetes and Prior MI: Findings from the TRA 2°P-TIMI 50 Trial
Background—Vorapaxar reduces cardiovascular death (CVD), myocardial infarction (MI), or stroke in patients with prior MI while increasing bleeding. Patients with diabetes mellitus (DM) are at high risk of recurrent thrombotic events despite standard therapy and may derive particular benefit from antithrombotic therapies. TRA 2°P-TIMI 50 was a randomized, double-blind, placebo-controlled trial of vorapaxar in patients with stable atherosclerosis.
Methods and Results—We examined the efficacy of vorapaxar in patients with and without DM who qualified for the trial with a prior MI. Because vorapaxar is contraindicated in patients with a history of stroke or transient ischemic attack, the analysis (n=16,896) excluded such patients. The primary endpoint of CVD, MI, or stroke occurred more frequently in patients with DM than in patients without DM (Rates in placebo-group: 14.3% vs. 7.6%, adjusted-HR 1.47, p<0.001). In patients with DM (n=3,623), vorapaxar significantly reduced the primary endpoint (11.4% vs. 14.3%, HR 0.73, 95% CI 0.60-0.89; p=0.002) with a number needed to treat to avoid 1 major CV event of 29. The incidence of GUSTO moderate/severe bleeding was increased with vorapaxar in patients with DM (4.4% vs. 2.6%, HR 1.60, 95% CI 1.07-2.40). However, net clinical outcome integrating these 2 endpoints (efficacy and safety) was improved with vorapaxar (HR 0.79; 95% CI 0.67-0.93).
Conclusions—In patients with prior MI and DM, the addition of vorapaxar to standard therapy significantly reduced the risk of major vascular events with greater potential for absolute benefit in this group at high risk of recurrent ischemic events.
Clinical Trial Registration Information—www.clinicaltrials.gov. Identifier: NCT00526474.
- Received October 18, 2014.
- Revision received January 2, 2015.
- Accepted January 7, 2015.
Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDervis License (http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.