Vorapaxar Associated with Reductions in Cardiovascular Death, MI, and other Negative Outcomes in Patient with Peripheral Artery Disease

DALLAS — November 19, 2013 – Patients with non-ST-segment elevation (non-STEMI) acute coronary syndrome and peripheral artery disease (PAD) treated with the PAR-1 antagonist vorapaxar experienced a reduction in ischemic events and other outcomes compared to patients who received placebo, with no increased risk of bleeding compared to patients who did not have PAD.

Results from a prior double-blind, randomized study (the TRACER Study) showed that adding vorapaxar to standard care for patients with non-ST-segment elevation acute coronary syndrome was associated with modest reductions in ischemic events such as cardiovascular death, myocardial infarction, and stroke. However, this treatment was also associated with significantly increased bleeding.

For the current study, researchers looked at data from TRACER for patients who also had PAD, noting that “a history of peripheral artery disease (PAD) was a risk enrichment inclusion criterion” for TRACER.

To investigate the efficacy and safety of vorapaxar in patients with PAD vs. patients with no history of PAD, they compared the incidence of ischemic events, incidence of GUSTO-defined moderate or severe bleeding, and the number of peripheral revascularization procedures between the two groups.

For TRACER, investigators enrolled 12,944 patients with non-ST-segment elevation acute coronary syndrome, 936 (7.2%) of whom also had a documented history of PAD. Overall, patients with PAD experienced a higher incidence of ischemic events such as cardiovascular death, myocardial infarction, and stroke compared with non-PAD patients (25.3% vs. 12.2%, respectively; p<0.001). Patients with PAD also experienced a higher incidence of GUSTO-defined moderate or severe bleeding (9.1%) compared with non-PAD patients (5.0%) (p<0.001).

However, patients with PAD who were treated with vorapaxar experienced a 21% reduction in the rate of ischemic events such as cardiovascular death, myocardial infarction, and stroke (p = 0.787), with “no significant interaction of treatment and PAD,” according to the authors.

PAD patients treated with vorapaxar also experienced “a numerical reduction in the number of peripheral revascularization procedures (8.1% vs. 9.0%, p=0.158) and lower extremity amputation (0.9% vs. 1.5%, p=0.107)” compared with patients who received placebo, with a similar rate of increase in GUSTO-defined moderate or severe bleeding among both groups (PAD vs. non-PAD)

These results led the authors to write in their conclusion that, in this study of the efficacy and safety of vorapaxar in patients who have non-ST-segment elevation acute coronary syndrome and PAD, they “observed trends suggesting lower rates of ischemic endpoints, peripheral revascularization, and amputation with vorapaxar, warranting further investigation. Despite higher bleeding risk in PAD patients, vorapaxar did not appear to incrementally increase bleeding risk compared with non-PAD patients.”