Terutroban Versus Aspirin in Patients With Cerebral Ischaemic Events (PERFORM): A Randomised, Double-Blind, Parallel-Group Trial

Study Questions:

What is the safety and efficacy of terutroban (thromboxane-prostaglandin receptor antagonist) compared with aspirin in the prevention of cerebral and cardiovascular ischemic events in patients with a recent noncardioembolic cerebral ischemic event?

Methods:

PERFORM was a randomized, double-blind, parallel-group trial performed at 802 centers in 46 countries. The trial randomized patients who had an ischemic stroke in the previous 3 months or a transient ischemic attack in the previous 8 days to 30 mg per day of terutroban or 100 mg per day of aspirin. The primary efficacy endpoint was a composite of fatal or nonfatal ischemic stroke, fatal or nonfatal myocardial infarction (MI), or other vascular death. The study was stopped prematurely for futility.

Results:

The study randomized 9,562 patients to terutroban and 9,558 to aspirin. The mean follow-up was 28 months. There was no difference in the primary endpoint between the two arms (11% vs. 11%; hazard ratio [HR],1.02; 95% confidence interval [CI], 0.94-1.12). There was an increase in minor bleeding with terutroban compared with aspirin (12% vs. 11%; HR, 1.11; 95% CI, 1.02-1.21), but no significant differences in other safety endpoints were noted.

Conclusions:

The investigators concluded that the trial did not meet the predefined criteria for noninferiority, but showed similar rates of the primary endpoint with terutroban and aspirin, without any safety or efficacy advantage for terutroban.

Perspective:

Terutroban joins many other agents that have failed to demonstrate a clinically relevant advantage over aspirin for secondary prevention in patients with prior cerebral events. These patients have a high risk of future adverse events with a nearly 5% annual risk of stroke, MI, or death and a 3.5% risk of stroke, and there remains a need to define strategies that can reduce this risk further.

Clinical Topics: Dyslipidemia, Prevention, Lipid Metabolism

Keywords: Myocardial Infarction, Prostaglandins, Stroke, Follow-Up Studies, Ischemic Attack, Transient, Thromboxanes, Propionates, Receptors, Thromboxane, Secondary Prevention, Prostaglandin Antagonists, Cardiovascular Diseases, Naphthalenes, Receptors, Prostaglandin, Medical Futility, Confidence Intervals, Hemorrhage


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