Prevention of cerebrovascular and cardiovascular Events of ischaemic origin with teRutroban in patients with a history oF ischaemic stroke or tRansient ischaeMic attack - PERFORM

May 30, 2011
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Servier, France.
Date Published:
01/01/2011
Date Updated:
05/30/2011
Original Posted Date:
05/30/2011
References

Description:

The goal of the trial was to evaluate treatment with the selective thromboxane-prostaglandin antagonist terutroban compared with aspirin among patients with recent ischemic stroke or transient ischemic attack (TIA).

Hypothesis:

Terutroban will be noninferior at preventing cerebrovascular and cardiovascular ischemic events.

Study Design

  • Randomized
  • Blinded
  • Parallel
  • Stratified

Patient Populations:

  • Patients at least 55 years of age with recent ischemic stroke (previous 3 months) or TIA (previous 8 days)

    Number of enrollees: 19,120
    Duration of follow-up: 28.3 months (mean)
    Mean patient age: 67 years
    Percentage female: 37%

Exclusions:

  • Cognitive impairment or known dementia
  • Cardiac source of embolism requiring long-term oral anticoagulation

Primary Endpoints:

  • Vascular death (excluding hemorrhagic death), fatal or nonfatal ischemic stroke, or fatal or nonfatal myocardial infarction

Secondary Endpoints:

  • Composite of any stroke, any myocardial infarction, or other vascular death (excluding hemorrhagic death)
  • All-cause mortality
  • Any stroke
  • Fatal stroke
  • Any ischemic stroke
  • Any myocardial infarction
  • Cognitive decline
  • Dementia
  • Major bleeding (including intracranial and gastrointestinal)

Drug/Procedures Used:

Patients with recent ischemic stroke or TIA were randomized to terutroban 30 mg daily (n = 9,562) versus aspirin 100 mg daily (n = 9,558).

Concomitant Medications:

At the time of randomization, the use of aspirin was 87%, dipyridamole was 9%, clopidogrel was 7%, and aspirin/dipyridamole was 5%. Also, the use of statin was 58%.

Principal Findings:

Overall, 19,120 patients were randomized. The mean age was 67 years, 37% were women, 84% were white, body mass index was 27 kg/m2, systolic blood pressure was 139 mm Hg, heart rate was 72 bpm, 27% were current smokers, 84% had hypertension, 48% had hypercholesterolemia, and 28% had diabetes.

The mean delay between ischemic stroke and randomization was 26.9 days and the mean delay between TIA and randomization was 5.8 days. The mean duration of follow-up was 28.3 months.

The primary composite outcome occurred in 11% of the terutroban group versus 11% of the aspirin group (95% confidence interval [CI] 0.94-1.12). The upper limit for noninferiority was 1.05. The only subgroup which demonstrated enhanced benefit for terutroban was among patients with prior history of ischemic stroke before their qualifying event.

Any stroke was 9% versus 9%, any fatal stroke was 1% versus 1%, fatal or nonfatal myocardial infarction was 2% versus 1%, all-cause mortality was 6% versus 6%, and vascular death was 2% versus 2%, respectively, for terutroban versus aspirin.

Major bleeds occurred in 2% versus 2%, minor bleeds in 12% versus 11% (95% CI 1.02-1.21), intracranial hemorrhage in 2% versus 1%, gastrointestinal bleeds occurred in 3% versus 3%, and adverse events occurred in 84% versus 84%, respectively, for terutroban versus aspirin.

Interpretation:

Among patients with recent ischemic stroke or TIA, terutroban was not superior compared with aspirin in preventing ischemic cerebrovascular or cardiovascular events. Although event rates were similar between the groups, terutroban also failed to meet the criteria for noninferiority. Bleeding events (intracranial and gastrointestinal) were similar, except for a small excess in minor bleeds with terutroban.

The only subgroup which demonstrated enhanced benefit for terutroban was patients who had an ischemic stroke prior to their qualifying event. Although conclusions are limited from subgroup analysis, this finding could be plausible since these patients likely suffered their event on aspirin therapy, and a different antiplatelet agent might be more beneficial.

References:

Bousser MG, Amarenco P, Chamorro A, et al. Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial. Lancet 2011;May 25:[Epub ahead of print].

Keywords: Myocardial Infarction, Stroke, Follow-Up Studies, Ischemic Attack, Transient, Platelet Aggregation Inhibitors, Thromboxanes, Propionates, Blood Pressure, Hypercholesterolemia, Heart Rate, Intracranial Hemorrhages, Body Mass Index, Prostaglandin Antagonists, Naphthalenes, Confidence Intervals, Hypertension, Diabetes Mellitus


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