About Index

PRoFESS

"Comparison of Aspirin plus Extended-Release Dipyridamole versus Clopidogrel for Recurrent Stroke". The New England Journal of Medicine. PubMed•Full

Links to original sources: Wiki Journal Post Full Journal Article

Clinical Question


Does the combination of aspirin plus extended-release dipyridamole (ASA–ERDP) reduce the risk of recurrent stroke compared to clopidogrel alone in patients with a recent ischemic stroke?

Bottom Line


Aspirin plus extended-release dipyridamole (ASA–ERDP) is not inferior to clopidogrel in reducing the risk of recurrent stroke, but does not meet predefined criteria for noninferiority. There is no evidence that either treatment is superior to the other for preventing recurrent stroke.

Major Points


Dual antiplatelet therapy with aspirin and extended-release dipyridamole (ASA-ERDP) and monotherapy with clopidogrel are both approved options for secondary prevention of ischemic stroke. Prior indirect comparisons suggested ASA-ERDP might be superior to clopidogrel for preventing recurrent stroke. However, this trial (PRoFESS) directly compared the two approaches and showed no evidence of superiority for either treatment.

Guidelines


Current guidelines do not specifically recommend one antiplatelet therapy over the other for secondary stroke prevention.

Design


Multicenter, double-blind, parallel group, randomized, controlled 2-by-2 factorial trial comparing ASA–ERDP and clopidogrel.

Population


Inclusion Criteria: - Recent ischemic stroke - Age ≥55 years or older (later amended to ≥50 years with additional risk factors) - Clinically and neurologically stable prior to randomization

Exclusion Criteria: - Contraindications to the antiplatelet agents - Unsuitability for randomization based on clinical judgment

Baseline Characteristics: Age 66.1 years, 36.0% female, majority had a history of hypertension, 28.2% had diabetes.

Interventions


Patients were randomly assigned to receive either ASA–ERDP or clopidogrel.

Outcomes


Primary Outcome: - Recurrence of stroke

Secondary Outcome: - Composite of stroke, myocardial infarction, or death from vascular causes

Outcomes


- Recurrence of stroke or major hemorrhagic event - New or worsening congestive heart failure

Criticisms


- The trial's noninferiority margin was conservative, leading to the inability to claim noninferiority despite similar effectiveness in the two treatment groups. - The trial was underpowered for noninferiority if the actual effectiveness was equivalent between the treatments.

Funding


Funded by Boehringer Ingelheim, manufacturer of Aggrenox (ASA-ERDP) and Micardis (telmisartan). Additional support in selected countries by Bayer Schering Pharma and GlaxoSmithKline for the telmisartan comparison.

Further Reading


ClinicalTrials.gov: NCT00153062.