a) Background:
The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial.
b) Aim/objective
To compare the efficacy and safety of the fixed-dose combination product Aspirin plus extended-release dipyridamole (Aggrenox®, ASA+ER-DP) with that of clopidogrel and to compare the efficacy and safety of telmisartan (Micardis®) with that of placebo in the prevention of recurrent stroke.
c) Methods:
Prospective, randomised, multi-national, double-blind, double-dummy, active and placebo-controlled, parallel-group, 2x2 factorial design. The enrolment period was 2 years 10 months; total study duration was 4 years 5 months.
Patients who had had an ischaemic stroke were randomly assigned in a two by two factorial design to receive either 25 mg aspirin (ASA) and 200 mg extended-release dipyridamole (ER-DP) twice a day or 75 mg clopidogrel once a day, and either 80 mg telmisartan or placebo once per day. The predefined endpoints for this substudy were disability after a recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed with the mini-mental state examination (MMSE) score at 4 weeks after randomisation and at the penultimate visit. Analysis was by intention to treat.
d) Results:
A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA–ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA–ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA–ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA–ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11).
e) Total recruitment & no. of sites:
Global 20,332 from 695 sites, India : 1,620 form 30 sites.
f) Conclusion:
The trial did not meet the predefined criteria for non-inferiority but showed similar rates of recurrent stroke with ASA–ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke.
The PRoFESS trial showed that, among patients with a noncardioembolic ischemic stroke, the risks of recurrent stroke or the composite of stroke, myocardial infarction, or death from vascular causes are similar with aspirin plus extended-release dipyridamole and with clopidogrel. Despite the increased risk of hemorrhagic strokes with aspirin plus extended-release dipyridamole as compared with clopidogrel, the net benefit with regard to the risk of recurrent stroke or major hemorrhagic event was similar in the two groups. Furthermore, there was no significant difference between the two treatments in the risk of fatal or disabling strokes. The large number and international representation of patients, who were from 35 countries or regions, enhances the generalizability of our findings. These findings provide additional safety and efficacy data physicians need in making individual treatment decisions for prevention of recurrent stroke or the combined end point of stroke, myocardial infarction, or death from vascular causes in their patients with stroke.
g) Publication status (Name & year):
Lancet Neurol 2008; Cerebrovasc Dis. 2007; New Eng J Med. 2008;
h) Publication link:
https://www.sciencedirect.com/science/article/abs/pii/S1474442208701984?via%3Dihub
https://pubmed.ncbi.nlm.nih.gov/17868007/;
i) Updated as on: 30th June 2023