PRoFESS®, the Largest Recurrent Stroke Prevention Trial Results were Presented at the 17th European Stroke Conference
May 21, 2008 By Vijayalakshmi Kunadian MBBS MD MRCP 
17th European Stroke Conference, Nice, France: The PRoFESS® trial demonstrates similar recurrent stroke rates with the combination of dipyridamole plus aspirin versus clopidogrel with slightly increased major bleeding events in the dipyridamole/aspirin group.
The results of the PRoFESS® trial (Prevention Regimen for Effectively avoiding Second strokes) , the world’s largest trial on the secondary prevention of stroke were presented at the European stroke Conference in Nice last week by the three principal investigators of the trial [Professors Diener (Germany), Sacco (USA) and Yusuf (Canada)].
This study consisted of a 2 X 2 factorial design and enrolled 20,333 patients. In group 1, in addition to telmisartan (80 mg), patients were randomized to receive extended release (ER)-dipyridamole (200 mg) plus aspirin (50 mg) or clopidogrel (75 mg). In group 2, in addition to placebo, patients were randomized to receive the same doses of ER-dipyridamole (DP) plus aspirin (ASA) or clopidogrel.
The inclusion criteria for this trial consisted of patients with age ≥ 55 years who had an ischemic stroke within 90 days prior to study entry or patients aged 50-54 years and/or 90-120 after qualifying stroke provided at least two of the following risk factors:
- Diabetes mellitus
- Hypertension (systolic blood pressure ≥140 or diastolic blood pressure ≥90 mmHg)
- Smoker at the time of qualifying stroke
- Obesity (BMI >30)
- Vascular disease (stroke, myocardial infarction, or peripheral artery disease) prior to qualifying stroke
- End-organ damage (retinopathy, left-ventricular hypertrophy, or microalbuminuria)
- Neurologically and clinically stable
The primary endpoint of this trial consisted of time to recurrent stroke. The secondary endpoints consisted of vascular events (stroke, myocardial infarction or vascular death), vascular events or congestive heart failure and new onset diabetes. The 4 main sub-studies consisted of cognitive sub-study, hemodynamic sub-study, MRI sub-study, and biomarker and genetic sub-study.
During a follow-up period of 2.5 years, there was no difference in the occurrence of first recurrent stroke between the two treatment groups (ER-DP+ASA vs. clopidogrel: 9% vs. 8.8%; HR 1.01, 95% CI 0.92 to 1.11). The rates of secondary endpoints were also similar (13.1% vs. 13.1%; HR 0.99, 95% CI 0.92 to 1.07, p=0.83). ER-DP+ASA group was associated with increased major hemorrhagic events and intracranial bleeds compared with clopidogrel (4.1% vs. 3.6%; HR 1.15, 95% CI 1 to 1.32, p=0.06).
Furthermore, blood pressure lowering with telmisartan compared with placebo did not result in significant reduction in the occurrence of recurrent stroke (8.7% vs. 9.2%; HR 0.95, 95% CI 0.86 to 1.04, p=0.23). There was also no difference in the secondary endpoints between the two groups [Major vascular events: 13.5% vs. 14.4%; HR 0.94, 95% CI 0.87 to 1.01, p=0.11 and new onset diabetes: HR 0.82, 95% CI 0.65 to 1.04, p=0.10].
Although there was no difference in the rates of recurrent stroke and major vascular events durng the first six months with telmisartan vs. placebo [3.4% vs. 3.2%; HR 1.07, 95% CI 0.92 to 1.25, p=0.38 and 4.7% vs. 4.3%; HR 1.10, 95% CI 0.97 to 1.26, p=0.14], exploratory analysis revealed that treatment with telmisartan did reduce the incidence of recurrent strokes beyond 6 months compared with placebo (5.3% vs. 6%; HR 0.88, 95% CI 0.78 to 0.99, p=0.029) and major vascular events (8.8% vs. 10.1%; HR 0.87, 95% CI 0.80 to 0.95, p=0.0029).
Likewise, there was no difference in the functional outcome and cognitive impairment following recurrent stroke between the ER-DP+ASA vs. clopidogrel and telmisartan vs. placebo groups during a follow-up of 2.5 years.
In conclusion, the PRoFESS® trial demonstrated similar results with ER-DP+ASA vs. clopidogrel and telmisartan vs. placebo in the prevention of recurrent stroke, major vascular events, cognitive and functional outcomes following recurrent stroke among neurologically and clinically stable patients with a history of prior stroke.
- 17th European stroke Conference 2008,Nice France. Presented by Professors Sacco, Diener and Yusuf.
- Diener HC, Sacco R, Yusuf S (2007). "Rationale, design and baseline data of a randomized, double-blind, controlled trial comparing two antithrombotic regimens (a fixed-dose combination of extended-release dipyridamole plus ASA with clopidogrel) and telmisartan versus placebo in patients with strokes: the Prevention Regimen for Effectively Avoiding Second strokes Trial (PRoFESS)". Cerebrovasc. Dis. 23 (5-6): 368–80. PMID 17337887. doi:10.1159/000100105.