Marc Fisher MD Kennedy Lees MD Section Editors
Investigators at nearly 700 sites enrolled over 20 000 patients in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. As clinicians, we recognized an important practical question that was unanswered by indirect comparisons. We understood that the combination of aspirin with dipyridamole better prevented stroke recurrence than aspirin but incurs some intolerance. We believed that clopidogrel monotherapy offered a smaller advantage over aspirin but at greater cost. When the race began, the betting favored the aspirin–dipyridamole combination on cost and efficacy grounds.
PRoFESS gave us the answer we should have desired. We need an array of strategies so that we can tailor treatment to our patients and respond to restrictions caused by side effects. In practice, poorer adherence to treatment resulting from intolerance to dipyridamole may have balanced any greater inherent efficacy, rendering the aspirin–dipyridamole combination equal to clopidogrel. Drs Selim and Algra offer helpful insights into the interpretation of the antiplatelet results in the context of the previous trials. Both agree that whatever the scientific reasons behind the results of PRoFESS, clopidogrel has been found equivalent to the aspirin and dipyridamole combination.
Telmisartan conferred no additional benefit, raising questions over the optimal timing for initiation of antihypertensives after stroke and over the claimed benefits, beyond blood pressure-lowering, of angiotensin receptor blockers. Drs McInnes and Selim both suggest that the relatively short duration of the trial militated against a definitive result. This may be fair criticism, although a counterproposal may be that PRoFESS has excluded any benefit of clinically useful extent.
Regardless, clopidogrel is likely now to be more widely considered, whereas telmisartan will be discounted for early blood pressure reduction. PRoFESS has widened our choice of first-line antiplatelet strategy without adding to our patients’ pill count, and in this regard, it has been a straightforward win for the patient.
The author has received fees and expenses or institutional support from the following companies: Boehringer Ingelheim, AstraZeneca, Forest, Paion, Lundbeck, Ferrer, Mitsubishi, Glaxo-SmithKline, Servier, and Wyeth; participated as DMC chairman in the ECASS-III and DIAS trials; and was an investigator in the ProFESS study. He is a director of the UK Stroke Research Network and has grant support from the UK Medical Research Council for Vitatops and ENOS trials.
- Received November 4, 2008.
- Accepted November 7, 2008.