MedWire News: Telmisartan treatment does not confer an overall reduction in recurrent stroke risk relative to placebo over a 2.5-year period, but patients may accumulate benefits with continued use, the results of PRoFESS show.
The blood pressure (BP)-lowering arms of PRoFESS (Prevention Regimen for Effectively Avoiding Second Strokes Trial) enrolled 20,332 patients who had suffered stroke within the preceding 4 months and randomly assigned them to receive telmisartan 80 mg/day or placebo.
The researchers investigated the effects of telmisartan because results from previous studies, such as MOSES (Morbidity and Mortality After Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention) and HOPE (Heart Outcomes Prevention Evaluation), indicated that blocking the renin-angiotensin system may confer vascular protection beyond that provided by BP reduction.
In PRoFESS, 8.7% of the telmisartan group and 9.2% of the placebo group suffered stroke - a nonsignificant difference. There were also no differences in rates of major cardiovascular events (death from cardiovascular causes, myocardial infarction, recurrent stroke, or worsening or new heart failure), at 13.5% versus 14.4%, or of new-onset diabetes, at 1.7% versus 2.1%, respectively.
The lack of effect of active treatment was consistent across stroke subtypes according to TOAST classification, the results published in the New England Journal of Medicine show.
However, a post-hoc analysis revealed a possible time-dependent effect of telmisartan treatment. Stroke rates were similar in the active and placebo treatment groups during the first 6 months, at 3.4% and 3.2%, respectively. But the corresponding rates between 6 months and the end of follow-up were 5.3% and 6.0%, representing a significant 12% risk reduction.
"These findings, while provisional, suggest that the effect of telmisartan in our study was time dependent," comment Salim Yusuf (McMaster University, Hamilton, Ontario, Canada) and colleagues.
"In the HOPE and PROGRESS [Perindopril Protection Against Recurrent Stroke Study] trials, there was little or no apparent benefit in the first 6 months, whereas there was a gradual and continuing lowering in the rates of stroke and major cardiovascular events thereafter," they say.
"If this interpretation is correct, then the mean duration of follow-up in our study (2.5 years), which was shorter than that of the HOPE study (4.5 years) and the PROGRESS study (4 years), may have contributed to the lack of significant benefit associated with telmisartan in our study."
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