PRoFESS Study Results

Lori Alexander

doi:10.1177/155989771213020

Summary

A landmark analysis is providing insight into the relationship between resting heart rate and outcomes after ischemic stroke. An analysis of data from the 20,165 patients enrolled in the Prevention Regimen for Effectively Avoiding Second Stroke [PRoFESS] study showed that heart rate is associated with mortality among patients with stroke and that a low heart rate is associated with a better functional outcome and less cognitive decline after an ischemic stroke.

Cerebrovascular Disease
Cardiology Clinical Trials
Ischemia

PRoFESS was a 2×2 factorial trial that evaluated the safety and efficacy of aspirin and extended-release dipyridamole compared with clopidogrel (as noninferiority first then superiority), and the safety and efficacy of telmisartan compared with placebo (superiority) [Diener HC et al. Cerebrovasc Dis 2007]. The primary results of both comparisons have been previously published [Yusuf et al. N Engl J Med 2008; Sacco et al. N Engl J Med 2008].

Prior studies have shown an association between resting heart rate and cardiovascular (CV) events along the CV continuum, and stress models have shown that reducing heart rate may reduce the size of a stroke, explained Michael Böhm, MD, Universitätskliniken des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany, who presented the findings of the study. Thus, the current study was designed to answer the questions of whether baseline heart rate predicts recurrent stroke, myocardial infarction (MI), heart failure, or death after stroke or is associated with functional outcome or cognitive decline after recurrent stroke [Böhm M et al. Eur Heart J 2012].

The patients were grouped according to baseline heart rates, with quintiles of ≤64, 65 to 70, 71 to 76, 77 to 82, and >82 beats per minute (bpm). The predefined endpoints were disability after a recurrent stroke, as assessed with the modified Rankin Scale score and the Barthel Index, and cognitive function, as assessed with the Mini-Mental State Examination (MMSE) score. Disability was assessed at 3 weeks, and the MMSE score was determined at 4 weeks after randomization and at the penultimate visit.

Overall, increasing quartile of heart rate was associated with female gender and diabetes mellitus. β-blocker use, statin use, hypertension, and age were associated with lower heart rates.

All-cause mortality was higher among patients in the 3 highest quintiles of heart rate compared with the lowest quintile (71 to 76 bpm: HR, 1.32; 95% CI, 1.11 to 1.56; 77 to 82 bpm; HR, 1.42; 95% CI, 1.19 to 1.69; and >82 bpm: HR, 1.74; 95% CI, 1.48 to 2.06; p<0.0001 for both). Prof. Böhm noted that the heart rate threshold differed for CV and non-CV mortality (Figure 1). Baseline heart rate was not associated with MI, recurrent stroke, or new or worsening heart failure.

Figure 1.

All-Cause Mortality, CV Death, and Non-CV Death According to Resting Heart Rate.

Among 1627 patients who had a recurrent stroke, the functional outcome at 3 months was better in patients with a lower heart rate at baseline. The baseline heart rate was also significantly associated with cognitive decline according to the MMSE score (≤24 points; p=0.0001; Figure 2); more patients with a heart rate >82 bpm had a decrease of 2 points on the MMSE between the 1 month and penultimate visits.

Figure 2.

Mini-Mental State Examination ≤24 Points.

Prof. Böhm interpreted these findings as suggestive that lower heart rates may be associated with smaller strokes rather than fewer recurrent strokes. Further study will be needed to better understand whether heart rate plays a causative role in outcomes after stroke and whether therapies to reduce heart rate will be beneficial in patients experiencing a first stroke.

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