High Resting Heart Rate Predicts Poor Neurological Outcomes in Stroke Survivors

August 27, 2012

August 27, 2012 (Munich, Germany) — A new analysis of the PROFESS trial has shown that resting heart rate has important prognostic implications for people who have survived a stroke [1]. Those in the two highest quintiles of heart rate (77–82 and >82 bpm) had as much as a 70% higher risk for total death compared with patients in the lowest quintile, and, importantly, lower baseline heart rate was associated with better neurological outcomes, Dr Michael Böhm (Saarland University Hospital, Homburg/Saar, Germany) told the European Society of Cardiology (ESC) 2012 Congress yesterday.

Dr Michael Böhm

Böhm reported the findings during a clinical-trial-update session, and they were also published online simultaneously in the European Heart Journal.

In an editorial accompanying the paper [2], Dr Sverre Kjeldsen (University of Oslo, Norway) and Dr Peter Okin (Weill Cornell Medical College, New York, NY) [2], say: "The exciting news with the current data . . . is that that the prognostic impact of a high heart rate is brought forward into a population of stroke survivors. While the influence on cardiovascular disease and mortality was not unexpected, the prognostic relationship of heart rate to disability and early cognitive decline after recurrent stroke is a major new finding."

They go on to suggest that randomized controlled trials with the heart-rate-reducing selective If-channel inhibitor ivabradine (Procoralan, Servier) could be performed in stroke survivors to see whether this agent conveys any benefit.

Results Set Stage to Evaluate HR Lowering in Stroke Survivors

PROFESS was the largest secondary-stroke prevention trial ever conducted and randomized more than 20 000 ischemic-stroke patients to aspirin plus extended-release dipyridamole (Aggrenox, Boehringer Ingelheim) or clopidogrel. Subjects were further randomized to the blood-pressure-lowering drug telmisartan (Micardis, Boehringer Ingelheim) or placebo. The main findings of the study, released in 2008, showed that neither approach (aspirin/dipyridamole or clopidogrel) was superior to the other for the prevention of stroke, nor did telmisartan appear to have any benefit in terms of stroke recurrence, major CV events, or diabetes.

The prognostic relationship of heart rate to disability and early cognitive decline after recurrent stroke is a major new finding.

In this new analysis, Böhm and coworkers report on the relationship of cardiovascular and neurological outcomes to baseline heart rate in the PROFESS participants. They were grouped by quintiles of heart rate and were evaluated for a primary outcome of recurrent stroke and a secondary outcome of the composite of recurrent stroke, MI, or death from a vascular cause.

They were further assessed for new or worsening heart failure and nonvascular death and additional predefined end points, including disability after recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at three months, and cognitive function, assessed with the Mini-Mental State Examination (MMSE) score.

"Perhaps most interesting," say Kjeldsen and Okin, is that in the group of patients with recurrent stroke, "lower baseline heart rate was associated with better neurological outcomes as measured with the Barthel index and mRS score and with less cognitive decline according to an MMSE score. Thus, a high baseline heart rate is a risk indicator for mortality in patients with stroke and, importantly, low heart rate is associated with better functional outcome and less cognitive decline after ischemic stroke."

The authors concur and agree that trials of agents that lower heart rate should be performed in stroke survivors.

"This analysis is hypothesis generating and sets the stage for the evaluation of potential pharmacological interventions to reduce the heart rate in patients after an ischemic stroke," they state.

Heart Rate Strongly Predicts Mortality, Even After Multivariate Adjustment

This analysis is hypothesis generating and sets the stage for the evaluation of potential pharmacological interventions to reduce the heart rate in patients after an ischemic stroke.

Overall in the new analysis of PROFESS, there was no significant relationship between baseline heart rate and the primary outcome (recurrent stroke), the composite secondary end point, or heart failure. The latter is probably at least partly due to the fact that the researchers were unable to evaluate the predictive value of serial measures of heart rate over time during the study, a limitation they acknowledge, say Kjeldsen and Okin.

But a strong association between heart rate and mortality emerged.

Patients in the two highest quintiles of heart rate were at higher risk for total death (hazard ratio [HR] 1.42 and HR 1.74; p<0.0001) compared with patients in the lowest quintile. Risk of vascular death (starting at heart rates from 71 to ≤76 bpm, HR 1.39; p<0.0001) and nonvascular death (from >82 bpm, HR 1.66, p=0.0016) was also strongly associated with higher baseline heart rate.

And importantly, increased mortality risk persisted after adjustment for multiple confounders, including baseline blood pressure.

PROFESS was sponsored by Boehringer Ingelheim. Böhm has received study support and honoraria from AstraZeneca, Bayer AG, Boehringer Ingelheim, Novartis, Pfizer, Sanofi, Servier, Adrian-Medtronic, Daiichi-Sankyo, MSD, AWD Dresden, and Berlin-Chemie. Disclosures for the coauthors are listed in the paper. Kjeldsen and Okin were in the leadership of the LIFE and VALUE studies, supported by Merck and Novartis.

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