Relation of beta-blocker-induced heart rate lowering and cardioprotection in hypertension.

OBJECTIVES The purpose of this study was to evaluate the role of heart rate reduction with beta-blockers on the risk of cardiovascular events in patients with hypertension. BACKGROUND Resting heart rate has been shown to be a risk factor for cardiovascular morbidity and mortality in the general population and in patients with heart disease such as hypertension, myocardial infarction, and heart failure. Conversely, pharmacological reduction of heart rate is beneficial for patients with heart disease. However, the role of pharmacological reduction of heart rate using beta-blockers in preventing cardiovascular events in patients with hypertension is not known. METHODS We conducted a MEDLINE/EMBASE/CENTRAL database search of studies from 1966 to May 2008. We included randomized controlled trials that evaluated beta-blockers as first-line therapy for hypertension with follow-up for at least 1 year and with data on heart rate. We extracted the baseline characteristics, the blood pressure response, heart rate at the baseline and end of trial, and cardiovascular outcomes from each trial. RESULTS Of 22 randomized controlled trials evaluating beta-blockers for hypertension, 9 studies reported heart rate data. The 9 studies evaluated 34,096 patients taking beta-blockers against 30,139 patients taking other antihypertensive agents and 3,987 patients receiving placebo. Paradoxically, a lower heart rate (as attained in the beta-blocker group at study end) was associated with a greater risk for the end points of all-cause mortality (r = -0.51; p < 0.0001), cardiovascular mortality (r = -0.61; p < 0.0001), myocardial infarction (r = -0.85; p < 0.0001), stroke (r = -0.20; p = 0.06), or heart failure (r = -0.64; p < 0.0001). The same was true when the heart rate difference between the 2 treatment modalities at the end of the study was compared with the relative risk reduction for cardiovascular events. CONCLUSIONS In contrast to patients with myocardial infarction and heart failure, beta-blocker-associated reduction in heart rate increased the risk of cardiovascular events and death for hypertensive patients.