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.
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.
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.
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.
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.