Blood pressure lowering efficacy of beta-blockers as second-line therapy for primary hypertension.

BACKGROUND: Beta-blockers are one of the more commonly prescribed classes of anti-hypertensive drugs, both as first-line and second-line.

OBJECTIVES: To quantify the effect on systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate and withdrawals due to adverse effects of beta-blocker therapy when given as a second-line drug in adult patients with primary hypertension.

SEARCH STRATEGY: CENTRAL (The Cochrane Library 2009, Issue 2), MEDLINE (1966-Aug 2009), EMBASE (1988-Aug 2009) and bibliographic citations of articles and reviews were searched.

SELECTION CRITERIA: Double-blind, randomized controlled trials comparing a beta-blocker in combination with a drug from another class of anti-hypertensive drugs compared with that drug alone for a duration of 3 to 12 weeks in patients with primary hypertension were included.

DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted the data and assessed trial quality of each included study.

MAIN RESULTS: 20 double-blind RCTs evaluated the BP lowering efficacy of beta-blockers as second-line drug in 3744 hypertensive patients (baseline BP of 158/102 mmHg; mean duration of 7 weeks). The BP reduction from adding a beta-blocker as the second drug was estimated by comparing the difference in BP reduction between the combination and monotherapy groups. A reduction in BP was seen with adding a beta-blocker to thiazide diuretics or calcium channel blockers at doses as low as 0.25 times the manufacturer's recommended starting dose. The BP lowering efficacy of beta-blockers as a second drug was 6/4 mmHg at 1 times the starting dose and 8/6 mmHg at 2 times the starting dose. Beta-blockers reduced heart rate by 10 beats/min at 1 to 2 times the starting dose. Beta-blockers did not statistically significantly increase withdrawals due to adverse effects but this was likely due to the lack of reporting of this outcome in 35% of the included RCTs.

AUTHORS' CONCLUSIONS: Addition of a beta-blocker to diuretics or calcium-channel blockers reduces BP by 6/4mmHg at 1 times the starting dose and by 8/6 mmHg at 2 times the starting dose. When the blood pressure lowering effect of beta-blockers from this review was compared to that of thiazide diuretics from our previous review (Chen 2009), second-line beta-blockers reduce systolic BP to the same extent as second-line thiazide diuretics, but reduce diastolic BP to a greater degree. The different effect on diastolic BP means that beta-blockers have little or no effect on pulse pressure whereas thiazides cause a significant dose-related decrease in pulse pressure. This difference in the pattern of BP lowering with beta-blockers as compared to thiazides might be the explanation for the fact that beta-blockers appear to be less effective at reducing adverse cardiovascular outcomes than thiazide diuretics, particularly in older individuals.