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.


OBJECTIVE
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.


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


METHODS
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.


METHODS
Two reviewers independently extracted the data and assessed trial quality of each included study.


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.


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.
Chen
Jenny Mh
JM
Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.
Heran
Balraj S
BS
Perez
Marco I
MI
Wright
James M
JM
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000379:methods; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics