title: Blood pressure lowering efficacy of nonselective beta-blockers for primary hypertension.
abstract: BACKGROUND
  Beta-blockers are one of the classes of drugs frequently used to treat hypertension. Quantifying the blood pressure (BP) lowering effects of nonselective beta-blockers provides important information that aids clinical decision making.
  
  
  OBJECTIVE
  To quantify the dose-related effects of nonselective beta-adrenergic receptor blockers (beta-blockers) on systolic blood pressure (SBP) and diastolic blood pressure (DBP) as compared with placebo in people with primary hypertension.
  
  
  METHODS
  We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ClinicalTrials.gov for randomized controlled trials up to October 2013.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled, parallel or cross-over trials. Studies had to contain a nonselective beta-blocker monotherapy arm with a fixed dose. Participants enrolled into the studies had to have primary hypertension at baseline. Duration of studies had to be between three and 12 weeks.
  
  
  METHODS
  Two review authors (GW and AL) independently confirmed the inclusion of studies and extracted the data.
  
  
  RESULTS
  We included 25 RCTs that evaluated the BP lowering effects of seven nonselective beta-blockers in 1264 people with hypertension. Among the 25 RCTs, four were parallel studies and 21 were cross-over studies. Overall, nonselective beta-blockers lowered systolic BP and diastolic BP compared with placebo. Nonselective beta-blockers, in the recommended dose range, did not showed a convincing dose-response relationship by direct comparison. The once (1x) and twice (2x) starting dose subgroups contained the largest sample size. The estimate of BP lowering efficacy for nonselective beta-blockers by combining the 1x and 2x starting dose subgroup was -10 mmHg (95% CI -11 to -8) for systolic BP and -7 mmHg (95% CI -8 to -6) for diastolic BP (low-quality evidence). Nonselective beta-blockers starting at the 1x recommended starting doses lowered heart rate by 12 beats per minute (95% CI 10 to 13) (low-quality evidence). The dose-response relationship in heart rate was evident by both direct and indirect comparison. Due to imprecision, there was no clear evidence of an effect of nonselective beta-blockers on pulse pressure in any dose subgroups except for a small reduction with the 2x starting dose (-2.2 mmHg, 95% CI -3.7 to -0.7) (very low quality evidence). The point estimates in the 1x, four times (4x) and eight times (8x) starting dose subgroups were similar to the 2x starting dose subgroup. Therefore, it would appear that if nonselective beta-blockers do lower pulse pressure, the magnitude is likely to be about 2 mmHg. There were very limited data (two studies) on withdrawals due to adverse effects (risk ratio (RR) 0.84; 95% CI 0.38 to 1.82).
  
  
  CONCLUSIONS
  In people with mild-to-moderate hypertension, nonselective beta-blockers lowered peak BP by a mean of -10/-7 mmHg (systolic/diastolic) and reduced heart rate by 12 beats per minute. Propranolol and penbutolol were the two drugs that contributed to most of the data for nonselective beta-blockers. This estimate is likely exaggerated due to the presence of extreme outliers and other sources of bias. If we removed the extreme outliers from the analysis, the estimate for non-selective beta-blockers was lower (-8/-5 mmHg (systolic/diastolic)). Nonselective beta-blockers did not show a convincing graded dose-response in the recommended dose range for systolic BP and diastolic BP, while higher dose nonselective beta-blockers provided greater reduction of heart rate. Using higher dose nonselective beta-blockers might cause more side effects, such as bradycardia, without producing an additional BP lowering effect. The effect of nonselective beta-blockers on pulse pressure was likely small, at about 2 mmHg.
authors.affiliation: Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.
authors.forename: Gavin W K
authors.initials: GW
authors.lastname: Wong
authors.forename: James M
authors.initials: JM
authors.lastname: Wright
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents