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  • Title: A 16-week, randomized, double-blind, placebo-controlled, crossover trial to quantify the combined effect of an angiotensin-converting enzyme inhibitor and a beta-blocker on blood pressure reduction.
    Author: Wald DS, Law M, Mills S, Bestwick JP, Morris JK, Wald NJ.
    Journal: Clin Ther; 2008 Nov; 30(11):2030-9. PubMed ID: 19108791.
    Abstract:
    BACKGROUND: Although beta-blockers and angiotensin-converting enzyme (ACE) inhibitors are often used together, there is a lack of quantitative evidence for the efficacy of this combination in reducing blood pressure (BP). OBJECTIVE: The aim of this randomized, double-blind, placebo-controlled, crossover study was to quantify the combined effect of a beta-blocker (atenolol) and an ACE inhibitor (lisinopril) in lowering BP. METHODS: Participants who were > or = 40 years of age and enrolled in the hypertension or anticoagulation clinics at St. Bartholomew's Hospital, London, United Kingdom, were randomized to 3 consecutive 4-week treatments consisting of atenolol 25 mg plus placebo, lisinopril 5 mg plus placebo, and atenolol 25 mg plus lisinopril 5 mg, plus a period of 2 placebos. At the end of each period, seated BP was measured in the right arm using electronic monitors. RESULTS: The mean placebo-adjusted peak BP reductions among the 47 participants (mean age, 62 [range 42-82] years; 75% male; 70% white/30% Asian; mean baseline BP, 145/82 mm Hg) who completed all 4 periods were significantly greater with the combination of both drugs than with either drug alone (P < 0.001). The systolic reductions were 22.9 mm Hg with combination treatment, 16.1 mm Hg with atenolol treatment, and 12.5 mm Hg with lisinopril treatment, and the diastolic reductions were 13.9, 9.8, and 6.8 mm Hg, respectively. The BP-lowering effect of the 2 drugs together was similar to that expected from the sum of each alone, allowing for the reduced effect of 1 drug given the lower pretreatment BP due to the other. The incremental systolic BP reduction from the 2 drugs together compared with 1 alone was 79% (95% CI, 54%-126%) of the expected additive effect, 88% (95% CI, 58%-130%) for diastolic BP, and 84% (95% CI, 65%-118%) for the mean of systolic and diastolic BP. CONCLUSIONS: The combination of the beta-blocker atenolol 25 mg plus the ACE inhibitor lisinopril 5 mg was associated with a significantly greater decrease in BP compared with either alone. The BP reduction with the combination treatment was similar to and statistically consistent with the 2 drugs having additive effects. Clinical Trials Identification Number: ISRCTN97280940.
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