β-Adrenergic Antagonists in Hypertension: A Review of the Evidence

OBJECTIVE: To evaluate the effects of beta-adrenergic antagonist therapy on cardiovascular and cerebrovascular outcomes in the treatment of hypertension. DATA SOURCES: Literature searches were conducted using MEDLINE (1966-August 2009), International Pharmaceutical Abstracts (1970-August 2009), and Cochrane Database of Systematic Reviews (until third quarter 2009) to locate clinical trials and meta-analyses comparing beta-blocker therapy with placebo or other antihypertensive agents in patients with hypertension. Bibliographies from relevant research and review articles were reviewed for additional references. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data sources were reviewed. Articles describing original research with cardiovascular or cerebrovascular outcomes and/or death as either primary or secondary endpoints were included. Articles describing the use of beta-blocker therapy for conditions other than hypertension were not included. DATA SYNTHESIS: Five placebo-controlled studies and 10 active-controlled studies were reviewed. In addition, 11 meta-analyses were evaluated. Placebo-controlled trials of beta-blockers in hypertension provide evidence of reduced risk for stroke, cardiovascular events, and heart failure. Only 2 studies comparing beta-blockers with other antihypertensives found significant benefit with beta-blockers. However, the majority of meta-analyses comparing beta-blockers with other antihypertensive agents show increased risk for stroke with beta-blockers, and some data suggest increased risk for cardiovascular events and all-cause mortality. The majority of data results from studies of atenolol, and many studies employed combination antihypertensive therapies, which often included thiazide diuretics. CONCLUSIONS: Overall, data supporting beta-blockers as preferred therapy in hypertension are inadequate. Although most negative cardiovascular and cerebrovascular outcomes of beta-blockers were associated with atenolol therapy, data supporting other beta-blockers in hypertension are lacking.