Study Question: Does atenolol reduce cardiovascular morbidity and mortality in patients with hypertension?

Setting: Various (meta-analysis)

Study Design: Systematic review

Synopsis: The authors of this briefly described systematic review evaluated the effect of atenolol on cardiovascular morbidity and mortality in patients with hypertension. However, the search strategy may have prematurely restricted the field, causing the authors to miss potentially relevant studies. Their search strategy allowed them to include only studies of atenolol versus placebo and five other studies that compared atenolol with other drugs. More than 23,000 patients who were evaluated for an average of 4.6 years were involved in these studies.

Compared with placebo, atenolol lowered systolic blood pressure by approximately 10 mm Hg and diastolic blood pressure by 6 mm Hg. Atenolol and the other drugs, however, had approximately the same effect on lowering blood pressure. In the placebo-controlled trials, atenolol had no effect on all-cause mortality, cardiovascular mortality, myocardial infarction, or stroke. In the studies using other drugs, one study—the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study—included as many patients as the rest combined. The authors analyzed the studies with and without the LIFE data. When the LIFE study was included, no significant differences in all-cause mortality, cardiovascular mortality, myocardial infarction, or stroke were evident. When the LIFE data were not included, atenolol increased all-cause mortality (number needed to treat to harm [NNH] = 110 for 4.6 years; 95 percent confidence interval [CI], 59 to 798) and stroke (NNH = 79 for 4.6 years; 95 percent CI, 51 to 176).

The authors included several studies, including the LIFE trial, with questionable designs. One study was unblinded, two studies recruited patients with transient ischemic stroke or minor stroke, and one included only patients with left ventricular hypertrophy. Although most of the patients had hypertension, those studies were inappropriate to include as prevention trials. If these studies are excluded from the analysis, the authors’ point that the data supporting the use of atenolol are limited is well taken.

Bottom Line: If these authors have identified all relevant research, it appears that atenolol is more effective than placebo in lowering blood pressure. It is not more effective than other medications, however. Furthermore, it does not appear to reduce the rates of cardiovascular morbidity or mortality. (Level of Evidence: 1a–)