Background Atenolol is one of the most widely used β. blockers clinically, an d has often been used as a reference drug in randomised controlled trials of hyp ertension. However, questions have been raised about atenolol as the best refere nce drug for comparisons with other antihypertensives. Thus, our aim was to syst ematically review the effect of atenolol on cardiovascular morbidity and mortali ty in hypertensive patients. Methods Reports were identified through searches of The Cochrane Library, MEDLINE, relevant textbooks, and by personal communicatio n with established researchers in hypertension. Randomised controlled trials tha t assessed the effect of atenolol on cardiovascular morbidity or mortality in pa tients with primary hypertension were included. Findings We identified four stud ies that compared atenolol with placebo or no treatment, and five that compared atenolol with other antihypertensive drugs. Despite major differences in blood p ressure lowering, there were no outcome differences between atenolol and placebo in the four studies, comprising 6825 patients, who were followed up for a mean of 4.6 years on all-cause mortality(relative risk 1.01[95%CI 0.89-1.15]), car diovascular mortality(0.99[0.83-1.18]), or myocardial infarction(0.99[0.83-1.1 9]). The risk of stroke, however, tended to be lower in the atenolol than in the placebo group(0.85[0.72-1.01]). When atenolol was compared with other antihype rtensives, there were no major differences in blood pressure lowering between th e treatment arms. Our meta-analysis showed a significantly higher mortality(1.13[1.02-1.25]) with atenolol treatment than with other active treatment, in the five studies comprising 17671 patients who w ere followed up for a mean of 4.6 years. Moreover, cardiovascular mortality also tended to be higher with atenolol treatment than with other antihypertensive tr eatment. Stroke was also more frequent with atenolol treatment. Interpretation O ur results cast doubts on atenolol as a suitable drug for hypertensive patients. Moreover, they challenge the use of atenolol as a reference drug in outcome tri als in hypertension.
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