β-blockers and diuretics: to use or not to use

The present review scrutinizes the recommendations of many guidelines to use beta-blockers and diuretics as first-line therapy in hypertension. These recommendations were ostensibly based on multiple prospective randomized trials attesting to a reduction of morbidity and mortality with both beta-blockers and diuretics in monotherapy as well as in combination. Although diuretic-based therapy has been shown to prevent strokes (and, to a lesser extent, heart attacks, and cardiovascular and all-cause mortality), no such data are available for beta-blockers. To the contrary, a recent metaanalysis documented that although blood pressure was lowered significantly by beta-blockers, this drug class was ineffective in preventing coronary heart disease, and cardiovascular and all-cause mortality (odds ratio 1.01, 0.98, and 1.05, respectively). Patients who received a combination of beta-blockers and diuretics fared consistently worse than those taking diuretics alone. Although diuretics have an unparalleled track record of safety and efficacy, the recent findings suggesting that long-term use increased the risk for renal cell carcinoma (RCC) is of concern. Over the past decade, an association between RCC and diuretic therapy has been documented in nine case control studies (odds ratio 1.55, confidence interval [CI] 1.42-1.71). In three cohort studies, diuretic therapy was associated with a greater than twofold increased risk of RCC. The risk of RCC increased with cumulative diuretic doses. In the elderly, a low-dose diuretic probably remains a good choice for antihypertensive therapy; however, in middle-aged patients, particularly in women, diuretics should be avoided for the long-term treatment of hypertension. Sweeping recommendations for the use of beta-blockers and diuretics as preferred therapeutic strategies are inappropriate and a more sophisticated drug therapy regimen is often needed.