Hydrochlorothiazide Versus Chlorthalidone in the Management of Hypertension

Thiazide diuretics are a mainstay for the treatment of hypertension. Although there are several thiazide diuretics currently available, hydrochlorothiazide (HCTZ) continues to be the most popular thiazide used for treating high blood pressure. This is despite several clinical trials that have used and documented the benefits of chlorthalidone for hypertension management. In terms of blood pressure lowering, both HCTZ and chlorthalidone appear to be very effective. Head-to-head studies have shown trends favoring chlorthalidone as a more effective blood pressure lowering agent compared with HCTZ, but statistical significance in this regard has not been consistently demonstrated. Also unclear is the relative benefits of these 2 drugs with regards to reducing clinical complications of hypertension, namely cardiovascular morbidity and mortality. Whereas there is more aggregate clinical trial data documenting the benefits of chlorthalidone compared with HCTZ in terms of hard clinical outcomes, these trials are not direct comparisons and can only be used to fuel the debate as to which of the 2 thiazides are better. From a safety perspective, hypokalemia is a risk with any of the thiazide diuretics and has been shown to be dose-related. However, at equipotent dosages, the incidence of hypokalemia between chlorthalidone and HCTZ appears comparable. The available evidence therefore supports both HCTZ and chlorthalidone as safe and effective drugs for treating hypertension. Although there are favorable trends both in terms of antihypertensive efficacy as well as clinical outcomes data with chlorthalidone compared with HCTZ, the results are not conclusive, and as such may not be enough to shift the treatment paradigm in favor of chlorthalidone, given the comfort level that most prescribers have with HCTZ. A head-to-head study looking at hard clinical outcomes, which may or may not ever be performed, may be the only way to resolve the ongoing debate as to which is the preferred thiazide for treating hypertension.