Hydrochlorothiazide Versus Chlorthalidone in the Management of Hypertension

Abstract

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.

"Targeted" Consent for Pragmatic Clinical Trials

“…4 When prescribing either medication, the clinician standardly explains that treatment is likely to improve the patient's hypertension, and describes the most common side effects. She then asks whether the patient has any questions.…”

Hypertension in Children with Chronic Kidney Disease

“…Thiazide-like diuretics can be used when the GFR is more than 30-40 ml/min/1.73 m 2 but are not effective in children with a lower GFR. Due to a prolonged duration of action, chlorthalidone may provide improved BP control and cardiovascular risk reduction when compared to other thiazide-like diuretics [36,37]. In children with more advanced CKD, loop diuretics may be required.…”

Integrated control of hypertension by olmesartan medoxomil and hydrochlorothiazide and rationale for combination

“…The preference for HCTZ over chlorthalidone may also be due to concerns about hypokalemia with chlorthalidone;52 however, hypokalemia is a class-wide effect for diuretics 53. The Multiple Risk Factor Intervention Trial (MRFIT) was a randomized primary prevention trial in 12,866 high-risk men with hypertension that compared a special intervention (SI) program (stepped-care combination therapy, smoking cessation counseling, and dietary advice) with usual care (UC) available within the community 54.…”