Cardioprotective Effect of Thiazide-Like Diuretics: A Meta-Analysis

Background and purpose: Thiazide diuretics (TD), including thiazide-type (chlorothiazide and hydrochlorothiazide) and thiazide-like diuretics (indapamide and chlorthalidone), have been used for the treatment of hypertension for more than 5 decades. This meta-analysis aimed to evaluate whether TD, including thiazide-type and thiazide-like diuretics have additional cardioprotective effects.

Experimental approach: We performed a pooled study of 19 randomized clinical trials (RCTs). PubMed and EMBASE databases were searched for RCTs assessing TD treatment in patients with hypertension.

Key results: Nineteen RCTs involving 112,113 patients (56,802 in TD; 55,311 in control) were included. The incidence ratio of cardiac events (CVs) was 34.3 vs. 37.8 per 1,000 patient-years in patients randomized to TD and controls, respectively. TD treatment was associated with reductions in the risks of CVs (odds ratio (OR): 0.86, P = 0.007) and heart failure (OR: 0.62, P < 0.001), but not different in stroke (OR: 0.92, P = 0.438) or CHD (OR: 0.95, P = 0.378) between diuretics and controls. Further analysis showed that the observed benefits were mainly confined to thiazide-like diuretic therapy rather than thiazide-type diuretics with a significant reduction in the risk of CVs (OR: 0.78, P < 0.001), heart failure (OR: 0.57, P < 0.001) and stroke (OR: 0.82, P = 0.016).

Conclusions and implications: This study suggests that use of TD in hypertensive patients results in a reduction in the risk of CVs. Moreover, thiazide-like diuretics have greater protective effect against CVs than thiazide-type diuretics, especially on heart failure, suggesting that preferential use of thiazide-like diuretics over thiazide-type diuretics may result in greater cardiovascular benefits in hypertensive patients.