- Chlorthalidone did not show significant cardiovascular (CV) benefits compared with hydrochlorothiazide but was associated with a greater risk for renal and electrolyte abnormalities.
Why this matters
- Findings do not support current recommendations to prefer chlorthalidone over hydrochlorothiazide for hypertension treatment in first-time users.
- A retrospective, observational, comparative cohort study of 730,225 patients with hypertension who were prescribed chlorthalidone (n=36,918) or hydrochlorothiazide (n=693,337).
- Primary outcome: hospitalisation for acute myocardial infarction (MI), heart failure (HF), ischaemic or haemorrhagic stroke, and a composite CV outcome (MI, HF, ischaemic or haemorrhagic stroke and sudden cardiac death).
- Funding: None disclosed.
- No significant difference was observed between chlorthalidone and hydrochlorothiazide in the risk for:
- hospitalisation for MI (HR, 0.92; 95% CI, 0.64-1.31), HF (HR, 1.05; 95% CI, 0.82-1.34) or stroke (HR, 1.10; 95% CI, 0.86-1.41); and
- composite CV outcome (HR, 1.00; 95% CI, 0.85-1.17).
- Chlorthalidone was associated with a significantly higher risk for:
- hypokalemia (HR, 2.72; 95% CI, 2.38-3.12);
- hyponatremia (HR, 1.31; 95% CI, 1.16-1.47);
- acute renal failure (HR, 1.37; 95% CI, 1.15-1.63);
- chronic kidney disease (HR, 1.24; 95% CI, 1.09-1.42); and
- type 2 diabetes mellitus (HR, 1.21; 95% CI, 1.12-1.30).
- Chlorthalidone was associated with a significant reduction in the risk for diagnosed abnormal weight gain (HR, 0.73; 95% CI, 0.61-0.86).
- Retrospective design.
- Risk of residual confounding.