Hypertension: efficacy and safety of chlorthalidone vs hydrochlorothiazide

  • Hripcsak G & al.
  • JAMA Intern Med
  • 17 Feb 2020

  • curated by Sarfaroj Khan
  • UK Clinical Digest
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Takeaway

  • 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.

Study design

  • 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.

Key results

  • 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).

Limitations

  • Retrospective design.
  • Risk of residual confounding.