Diuretic Comparison Project - DCP

Contribution To Literature:

Highlighted text has been updated as of December 19, 2022.

The DCP trial showed that there are no differences in cardiovascular outcomes between chlorthalidone and HCTZ among elderly veterans with hypertension.


The goal of the trial was to evaluate the safety and efficacy of hydrochlorothiazide (HCTZ) compared with chlorthalidone in improving cardiovascular outcomes among patients with hypertension.

Study Design

Patients who were already taking HCTZ were randomized in an open-label 1:1 fashion to either chlorthalidone (n = 6,756) or continuing on HCTZ (n = 6,767). Patients on HCTZ 25 mg were converted to 12.5 mg chlorthalidone, and 50 mg HCTZ to 25 mg chlorthalidone.

  • Total screened: 16,595
  • Total randomized: 13,523
  • Duration of follow-up: median 2.4 years
  • Mean patient age: 72 years
  • Percentage female: 3%
  • African American: 15%

Inclusion criteria:

  • Over the age of 65 years (half outcomes from Medicare)
  • On HCTZ 25 or 50 mg/d from Veterans Affairs (VA) (not on combination drug)
  • Most recent systolic blood pressure (in electronic medical record) ≥120 mm Hg

Other salient features/characteristics:

  • Mean body mass index: 32 kg/m2
  • Diabetes: 44%
  • Myocardial infarction (MI): 8%
  • MI or stroke: 11%
  • HCTZ monotherapy at baseline: 13%
  • HCTZ + one additional antihypertensive: 34%

Principal Findings:

The primary outcome, major adverse cardiovascular events (MACE), for chlorthalidone vs. HCTZ: 10.4% vs. 10.0%; hazard ratio (HR) 1.04, 95% confidence interval (CI) 0.94-1.16 (p = 0.45).

  • For patients with prior MI or stroke: HR 0.73, 95% CI 0.57-0.94 (p for interaction = 0.035)

Secondary outcomes for chlorthalidone vs. HCTZ:

  • First hospitalization for MI: 2.1% vs. 2.1%; HR 1.02, 95% CI 0.80-1.28 (p = 0.91)
  • First hospitalization for stroke: 1.2% vs. 1.2%; HR 1.0, 95% CI 0.74-1.36 (p = 1.0)
  • First hospitalization for heart failure: 3.6% vs. 3.4%; HR 1.04, 95% CI 0.87-1.25 (p = 0.4)
  • Hypokalemia: 6.0% vs. 4.4% (p < 0.001)


The results of this trial show that there are no differences in cardiovascular outcomes between chlorthalidone and HCTZ among elderly veterans with hypertension. Among patients with prior MI or stroke, a benefit was observed. This is a hypothesis-generating finding and has to be viewed in the context of an overall negative trial. Hypokalemia was more common with chlorthalidone.

Although seeking to address a clinically relevant question in a pragmatic fashion, this trial had several design limitations, including open-label design, lower doses of both chlorthalidone and HCTZ than typically associated with cardiovascular benefit, and ascertainment of outcomes using VA and Medicare claims data. Very few patients were on HCTZ monotherapy at baseline (prior to randomization). Trial results could be affected by concomitant medications/doses (and compliance with these drugs) as well.


Ishani A, Cushman WC, Leatherman SM, et al., on behalf of the Diuretic Comparison Project Writing Group. Chlorthalidone vs. Hydrochlorothiazide for Hypertension–Cardiovascular Events. N Engl J Med 2022;387:2401-10.

Editorial: Ingelfinger JR. Thiazide-Like Versus Thiazide Diuretics — Finally, an Answer? N Engl J Med 2022;387:2462-3.

Presented by Dr. Areef Ishani at the American Heart Association Scientific Sessions, Chicago, IL, November 5, 2022.

Clinical Topics: Diabetes and Cardiometabolic Disease, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Statins, Acute Heart Failure, Hypertension

Keywords: AHA Annual Scientific Sessions, AHA22, Blood Pressure, Chlorthalidone, Diuretics, Geriatrics, Heart Failure, Hydrochlorothiazide, Hypertension, Hypokalemia, Medicare, Metabolic Syndrome, Myocardial Infarction, Secondary Prevention, Stroke, Vascular Diseases, Veterans

< Back to Listings