Diuretic Comparison Project (DCP) – Chlorthalidone Compared to Hydrochlorothiazide for the Prevention of Cardiovascular Events in Patients with Hypertension

Presented at the AHA Scientific Sessions 2022 by: Areef Ishani, MD- Minneapolis, MN, USA

Introduction and methods

Previous observational studies have suggested that use of chlorthalidone is associated with a reduction in CV events and the evidence for hydrochlorothiazide was not as strong. However, recent studies have suggested that there is no benefit to chlorthalidone and that it’s use results in a higher risk of adverse events including hypokalemia, acute kidney injury and chronic kidney disease.

A first large RCT was undertaken to compare chlorthalidone to hydrochlorothiazide. It was a pragmatic, open-label study. The electronic medical records were leveraged to consent providers as patients. Approximately 13.500 patients were randomized to continue hydrochlorothiazide 25 or 50 mg (n=6756) or switch to chlorthalidone 12.5 or 25 mg (n=6797). The investigators were passive observers. Patients were followed through the electronic medical records, as well as VA and Medicare claims and the National Death Index.

Included patients were veterans >65 years with hypertension. They had to be hydrochlorothiazide 25 or 50 mg a day and not on a combination drug with the most recent SBP >120 mmHg.

Primary endpoint was MACE, including stroke, MI, hospitalization for acute HF, urgent coronary revascularization, or non-cancer death. Median duration of follow-up was 2.4 years.

Main results

• Average age of the study population was 72 years, 97% was male (VA population), 15% was Afro-American, 45% lived in rural areas, 44% had a history of diabetes, 11% had a history of MI or stroke. 95% were on the low dose of hydrochlorothiazide at baseline, SBP was 139 mmHg.
• There was no difference in the primary outcome between the two groups (HR 1.04, 95%CI:0.94-1.16), nor in the individual components of the primary outcome.
• Patients in the chlorthalidone group had a slightly higher risk of lab-identified hypokalemic events (potassium <3.1 mEq/L) compared to the hydrochlorothiazide group.
• There was an interaction for the treatment effect in subgroups with or without history of MI or stroke (Pinteraction=0.035). In individuals with a history of MI or stroke, risk of the primary outcome was lower with chlorthalidone.
• There was no difference in SBP and potassium levels over time between the two groups. The percentage of patients who received potassium supplements was 11% at baseline, and went up in the chlorthalidone group and remained the same in the hydrochlorothiazide group.

Conclusion

Chlorthalidone did not reduce the incidence of major CV outcomes and non-cancer deaths compared to hydrochlorothiazide at doses commonly used in clinical practice. Subgroup analysis suggested a difference in the primary outcome in those with or without a history of MI or stroke. Furthermore, chlorthalidone was associated with a slight in increase in the risk of hypokalemia.

- Our reporting is based on the information provided at the AHA Scientific Sessions 2022 -