Trial reportJournal of the American Heart Association2026
Per-Protocol Analysis of Chlorthalidone Versus Hydrochlorothiazide for Cardiovascular Event Prevention-Diuretic Comparison Project.
Trial report in Journal of the American Heart Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02185417 (CSP #597 - Diuretic Comparison Project), which is not on this map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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CSP #597 - Diuretic Comparison Project
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe DCP (Diuretic Comparison Project), a pragmatic trial, evaluated whether chlorthalidone compared with hydrochlorothiazide would reduce the risk of nonfatal cardiovascular disease or noncancer-related death. The intent-to-treat analysis found no difference in such comparison (hazard ratio, 1.04 [95% CI, 0.94-1.16]). The objective of the current study is to estimate the per-protocol effect of chlorthalidone (12.5/25 mg daily) compared with hydrochlorothiazide (25/50 mg daily) in preventing major adverse cardiovascular events among older patients with hypertension.
methodsThe effect of adhering to treatment strategies was assessed by censoring at first instance of nonadherence, defined as a gap (>90-day gap in drug coverage), switch (switching between study medications), and discontinuation (stop taking chlorthalidone/hydrochlorothiazide altogether for >90 days before the end of the study). The primary outcome was a composite of nonfatal myocardial infarction, stroke, heart failure resulting in hospitalization, urgent coronary revascularization for unstable angina, and noncancer-related death. Using inverse probability weighting, we evaluated the per-protocol effect of chlorthalidone and hydrochlorothiazide using DCP trial data.
resultsNonadherence was found in 5476 (40%) participants; among 8047 (60%) adherents, 3905 (49%) were randomized to chlorthalidone and 4142 (51%) to hydrochlorothiazide. After censoring time when participants deviated from the assigned treatments, the estimated 5-year risk ratio of the composite primary outcome of nonfatal cardiovascular disease and noncancer-related death was 1.36 (95% CI, 0.96-2.12) in chlorthalidone compared with hydrochlorothiazide.
conclusionsThe per-protocol analysis indicated a lower risk with hydrochlorothiazide compared with chlorthalidone in preventing nonfatal cardiovascular disease and noncancer-related death; however, this difference was not statistically significant using dispensation data to identify adherence. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02185417.
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