Abstract 2118: A Population-based Comparison of the Cardiovascular Protective Effects of Hydrochlorothiazide and Chlorthalidone
Background Clinical practice guidelines for the treatment of hypertension recommend a thiazide diuretic as initial therapy for the majority of patients. Most clinicians consider chlorthalidone (CHL) and hydrochlorothiazide (HCTZ), the two most commonly prescribed thiazides, to be interchangeable, despite evidence suggesting these drugs are not equivalent.
Methods We constructed a population-based retrospective cohort study by linking the health records of 1.4 million residents of Ontario, Canada aged 66 or older between July 1, 1993 and March 1, 2002. The index event for entry into the cohort was a new prescription for either HCTZ or CHL. The primary outcome was the time from the index event to a composite outcome of acute myocardial infarction (AMI), stroke, or all-cause mortality. Secondary analyses explored each outcome individually. Analysis was done using Cox proportional hazards regression with the HCTZ group as the reference.
Results During 218,360 person-years of follow-up in the HCTZ group, there were 10 025 events (death, AMI or stroke), compared to 113 events during 4,214 person-years of follow-up in the CHL group. The unadjusted hazard ratio for the primary outcome was 0.73 (95% confidence interval 0.61 to 0.88), suggesting a substantially lower risk of events during CHL therapy. After adjustment for differences in baseline demographic and clinical characteristics, there was no statistically significant difference between the groups for the primary outcome (adjusted hazard ratio 0.85; 95% confidence interval 0.71 to 1.03). The hazard ratios for each component of the primary composite outcome all trended in the direction of a lower risk of events in users of CHL.
Conclusion In a large cohort of older patients treated with thiazide diuretics, the use of CHL was not associated with a statistically significant reduction in the risk of AMI, stroke, or death. However, treatment effects favored CHL for every outcome, raising the hypothesis that CHL is superior to HCTZ. Further research is needed to confirm or refute this hypothesis.