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Chlorthalidone vs Hydrochlorothiazide for Hypertension-CV Events: Did the Design Influence the Outcome?
Anil Pareek1, Franz H Messerli2, C Venkata S Ram3
1President, Department of Medical Affairs and Clinical Research, IPCA Laboratories, Mumbai, Maharashtra, India, Corresponding Author.
Insights
Chlorthalidone (CTD) showed a reduced risk of cardiovascular events compared to Hydrochlorothiazide (HCTZ) in high-risk elderly hypertensive patients. However, the real-world study design had limitations affecting outcome interpretation.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Elderly hypertensive patients often use Hydrochlorothiazide (HCTZ).
- Chlorthalidone (CTD) is an alternative diuretic for hypertension management.
- Real-world studies offer pragmatic insights but have design limitations.
Purpose of the Study:
- To pragmatically evaluate if Chlorthalidone (CTD) reduces cardiovascular disease (CVD) risk versus Hydrochlorothiazide (HCTZ).
- To assess outcomes in elderly hypertensive patients (≥65 years) on baseline HCTZ therapy.
Main Methods:
- A real-world study comparing CTD and HCTZ in elderly hypertensive patients.
- Participants were on 25 or 50 mg HCTZ at baseline.
- Analysis considered patient risk stratification (history of MI/Stroke).
Main Results:
- In high-risk patients (history of MI/Stroke), CTD showed a lower risk of the primary CVD outcome compared to HCTZ.
- No significant difference in outcomes was observed between CTD and HCTZ in low-risk populations.
- Study limitations included unequal diuretic exposure and lack of established dose equivalency.
Conclusions:
- CTD may offer a cardiovascular benefit over HCTZ in high-risk elderly hypertensive individuals.
- Real-world study design limitations, such as unequal exposure, may influence observed outcomes.
- Further research with robust trial designs is needed to confirm diuretic efficacy in hypertension.
Abstract:
The Diuretic Comparison Project (DCP)1 was a real world study planned to evaluate in a pragmatic manner whether Chlorthalidone (CTD), as compared with Hydrochlorothiazide (HCTZ), would reduce the risk of major nonfatal cardiovascular disease outcomes in elderly hypertensive participants (≥65 years) who were receiving HCTZ (25 or 50 mg) at baseline. This study being a real world study lacks the robustness of a randomized controlled trial. The principle limitation being unequal exposure of the two diuretics, prolonged unknown duration of exposure to HCTZ vs a short exposure to CTD (Median 2.4 years). In the high risk population with history of MI/Stroke, CTD conferred a lower risk of primary outcome as compared to low risk population where no significant difference in outcome was seen in both diuretics. Other factors included, lack of established dose equivalency of the two diuretics and absence of use of 12.5 mg HCTZ in older hypertensives. How to cite this article: Pareek A, Messerli FH, Ram CVS. Chlorthalidone vs Hydrochlorothiazide for Hypertension-CV Events: Did the Design Influence the Outcome? J Assoc Physicians India 2023;71(10):93-93.
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