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Chlorthalidone versus hydrochlorothiazide: major cardiovascular events, blood pressure, left ventricular mass, and
George C Roush1, Franz H Messerli2,3,4
1NYU School of Medicine, New York City, New York, USA.
Insights
Chlorthalidone (CTD) significantly reduces major cardiovascular events (MACE) more than hydrochlorothiazide (HCTZ) in the long term. While short-term data show no difference, prolonged follow-up reveals CTD
Area of Science:
- Cardiology and Pharmacology
- Hypertension Management
- Clinical Trial Analysis
Background:
- Ongoing debate exists regarding the comparative efficacy of chlorthalidone (CTD) and hydrochlorothiazide (HCTZ) in reducing major adverse cardiovascular events (MACE).
- Hydrochlorothiazide (HCTZ) is prescribed significantly more frequently than chlorthalidone (CTD).
Purpose of the Study:
- To systematically evaluate and compare the effectiveness of CTD versus HCTZ in reducing MACE.
- To investigate the impact of study duration on the observed differences in cardiovascular outcomes between CTD and HCTZ.
Main Methods:
- Conducted a systematic literature search, identifying 14 relevant references.
- Included two network meta-analyses of randomized controlled trials and observational cohort studies focusing on MACE and left ventricular mass.
- Analyzed data considering the duration of follow-up in the included studies.
Main Results:
- Network meta-analysis of randomized trials indicated CTD reduces MACE more effectively than HCTZ (HR=0.79, P<0.0001).
- An observational study corroborated this finding (HR=0.79, P=0.002), while others showed no difference, likely due to shorter follow-up periods (<1 year).
- CTD demonstrated superior reduction in left ventricular mass, improved endothelial function, and greater reductions in night-time blood pressure, oxidative stress, and platelet aggregation compared to HCTZ.
Conclusions:
- Short-term clinical benefits of HCTZ and CTD are comparable.
- Long-term data strongly support CTD's superior efficacy in reducing MACE compared to HCTZ.
- An ongoing Veterans Administration trial is expected to provide definitive answers on this comparison.
Background:
There is continuous debate whether chlorthalidone (CTD) and hydrochlorothiazide (HCTZ) differ in reducing major cardiovascular events (MACE). HCTZ is prescribed 10 times more commonly than CTD.
Method:
A systematic literature search yielded 14 references, including two network meta-analyses of randomized trials with MACE and left ventricular mass as outcomes.
Results:
The network meta-analysis of randomized trials showed CTD reducing MACE more than HCTZ, hazard ratio = 0.79 (0.72-0.88), P < 0.0001, and an observational cohort study gave an identical point estimate: hazard ratio = 0.79 (0.68-0.92), P = 0.002. In contrast, two observational cohort studies reported no differences between CTD and HCTZ. However, in the studies showing the superiority of CTD median follow-up was 4.3 and 7.0 years, respectively, whereas in the latter studies showing no difference between the two drugs follow-up was only 0.95 and 0.25 years. As differences in outcomes for MACE in hypertension trials with various interventions only emerge after prolonged (>1 year) therapy, differences in follow-up explain these discrepant results. CTD also more effectively reduced left ventricular mass in observational data and network analysis of trials. These advantages of CTD over HCTZ are consistent with greater reductions in night-time blood pressure, greater reductions in oxidative stress and platelet aggregation, and greater improvements in endothelial function.
Conclusion:
Over the short-term there were no differences in the net clinical benefit between HCTZ and CTD. However, long-term available data document CTD to be significantly more effective in reducing MACE than HCTZ. The Veterans Administration's trial in progress may provide definitive answer to these questions.
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