November 05, 2025

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Chlorthalidone More Effective In Reducing MACE Than HCTZ In Long Run: Study

Research Findings on HCTZ and CTD

Research Findings on HCTZ and CTD

Researchers from the NYU School of Medicine, New York City, New York, USA have recently observed that over the short-term there were no differences in the net clinical benefit between HCTZ and CTD in reducing major cardiovascular events.

The study is published in the Journal of Hypertension.

There is continuous debate whether chlorthalidone (CTD) and hydrochlorothiazide (HCTZ) differ in reducing major cardiovascular events (MACE). According to the literature, HCTZ is prescribed 10 times more commonly than CTD.

Hence, Roush, George C and associates conducted a systematic literature search that yielded 14 references, including two network meta-analyses of randomized trials with MACE and left ventricular mass as outcomes.

The results showed that:

  • 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, the authors described.

Therefore, it was concluded that "Over the short-term there were no differences in the net clinical benefit between HCTZ and CTD. However, long-term available data documents CTD to be significantly more effective in reducing MACE than HCTZ."

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