NYU School of Medicine, New York City, New York, USA.
Swiss Cardiovascular Center, Bern, Switzerland.
J Hypertens. 2021 Jun 1;39(6):1254-1260. doi: 10.1097/HJH.0000000000002771.
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.
A systematic literature search yielded 14 references, including two network meta-analyses of randomized trials with MACE and left ventricular mass as outcomes.
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.
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.
氯噻酮（CTD）和氢氯噻嗪（HCTZ）在降低主要心血管事件（MACE）方面是否存在差异一直存在争议。HCTZ 的处方量是 CTD 的 10 倍。
系统文献检索产生了 14 篇参考文献，包括两项以 MACE 和左心室质量为结局的随机试验的网络荟萃分析。
随机试验的网络荟萃分析表明，CTD 降低 MACE 的效果优于 HCTZ，风险比为 0.79（0.72-0.88），P<0.0001，一项观察性队列研究给出了相同的点估计：风险比为 0.79（0.68-0.92），P=0.002。相比之下，两项观察性队列研究报告 CTD 和 HCTZ 之间没有差异。然而，在显示 CTD 优越性的研究中，中位随访时间分别为 4.3 年和 7.0 年，而在显示两种药物之间无差异的研究中，随访时间仅为 0.95 年和 0.25 年。由于不同干预措施的高血压试验中 MACE 的结果差异仅在长期（>1 年）治疗后才出现，因此随访时间的差异解释了这些不一致的结果。在观察数据和试验网络分析中，CTD 还能更有效地降低左心室质量。CTD 优于 HCTZ 的这些优势与夜间血压降低幅度更大、氧化应激和血小板聚集降低幅度更大、内皮功能改善幅度更大相一致。
在短期治疗中，HCTZ 和 CTD 的净临床获益没有差异。然而，长期可用的数据表明，CTD 降低 MACE 的效果明显优于 HCTZ。正在进行的退伍军人管理局试验可能会对这些问题提供明确的答案。
