Department of Medical Informatics, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Department of Medical Informatics, Erasmus Medical Center, Rotterdam, the Netherlands; Dutch Medicines Evaluation Board, Utrecht, the Netherlands.
Am J Med. 2014 Aug;127(8):763-71. doi: 10.1016/j.amjmed.2014.04.014. Epub 2014 May 5.
Chlorthalidone and hydrochlorothiazide are often considered as interchangeable. However, greater (nighttime) blood pressure reduction, and alleged pleiotropic effects have renewed the interest in chlorthalidone. A recent study showed an increased risk of adverse events with chlorthalidone, including hyponatremia.
To investigate differences in risk of hyponatremia between chlorthalidone and hydrochlorothiazide, adjusted for daily dose, we conducted a population-based case-control study within the Dutch IPCI (Integrated Primary Care Information) database. The study population included all subjects ≥18 years without diabetes mellitus, heart failure, liver failure, and malignancy, who were registered in the IPCI database from 1996 to 2011. Cases were subjects with a serum sodium <130 millimoles per liter or hospitalization due to hyponatremia. Controls were matched on practice, age within 5 years, sex, and date of onset.
A total of 1033 cases of hyponatremia were identified. Hyponatremia was more common with chlorthalidone than with hydrochlorothiazide at equal dose per day: adjusted odds ratio was 2.09 (95% confidence interval [CI], 1.13-3.88) for 12.5 milligrams per day and 1.72 (95% CI, 1.15-2.57) for 25 milligrams per day. Risks were not significantly increased with chlorthalidone compared with twice the dose per day of hydrochlorothiazide.
This is the first study that shows an increased risk of hyponatremia with chlorthalidone relative to hydrochlorothiazide at equal milligram-to-milligram dose per day. The need for a lower dose of chlorthalidone than hydrochlorothiazide to achieve similar blood pressure reduction likely compensates for the increased risk of hyponatremia at equal dose.
氯噻酮和氢氯噻嗪通常被认为是可互换的。然而，更大的（夜间）血压降低和所谓的多效作用重新引起了人们对氯噻酮的兴趣。最近的一项研究表明，氯噻酮的不良事件风险增加，包括低钠血症。
为了研究氯噻酮和氢氯噻嗪之间发生低钠血症的风险差异，我们在荷兰 IPCI（综合初级保健信息）数据库中进行了一项基于人群的病例对照研究。该研究人群包括所有年龄在 18 岁以上、无糖尿病、心力衰竭、肝功能衰竭和恶性肿瘤的患者，他们在 1996 年至 2011 年期间在 IPCI 数据库中登记。病例为血清钠 <130 毫摩尔/升或因低钠血症住院的患者。对照组按照实践、5 年内年龄、性别和发病日期进行匹配。
共确定了 1033 例低钠血症病例。与氢氯噻嗪相比，氯噻酮在每天相等剂量时更常见低钠血症：每天 12.5 毫克时调整后的优势比为 2.09（95%置信区间[CI]，1.13-3.88），每天 25 毫克时调整后的优势比为 1.72（95% CI，1.15-2.57）。与每天氯噻酮剂量增加一倍相比，氯噻酮的风险并未显著增加。
这是第一项表明在每天毫克到毫克剂量相等的情况下，氯噻酮与氢氯噻嗪相比发生低钠血症的风险增加的研究。氯噻酮需要的剂量低于氢氯噻嗪以达到相似的血压降低，这可能弥补了在相等剂量下低钠血症风险增加的问题。
