Yan Vincent Ka Chun, Ju Chengsheng, MacDonald Thomas MacLennan, Mackenzie Isla S, Flynn Robert, Williams Bryan, Chen Yang, Chan Esther W, George Jacob, Wei Li
Research Department of Practice and Policy, University College London, London, UK.
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
BMJ Med. 2025 Feb 25;4(1):e000857. doi: 10.1136/bmjmed-2024-000857. eCollection 2025.
To investigate the prescribing trends of indapamide, a thiazide-like diuretic, and the long term comparative effectiveness of modified release versus immediate release indapamide.
Cohort study.
IQVIA Medical Research Data UK database, incorporating data from The Health Improvement Network database, 1 January 2005 to 31 December 2020.
Of 1 904 289 patients with hypertension, 86 388 started indapamide treatment during the study period. 30 021 patients received modified release and 56 367 immediate release indapamide.
Monthly prescribing trends of modified release and immediate release indapamide are described. A pragmatic trial was emulated to compare the five year risks of composite cardiovascular events (myocardial infarction and stroke) and death between modified release and immediate release indapamide. Intention-to-treat and per protocol effects of treatment were estimated with pooled logistic regression models. Confounding and selection bias were accounted for by multivariable adjustments and inverse probability weights.
1 38 414 patients who used indapamide were identified among 1 904 289 patients with hypertension. A greater increase was seen in the proportion of users of immediate release indapamide (from 0.43% in 2005 to 2.31% in 2020) than in users of modified release indapamide (from 0.71% to 0.79%). 86 388 patients (30 021 and 56 367 who started modified release and immediate release indapamide, respectively) were eligible for the trial emulation. In the intention-to-treat analysis, no difference was found in the risk of cardiovascular events (hazard ratio 0.99, 95% confidence interval (CI) 0.90 to 1.08) or death (hazard ratio 0.97, 0.92 to 1.02) between modified release and immediate release indapamide. In the per protocol analysis, a lower risk of cardiovascular events was found with modified release indapamide than with immediate release indapamide (risk difference -0.39%, 95% CI -0.71% to -0.06%; hazard ratio 0.81, 95% CI 0.68 to 0.98), which was mainly driven by myocardial infarction (risk difference -0.36%, 95% CI -0.64% to -0.08%; hazard ratio 0.80, 95% CI 0.64 to 1.01). Similar risks of death (hazard ratio 1.03, 95% CI 0.90 to 1.17) were found for the two formulations.
In patients treated with indapamide for hypertension, starting treatment with modified release or immediate release indapamide had similar risks for cardiovascular events or all cause mortality. In an exploratory secondary analysis, sustained treatment with modified release preparations was associated with a lower the risk of cardiovascular events but not all cause mortality compared with immediate release preparations. These findings need to be confirmed in prospective studies.
研究类噻嗪利尿剂吲达帕胺的处方趋势，以及缓释型与速释型吲达帕胺的长期比较疗效。
队列研究。
IQVIA英国医学研究数据库，纳入了来自健康改善网络数据库2005年1月1日至2020年12月31日的数据。
在1904289例高血压患者中，86388例在研究期间开始使用吲达帕胺治疗。30021例患者接受缓释型吲达帕胺，56367例接受速释型吲达帕胺。
描述缓释型和速释型吲达帕胺的月度处方趋势。模拟一项实用试验，比较缓释型和速释型吲达帕胺发生复合心血管事件（心肌梗死和中风）及死亡的五年风险。采用合并逻辑回归模型估计治疗的意向性分析和符合方案分析效应。通过多变量调整和逆概率加权来处理混杂因素和选择偏倚。
在1904289例高血压患者中，识别出138414例使用吲达帕胺的患者。速释型吲达帕胺使用者的比例增幅更大（从2005年的0.43%增至2020年的2.31%），高于缓释型吲达帕胺使用者（从0.71%增至0.79%）。86388例患者（分别为30021例和56367例开始使用缓释型和速释型吲达帕胺的患者）符合试验模拟条件。在意向性分析中，缓释型和速释型吲达帕胺在心血管事件风险（风险比0.99，95%置信区间（CI）0.90至1.08）或死亡风险（风险比0.97，0.92至1.02）方面未发现差异。在符合方案分析中，与速释型吲达帕胺相比，缓释型吲达帕胺的心血管事件风险更低（风险差-0.39%，95%CI-0.71%至-0.06%；风险比0.81，95%CI0.68至0.98），这主要由心肌梗死导致（风险差-0.36%，95%CI-0.64%至-0.08%；风险比0.80，95%CI0.64至1.01）。两种剂型的死亡风险相似（风险比1.03，95%CI0.90至1.17）。
在接受吲达帕胺治疗高血压的患者中，开始使用缓释型或速释型吲达帕胺治疗时，心血管事件或全因死亡率的风险相似。在一项探索性的二次分析中，与速释型制剂相比，持续使用缓释型制剂与较低的心血管事件风险相关，但与全因死亡率无关。这些发现需要在前瞻性研究中得到证实。
