Faculty of Pharmacy, School of Pharmaceutical Science, National Yang-Ming University, Taipei, 112, Taiwan.
Department of Medicine, College of Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan.
Br J Clin Pharmacol. 2018 May;84(5):1045-1056. doi: 10.1111/bcp.13537. Epub 2018 Mar 13.
Previous studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with higher cardiovascular risks. However, few have been active comparison studies that directly assessed the potential differential cardiovascular risk between NSAID classes or across individual NSAIDs. We compared the risk of major cardiovascular events between cyclooxygenase 2 (COX-2)-selective and nonselective NSAIDs in patients with hypertension.
We conducted a cohort study of patients with hypertension who initiated COX-2-selective or nonselective NSAIDs in a population-based Taiwanese database. The outcomes included hospitalization for the following major cardiovascular events: ischaemic stroke, acute myocardial infarction, congestive heart failure, transient ischaemic attack, unstable angina or coronary revascularization. We followed patients for up to 4 weeks, based on the as-treated principle. We used inverse probability weighting to control for baseline and time-varying covariates, and estimated the on-treatment hazard ratios (HRs) and 95% conservative confidence interval (CIs).
We identified 2749 eligible COX-2-selective NSAID users and 52 880 eligible nonselective NSAID users. The HR of major cardiovascular events comparing COX-2-selective with nonselective NSAIDs after adjusting for baseline and time-varying covariates was 1.07 (95% CI 0.65, 1.74). We did not observe a differential risk when comparing celecoxib to diclofenac (HR 1.17; 95% CI 0.61, 2.25), ibuprofen (HR 1.36; 95% CI 0.58, 3.18) or naproxen (HR 0.75; 95% CI 0.23, 2.44). There was an increased risk with COX-2-selective NSAIDs, however, when comparing COX-2-selective NSAIDs with mefenamic acid (HR 2.11; 95% CI 1.09, 4.09).
Our results provide important information about the comparative cardiovascular safety of NSAIDs in patients with hypertension.
先前的研究表明，非甾体抗炎药（NSAIDs）可能与更高的心血管风险相关。然而，很少有积极的对照研究直接评估 NSAID 类药物之间或个别 NSAIDs 之间潜在的心血管风险差异。我们比较了高血压患者中环氧化酶 2（COX-2）选择性和非选择性 NSAIDs 之间主要心血管事件的风险。
我们在一个基于人群的台湾数据库中进行了一项高血压患者 COX-2 选择性或非选择性 NSAIDs 起始治疗的队列研究。结局包括因以下主要心血管事件住院：缺血性卒中、急性心肌梗死、充血性心力衰竭、短暂性脑缺血发作、不稳定型心绞痛或冠状动脉血运重建。我们根据治疗原则对患者进行了长达 4 周的随访。我们使用逆概率加权法来控制基线和随时间变化的协变量，并估计治疗期间的危险比（HR）和 95%保守置信区间（CI）。
我们确定了 2749 名符合条件的 COX-2 选择性 NSAID 使用者和 52880 名符合条件的非选择性 NSAID 使用者。调整基线和随时间变化的协变量后，主要心血管事件比较 COX-2 选择性与非选择性 NSAIDs 的 HR 为 1.07（95%CI 0.65，1.74）。我们没有观察到塞来昔布与双氯芬酸（HR 1.17；95%CI 0.61，2.25）、布洛芬（HR 1.36；95%CI 0.58，3.18）或萘普生（HR 0.75；95%CI 0.23，2.44）之间的差异风险。然而，与甲芬那酸（HR 2.11；95%CI 1.09，4.09）相比，COX-2 选择性 NSAIDs 的风险增加。
我们的研究结果为高血压患者 NSAIDs 的比较心血管安全性提供了重要信息。
