二氯芬酸与其他 older COX-2 抑制剂（美洛昔康和依托度酸）和新型 COX-2 抑制剂（塞来昔布和依托考昔）的心血管风险：一系列全国模拟试验。

Cardiovascular Risks of Diclofenac Versus Other Older COX-2 Inhibitors (Meloxicam and Etodolac) and Newer COX-2 Inhibitors (Celecoxib and Etoricoxib): A Series of Nationwide Emulated Trials.

机构信息

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.

出版信息

Drug Saf. 2022 Sep;45(9):983-994. doi: 10.1007/s40264-022-01211-1. Epub 2022 Jul 31.

DOI:10.1007/s40264-022-01211-1

PMID:35909207

Abstract

INTRODUCTION

Diclofenac has increased cardiovascular risks, but its risk profile compared with other COX-2 inhibitors remains unknown.

AIMS

The aim of this study was to compare the cardiovascular risks of diclofenac versus other older and newer COX-2 inhibitors (coxibs).

METHODS

Using Danish nationwide health registries (1999-2020), we conducted a series of emulated trials (n = 264). Eligible adults had no recent NSAID prescriptions, contraindications or conditions with low adherence. We included initiators of diclofenac (n = 1,600,202), meloxicam (n = 10,903), etodolac (n = 238,538), celecoxib (n = 77,591), and etoricoxib (n = 12,122). We computed the adjusted intention-to-treat incidence rate ratio (aIRR) with 95% confidence interval (CI) of major adverse cardiovascular events (MACE) within 30 days of initiation (5562 events).

RESULTS

MACE was 20% increased among initiators of diclofenac compared with other older COX-2 inhibitors (aIRR 1.19, 95% CI 1.10-1.28), driven by cardiac death (aIRR 1.57, 95% CI 1.21-2.03). The effect appeared strongest for women (aIRR 1.28, 95% CI 1.15-1.43), individuals with high baseline cardiovascular risk (aIRR 1.32, 95% CI 1.05-1.66), and when comparing high-dose diclofenac with low doses of the other older COX-2 inhibitors (aIRR 1.31, 95% CI 1.13-1.52). The results reflected increased rates compared with both meloxicam (aIRR 1.46, 95% CI 0.94-2.26) and etodolac (aIRR 1.18, 95% CI 1.09-1.28). Diclofenac initiators had similar increased rates of MACE compared with coxibs (aIRR 0.96, 95% CI 0.85-1.08), consistent for celecoxib (aIRR 1.02, 95% CI 0.88-1.19) and etoricoxib (aIRR 0.85, 95% CI 0.66-1.10).

CONCLUSIONS

The increased cardiovascular risks associated with diclofenac initiation were higher than for other older COX-2 inhibitors (meloxicam/etodolac) and comparable to coxibs (celecoxib/etoricoxib).

摘要

简介

双氯芬酸增加了心血管风险，但与其他 COX-2 抑制剂（昔布类药物）的风险状况仍不清楚。

目的

本研究旨在比较双氯芬酸与其他较老和较新的 COX-2 抑制剂（昔布类药物）的心血管风险。

方法

使用丹麦全国健康登记处（1999-2020 年），我们进行了一系列模拟试验（n=264）。合格的成年人最近没有服用 NSAID 药物、没有禁忌证或没有低依从性的疾病。我们纳入了双氯芬酸（n=1,600,202）、美洛昔康（n=10,903）、依托度酸（n=238,538）、塞来昔布（n=77,591）和依托考昔（n=12,122）的起始者。我们计算了主要不良心血管事件（MACE）的校正意向治疗发生率比（aIRR），30 天内的风险（5562 例事件）。

结果

与其他较老的 COX-2 抑制剂相比，双氯芬酸的起始者发生 MACE 的风险增加了 20%（aIRR 1.19，95%CI 1.10-1.28），这主要归因于心脏死亡（aIRR 1.57，95%CI 1.21-2.03）。对于女性（aIRR 1.28，95%CI 1.15-1.43）、基线心血管风险较高的个体（aIRR 1.32，95%CI 1.05-1.66）和与其他较老的 COX-2 抑制剂的低剂量相比，高剂量双氯芬酸（aIRR 1.31，95%CI 1.13-1.52），这种影响最为明显。与美洛昔康（aIRR 1.46，95%CI 0.94-2.26）和依托度酸（aIRR 1.18，95%CI 1.09-1.28）相比，这些结果反映了更高的发生率。双氯芬酸的起始者与昔布类药物（coxibs）相比，发生 MACE 的风险相似（aIRR 0.96，95%CI 0.85-1.08），塞来昔布（aIRR 1.02，95%CI 0.88-1.19）和依托考昔（aIRR 0.85，95%CI 0.66-1.10）也一致。