Background

Both antidepressants and non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to affect platelet aggregation, blood pressure and heart rate. Despite the high prevalence of the combined use of antidepressants and NSAIDs, there is limited evidence on the potential risk of major adverse cardiovascular events (MACE) associated with their use.

Objective

The objective of this study was to assess the association between concomitant antidepressant and NSAID use and MACE.

Methods

We conducted a retrospective cohort study using South Korea’s nationwide healthcare database. The study cohort was defined as those with new prescriptions for antidepressants and NSAIDs between 2004 and 2015. Exposure was assessed as time varying into four discrete periods: non-use, antidepressant use, NSAID use and concomitant use. Our primary outcome was MACE, a composite of haemorrhagic and thromboembolic events; secondary outcomes were the individual events of MACE. A multivariable Cox proportional hazards model was used to estimate hazards ratios with 95% confidence intervals. We also performed subgroup analyses by class of antidepressant/type of NSAIDs, age and sex.

Results

From 240,982 patients, 235,080, 4393 and 1509 patients were users of NSAIDs, antidepressants or both drugs at cohort entry, respectively. The cohort generated 2.1 million person-years of follow-up with 22,453 events of MACE (incidence rate 1.07 per 100 person-years). Compared with non-use, concomitant use (hazard ratio 1.13, 95% confidence interval 1.01–1.26) and NSAID-only use (1.05, 1.001–1.10) were positively associated with MACE, while antidepressant-only use showed a negative association (0.91, 0.83–0.99). Concomitant use increased the individual risk of haemorrhagic stroke (1.46, 1.06–2.00), ischaemic stroke (1.22, 1.07–1.38) and heart failure (1.19, 1.02–1.38), but showed a protective effect on cardiovascular deaths (0.36, 0.21–0.62). Of the six possible combinations of antidepressants and NSAIDs by their classes, only concomitant use of tricyclic antidepressants and non-selective NSAIDs was positively associated with MACE (1.26, 1.09–1.47). The risk of MACE remained elevated with concomitant use among those aged ≥ 45 years (1.14, 1.01–1.29) and male patients (1.19, 1.01–1.42).

Conclusions

Concomitant use of antidepressants and NSAIDs moderately elevated the risk of MACE, of which the observed risk appears to be driven by the concomitant use of tricyclic antidepressants and non-selective NSAIDs. Thus, healthcare providers should take precaution when co-prescribing these drugs, weighing the potential benefits and risks associated with their use.

中文翻译：

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与同时使用抗抑郁药和非甾体抗炎药相关的主要不良心血管事件的风险：一项回顾性队列研究。

背景

据报道，抗抑郁药和非甾体抗炎药 (NSAID) 都会影响血小板聚集、血压和心率。尽管抗抑郁药和非甾体抗炎药联合使用的流行率很高，但关于与它们的使用相关的主要不良心血管事件 (MACE) 的潜在风险的证据有限。

客观的

本研究的目的是评估伴随抗抑郁药和 NSAID 使用与 MACE 之间的关联。

方法

我们使用韩国的全国医疗保健数据库进行了一项回顾性队列研究。研究队列被定义为在 2004 年至 2015 年间开具抗抑郁药和非甾体抗炎药新处方的人群。暴露评估为随时间变化的四个独立时期：未使用、抗抑郁药使用、非甾体抗炎药使用和伴随使用。我们的主要结果是 MACE，出血和血栓栓塞事件的复合；次要结果是 MACE 的个别事件。使用多变量 Cox 比例风险模型来估计具有 95% 置信区间的风险比。我们还按抗抑郁药类别/非甾体抗炎药类型、年龄和性别进行了亚组分析。

结果

在 240,982 名患者中，分别有 235,080、4393 和 1509 名患者在进入队列时使用了 NSAID、抗抑郁药或这两种药物。该队列产生了 210 万人年的随访，发生了 22,453 起 MACE 事件（发生率为 1.07/100 人年）。与不使用相比，伴随使用（风险比 1.13，95% 置信区间 1.01-1.26）和仅使用 NSAID（1.05，1.001-1.10）与 MACE 呈正相关，而仅使用抗抑郁药显示负相关（0.91 , 0.83–0.99)。同时使用会增加出血性中风 (1.46, 1.06-2.00)、缺血性中风 (1.22, 1.07-1.38) 和心力衰竭 (1.19, 1.02-1.38) 的个体风险，但对心血管死亡有保护作用 (0.36, 0.21-) 0.62）。在抗抑郁药和 NSAID 的六种可能组合中，按类别分类，只有同时使用三环类抗抑郁药和非选择性 NSAIDs 与 MACE 呈正相关 (1.26, 1.09–1.47)。在年龄≥ 45 岁的患者 (1.14, 1.01–1.29) 和男性患者 (1.19, 1.01–1.42) 中，同时使用 MACE 的风险仍然升高。

结论

同时使用抗抑郁药和 NSAIDs 会适度增加 MACE 的风险，观察到的风险似乎是由同时使用三环类抗抑郁药和非选择性 NSAIDs 驱动的。因此，医疗保健提供者在共同开具这些药物时应采取预防措施，权衡与其使用相关的潜在益处和风险。