斯堪的纳维亚电子医疗保健登记册提供了一个独特的环境来调查潜在的未识别的药物副作用。我们分析了在挪威和瑞典分配的处方药与发生肺栓塞的短期风险之间的关联。在挪威(2004-2014年)和瑞典(2005-2014年)的36,088例患者和死因登记处共发现12,104例肺栓塞病例。病例交叉设计用于比较肺栓塞诊断日期前1-30天分配的单个药物与61-90天时间窗口中的分配。同时控制其他药物的接收。BOLASSO方法用于选择与肺栓塞短期风险相关的药物。在对挪威和瑞典数据的综合分析中,有38种药物与肺栓塞有关。与肺栓塞风险增加相关的药物包括某些质子泵抑制剂,抗生素,抗血栓药,血管扩张剂,呋塞米,抗静脉曲张药物,皮质类固醇,免疫刺激剂(pegfilgrastim),阿片类药物,镇痛药,抗焦虑药,抗抑郁药,抗原生动物,以及治疗咳嗽和感冒的药物.矿物质补充剂,氢氯噻嗪和钾保护剂,β受体阻滞剂,血管紧张素2受体阻滞剂,他汀类药物,甲氨蝶呤与较低的风险相关。大多数协会坚持,还有一些其他的药物,当使用90天而不是30天的较长时间窗时,患有肺栓塞。这些结果提供了探索性,药典范围内的药物可能增加或降低肺栓塞风险的证据.其中一些发现是基于药物适应症的预期结果,而其他人则是新颖的,需要进一步研究作为肺栓塞的潜在可改变的沉淀剂。
Scandinavian electronic health-care registers provide a unique setting to investigate potential unidentified side effects of
drugs. We analysed the association between prescription
drugs dispensed in Norway and Sweden and the short-term risk of developing pulmonary embolism. A total of 12,104 pulmonary embolism cases were identified from patient- and cause-of-death registries in Norway (2004-2014) and 36,088 in Sweden (2005-2014). A case-crossover design was used to compare individual drugs dispensed 1-30 days before the date of pulmonary embolism diagnosis with dispensation in a 61-90 day time-window, while controlling for the receipt of other
drugs. A BOLASSO approach was used to select drugs that were associated with short-term risk of pulmonary embolism. Thirty-eight
drugs were associated with pulmonary embolism in the combined analysis of the Norwegian and Swedish data. Drugs associated with increased risk of pulmonary embolism included certain proton-pump inhibitors, antibiotics, antithrombotics, vasodilators, furosemide, anti-varicose medications, corticosteroids, immunostimulants (pegfilgrastim), opioids, analgesics, anxiolytics, antidepressants, antiprotozoals, and drugs for cough and colds. Mineral supplements, hydrochlorothiazide and potassium-sparing agents, beta-blockers, angiotensin 2 receptor blockers, statins, and methotrexate were associated with lower risk. Most associations persisted, and several additional
drugs were associated, with pulmonary embolism when using a longer time window of 90 days instead of 30 days. These results provide exploratory, pharmacopeia-wide evidence of medications that may increase or decrease the risk of pulmonary embolism. Some of these findings were expected based on the drugs\' indications, while others are novel and require further study as potentially modifiable precipitants of pulmonary embolism.