Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data
Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data
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DOI：
10.1016/s0140-6736(09)61751-7
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发表时间：
2009-12-12
期刊：
影响因子：
168.9
通讯作者：
Gislason, Gunnar H.
中科院分区：
文献类型：
--
作者：
Sorensen, Rikke;Hansen, Morten L.;Gislason, Gunnar H.
背景：阿司匹林、氯吡格雷和维生素K拮抗剂的联合应用广泛应用于心肌梗死患者。然而，关于联合用药安全性的数据很少。我们研究了不同的抗血栓治疗方案相关的出血入院的风险。方法通过使用来自丹麦的全国登记册，我们确定了40 812例年龄在30岁或以上的患者，他们在2000年至2005年之间首次入院治疗心肌梗死。从出院时开始，使用声称的处方来确定根据以下组开出的治疗方案：阿司匹林、氯吡格雷或维生素K拮抗剂单药治疗;阿司匹林加氯吡格雷、阿司匹林加维生素K拮抗剂或氯吡格雷加维生素K拮抗剂的双重治疗;或包括所有三种药物的三联疗法。入院出血，复发性心肌梗死和死亡的风险进行了评估，考克斯比例风险模型与药物暴露组作为随时间变化的covariates.Findings在平均随访476.5天（SD 142.0），1891（4.6%）例患者入院出血。阿司匹林组的年出血发生率为2.6%，氯吡格雷组为4.6%，维生素K拮抗剂组为4.3%，阿司匹林+氯吡格雷组为3.7%，阿司匹林+维生素K拮抗剂组为5.1%，氯吡格雷+维生素K拮抗剂组为12.3%，三联治疗组为12.0%。以阿司匹林为参照，出血的校正风险比为1.33（95% CI 1.11-1.59）氯吡格雷，1.23维生素K拮抗剂为0.94-1.61，（1.28-1.69）阿司匹林+氯吡格雷，1.84阿司匹林+维生素K拮抗剂组（1.51-2.23），氯吡格雷+维生素K拮抗剂组（3.52 ~ 5.11），三联疗法组（4.05 ~ 5.33）。阿司匹林+氯吡格雷、阿司匹林+维生素K拮抗剂、氯吡格雷+维生素K拮抗剂和三联疗法的需要伤害的人数分别为81.2、45.4、15.2和12.5。在研究期间，1852例非致死性出血患者中有702例（37.9%）复发心肌梗死或死亡，而38960例非致死性出血患者中有7178例（18.4%）复发心肌梗死或死亡（HR 3.00，2.75-3.27，p
Background Combinations of aspirin, clopidogrel, and vitamin K antagonists are widely used in patients after myocardial infarction. However, data for the safety of combinations are sparse. We examined the risk of hospital admission for bleeding associated with different antithrombotic regimens.Methods By use of nationwide registers from Denmark, we identified 40 812 patients aged 30 years or older who had been admitted to hospital with first-time myocardial infarction between 2000 and 2005. Claimed prescriptions starting at hospital discharge were used to determine the regimen prescribed according to the following groups: monotherapy with aspirin, clopidogrel, or vitamin K antagonist; dual therapy with aspirin plus clopidogrel, aspirin plus vitamin K antagonist, or clopidogrel plus vitamin K antagonist; or triple therapy including all three drugs. Risk of hospital admission for bleeding, recurrent myocardial infarction, and death were assessed by Cox proportional hazards models with the drug exposure groups as time-varying covariates.Findings During a mean follow-up of 476.5 days (SD 142.0), 1891 (4.6%) patients were admitted to hospital with bleeding. The yearly incidence of bleeding was 2.6% for the aspirin group, 4.6% for clopidogrel, 4.3% for vitamin K antagonist, 3.7% for aspirin plus clopidogrel, 5.1% for aspirin plus vitamin K antagonist, 12.3% for clopidogrel plus vitamin K antagonist, and 12.0% for triple therapy. With aspirin as reference, adjusted hazard ratios for bleeding were 1.33 (95% CI 1.11-1.59) for clopidogrel, 1.23 (0.94-1.61) for vitamin K antagonist, 1.47 (1.28-1.69) for aspirin plus clopidogrel, 1.84 (1.51-2.23) for aspirin plus vitamin K antagonist, 3.52 (2.42-5.11) for clopidogrel plus vitamin K antagonist, and 4.05 (3.08-5.33) for triple therapy. Numbers needed to harm were 81.2 for aspirin plus clopidogrel, 45.4 for aspirin plus vitamin K antagonist, 15.2 for clopidogrel plus vitamin K antagonist, and 12.5 for triple therapy. 702 (37.9%) of 1852 patients with non-fatal bleeding had recurrent myocardial infarction or died during the study period compared with 7178 (18.4%) of 38 960 patients without non-fatal bleeding, (HR 3.00, 2.75-3.27, p