丹麦接受不同组合的阿司匹林、氯吡格雷和维生素 K 拮抗剂治疗的急性心肌梗死患者的出血风险：全国登记数据的回顾性分析。

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.

机构信息

Department of Cardiology, Copenhagen University Hospital Gentofte, Hellerup, Denmark.

出版信息

Lancet. 2009 Dec 12;374(9706):1967-74. doi: 10.1016/S0140-6736(09)61751-7.

DOI:10.1016/S0140-6736(09)61751-7

PMID:20006130

Abstract

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<0.0001).

INTERPRETATION

In patients with myocardial infarction, risk of hospital admission for bleeding increased with the number of antithrombotic drugs used. Treatment with triple therapy or dual therapy with clopidogrel plus vitamin K antagonist should be prescribed only after thorough individual risk assessment.

FUNDING

Danish Heart Foundation and the Danish Medical Research Council.

摘要

背景

阿司匹林、氯吡格雷和维生素 K 拮抗剂的联合用药广泛用于心肌梗死后的患者。然而，关于这些联合用药安全性的数据很少。我们研究了不同抗血栓治疗方案与出血相关的住院风险。

方法

利用丹麦全国登记处的数据，我们确定了 40812 名年龄在 30 岁或以上的患者，他们在 2000 年至 2005 年期间因首次心肌梗死住院。根据以下分组确定出院时开具的处方方案：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 拮抗剂双联治疗；或包括所有三种药物的三联治疗。采用 Cox 比例风险模型评估出血、复发性心肌梗死和死亡的住院风险，药物暴露组作为时变协变量。

结果

在平均 476.5 天（SD 142.0）的随访期间，1891 名（4.6%）患者因出血住院。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%，阿司匹林加氯吡格雷组为 3.7%，阿司匹林加维生素 K 拮抗剂组为 5.1%，氯吡格雷加维生素 K 拮抗剂组为 12.3%，三联治疗组为 12.0%。以阿司匹林为参照，出血的调整后的危险比为氯吡格雷 1.33（95%CI 1.11-1.59），维生素 K 拮抗剂 1.23（0.94-1.61），阿司匹林加氯吡格雷 1.47（1.28-1.69），阿司匹林加维生素 K 拮抗剂 1.84（1.51-2.23），氯吡格雷加维生素 K 拮抗剂 3.52（2.42-5.11），三联治疗组 4.05（3.08-5.33）。需要治疗的人数分别为：阿司匹林加氯吡格雷组 81.2 人，阿司匹林加维生素 K 拮抗剂组 45.4 人，氯吡格雷加维生素 K 拮抗剂组 15.2 人，三联治疗组 12.5 人。在研究期间，1852 名非致命性出血患者中有 702 名（37.9%）发生了复发性心肌梗死或死亡，而 38960 名无非致命性出血患者中有 7178 名（18.4%）（HR 3.00，2.75-3.27，p<0.0001）。