Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, and Department of Oncology, McGill University, 3755 Côte-Sainte-Catherine, H-461, Montreal, Quebec, H3T 1E2, Canada.
Thromb Haemost. 2013 Mar;109(3):431-9. doi: 10.1160/TH12-08-0542. Epub 2013 Jan 10.
Patients with atrial fibrillation (AF) often receive, in addition to warfarin, antithrombotic drugs to manage other comorbid conditions. To date, few population-based studies have quantified the bleeding risk associated with the concurrent use of these therapies. The United Kingdom General Practice Research Database was used to identify a cohort of 70,760 patients newly-diagnosed with AF between 1993 and 2008. A nested case-control analysis was conducted within that cohort, and conditional logistic regression was used to estimate adjusted rate ratios (RRs) of bleeding associated with current use of warfarin, aspirin, and clopidogrel in single therapy, as well as in dual and triple therapy, as compared with non-use of any therapy. A total of 10,850 patients experienced a bleeding event during follow-up. In single therapy, warfarin was associated with the highest increased risk (RR: 2.08, 95% confidence interval [CI]: 1.95-2.23), followed by clopidogrel (RR: 1.57, 95% CI: 1.37-1.81) and aspirin (RR: 1.25, 95% CI: 1.17-1.34). In dual therapy, combinations containing warfarin were associated with a higher increased risk (warfarin-aspirin: RR: 2.87, 95% CI: 2.58-3.19, and warfarin-clopidogrel: RR: 2.74, 95% CI: 2.14-3.51), than those not containing warfarin (aspirin-clopidogrel: RR: 1.68, 95% CI: 1.44-1.97). Triple therapy of warfarin-aspirin-clopidogrel was associated with the highest increased risk (RR: 3.75, 95% CI: 2.71-5.19). This large population-based study suggests that while all antithrombotic therapies are associated with an elevated risk of bleeding, the risks increase in an additive fashion with dual and triple therapy, particularly in combinations containing warfarin.
患者房颤（AF）经常收到，除了华法林，抗血栓药物来管理其他合并症。到目前为止，很少有基于人群的研究已经量化了与这些疗法同时使用相关的出血风险。英国普通实践研究数据库被用来确定一个队列的 70760 例新诊断为 AF 的患者之间 1993 年至 2008 年。嵌套病例对照分析在该队列内进行，条件逻辑回归被用来估计调整后的出血率比值（RR）与目前使用华法林、阿司匹林和氯吡格雷单一疗法相关联，以及双重和三重疗法，与任何治疗不使用相比。共有 10850 例患者在随访期间经历了出血事件。在单一疗法中，华法林与最高的风险增加相关（RR：2.08，95%置信区间[CI]：1.95-2.23），其次是氯吡格雷（RR：1.57，95%置信区间[CI]：1.37-1.81）和阿司匹林（RR：1.25，95%置信区间[CI]：1.17-1.34）。在双重治疗中，含有华法林的组合与更高的风险增加相关（华法林-阿司匹林：RR：2.87，95%置信区间[CI]：2.58-3.19，华法林-氯吡格雷：RR：2.74，95%置信区间[CI]：2.14-3.51），比那些不含有华法林（阿司匹林-氯吡格雷：RR：1.68，95%置信区间[CI]：1.44-1.97）。华法林-阿司匹林-氯吡格雷三联疗法与最高的风险增加相关（RR：3.75，95%置信区间[CI]：2.71-5.19）。这项大型基于人群的研究表明，虽然所有抗血栓治疗都与出血风险增加相关，但风险随着双重和三重治疗的增加而呈累加方式增加，特别是在含有华法林的组合中。
