Linder Marie, Iliadou Nyman Anastasia, Kieler Helle, Danielsson Bengt, Borg Natalia, Gry Marcus, Collin Julius
Centre for Pharmacoepidemiology, Karolinska Institutet, T2, Karolinska University Hospital, Stockholm, Sweden.
The National Board of Health and Welfare, Stockholm, Sweden.
Clin Epidemiol. 2020 Oct 5;12:1029-1038. doi: 10.2147/CLEP.S258373. eCollection 2020.
To evaluate associations between first-time use of direct oral anticoagulants or vitamin K antagonists and bleeding risk or mortality in the elderly with atrial fibrillation in a real-world setting in Sweden.
The study population comprises first-time users, above age 60, of dabigatran, apixaban, rivaroxaban, or warfarin, with first atrial fibrillation occurrence within 6 months before dispensing (2012-2016). Outcomes were gastrointestinal, any, or intracranial bleeding, and mortality. Exposure started at first dispensing of a study drug. Follow-up continued until outcome, end of drug supply, dispensing of another study drug, death or end of study (December 2016). We conducted a propensity score matched, nationwide register-based cohort study including three treatment groups: direct thrombin inhibitors, direct factor Xa inhibitors and vitamin K antagonists, each compared to the other two, focusing on subgroups of age and sex. Cox proportional hazard models adjusted for CHA2DS2VASc and HAS-BLED scores provided hazard ratios with 95% confidence intervals.
The matched study populations consisted of 7,264 patients for the direct thrombin inhibitors vs vitamin K antagonists comparison, 12,566 patients for the direct factor Xa inhibitors vs vitamin K antagonists comparison and 6,606 patients for the direct factor Xa inhibitors vs direct thrombin inhibitors comparison, in total 26,436 patients. Numerically high, but imprecise, hazard ratios for gastrointestinal bleeding were observed for women aged 75-80, 80-85, or above 85 years, eg 6.00 (1.02, 113.47) for direct thrombin inhibitors vs vitamin K antagonists. For both sexes, numerically high hazard ratios for any bleeding were observed in ages 80-85, or above 85 years, eg 2.90 (1.01, 10.41) for direct thrombin inhibitors vs vitamin K antagonists. Numerically high HRs for intracranial bleeding were observed for women aged 75-80 or 80-85 years, eg 2.70 (0.65, 18.19) for direct factor Xa inhibitors vs vitamin K antagonists. Excess mortality was observed in both sexes, across age groups, for naive and experienced anticoagulant users.
The observed increased gastrointestinal bleeding risk in first-time users of direct thrombin inhibitors or direct factor Xa inhibitors is consistent with previous studies. The possible risk of excess mortality merits further studies.
在瑞典的实际环境中，评估首次使用直接口服抗凝剂或维生素K拮抗剂与老年房颤患者出血风险或死亡率之间的关联。
研究人群包括年龄在60岁以上、首次使用达比加群、阿哌沙班、利伐沙班或华法林且在配药前6个月内首次发生房颤（2012 - 2016年）的患者。观察指标为胃肠道出血、任何出血或颅内出血以及死亡率。暴露从首次配给研究药物开始。随访持续至出现观察指标、药物供应结束、配给另一种研究药物、死亡或研究结束（2016年12月）。我们进行了一项基于全国登记的倾向评分匹配队列研究，包括三个治疗组：直接凝血酶抑制剂组、直接Xa因子抑制剂组和维生素K拮抗剂组，每组与另外两组进行比较，重点关注年龄和性别的亚组。对CHA2DS2VASc和HAS - BLED评分进行调整的Cox比例风险模型提供了带有95%置信区间的风险比。
在直接凝血酶抑制剂与维生素K拮抗剂比较中，匹配的研究人群有7264例患者；直接Xa因子抑制剂与维生素K拮抗剂比较中有12566例患者；直接Xa因子抑制剂与直接凝血酶抑制剂比较中有6606例患者，总计26436例患者。在75 - 80岁、80 - 85岁或85岁以上的女性中，观察到胃肠道出血的风险比在数值上较高但不精确，例如直接凝血酶抑制剂与维生素K拮抗剂比较时为6.00（1.02，113.47）。对于男女两性，在80 - 85岁或85岁以上的年龄组中，观察到任何出血的风险比在数值上较高，例如直接凝血酶抑制剂与维生素K拮抗剂比较时为2.90（1.01，10.41）。在75 - 80岁或80 - 85岁的女性中，观察到颅内出血的风险比在数值上较高，例如直接Xa因子抑制剂与维生素K拮抗剂比较时为2.70（0.65，18.19）。在初次使用和有经验的抗凝剂使用者中，各年龄组的男女均观察到额外死亡率。
首次使用直接凝血酶抑制剂或直接Xa因子抑制剂的患者中观察到的胃肠道出血风险增加与先前研究一致。额外死亡率的可能风险值得进一步研究。
