Bahit M Cecilia, Lopes Renato D, Wojdyla Daniel M, Held Claes, Hanna Michael, Vinereanu Dragos, Hylek Elaine M, Verheugt Freek, Goto Shinya, Alexander John H, Wallentin Lars, Granger Christopher B
INECO Neurociencias Oroño, Rosario, Santa Fe, Argentina.
Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Heart. 2017 Apr;103(8):623-628. doi: 10.1136/heartjnl-2016-309901. Epub 2016 Oct 24.
We describe the incidence, location and management of non-major bleeding, and assess the association between non-major bleeding and clinical outcomes in patients with atrial fibrillation (AF) receiving anticoagulation therapy enrolled in Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE).
We included patients who received ≥1 dose of study drug (n=18 140). Non-major bleeding was defined as the first bleeding event considered to be clinically relevant non-major (CRNM) or minor bleeding, and not preceded by a major bleeding event.
Non-major bleeding was three times more common than major bleeding (12.1% vs 3.8%). Like major bleeding, non-major bleeding was less frequent with apixaban (6.4 per 100 patient-years) than warfarin (9.4 per 100 patient-years) (adjusted HR 0.69, 95% CI 0.63 to 0.75). The most frequent sites of non-major bleeding were haematuria (16.4%), epistaxis (14.8%), gastrointestinal (13.3%), haematoma (11.5%) and bruising/ecchymosis (10.1%). Medical or surgical intervention was similar among patients with non-major bleeding on warfarin versus apixaban (24.7% vs 24.5%). A change in antithrombotic therapy (58.6% vs 50.0%) and permanent study drug discontinuation (5.1% (61) vs 3.6% (30), p=0.10) was numerically higher with warfarin than apixaban. CRNM bleeding was independently associated with an increased risk of overall death (adjusted HR 1.70, 95% CI 1.32 to 2.18) and subsequent major bleeding (adjusted HR 2.18, 95% CI 1.56 to 3.04).
In ARISTOTLE, non-major bleeding was common and substantially less frequent with apixaban than with warfarin. CRNM bleeding was independently associated with a higher risk of death and subsequent major bleeding. Our results highlight the importance of any severity of bleeding in patients with AF treated with anticoagulation therapy and suggest that non-major bleeding, including minor bleeding, might not be minor.
NCT00412984; post-results.
我们描述了非大出血的发生率、部位及处理情况，并评估了参与阿哌沙班用于降低房颤患者卒中和其他血栓栓塞事件（ARISTOTLE）研究的接受抗凝治疗的房颤（AF）患者中非大出血与临床结局之间的关联。
我们纳入了接受≥1剂研究药物的患者（n = 18140）。非大出血被定义为首次被认为具有临床相关性的非大出血（CRNM）或小出血事件，且之前无大出血事件。
非大出血的发生率是大出血的3倍（12.1%对3.8%）。与大出血情况类似，阿哌沙班治疗的患者中非大出血的发生率（每100患者年6.4例）低于华法林治疗的患者（每100患者年9.4例）（校正风险比0.69，95%可信区间0.63至0.75）。非大出血最常见的部位是血尿（16.4%）、鼻出血（14.8%）、胃肠道出血（13.3%）、血肿（11.5%）和瘀斑（10.1%）。接受华法林或阿哌沙班治疗的非大出血患者中，医疗或手术干预情况相似（24.7%对24.5%）。华法林治疗的患者中，抗栓治疗的改变（58.6%对50.0%）和研究药物永久停用（5.1%（61例）对3.6%（30例），p = 0.10）在数值上高于阿哌沙班治疗的患者。CRNM出血与全因死亡风险增加（校正风险比1.70，95%可信区间1.32至2.18）及随后的大出血风险增加（校正风险比2.18，95%可信区间1.56至3.04）独立相关。
在ARISTOTLE研究中，非大出血很常见，且阿哌沙班治疗的患者中非大出血的发生率显著低于华法林治疗的患者。CRNM出血与更高的死亡风险及随后的大出血独立相关。我们的结果凸显了抗凝治疗的房颤患者中任何严重程度出血的重要性，并表明非大出血，包括小出血，可能并非微不足道。
NCT00412984；结果公布后。
Zotero 插件
