Liverpool University Hospitals NHS Foundation Trust Liverpool United Kingdom.
Liverpool Heart and Chest Hospital Liverpool United Kingdom.
J Am Heart Assoc. 2021 Apr 20;10(8):e019467. doi: 10.1161/JAHA.120.019467. Epub 2021 Apr 9.
Background Major bleeding after acute coronary syndrome predicts a poor outcome but is challenging to define. The choice of antiplatelet influences bleeding risk. Methods and Results Major bleeding, subsequent myocardial infarction (MI), and all-cause mortality to 1 year were compared in consecutive patients with acute coronary syndrome treated with clopidogrel (n=2491 between 2011 and 2013) and ticagrelor (n=2625 between 2012 and 2015) in 5 English hospitals. Clinical outcomes were identified from national hospital episode statistics. Bleeding and MI events were independently adjudicated by 2 experienced clinicians, blinded to drug, sequence, and year. Bleeding events were categorized using Bleeding Academic Research Consortium 3 to 5 and PLATO (Platelet Inhibition and Patient Outcomes) criteria and MI by the Third Universal Definition. Multivariable regression analysis was used to adjust outcomes for case mix. The median age was 68 years and 34% were women. 39% underwent percutaneous coronary intervention and 13% coronary artery bypass graft surgery. Clinical outcome data were 100% complete for bleeding and 99.7% for MI. No statistically significant difference was seen in crude or adjusted major bleeding for ticagrelor compared with clopidogrel (Bleeding Academic Research Consortium 3-5, hazard ratio [HR], 1.23; 95% CI, 0.90-1.68; =0.2, PLATO major adjusted HR, 1.30; 95% CI, 0.98-1.74; =0.07) except in the non-coronary artery bypass graft cohort (n=4464), where bleeding was more frequent with ticagrelor (Bleeding Academic Research Consortium 3-5, adjusted HR, 1.58; 95% CI, 1.09-2.31; =0.017; and PLATO major HR, 1.67; 95% CI, 1.18-2.37; =0.004). There was no difference in crude or adjusted subsequent MI (adjusted HR, 1.20; 95% CI, 0.87-1.64; =0.27). Crude mortality was higher in the clopidogrel group but not after adjustment, using either Cox proportional hazards or propensity matched population (HR, 0.90; 95% CI, 0.76-1.10; =0.21) as was the case for stroke (HR, 0.82; 95% CI, 0.52-1.32; =0.42). Conclusions This observational study indicates that the apparent benefit of ticagrelor demonstrated in a clinical trial population may not be observed in the broader population encountered in clinical practice. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02484924.
急性冠状动脉综合征（acute coronary syndrome）后发生大出血预示着预后不良，但出血的定义颇具挑战。抗血小板药物的选择会影响出血风险。
在 5 家英国医院中，对分别于 2011 年至 2013 年（n=2491）和 2012 年至 2015 年（n=2625）接受氯吡格雷和替格瑞洛治疗的急性冠状动脉综合征连续患者，比较大出血、随后发生心肌梗死（myocardial infarction，MI）和 1 年全因死亡率。通过国家医院住院统计数据确定临床结局。出血和 MI 事件由 2 位有经验的临床医生独立判定，判定过程中药物、序列和年份均设盲。使用 Bleeding Academic Research Consortium 3-5 和 PLATO（血小板抑制和患者结局）标准对出血事件进行分类，并根据第三次通用定义（Third Universal Definition）对 MI 进行分类。使用多变量回归分析调整结局，以适应病例组合。中位年龄为 68 岁，34%为女性。39%接受经皮冠状动脉介入治疗，13%接受冠状动脉旁路移植术。出血和 MI 的临床结局数据完整率分别为 100%和 99.7%。替格瑞洛与氯吡格雷相比，无论在未校正还是校正后的大出血发生率方面均未见统计学差异（Bleeding Academic Research Consortium 3-5，风险比[hazard ratio，HR]1.23；95%置信区间[confidence interval，CI]0.90-1.68；=0.2，PLATO 大出血校正 HR 1.30；95% CI 0.98-1.74；=0.07），但在非冠状动脉旁路移植术患者队列（n=4464）中除外（Bleeding Academic Research Consortium 3-5，校正 HR 1.58；95% CI 1.09-2.31；=0.017；和 PLATO 大出血校正 HR 1.67；95% CI 1.18-2.37；=0.004），替格瑞洛的出血发生率更高。无论在未校正还是校正后的 MI 发生率方面，替格瑞洛与氯吡格雷相比也均无差异（校正 HR 1.20；95% CI 0.87-1.64；=0.27）。氯吡格雷组死亡率更高，但校正后或使用 Cox 比例风险或倾向匹配人群（HR 0.90；95% CI 0.76-1.10；=0.21）后死亡率无差异，卒中发生率也如此（HR 0.82；95% CI 0.52-1.32；=0.42）。
本观察性研究表明，替格瑞洛在临床试验人群中表现出的明显获益，在临床实践中更广泛的人群中可能无法观察到。
