经导管主动脉瓣置换术后联合或不联合氯吡格雷的抗凝治疗。
Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation.
机构信息
From the Department of Cardiology, St. Antonius Hospital, Nieuwegein (V.J.N., J. Brouwer, J.P., D.R.P.P.C.P.Y., M.J.S., B.J.W.M.R., L.T., J.C.K., J.M.B.), the Department of Cardiology, Amsterdam University Medical Centers, Location AMC, Amsterdam (R.D., J. Baan), the Department of Cardiology, Isala Hospital, Zwolle (R.S.H.), the Department of Cardiology, Maastricht University Medical Center and Cardiovascular Research Institute, Maastricht (W.H., L.V., A.W.J.H.), the Department of Cardiology, Medisch Spectrum Twente, Enschede (G.K.H.), the Department of Cardiology, Leiden University Medical Center, Leiden (F.K.), the Department of Cardiology, Haga Hospital, The Hague (C.E.S.), the Department of Cardiology, University Medical Center Groningen, Groningen (P.H.), Erasmus School of Health Policy and Management, Erasmus University, Rotterdam (F.W.F.T.), the Department of Cardiology, Zuyderland Medical Center, Heerlen (A.W.J.H.), and the Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht University, Utrecht (P.R.S.) - all in the Netherlands; the Department of Cardiology, University Hospital Leuven, Leuven (C.L.F.D.), the Department of Cardiology, Onze Lieve Vrouwe Hospital (B.D.B.), and the Department of Cardiology, Algemeen Stedelijk Hospital Aalst (I.B.), Aalst, the Department of Cardiology, Sint-Jan Hospital, Brugge (J.A.S.V.D.H.), the Department of Cardiology, Hospital Oost-Limburg, Genk (B.F.), and the Department of Cardiology, Imelda Hospital, Bonheiden (J.R.) - all in Belgium; the Department of Cardiology, Institut National de Chirurgie Cardiaque et de Cardiologie Interventionnelle, Luxembourg, Luxembourg (P.F.); and the Department of Cardiology, University Hospital Královské Vinohrady and Third Medical Faculty, Charles University, Prague, Czech Republic (P.T.).
出版信息
N Engl J Med. 2020 Apr 30;382(18):1696-1707. doi: 10.1056/NEJMoa1915152. Epub 2020 Mar 29.
BACKGROUND
The roles of anticoagulation alone or with an antiplatelet agent after transcatheter aortic-valve implantation (TAVI) have not been well studied.
METHODS
We performed a randomized trial of clopidogrel in patients undergoing TAVI who were receiving oral anticoagulation for appropriate indications. Patients were assigned before TAVI in a 1:1 ratio not to receive clopidogrel or to receive clopidogrel for 3 months. The two primary outcomes were all bleeding and non-procedure-related bleeding over a period of 12 months. Procedure-related bleeding was defined as Bleeding Academic Research Consortium type 4 severe bleeding, and therefore most bleeding at the puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction at 12 months (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2), both tested for noninferiority (noninferiority margin, 7.5 percentage points) and superiority.
RESULTS
Bleeding occurred in 34 of the 157 patients (21.7%) receiving oral anticoagulation alone and in 54 of the 156 (34.6%) receiving oral anticoagulation plus clopidogrel (risk ratio, 0.63; 95% confidence interval [CI], 0.43 to 0.90; P = 0.01); most bleeding events were at the TAVI access site. Non-procedure-related bleeding occurred in 34 patients (21.7%) and in 53 (34.0%), respectively (risk ratio, 0.64; 95% CI, 0.44 to 0.92; P = 0.02). Most bleeding occurred in the first month and was minor. A secondary composite 1 event occurred in 49 patients (31.2%) receiving oral anticoagulation alone and in 71 (45.5%) receiving oral anticoagulation plus clopidogrel (difference, -14.3 percentage points; 95% CI for noninferiority, -25.0 to -3.6; risk ratio, 0.69; 95% CI for superiority, 0.51 to 0.92). A secondary composite 2 event occurred in 21 patients (13.4%) and in 27 (17.3%), respectively (difference, -3.9 percentage points; 95% CI for noninferiority, -11.9 to 4.0; risk ratio, 0.77; 95% CI for superiority, 0.46 to 1.31).
CONCLUSIONS
In patients undergoing TAVI who were receiving oral anticoagulation, the incidence of serious bleeding over a period of 1 month or 1 year was lower with oral anticoagulation alone than with oral anticoagulation plus clopidogrel. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.).
背景
经导管主动脉瓣置换术（TAVI）后单独使用抗凝剂或联合抗血小板药物的作用尚未得到充分研究。
方法
我们对正在接受口服抗凝治疗的 TAVI 患者进行了氯吡格雷随机试验，这些患者有适当的适应证。在 TAVI 前，将患者以 1:1 的比例随机分配，不接受氯吡格雷或接受氯吡格雷治疗 3 个月。两个主要结局是 12 个月期间所有出血和与操作无关的出血。操作相关出血定义为 Bleeding Academic Research Consortium 4 级严重出血，因此大多数穿刺部位出血被归类为与操作无关的出血。两个次要结局是 12 个月时心血管原因死亡、与操作无关的出血、卒中和心肌梗死的复合终点（次要复合终点 1）和心血管原因死亡、缺血性卒中和心肌梗死的复合终点（次要复合终点 2），均进行非劣效性（非劣效性边界为 7.5 个百分点）和优越性检验。
结果
单独接受口服抗凝治疗的 157 例患者中有 34 例（21.7%）发生出血，联合接受口服抗凝和氯吡格雷治疗的 156 例患者中有 54 例（34.6%）发生出血（风险比，0.63；95%置信区间[CI]，0.43 至 0.90；P=0.01）；大多数出血事件发生在 TAVI 入路部位。单独接受口服抗凝治疗的 34 例患者（21.7%）和联合接受口服抗凝和氯吡格雷治疗的 53 例患者（34.0%）分别发生与操作无关的出血（风险比，0.64；95%CI，0.44 至 0.92；P=0.02）。大多数出血发生在第一个月且程度较轻。单独接受口服抗凝治疗的 49 例患者（31.2%）和联合接受口服抗凝和氯吡格雷治疗的 71 例患者（45.5%）发生次要复合终点 1（差异，-14.3 个百分点；95%CI 非劣效性，-25.0 至-3.6；风险比，0.69；95%CI 优越性，0.51 至 0.92）。单独接受口服抗凝治疗的 21 例患者（13.4%）和联合接受口服抗凝和氯吡格雷治疗的 27 例患者（17.3%）分别发生次要复合终点 2（差异，-3.9 个百分点；95%CI 非劣效性，-11.9 至 4.0；风险比，0.77；95%CI 优越性，0.46 至 1.31）。
结论
在接受口服抗凝治疗的 TAVI 患者中，与单独使用口服抗凝治疗相比，在 1 个月或 1 年内严重出血的发生率较低。（由荷兰卫生研究与发展组织资助；POPular TAVI EU 临床试验注册编号，2013-003125-28；临床试验.gov 编号，NCT02247128。）
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