背景:12个月的双重抗血小板治疗(DAPT)是急性冠脉综合征(ACS)患者冠状动脉支架置入术后的标准治疗方法。本个体患者级荟萃分析的目的是总结冠状动脉药物洗脱支架植入后12个月DAPT降低至替格瑞洛单药治疗与持续DAPT比较的证据。
方法:对具有中央裁定终点的随机试验进行系统评价和个体患者数据(IPD)水平的荟萃分析,以评估在接受冠状动脉药物洗脱支架经皮冠状动脉介入治疗的患者中,短期DAPT(2周至3个月)与12个月DAPT后替格瑞洛单药治疗(每天两次)的疗效和安全性。在OvidMEDLINE中搜索了冠状动脉血运重建后比较P2Y12抑制剂单一疗法与DAPT的随机试验,Embase,和两个网站(www.tctmd.com和www.escardio.org)从数据库开始到2024年5月20日。排除长期口服抗凝剂适应症患者的试验。使用修订后的Cochrane偏差风险工具评估偏差风险。符合条件的试验的主要研究者通过匿名电子数据集提供IPD。三个排名的主要终点是主要的不良心血管或脑血管事件(MACCE;全因死亡的复合,心肌梗塞,或卒中)在符合方案的人群中进行非劣效性测试;以及出血学术研究联盟(BARC)3或5出血和全因死亡在意向治疗人群中的优越性测试。所有结果均报告为Kaplan-Meier估计值。非劣效性使用0·025的单侧α和1·15的预设非劣效性界限进行测试(风险比[HR]量表),其次是在0·05的双侧α进行排序的优势测试。本研究在PROSPERO(CRD42024506083)注册。
结果:共筛选了8361篇独特引文,其中610条记录在筛选标题和摘要时被认为可能符合条件。其中,确定了6项随机分配患者接受替格瑞洛单药治疗或DAPT治疗的试验.降级发生在干预后的中位数为78天(IQR31-92),中位治疗时间为334天(329-365)。在符合方案人群中的23256名患者中,替格瑞洛单药治疗297例(Kaplan-Meier估计2·8%)发生MACCE,DAPT治疗332例(Kaplan-Meier估计3·2%)发生MACCE(HR0·91[95%CI0·78-1·07];非劣效性p=0·0039;τ2<0·0001)。在意向治疗人群中的24407名患者中,BARC3或5出血的风险(Kaplan-Meier估计0·9%vs2·1%;HR0·43[95%CI0·34-0·54];p<0·0001表示优厚;τ2=0·079)和全因死亡(Kaplan-Meier估计0·9%vs1·2%;0·76[0·59-0·98];p=00000<034试验顺序分析显示,在总体和ACS人群中,MACCE具有非劣效性和出血优势的有力证据(z曲线越过了监测边界或所需的信息大小,而没有越过无用边界或接近零)。MACCE(p交互作用=0·041)和全因死亡(p交互作用=0·050)的治疗效果因性别而异,表明替格瑞洛单药治疗的女性可能有益处,以及出血的临床表现(p相互作用=0.022),表明替格瑞洛单药治疗对ACS的益处。
结论:我们的研究发现了有力的证据,与12个月的DAPT相比,替格瑞洛单药降阶梯不会增加缺血风险,也不会降低大出血风险,尤其是ACS患者。替格瑞洛单药治疗也可能与死亡率获益相关,尤其是在女性中,这需要进一步调查。
背景:提契诺心脏中心研究所,OspedalieroCantonale.
BACKGROUND: Dual antiplatelet therapy (DAPT) for 12 months is the standard of care after coronary stenting in patients with acute coronary syndrome (ACS). The aim of this individual patient-level meta-analysis was to summarise the evidence comparing DAPT de-escalation to
ticagrelor monotherapy versus continuing DAPT for 12 months after coronary drug-eluting stent implantation.
METHODS: A systematic review and individual patient data (IPD)-level meta-analysis of randomised trials with centrally adjudicated endpoints was performed to evaluate the comparative efficacy and safety of
ticagrelor monotherapy (90 mg twice a day) after short-term DAPT (from 2 weeks to 3 months) versus 12-month DAPT in patients undergoing percutaneous coronary intervention with a coronary drug-eluting stent. Randomised trials comparing P2Y12 inhibitor monotherapy with DAPT after coronary revascularisation were searched in Ovid MEDLINE, Embase, and two websites (www.tctmd.com and www.escardio.org) from database inception up to May 20, 2024. Trials that included patients with an indication for long-term oral anticoagulants were excluded. The risk of bias was assessed using the revised Cochrane risk-of-bias tool. The principal investigators of the eligible trials provided IPD by means of an anonymised electronic dataset. The three ranked coprimary endpoints were major adverse cardiovascular or cerebrovascular events (MACCE; a composite of all-cause death, myocardial infarction, or stroke) tested for non-inferiority in the per-protocol population; and Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding and all-cause death tested for superiority in the intention-to-treat population. All outcomes are reported as Kaplan-Meier estimates. The non-inferiority was tested using a one-sided α of 0·025 with the prespecified non-inferiority margin of 1·15 (hazard ratio [HR] scale), followed by the ranked superiority testing at a two-sided α of 0·05. This study is registered with PROSPERO (CRD42024506083).
RESULTS: A total of 8361 unique citations were screened, of which 610 records were considered potentially eligible during the screening of titles and abstracts. Of these, six trials that randomly assigned patients to
ticagrelor monotherapy or DAPT were identified. De-escalation took place a median of 78 days (IQR 31-92) after intervention, with a median duration of treatment of 334 days (329-365). Among 23 256 patients in the per-protocol population, MACCE occurred in 297 (Kaplan-Meier estimate 2·8%) with
ticagrelor monotherapy and 332 (Kaplan-Meier estimate 3·2%) with DAPT (HR 0·91 [95% CI 0·78-1·07]; p=0·0039 for non-inferiority; τ2<0·0001). Among 24 407 patients in the intention-to-treat population, the risks of BARC 3 or 5 bleeding (Kaplan-Meier estimate 0·9% vs 2·1%; HR 0·43 [95% CI 0·34-0·54]; p<0·0001 for superiority; τ2=0·079) and all-cause death (Kaplan-Meier estimate 0·9% vs 1·2%; 0·76 [0·59-0·98]; p=0·034 for superiority; τ2<0·0001) were lower with ticagrelor monotherapy. Trial sequential analysis showed strong evidence of non-inferiority for MACCE and superiority for bleeding among the overall and ACS populations (the z-curve crossed the monitoring boundaries or the required information size without crossing the futility boundaries or approaching the null). The treatment effects were heterogeneous by sex for MACCE (p interaction=0·041) and all-cause death (p interaction=0·050), indicating a possible benefit in women with ticagrelor monotherapy, and by clinical presentation for bleeding (p interaction=0·022), indicating a benefit in ACS with ticagrelor monotherapy.
CONCLUSIONS: Our study found robust evidence that, compared with 12 months of DAPT, de-escalation to ticagrelor monotherapy does not increase ischaemic risk and reduces the risk of major bleeding, especially in patients with ACS.
Ticagrelor monotherapy might also be associated with a mortality benefit, particularly among women, which warrants further investigation.
BACKGROUND: Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale.