ACS后DAPT出血风险可预测

<正>指南推荐,急性冠状动脉综合征(ACS)患者应采用阿司匹林+P2Y12受体抑制剂行双联抗血小板治疗(DAPT)至少12个月;若患者存在较高出血风险可考虑缩短DAPT时长。但是,目前尚无可预测ACS后DAPT治疗期间患者个体出血风险的决策支持工具。近期,Heart上发表的一项最新研究对TRILOGY ACS研究中9240例未进行血运重建、接受DAPT治疗的不稳定性心绞痛/非ST段抬高型心肌梗死     

SMART-DATE研究:ACS患者仅应用6个月双抗也安全可行?

正目前的欧美临床指南对于急性冠脉综合征(ACS)的患者,如无严重出血风险,均推荐进行至少12个月的双联抗血小板治疗(DAPT),但是并无临床随机对照试验能够证实ACS患者中最佳的DAPT时间究竟是多少。今天公布于奥兰多的美国心脏病学会年会(ACC.2018)的SMART-DATE试验就旨在通过随机对照试验验证ACS患者接受6个月的     

急性冠脉综合征和冠脉支架患者的抗血小板优化治疗

双联抗血小板治疗(DAPT)是急性冠状动脉综合征(ACS)和冠状动脉(冠脉)支架的标准抗血小板方案。患者的DAPT时程和强度应根据其缺血和出血风险进行个性化调整。本文总结了最新的循证医学证据和欧美指南内容,为临床优化DAPT方案提供一定的理论依据。     

经皮冠状动脉介入治疗后短程双联抗血小板治疗的研究进展

目前国内外指南大多数推荐经皮冠状动脉介入治疗(PCI)后采取标准双联抗血小板治疗(DAPT),以减少支架内血栓形成、预防缺血事件的发生。但长程DAPT方案势必会增加出血风险。新型药物洗脱支架使支架内血栓事件的发生率显著下降,新型P2Y12受体抑制剂具有更强的抗血小板作用以及PCI术中腔内影像学的应用,都大大降低了PCI术后心血管不良事件的发生率。对此,国内外开展了许多大型临床研究,以探求PCI术后最佳DAPT疗程,进而改善患者的临床净获益。现依据最新的研究进展,对短程DAPT的循证医学证据进行综述。     

PCI术后标准双联抗血小板治疗不耐受的处理策略

双联抗血小板治疗(DAPT)是目前冠心病患者行经皮冠状动脉介入治疗(PCI)术后的基础治疗,是减少包括支架内血栓形成在内的心血管缺血事件的关键。阿司匹林和一种P2Y12受体抑制剂联用在稳定性冠心病(SACD)患者PCI术后维持6个月,急性冠状动脉综合征(ACS)维持12个月是目前的标准DAPT策略,但在临床实践过程中,部分患者因出现胃肠道不适、出血、呼吸困难等不良反应不能耐受标准DAPT,导致自行停药,增加心血管不良事件发生风险。现结合临床实践及证据对PCI术后标准DAPT不耐受的处理策略进行综述。     

冠状动脉支架植入术后抗血小板策略的研究进展

对于经皮冠状动脉介入术(PCI)后患者,国内外指南均首选推荐12个月的双联抗血小板治疗(DAPT)方案,但由于患者对抗血小板药物治疗反应多样,如何选择适宜的个体化DAPT方案有待进一步研究。该文介绍近年来不同抗血小板药物策略的临床试验获益情况,以期为临床治疗提供一定参考。     

冠心病双联抗血小板治疗优化策略的思考

双联抗血小板治疗(DAPT)是经皮冠状动脉介入治疗术后抗栓常用策略。随着新型P2Y12受体拮抗剂(普拉格雷、替格瑞洛)的出现和循证医学证据的增加,DAPT策略不断更新。个体间对抗血小板药物治疗表现出多样性差异,这些差异与再发血栓或出血有关。平衡缺血与出血风险是冠心病DAPT的关键。现阶段,采用血小板功能检测能够评估DAPT后出血与血栓风险,能否通过检测结果调整DAPT策略尚无定论。多部指南对于血小板功能检测及基因检测推荐等级不高,根据检测结果调整DAPT方案并未显现出临床获益。     

经皮冠状动脉介入治疗术后双联抗血小板治疗最佳时限的选择

双联抗血小板治疗(DAPT)是目前经皮冠状动脉介入治疗(PCI)术后预防血栓形成及其他缺血事件的药物基础,但延长DAPT时限将会增加出血风险。目前,大量研究试图找出PCI术后最佳的DAPT时限,以达到最大化的临床净获益,但研究结果不尽一致。患者的临床情况、支架类型、冠状动脉病变情况、合并症及出血和缺血风险比都会影响DAPT时限的选择。     

经皮冠状动脉介入治疗6～12个月后患者抗栓治疗的研究进展

双联抗血小板治疗(DAPT)一直是冠状动脉粥样硬化性心脏病(CAD)患者经皮冠状动脉介入治疗(PCI)术后的标准药物治疗方案。当前指南建议,在无危及生命的出血风险情况下,急性冠状动脉综合征患者PCI术后DAPT时程至少12个月,慢性冠状动脉综合征患者DAPT时程至少6个月。但目前DAPT的最佳治疗时程及6～12个月后进一步抗栓方案的临床研究结果尚不一致。本文主要对CAD患者PCI术后DAPT时程的影响因素及6～12个月后的进一步抗栓方案进行综述,以期为临床实践提供参考。     

药物洗脱支架置入后双联抗血小板疗程的研究进展

药物洗脱支架(DES)和有效的药物治疗降低了冉狭窄率,提高了血运重建率,但对降低临床血栓事件的效果并未确定,抗血小板药物疗程却只增不减[1].2006年一项观察停用氯比格雷对DES和裸金属支架(BMS)晚期事件影响研究(BASKET-LATE)报告,停药使DES相关的晚期血栓形成,增加了死亡或非致死性心肌梗死(MI)的发生率[2].随后研究也显示,DES后服用12个月或以上的阿司匹林和氯吡格雷双联抗血小板治疗(DAPT)有益于防治支架相关的血栓形成[3].因此,目前国内外指南都建议,除有出血高危因素的患者,在DES置入后,患者接受12个月或更长疗程的DAPT已成为标准处方[4-6].然而,随着DES工艺、介入方法和技术及血管内影像设备的改良,针对介入治疗后现行DAPT疗程是真实地增加临床获益,还是增加出血风险的疑问,新的临床试验提出DAPT疗程并非是划一的,它可能短于现行指南建议的12个月.因此,DES术后如何优选DAPT疗程是今天需要探索的课题.     

Lights and shadows of long-term dual antiplatelet therapy in “real life” clinical scenarios

Dual antiplatelet therapy (DAPT) is a cornerstone of treatment for patients with acute coronary syndromes (ACS). Mounting evidences have opened the debate about the optimal DAPT duration. Considering the ACS-pathophysiology, the most recent guidelines recommend DAPT in all ACS patients for at least 12 months unless there are contraindications such as excessive risk of bleeding. Thus, it can be considered acceptable earlier discontinuation if the risk of morbidity from bleeding outweighs the anticipated benefit. On the other hand, several studies have clearly indicated that a significant burden of platelet related-events, such as stroke and new ACS might occur after this period, suggesting that potential benefits might derive by prolonging DAPT beyond 12 months (Long DAPT). Indeed, although current guidelines give some indications about patients eligible for Long DAPT, they do not embrace several real-life clinical scenarios. Thus, in such scenarios, how to decide whether a patient is eligible for Long DAPT or not might be still challenging for clinicians. This position paper presents and discusses various “real-life” clinical scenarios in ACS patients, in order to propose several possible recommendations to overcome guidelines potential limitations.     

Cost‐effectiveness analysis of 30‐month vs 12‐month dual antiplatelet therapy with clopidogrel and aspirin after drug‐eluting stents in patients with acute coronary syndrome

Continuation of dual antiplatelet therapy (DAPT) beyond 1 year reduces late stent thrombosis and ischemic events after drug‐eluting stents (DES) but increases risk of bleeding. We hypothesized that extending DAPT from 12 months to 30 months in patients with acute coronary syndrome (ACS) after DES is cost‐effective. A lifelong decision‐analytic model was designed to simulate 2 antiplatelet strategies in event‐free ACS patients who had completed 12‐month DAPT after DES: aspirin monotherapy (75–162 mg daily) and continuation of DAPT (clopidogrel 75 mg daily plus aspirin 75–162 mg daily) for 18 months. Clinical event rates, direct medical costs, and quality‐adjusted life‐years (QALYs) gained were the primary outcomes from the US healthcare provider perspective. Base‐case results showed DAPT continuation gained higher QALYs (8.1769 vs 8.1582 QALYs) at lower cost (USD42 982 vs USD44 063). One‐way sensitivity analysis found that base‐case QALYs were sensitive to odds ratio (OR) of cardiovascular death with DAPT continuation and base‐case cost was sensitive to OR of nonfatal stroke with DAPT continuation. DAPT continuation remained cost‐effective when the ORs of nonfatal stroke and cardiovascular death were below 1.241 and 1.188, respectively. In probabilistic sensitivity analysis, DAPT continuation was the preferred strategy in 74.75% of 10 000 Monte Carlo simulations at willingness‐to‐pay threshold of 50 000 USD/QALYs. Continuation of DAPT appears to be cost‐effective in ACS patients who were event‐free for 12‐month DAPT after DES. The cost‐effectiveness of DAPT for 30 months was highly subject to the OR of nonfatal stroke and OR of death with DAPT continuation.     

Optimal Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome: Insights From a Network Meta-Analysis of Randomized Trials

BackgroundWith newer generation drug eluting stents (DES), the minimal duration of dual antiplatelet therapy (DAPT) recommended by guidelines has been reduced to 6 months in patients with stable coronary artery disease. Whether shorter duration of DAPT is safe in patients presenting with acute coronary syndrome (ACS) remains controversial. Our aim of this study was to investigate the optimal DAPT duration (≤3 months vs. 6 months vs. 12 months vs. >12 months) among patients with ACS undergoing percutaneous coronary intervention (PCI).MethodsPUBMED and EMBASE were searched through January 2020 for randomized controlled trials of DAPT duration in patients with ACS. The ischemic outcomes were all-cause death, myocardial infarction, and stent thrombosis. The safety outcome was major and/or clinically relevant bleeding.ResultsOur search identified 14 eligible trials enrolling a total of 31,837 patients comparing different DAPT duration in patients with ACS. Short-term DAPT (≤3 months or 6 months) did not increase ischemic outcomes compared to long-term DAPT (12 months and >12 months). For bleeding outcomes, ≤3 months DAPT was associated with significant reduction in bleeding compared to 6 months, 12 months or >12 months DAPT (OR [95% CI]: 0.60 [0.37–0.98]; 0.68 [0.54–0.85] and 0.43 [0.34–0.54], respectively). These findings were similar when limited to 2nd generation DES.ConclusionsData from this meta-analysis of randomized trials support short-term (≤3 months and 6 months) DAPT in patients with ACS undergoing PCI. Guidelines might need to consider short-term DAPT even in patients presenting with ACS, especially in this era of newer generation DES.     

Combination of a new oral anticoagulant, aspirin and clopidogrel after acute coronary syndrome: new therapeutic standard?

Effective secondary prevention after acute coronary syndrome (ACS) is largely dependent on dual antiplatelet therapy (DAPT). Despite DAPT, however, patients remain at substantial risk of major adverse cardiovascular events (i.e., cardiovascular death, myocardial infarction, stroke), and, therefore, combination therapy of oral anticoagulant and antiplatelets has been previously proposed. Because of the increase in bleeding and the cumbersome management of vitamin K antagonists, such combination therapy has never gained much popularity. The recent development of new, non vitamin K antagonists, direct oral anticoagulants (NOACs), including dabigatran, apixaban, rivaroxaban, and darexaban, which have more favorable pharmacokinetics and pharmacodynamics, as well as higher safety, has renewed the interest on combination therapy. Whereas phase II trials with dabigatran, apixaban, rivaroxaban, and darexaban have consistently shown an increased bleeding risk with combination therapy, a potential increased efficacy has emerged for apixaban and rivaroxaban, thereby prompting phase III studies. Both APPRAISE-2 and ATLAS ACS 2-TIMI 51 trials confirm a dose-dependent increase in major bleeding events, including intracranial, with apixaban and rivaroxaban when combined with DAPT. Low-dose (2.5 mg twice daily) rivaroxaban on the other hand, is associated with a significantly higher efficacy on the occurrence of combined cardiovascular death, myocardial infarction, stroke, and of stent thrombosis. Owing to the persistent uncertainty regarding the net clinical benefit of combined therapy of NOAC, namely low-dose (2.5 mg twice daily) rivaroxaban and DAPT of aspirin and clopidogrel, further studies are warranted to identify the ACS patient who will benefit most from such treatment, also in comparison to the current therapeutic standard represented by DAPT of aspirin and ticagrelor (or prasugrel).     

Long-term outcomes in high-risk patients with non-ST-segment elevation myocardial infarction

Greater use of evidence-based therapies has improved outcomes for patients with acute coronary syndromes (ACS) in recent decades. Consequently, more ACS patients are surviving beyond 12 months; however, limited data exist to guide treatment in these patients. Long-term outcomes have not improved in non-ST-segment elevation myocardial infarction (NSTEMI) patients at the same rate seen in ST-segment elevation myocardial infarction patients, possibly reflecting NSTEMI patients’ more complex clinical phenotype, including older age, greater burden of comorbidities and higher likelihood of a previous myocardial infarction (MI). This complexity impacts clinical decision-making, particularly in high-risk NSTEMI patients, in whom risk–benefit assessments are problematical. This review examines the need for more effective long-term management of NSTEMI patients who survive ≥12 months after MI. Ongoing risk assessment using objective measures of risk (for bleeding and ischemia) should be used in all post-MI patients. While 12 months appears to be the optimal duration of dual antiplatelet therapy for most patients, this may not be the case for high-risk patients, and more research is urgently needed in this population. A recent subgroup analysis from the DAPT study in patients with or without MI who had undergone coronary stenting (31 % presented with MI; 53 % had NSTEMI) and the prospective PEGASUS-TIMI 54 trial in patients with a prior MI and at least one other risk factor (40 % had NSTEMI) demonstrated that long-term dual antiplatelet therapy improved cardiovascular outcomes but increased bleeding. Further studies will help clarify the role of dual antiplatelet therapy in stable post-NSTEMI patients.     

Dual Antiplatelet Therapy and Outcomes in Patients With Atrial Fibrillation and Acute Coronary Syndromes Managed Medically Without Revascularization: Insights From the TRILOGY ACS Trial

Associations between atrial fibrillation (AF), outcomes, and response to antiplatelet therapies in patients with acute coronary syndrome (ACS) managed medically without revascularization remain uncertain. We examined these associations for medically managed ACS patients randomized to dual antiplatelet therapy (DAPT) using patient data from the TRILOGY ACS trial. DAPT included aspirin plus clopidogrel 75 mg/d or prasugrel 10 mg/d (5 mg/d for those <60 kg or age ≥75 years). Patients receiving oral anticoagulants were excluded. Cox proportional hazards regression modeling was used to characterize associations between patients with AF (AF+) vs those without (AF?) and risk of ischemic and bleeding events, and to explore effects of randomized treatment on outcomes. Among 9101 patients with baseline AF status, 710 (7.8%) had AF. AF+ patients were older and had more comorbidities. Unadjusted associations of the composite of cardiovascular death/myocardial infarction/stroke were significantly higher among AF patients at 30 months (31.1% vs 18.4%; HR: 1.61, 95% CI: 1.35‐1.92, P < 0.001), but differences did not persist after adjustment (HR: 1.16, 95% CI: 0.97‐1.39, P = 0.11). When individual components of the composite endpoint were evaluated, 30‐month risk of events in AF+ patients was significantly higher. Thirty‐month risk of all‐cause death was significantly higher in AF+ patients: 18.1% vs 11.1% (HR: 1.62, 95% CI: 1.30‐2.02, P < 0.001). There was no significant interaction with randomized treatment and AF for the primary endpoint. Among medically managed high‐risk ACS patients receiving DAPT, AF was associated with higher unadjusted risks of ischemic and bleeding outcomes that were similar by treatment group.     

Meta-Analysis of the Efficacy and Safety of P2Y12 Inhibitor Monotherapy After Short Course of Dual-Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention

BackgroundGuidelines recommend dual antiplatelet therapy (DAPT) following drug-eluting stent (DES) placement for ≥12 months in acute coronary syndrome or 6 months in stable coronary artery disease. However, with the advent of newer-generation stents, the optimal duration of DAPT to balance bleeding and thrombotic risks has been debated.ObjectivesWe aimed to perform a meta-analysis of randomized controlled trials (RCT) comparing P2Y₁₂ monotherapy in short-duration group (SDG) vs. standard treatment group (STG) course of DAPT in patients undergoing PCI.MethodsElectronic databases were searched for RCTs of patients undergoing percutaneous coronary intervention (PCI) with DES placement who received short (≤ 3 months) vs. standard DAPT course (≥12 months) and were followed for ≥12-months. Rates of major adverse cardiovascular events (a composite of cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke) were the primary outcome. Study-specific odds ratios (OR) and corresponding 95% confidence intervals were calculated using random-effects model.ResultsA total of 20,706 patients (10,344 in the SDG and 10,362 in the STG) were analysed from four studies. There was no significant difference observed for MACE (OR = 0.95, 95% CI: 0.81–1.08, P = .92, I² = 0%) myocardial infarction or stent thrombosis. However, lower rates of major bleeding were noted in the SDG (1.20 vs. 1.80%; OR: 0.61; 95% CI: 0.37–0.99; P = .04; I² = 71%) albeit with increased heterogeneity.ConclusionA short duration of DAPT followed by P2Y₁₂ inhibitor monotherapy was comparable to 12 months of DAPT with respect to MACE and thrombotic events, with lower rates of major bleeding events in select group of patients undergoing PCI. More data is needed to assess efficacy in patients with complex lesions and high risk ACS population including those with STEMI presentation.     

Dual Antiplatelet Therapy with Prasugrel or Ticagrelor Versus Clopidogrel in Interventional Cardiology

For several years, clopidogrel plus aspirin has been the dual antiplatelet therapy (DAPT) of choice for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with stent implantation. More recently, prasugrel and ticagrelor have demonstrated greater efficacy than clopidogrel. In TRITON-TIMI 38, the risk of TIMI major bleeding unrelated to coronary artery bypass graft (CABG) surgery was similar for prasugrel and clopidogrel after excluding subgroups with increased bleeding risk (previous stroke or transient ischemic event; age ≥75 years; weight <60 kg). In the PLATO trial, rates of TIMI major bleeding were similar for ticagrelor and clopidogrel, but ticagrelor was associated with a significantly higher rate of non-CABG-related TIMI major bleeding. Current evidence suggests that prasugrel or ticagrelor plus aspirin should be the DAPT of choice in patients with ACS undergoing PCI unless they are at particularly high risk of bleeding. No studies have yet compared prasugrel and ticagrelor in ACS patients, however prasugrel and ticagrelor have different side effect profiles, and the choice of agent should be made either as a default choice and/or on an individual patient basis. Ongoing trials in ACS patients will increase the evidence base for new P2Y₁₂ receptor inhibitors and help to establish the most effective DAPT regimens.     

Duration of Dual Antiplatelet Therapy in Coronary Artery Disease: a Review Article

Dual antiplatelet therapy (DAPT) following an acute coronary syndrome or after placement of a coronary artery stent is superior to aspirin alone for prevention of atherothrombotic events but carries an increased bleeding risk. DAPT should be continued for at least 12 months based on current guidelines. Recent randomized trials demonstrate reduced ischemic events including myocardial infarction (MI), stroke, and death with continued DAPT for up to 30 months or longer, particularly in the post-MI population. However, this clinical benefit is accompanied by an increased risk of bleeding. Additional trials show mixed safety and efficacy with duration of DAPT of less than 12 months. The current data emphasizes the need to individualize DAPT duration at the patient level to balance the clinical benefits of a reduced risk of cardiovascular ischemic events with the greater risk of clinically significant bleeding. Patients at an increased risk of ischemic events and a lower risk of bleeding should be strongly considered for prolonged DAPT beyond the 1 year currently recommended in the practice guidelines.     

Antiplatelet Therapy and Coronary Artery Bypass Grafting: Analysis of Current Evidence With a Focus on Acute Coronary Syndrome

This review was undertaken to summarize and discuss the current evidence around antiplatelet therapy and coronary artery bypass grafting (CABG). Aspirin (ASA) monotherapy remains the standard of care among patients before and after CABG. The role of more intense antiplatelet therapy—specifically, P2Y12 inhibitors—in improving clinical outcomes and graft patency is becoming increasingly apparent. As such, we provide an overview of a variety of antiplatelet regimens. The review discusses the evidence around preoperative management of antiplatelet therapies, with a particular focus on timing of cessation. It also evaluates the current literature to elucidate the best antiplatelet therapy regimen after CABG, focusing on acute coronary syndrome (ACS). Whenever possible, data are presented from randomized controlled trials (RCTs) and meta-analyses. Although guidelines recommend use of dual antiplatelet therapy (DAPT) after CABG for patients with ACS, available evidence is limited to small RCTs, and meta-analyses are of substudies of larger RCTs. There is also considerable heterogeneity in patient population of these studies; a significant number of patients underwent off-pump CABG (OPCAB) in trials that demonstrate graft-patency benefit with DAPT. With this limited evidence, DAPT remains underused in the CABG population, even among patients presenting after ACS.