Drug insight: antithrombotic therapy after percutaneous coronary intervention in patients with an indication for anticoagulation

Antiplatelet therapy with aspirin and clopidogrel is standard care following revascularization by percutaneous coronary intervention with stent insertion. This so-called dual therapy is recommended for up to 4 weeks after intervention for bare-metal stents and for 6-12 months after intervention for drug-eluting stents. Although it is estimated that 5% of patients undergoing percutaneous coronary intervention require long-term anticoagulation because of an underlying chronic medical condition, continuing treatment with triple therapy (warfarin, aspirin and clopidogrel) increases the risk of bleeding. In most patients triple antithrombotic therapy seems justified for a short period of time. In some patients, however, a more considered judgment based on absolute need for triple therapy, risk of bleeding and risk of stent thrombosis is required, but the optimum antithrombotic treatment for these patients who require long-term anticoagulation has not been defined. This Review summarizes the existing literature concerning antithrombotic therapy and makes recommendations for initiation and duration of triple therapy in the small proportion of patients already receiving anticoagulant therapy who require percutaneous coronary intervention.     

Antithrombotic strategies in patients with an indication for long-term anticoagulation undergoing coronary artery stenting: safety and efficacy data from a single center.

BACKGROUND: Dual antiplatelet therapy is the antithrombotic treatment generally recommended after percutaneous coronary intervention with stent implantation (PCI-S). However, the optimal antithrombotic treatment after PCI-S in case of a concomitant indication for anticoagulation (AC) is unknown. The aim of our study was to determine the strategies adopted at our Institution (where the management of these patients is at the physician's discretion), and to evaluate their relative efficacy and safety. METHODS: A retrospective analysis of all PCI-S performed between January 2002-April 2004, was carried out. All patients on AC at the time of PCI-S were identified and the hemorrhagic and thromboembolic complications recorded. RESULTS: Twenty-seven patients (21 males, 6 females, mean age 66.9 +/- 10.6 years) on AC because of atrial fibrillation, post-myocardial infarction cardiomyopathy, left ventricular or arterial thrombus, previous cerebrovascular event, and mechanical aortic or mitral valve, were identified. The adopted antithrombotic treatment included: dual antiplatelet therapy in 6 patients (22%), a combination of a single antiplatelet with either aspirin or a thienopyridine and oral AC in 5 (19%), and triple therapy with dual antiplatelet and either oral AC or low-molecular-weight heparin administration in 16 (59%). The overall complication rate at 32.3 +/- 5.4 days was 18%, accounted for by two in-hospital major hemorrhages requiring blood transfusion (7%), two minor hemorrhages treated conservatively (7%), and one subacute stent thrombosis requiring emergency percutaneous reintervention (4%). CONCLUSIONS: At our Institution, variable antithrombotic strategies are adopted after PCI-S in patients with an indication for AC. Since the overall complication rate was relevant, further properly sized and designed studies are warranted in order to identify the optimal antithrombotic treatment in this patient subset.     

Periprocedural myocardial infarction in patients undergoing percutaneous coronary intervention

Percutaneous coronary intervention (PCI) in addition to guideline-directed medical therapy reduces the risk of spontaneous myocardial infarction (MI), urgent revascularization, and improves angina status; however, PCI is associated with an increased risk of periprocedural myocardial injury and MI. Numerous studies have investigated the mechanisms, predictors, and therapeutic strategies for periprocedural MI. Various definitions of periprocedural MI have been proposed by academic groups and professional societies requiring different cardiac biomarker thresholds and ancillary criteria for myocardial ischemia. The frequency and clinical significance of periprocedural MI substantially varies according to the definitions applied. In daily practice, accurate diagnosis of clinically-relevant periprocedural MI is essential because it may have a substantial impact on subsequent patient management. In the clinical trial setting, only clinically relevant periprocedural MI definitions should be applied as a clinical endpoint in order to avoid obscuring meaningful outcomes. In this review, we aim to summarize the mechanisms, predictors, frequency, and prognostic impact of periprocedural MI in patients undergoing PCI and to provide the current perspective on this issue.     

Contemporary antithrombotic strategies in patients undergoing coronary stent implantation

The number of annual stenting procedures has been increasing at a rapid pace since coronary stents were first used in clinical practice just over a decade ago. Subacute stent thrombosis, which usually has serious clinical consequences, plagued the stent early experience despite intense anticoagulation therapy. The reduction of stent thrombosis was among the factors that contributed to stent growth and widespread acceptance in recent years. This was the result of improved implantation techniques, advances in adjunctive pharmacotherapy and evolution in stent designs, delivery systems and non-thrombogenic coatings. However, novel designs and materials customized for particular lesion types and newer anti-restenotic treatments could influence stent thrombogenicity. Intravascular brachytherapy and drug-eluting stents have been shown to reduce the incidence of in-stent restenosis preventing cellular proliferation. However, by interfering with the re-endothelization process they may also increase the risk of stent thrombosis. To prevent a recrudescence of this feared complication, future research direction must focus on the hemocompatibility aspects of new technologies, along with further refinement of stent-deployment techniques and antithrombotic strategies.     

冠心病介入抗栓治疗相关最新进展概要

近年经皮冠状动脉介入治疗（PCI）相关抗栓领域取得了许多关键性的进展。以TWILIGHT等研究为代表的降阶治疗探索是目前PCI术后抗血小板策略研究的主流方向之一,而在合并心房颤动PCI患者中,联合新型口服抗凝药物的双联或短程三联抗栓方案的有效和安全性已获多项新研究的印证。比伐芦定新的研究结果将更新直接PCI抗凝的循证证...     

The antithrombotic management of patients on oral anticoagulation undergoing coronary stent implantation: an update

Triple therapy (TT) of warfarin, aspirin, and clopidogrel is currently recommended as the optimal antithrombotic treatment in patients on long-term oral anticoagulation (OAC) for clinical conditions at moderate?Chigh thromboembolic risk, such as moderate-high risk atrial fibrillation, mechanical heart valve, cardiogenic embolism, etc., who undergo coronary stent implantation. While being recognized as the most effective treatment for preventing major adverse cardiac events, stent thrombosis and stroke, TT is associated with an increased risk of bleeding, which apparently increases as the duration of TT is prolonged. Available evidence, however, is flawed by important limitations, including the limited size and retrospective design of most of the studies, as well as, the underreporting of the treatment that was actually ongoing at the time of an event. Recent data derived from larger, prospective studies have broadened and strengthened the recommendations that have been earlier issued by Scientific Associations. While confirming the overall superior net clinical benefit of TT in patients at moderate-high thromboembolic risk, recent data suggest that: (1) TT is likely associated with minor rather than major bleeding complications, and (2) accurate stratification of thromboembolic and bleeding risk may allow optimization of the antithrombotic treatment at discharge. Therefore, while still awaiting well designed, prospective, randomized trials, current data indicate that TT is the treatment of choice for patients on OAC at moderate-high thromboembolic risk, provided that meticulous review is frequently carried out in order to minimize and to detect early bleeding complications, while discontinuation of OAC and substitution with dual antiplatelet treatment is warranted in low-risk patients.     

Periprocedural myocardial infarction in patients undergoing complex versus noncomplex percutaneous coronary intervention

Background

Limited data are available on the risk of periprocedural myocardial infarction (MI) in patients undergoing complex versus noncomplex percutaneous coronary intervention (PCI).

Methods

We assessed the risk of periprocedural MI according to the fourth Universal definition of myocardial infarction (UDMI) and several other criteria among patients undergoing elective PCI in a prospective, single-center registry. Complex PCI included at least one of the following: 3 coronary vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, treatment of chronic total occlusion, and use of rotational atherectomy.

Results

Between 2017 and 2021, we included 1010 patients with chronic coronary syndrome, of whom 226 underwent complex PCI (22.4%). The rate of periprocedural MI according to the fourth UDMI was significantly higher in complex compared to noncomplex PCI patients (26.5% vs. 14.5%, p < 0.001). Additionally, periprocedural MI was higher in the complex PCI group using SCAI (4% vs. 1.1%, p = 0.009), ARC-2 (13.7% vs. 8.0%, p = 0.013), ISCHEMIA (5.8% vs. 1.7%, p = 0.002), and EXCEL criteria (4.9% vs. 2.0%, p = 0.032). SYNTAX periprocedural MI occurred at low rates in both groups (0.9% vs. 0.6%, p = 0.657). Complex PCI was an independent predictor of the fourth UDMI periprocedural MI (odds ratio [OR] 1.54, 95% confidence interval [CI]: 1.04–2.27, p = 0.031).

Conclusions

In patients with chronic coronary syndrome undergoing elective PCI, complex PCI is associated with a significantly higher risk of periprocedural MI using multiple definitions. These findings highlight the importance of considering upfront this risk in the planning of complex PCI procedures.     

Dual versus single antiplatelet therapy for patients with long-term oral anticoagulation undergoing coronary intervention: a systematic review and meta-analysis

Objective The main aim of this meta-analysis is to compare the efficacy and safety of dual versus single antiplatelet therapy for patients taking oral anticoagulation (OAC) after coronary intervention. Background The optimal regimen remains controversial patients taking OAC after coronary intervention. Methods PubMed, Embase and Cochrane Central Register of Controlled Trials were searched for eligible studies including data of triple therapy (TT) versus OAC plus single antiplatelet therapy for patients requiring OAC after coronary intervention. The primary outcome was major adverse cardiac and cerebrovascular event (MACCE). The safety outcome was major bleeding. Results Fourteen studies with 32825 patients were included. Among prospective studies, patients with TT had a trend toward a higher risk of major bleeding [odds ratios (OR): 1.56, 95% confidence interval (CI): 0.98–2.49, P = 0.06] and a markedly higher risk of all-cause death (OR; 2.11, 95% CI: 1.10–4.06 P = 0.02) compared with OAC plus clopidogrel. Meanwhile, TT was associated with decreased risks of MACCE (OR: 0.63, 95% CI: 051–0.77 P < 0.0001), all-cause death (OR: 0.45, 95% CI: 0.20–0.97, P = 0.04), and stroke/transient ischemic attack (TIA)/peripheral embolism (PE) (OR: 0.29, 95% CI: 0.09–0.96, P = 0.04) compared with OAC plus aspirin.     

Periprocedural management of anticoagulation and antiplatelet therapies in patients undergoing electrophysiologic procedures

Electrophysiologic studies, radiofrequency ablation, and device implantations including pacemakers and defibrillators have become essential tools in the armamentarium of electrophysiologists. These procedures are being performed in patients with complex comorbidities, many of whom chronically take anticoagulation or antiplatelet agents. Careful management of anticoagulation before, during, and after electrophysiologic procedures including device implantations is critical to minimize bleeding and thrombotic complications and to optimize patient outcomes.     

Impact of triple antithrombotic therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention in real-world practice

Objective The optimal antithrombotic regimen for patients on oral anticoagulation (OAC) after acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI) remains debated. This study sought to evaluate the efficacy and safety of OAC plus clopidogrel with or without aspirin in a real-world setting. Methods We retrospectively analyzed data from an international, multi-center registry between 2003 and 2014 (n = 15,401). Patients with ACS and receiving OAC after PCI were screened. The composite primary endpoint was 1-year all-cause death, re-infarction, or severe bleeding. Results The final analysis enrolled 642 patients including 62 patients (9.7%) with OAC and clopidogrel (dual therapy), and 580 patients (90.3%) with the combination of aspirin, OAC and clopidogrel (triple therapy). Patients on triple therapy were more often female and were more likely to have comorbidities. There was no significant difference regarding the primary end point between dual therapy with triple therapy patients [17.74% vs. 17.24%; unadjusted hazard ratio (HR): 1.035; 95% confidence interval (CI): 0.556–1.929; adjusted HR: 1.026; 95% CI: 0.544–1.937]. However, the re-infarction rate was significantly higher in dual therapy than triple therapy patients (14.52% vs. 5.34%; unadjusted HR: 2.807; 95% CI: 1.329–5.928; adjusted HR: 2.333; 95% CI: 1.078–5.047). In addition, there was no difference between two regimes in all-cause death and severe bleeding. Conclusions In real-life patients with ACS following PCI and with an indication of OAC, triple therapy was not associated with an increased rate of adverse outcomes compared to dual therapy. Moreover, it decreased risk of re-infarction and did not increase risk of severe bleeding.     

预测冠心病患者冠状动脉介入术后长期效果的预测因素

目的:分析预测冠心病患者冠状动脉介入治疗术(PCI)后长期临床效果的预测因素。方法:收集592例冠心病患者PCI后的临床资料并进行随访,随访主要不良心血管事件(MACE)发生情况并经多元logistic回归的方法分析这些事件的相关因素。结果:平均随访时间18.96(3～57)个月。MACE的发生率为7.6%,全因性死亡率为2.4%,非致死性心肌梗死发生率为1.5%。MACE发生的预测因素有PCI方式、近段病变、参考血管的直径及氯吡格雷的应用时间,年龄、有心肌梗死史及氯吡格雷应用时间可预测全因性死亡,术后未戒烟及完全停止抗血小板治疗增加非致死性心肌梗死的危险。结论:高龄、单纯经皮冠状动脉球囊成形术或置入金属裸支架、小血管病变、近段病变和对抗血小板治疗及戒烟的依从性差是预测PCI后不良预后的因素。     

非瓣膜性心房颤动患者围术期的抗凝治疗

大多数非瓣膜性心房颤动(NVAF)患者需长期应用口服抗凝药物,以减少中风及系统性栓塞的风险。这些患者在接受外科手术或侵入性操作时出血风险增加,部分患者在围术期需暂时中断抗凝治疗。近年来,对于NVAF患者围术期暂时中断抗凝治疗的适应症、时间、暂时中断口服抗凝药物后抗凝治疗的桥接,以及术后抗凝治疗的重新应用已有较多的临床研究。本文简要介绍NVAF患者围术期抗凝治疗的研究现状。