Premature Ticagrelor Discontinuation in Secondary Prevention of Atherosclerotic CVD: JACC Review Topic of the Week

Ticagrelor is a cornerstone of modern antithrombotic therapy alongside aspirin in patients with acute coronary syndrome and after percutaneous coronary intervention. Adverse effects such as bleeding and dyspnea have been associated with premature ticagrelor discontinuation, which may limit any potential advantage of ticagrelor over clopidogrel. The randomized trials of ticagrelor captured adverse events, offering the opportunity to more precisely quantify these effects across studies. Therefore, a meta-analysis of 4 randomized clinical trials of ticagrelor conducted between January 2007 and June 2017 was performed to quantify the incidence and causes of premature ticagrelor discontinuation. Among 66,870 patients followed for a median 18 months, premature ticagrelor discontinuation was seen in 25%; bleeding was the most common cause of discontinuation followed by dyspnea. Versus the comparators, the relative risk of dyspnea-related discontinuation during follow-up was 6.4-fold higher, the relative risk of bleeding was 3.2-fold higher, and the relative risk of discontinuation due to any adverse event was 59% higher for patients receiving ticagrelor. Understanding these potential barriers to adherence to ticagrelor is crucial for informed patient-physician decision making and can inform future efforts to improve ticagrelor adherence. This review discusses the incidence, causes, and biological mechanisms of ticagrelor-related adverse effects and offers strategies to improve adherence to ticagrelor.     

Ticagrelor Versus Clopidogrel in Patients With STEMI Treated With Fibrinolysis: TREAT Trial

BackgroundThe efficacy of ticagrelor in the long-term post–ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain.ObjectivesThe purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy.MethodsThis international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age <75 years) with STEMI receiving fibrinolytic therapy. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months.ResultsThe combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups.ConclusionAmong patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088)     

不同抗血小板治疗策略对非透析慢性肾功能不全患者冠状动脉搭桥术后胸廓内动脉及大隐静脉桥血管通畅率的影响

目的 比较阿司匹林联合替格瑞洛或者氯吡格雷的双联抗血小板药物治疗(DAPT)，对慢性肾功能不全患者冠脉搭桥手术（CABG）术后早期桥血管通畅率的影响。方法 我科接受CABG手术患者77例，随机纳入A组（阿司匹林+替格瑞洛）与B组（阿司匹林+氯吡格雷）。A组35例，B组42例。术后1年行计算机断层扫描血管造影（CTA）检查，评估桥血管通畅性。并随访主要心血管事件、出血事件发生情况。结果 随访期间7例失访。70例完成CTA检查，A组32例，B组38例。静脉桥血管通畅率A组显著高于B组（46/51 90.2% vs 42/56 75.0%，P=0.024）。小型出血事件发生率A组高于B组（P=0.022）。Logistic回归分析提示替格瑞洛+阿司匹林双联抗血小板治疗可以降低桥血管狭窄风险（OR=0.193, 95%CI=0.043 0.861，P=0.031）。结论 在CKD患者接受冠状动脉搭桥术后，DAPT替格瑞洛联合阿司匹林可能更好地维护静脉桥血管的通畅率，并未增加主要出血事件的风险。     

PCI术后患者抗血小板治疗方案的药物经济学评价

目的 从医疗保险角度,对经皮冠脉支架置入（percutaneous coronary intervention,PCI）术后3种抗血小板药物治疗方案进行经济学评价。方法 3种治疗方案为在使用阿司匹林基础上,经验性给予国产氯吡格雷,或经验性给予替格瑞洛,或根据CYP2C19基因型指导选择国产氯吡格雷或替格瑞洛,由此建立决策树模型并进行成本效果分析,预测该3种方案避免主要心血管事件的发生率以及成本,研究时间为1年。结果 经验性给予国产氯吡格雷联合阿司匹林治疗方案为成本最低方案,但直接给予替格瑞洛联合阿司匹林治疗方案的经济性最好。结论 对于PCI术后的患者,最推荐直接采用替格瑞洛联合阿司匹林的治疗方案。     

替格瑞洛治疗急性冠状动脉综合征患者的临床研究

目的观察长期服用替格瑞洛对急性冠状动脉综合征患者的临床疗效及其对肌钙蛋白T(cTnT)、脑钠素(BNP)、C-反应蛋白(CRP)和D-二聚体(D-D)水平的影响。方法将84例急性冠状动脉综合征患者随机分为对照组42例和试验组42例。2组均给予常规治疗及对症治疗,术前服用阿司匹林150mg联合氯吡格雷300 mg,口服,每日1次,持续用药7 d,进行经皮冠状动脉介入(PCI)术。对照组术后服用阿司匹林100 mg,每日1次,连续服用6个月。试验组术后服用阿司匹林100 mg+替格瑞洛90 mg,每日1次,连续服用6个月。比较2组患者的临床疗效和急性心肌梗死发作次数、发作持续时、ST段下移水平、cTnT、BNP、CRP、D-D水平及药物不良反应发生情况。结果治疗后,对照组和试验组临床总有效率分别为78.57%(33例/42例)和95.24%(40例/42例),差异有统计学意义(P<0.05)。对照组和试验组治疗后急性心肌梗死发作次数分别为(4.52±0.55)和(2.02±0.27)次/周,发作持续时间分别为每次(4.14±0.43)和(2.76±0.31)min,ST段下移水平1.25±0.17和0.63±0.07,差异均有统计学意义(均P<0.05)。治疗后,对照组血清cTnT、BNP、CRP、D-D水平分别为(1.54±0.18)ng·mL^-1,(63.52±6.73)ng·mL^-1,(8.94±0.94)mg·mL^-1和(133.53±15.73)ng·mL^-1,试验组分别为(0.25±0.03)ng·mL^-1,(28.43±3.02)ng·mL^-1,(4.57±0.55)mg·mL^-1和(59.54±5.74)ng·mL^-1,差异均有统计学意义(均P<0.05)。对照组出现头痛2例,腹泻2例,恶心呕吐1例,眩晕2例,药物不良反应发生率为16.67%(7例/42例);试验组出现胃肠道出血1例,血肌酸酐轻度上升1例,眩晕1例,药物不良反应发生率为7.14%(3例/42例),2组差异无统计学意义(P>0.05)。结论长期服用替格瑞洛治疗急性冠状动脉综合征患者的临床疗效显著,安全性高。     

Ticagrelor for the prevention of ischemic events in patients with prior myocardial infarction and peripheral artery disease

Introduction: Cardiovascular disease (CVD) is the main cause of death in the world. Coronary artery disease (CAD) is the most common form of CVD presentation, but the prevalence of peripheral artery disease (PAD) is increasing. Patients with polyvascular disease comprise a very high-risk population that has been infrequently studied.

Areas covered: The authors review the current evidence of the efficacy and safety of ticagrelor in the setting of acute coronary syndrome and stable patients post-MI with and without PAD and summarize its pharmacokinetics, pharmacodynamics, and regulatory issues.

Expert opinion: Randomized studies showed that ticagrelor is superior to clopidogrel in patients with acute coronary syndromes, and is superior to placebo in the chronic phase (>1 year) post-myocardial infarction. Sub-analyses of these studies suggest that patients with myocardial infarction and PAD, compared to patients without these characteristics, may have greater benefit with ticagrelor. Nonetheless, the global evidence about the role of ticagrelor in patients with myocardial infarction and PAD remains relatively sparse, and a prospective randomized trial testing this hypothesis would be necessary to provide more definite data regarding the efficacy and safety of ticagrelor in this very high-risk population.     

P2Y12 receptor inhibitors for secondary prevention of ischemic stroke

Introduction: Ischemic stroke (IS) is a major cause of death and disability worldwide. The P2Y₁₂ receptor plays a critical role in the formation of a stable thrombus leading to ischemic complications. Therefore, P2Y₁₂ receptor inhibitors constitute a major antiplatelet strategy in the secondary prevention of IS.

Areas covered: We searched articles about P2Y₁₂ receptor inhibitors and stroke in PubMed published until December 2014. This is a comprehensive review of the role of P2Y₁₂ receptor inhibitors alone and in combination with aspirin in the secondary prevention of noncardioembolic stroke.

Expert opinion: The potential benefit of more potent antiplatelet therapy for secondary stroke prevention must be weighed against the risk of bleeding in patients with IS. Short-term (≤ 3 months) dual antiplatelet therapy with clopidogrel and aspirin that is initiated early after IS or transient ischemic attack due to large artery atherosclerosis appears most efficient.