替格瑞洛治疗行PCI的ST段抬高型心肌梗死合并糖尿病患者效果观察

目的:观察行PCI治疗的ST段抬高型心肌梗死(STEMI)合并2型糖尿病(DM)患者应用替格瑞洛的有效性与安全性。方法:STEMI合并2型糖尿病患者154例,随机分为替格瑞洛组79例,氯吡格雷组75例,比较分析2组治疗1,6,12个月时全因死亡率、不良心血管事件(MACE)发生率、支架内血栓发生率、左室射血分数、出血事件及呼吸困难等指标。采用血栓弹力图检测2组患者治疗5 d时血小板抑制率和抵抗率。结果:替格瑞洛组1,6,12个月时全因病死率、MACE发生率、支架内血栓发生率较氯吡格雷组比较差异无统计学意义(P>0.05);替格瑞洛组支架内再狭窄发生率低于氯吡格雷组,左室射血分数优于氯吡格雷组(P<0.05);替格瑞洛组呼吸困难发生率高于氯吡格雷组(P<0.05),但症状轻微,无需特殊治疗;2组出血事件发生率比较差异无统计学意义(P>0.05);治疗5 d时替格瑞洛组血小板抑制率高于氯吡格雷组(69.22±12.34)% vs (46.87±22.1)%(P<0.05),血小板抵抗率低于氯吡格雷组(2.53% vs 22.67%)(P<0.05)。结论:在行PCI治疗的STEMI合并DM患者中应用替格瑞洛可改善预后,且安全性好。     

替格瑞洛联合川芎嗪注射液治疗冠心病心绞痛疗效观察

目的 探讨替格瑞洛联合川芎嗪注射液治疗冠心病心绞痛患者的临床疗效.方法 将120例冠心病心绞痛患者按照随机数字表法分为研究组与对照组,各60例.两组均给予替格瑞洛治疗,研究组在此基础上联合川芎嗪注射液治疗.比较两组临床疗效、治疗前后两组心绞痛发作次数及持续时间以及两组左室收缩末期内径、舒张末期内径、左室射血分数、总胆固...     

Clinical implications of drug–drug interactions with P2Y12 receptor inhibitors

Polypharmacy in patients undergoing coronary artery stenting or in those presenting with an acute coronary syndrome is common. Nevertheless, the risk of drug–drug interactions in patients treated simultaneously with P2Y₁₂ receptor inhibitors is less well considered in routine clinical practice. Whereas the irreversible P2Y₁₂ receptor inhibitors clopidogrel and prasugrel are prodrugs requiring cytochrome P450 (CYP) enzymes for metabolic activation, such activation is not necessary for the direct‐acting reversible P2Y₁₂ receptor inhibitor ticagrelor. Several drugs frequently used in cardiology have been shown to interact with the metabolism of P2Y₁₂ receptor inhibitors in pharmacodynamic studies. Whereas several drug–drug interactions have been described for clopidogrel and ticagrelor, prasugrel seems to have a low potential for drug–drug interactions. The clinical implications of these interactions have raised concern. In general, concomitant administration of P2Y₁₂ receptor antagonists and strong inhibitors or inducers of CYP3A/CYP2C19 should be performed with caution in patients treated with clopidogrel/ticagrelor. Under most circumstances, clinicians have the option of prescribing alternative drugs with less risk of drug–drug interactions when used concomitantly with P2Y₁₂ receptor inhibitors.     

替格瑞洛联合溶栓治疗 ST 段抬高型心肌梗死疗效及对患者心肌损伤标志物与炎性因子水平的影响

目的 探讨替格瑞洛联合溶栓治疗ST段抬高型心肌梗死(STEMI)疗效及对患者心肌损伤标志物与炎性因子水平的影响。方法 114例符合纳入标准的STEMI患者随机分为对照组57例和试验组57例。常规治疗基础上,对照组给予氯吡格雷＋尿激酶溶栓治疗,试验组给予替格瑞洛＋尿激酶溶栓治疗。2周后,观察比较两组临床疗效,心电图ST回落、超声心动图及冠脉造影状况,心肌损伤标志物,炎性因子水平及不良反应发生情况。结果 试验组的治疗总有效率为94.7%,明显高于对照组80.7%的总有效率,比较有统计学差异(P＜0.05)。试验组ST回落>50%比率显著高于对照组,LVEF显著高于对照组,LVEDd显著短于对照组,差异均具有统计学意义(P<0.05),两组TIMI 3级比率无显著统计学差异(P>0.05)。治疗后,两组患者损伤标志物CK-MB和cTnI均显著降低;对照组CK-MB和cTnI分别为(16.36±2.45)U·L-1与(1.84±0.39)μg·L-1,试验组CK-MB和cTnI分别为(12.17±2.10)U·L-1与(1.02±0.25)μg·L-1,均显著低于对照组,比较均有统计学差异(P均＜0.05)。治疗后,对照组炎性因子TNF-α和IL-6分别为(103.7±15.4)和(26.7±2.5)ng·L-1,试验组TNF-α和IL-6分别为(76.8±10.9)和(13.8±1.6)ng·L-1,均显著低于对照组,比较均有统计学差异(P均＜0.05)。治疗期间,两组患者均未出现严重不良反应。结论 替格瑞洛联合溶栓是STEMI的有效治疗方案,可以显著提高临床疗效,减轻心肌损伤和炎性反应,且不良反应轻微,临床上值得进一步研究。     

Intestinal permeability and P‐glycoprotein‐mediated efflux transport of ticagrelor in Caco‐2 monolayer cells

Ticagrelor is the unique reversible oral antiplatelet drug commercialized today. During this study, the intestinal permeability of ticagrelor and its potential P‐glycoprotein (P‐gp)‐mediated active transport were assessed. To this end, bidirectional transport of ticagrelor was performed across Caco‐2 (human epithelial colorectal adenocarcinoma) monolayer model in the presence and absence of potent P‐gp inhibitor valspodar. Ticagrelor presented an apical–basolateral apparent permeability coefficient (P_app) of 6.0 × 10^?6 cm/s. On the other hand, mean efflux ratio (ER) of 2.71 was observed for ticagrelor describing a higher efflux permeability compared to the influx component. Valspodar showed a significant inhibitory effect on the efflux of ticagrelor suggesting involvement of P‐gp in its oral disposition. Co‐incubation of the P‐gp inhibitor decreased the efflux P_app of ticagrelor from 1.60 × 10^?5 to 1.13 × 10^?5 cm/s and decreased its ER by 70%. Results suggest a modest active transport of ticagrelor by P‐gp across the Caco‐2 cell monolayer. The co‐administration of ticagrelor with a P‐gp inhibitor seems altogether unlikely to have an extended impact on pharmacokinetics of ticagrelor and cause bleeding events in patients.     

Clopidogrel,prasugrel, ticagrelor or vorapaxar in patients with renal impairment: do we have a winner?

The optimal utilization of antiplatelet therapy in patients with renal impairment (RI) following acute coronary syndromes (ACS) represents an urgent, unmet and yet unsolved need with regards to the choice of agents, duration of treatment and potential dose/regimen adjustment. The lack of any large randomized trials designed and powered specifically in such high-risk patients, absence of the uniformed efficacy and safety data reporting policy to the FDA and endless overoptimistic publications based on post hoc analyses of primary trials sometimes exaggerating benefits and hiding risks, clouds reality. In addition, triaging RI patients is problematic due to ongoing kidney deterioration and the fact that such patients are prone to both vascular occlusions and bleeding. The authors summarize available FDA-confirmed evidence from the latest trials with approved antiplatelet agents, namely clopidogrel (CAPRIE, CURE, CREDO, CLARITY, CHARISMA); prasugrel (TRITON, TRILOGY); ticagrelor (PLATO, and PEGASUS); and vorapaxar (TRACER and TRA2P) in RI patient cohorts on top of aspirin as part of dual antiplatelet therapy (DAPT). We deliberately avoided any results unless they were verified by the FDA, with the exception of the recent PEGASUS, since Agency reviews are not yet available. Despite differences among the trials and DAPT choices, RI patients universally experience much higher (HR = 1.3–3.1) rates of primary endpoint events, and bleeding risks (HR = 1.7–3.6). However, only ticagrelor increases creatinine and uric acid levels above that of clopidogrel; has the worst incidence of serious adverse events, more adverse events, and inferior outcomes in patients with severe (eGFR <30 ml/min), especially in the lowest (eGFR <15 ml/min) RI subsets. Clopidogrel, prasugrel and vorapaxar appear safer. Moreover, less aggressive half dose (5 mg/daily) prasugrel and strict DAPT, are well justified in RI, but not predominantly triple strategies with vorapaxar as tested in TRA2P and especially in TRACER. In conclusion, data from clinical trials, their sub-studies and affiliated FDA reviews indicate that RI cause more vascular occlusions and bleeding in ACS patients treated with DAPT. Among the novel antiplatelet agents, prasugrel and vorapaxar, but probably not ticagrelor, offer advantage in RI patients.     

Modern antiplatelet agents in coronary artery disease

Dual antiplatelet therapy is well recognized in the prevention of thrombotic complications of acute coronary syndrome and percutaneous coronary interventions. Despite clinical benefits of aspirin and clopidogrel therapy, a number of limitations curtail their efficacy: slow onset of action, variability in platelet inhibitory response and potential drug–drug interactions. Furthermore, the single platelet-activation pathway targeted by these agents allows continued platelet activation via other pathways, ensuring incomplete protection against ischemic events, thus, underscoring the need for alternate antiplatelet treatment strategies. A number of novel antiplatelet agents are currently in advance development and many have established superior effects on platelet inhibition, clinical outcomes and safety profile than clopidogrel in high-risk patients. The aim of this review is to provide an overview of the current status of P2Y12 receptor inhibition and PAR-1 antagonists in determining a future strategy for individualized antiplatelet therapy.