Impact of concomitant use of proton pump inhibitors and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome

Background There is great debate on the possible adverse interaction between proton pump inhibitors (PPIs) and clopidogrel. In addition, whether the use of PPIs affects the clinical efficacy of ticagrelor remains less known. We aimed to determine the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods We retrospectively analyzed data from a “real world”, international, multi-center registry between 2003 and 2014 (n = 15,401) and assessed the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year composite primary endpoint (all-cause death, re-infarction, or severe bleeding) in patients with ACS after PCI. Results Of 9,429 patients in the final cohort, 54.8% (n = 5165) was prescribed a PPI at discharge. Patients receiving a PPI were older, more often female, and were more likely to have comorbidities. No association was observed between PPI use and the primary endpoint for patients receiving clopidogrel (adjusted HR: 1.036; 95% CI: 0.903–1.189) or ticagrelor (adjusted HR: 2.320; 95% CI: 0.875–6.151) (P_interaction = 0.2004). Similarly, use of a PPI was not associated with increased risk of all-cause death, re-infarction, or a decreased risk of severe bleeding for patients treated with either clopidogrel or ticagrelor. Conclusions In patients with ACS following PCI, concomitant use of PPIs was not associated with increased risk of adverse outcomes in patients receiving either clopidogrel or ticagrelor. Our findings indicate it is reasonable to use a PPI in combination with clopidogrel or ticagrelor, especially in patients with a higher risk of gastrointestinal bleeding.     

Homocysteine levels and platelet reactivity in coronary artery disease patients treated with ticagrelor

Background and aimRecurrent atherothrombotic events have been reported in certain higher risk subsets of patients even with ticagrelor, a potent first-line antiplatelet agent for the management of patients with acute coronary syndrome (ACS). Hyperhomocysteinemia is a known determinant of platelet function abnormalities. Therefore, the aim of our study was to evaluate the impact of homocysteine (Hcy) levels on platelet reactivity in patients receiving Ticagrelor.Methods and resultsPatients with ACS undergoing percutaneous coronary revascularization and on dual antiplatelet therapy with ASA + Ticagrelor (90mg/twice a day) were scheduled for platelet function assessment 30–90 days post-discharge. Aggregation tests were performed by Multiple Electrode Aggregometry (MEA). Suboptimal platelet inhibition HRPR-high residual platelet reactivity was defined if above the lower limit of normality (417 AU*min).We included 432 patients, divided according to Hcy tertiles. Higher Hcy levels were associated with age, renal failure, creatinine levels and use diuretics (p < 0.001).Patients with higher Hcy levels displayed a higher platelet reactivity at COL test (p = 0.002), and ADP test (p = 0.04), with a linear relationship between Hcy and platelet aggregation after stimulation with collagen (r = 0.202, p < 0.001), thrombin receptor peptide (r = 0.104, p = 0.05) and ADP (r = 0.145, p = 0.006).However, Hcy levels did not significantly affect the rate of HRPR with Ticagrelor (9.9% vs 13.7% vs 10.7%, p = 0.89; adjusted OR [95% CI] = [0.616–1.51], p = 0.99).ConclusionsAmong patients with ACS, despite the elevated platelet reactivity associated to hyperhomocysteinemia, DAPT with ticagrelor could overcome such phenomenon, achieving an adequate platelet inhibition in the majority of the patients.     

替格瑞洛对经皮冠状动脉介入治疗老年急性ST段抬高型心肌梗死患者的疗效及安全性

目的探讨替格瑞洛对老年急性ST段抬高型心肌梗死(STEMI)患者经皮冠状动脉介入治疗(PCI)的疗效及安全性。方法回顾性分析208例STEMI老年患者,根据用药不同分为替格瑞洛组103例和氯吡格雷组105例。两组患者均接受PCI治疗,术前均口服阿司匹林300 mg,继以100 mg/d,此外,替格瑞洛组口服替格瑞洛180 mg,继以每次90 mg,2次/d,氯吡格雷组口服氯吡格雷600 mg,继以75 mg/d,两组患者均治疗12个月。比较两组患者PCI术后冠状动脉血流情况,血小板聚集率,左心室射血分数(LVEF)、左心室舒张末期内径(LVEDD),出血事件以及主要心血管不良事件(MACE)。结果替格瑞洛组患者PCI术后心肌梗死的溶栓治疗(TIMI)分级优于氯吡格雷组患者(Z=2.58,P=0.010),无复流或慢血流发生率低于氯吡格雷组患者的6.8%(7/103)与19.1%(20/105),χ^2=6.91,P=0.009。重复资料方差分析结果显示,两组患者血小板聚集率均随时间降低(F时间=87.54,P<0.001)。替格瑞洛组患者血小板聚集率下降幅度高于氯吡格雷组(F时间×组间=6.16,P<0.001)。替格瑞洛组患者血小板聚集率整体水平低于氯吡格雷组患者(F组间=17.84,P<0.001)。各时间点组间比较,替格瑞洛组患者血小板聚集率在术后1 h、1 d和3 d低于氯吡格雷组(t分别为14.39,13.19,6.53,P均<0.001)。两组患者PCI术后LVEF均升高(t分别为7.46,4.33,P均<0.001),组间比较,替格瑞洛组患者LVEF高于氯吡格雷组(t=4.28,P<0.001);两组患者PCI术后LVEDD均下降(t=9.36,6.47,P均<0.001),组间比较,替格瑞洛组患者LVEF低于氯吡格雷组(t=4.38,P<0.001)。两组患者出血和MACE发生率差异无统计学意义(χ^2=0.91,2.32,均P>0.05)。结论替格瑞洛在PCI术治疗老年STEMI中,抗血小板聚集效果好,能够降低无复流或慢血流发生率,改善患者心功能。     

替格瑞洛用于经皮冠状动脉介入治疗术后患者抗血小板治疗短期内的有效性和安全性研究

目的：观察替格瑞洛用于经皮冠状动脉介入治疗（PCI）患者抗血小板治疗的有效性和安全性。方法选择50例冠心病PCI术后应用氯吡格雷抗血小板,因血小板聚集率不达标且CYP2C19基因异常而改用替格瑞洛的患者。所有入选患者应用阿司匹林首次负荷剂量300 mg,维持剂量100 mg,每日一次;替格瑞洛维持剂量90 mg,每日二次,持续1年。研究主要终点为随访1个月的主要不良心血管事件（包括死亡、支架内血栓形成、支架内再狭窄、非致死性心肌梗死、靶血管血运重建）和脑卒中的发生率;次要终点为一般不良事件（包括轻微出血、过敏、呼吸困难）的发生率及血小板计数的变化情况。结果患者应用替格瑞洛后随访1个月未出现主要不良心血管事件和脑卒中;一般不良事件的发生率较低,2例（4%）出现呼吸困难,2例（4%）发生轻微出血,其中1例鼻出血,1例皮下淤血。应用替格瑞洛后血小板聚集率明显低于氯吡格雷,血小板计数未明显下降。结论替格瑞洛用于存在氯吡格雷抵抗的PCI患者抗血小板治疗,短期内安全有效。     

替格瑞洛用于急性冠脉综合征行经皮冠状动脉介入治疗术后抗血小板疗效分析

目的观察急性冠脉综合征(ACS)患者经皮冠状动脉介入(PCI)治疗后应用替格瑞洛的临床疗效与安全性。方法随机选取沈阳军区总医院2015年1—3月收治的ACS患者201例,均行PCI治疗,其中,101例接受替格瑞洛治疗,作为研究组(n=101)。选取同期接受氯吡格雷治疗的100例患者作为对照组(n=100)。两组患者术后均给予双联抗血小板治疗,在阿司匹林(100 mg,1次/d)基础上,研究组服用替格瑞洛(90 mg,2次/d),对照组服用氯吡格雷(75 mg,1次/d)。术后12个月,观察两组患者主要不良心脑血管事件(MACCE)及不良反应。结果研究组患者MACCE发生率明显低于对照组,差异有统计学意义(P<0.05);研究组患者出血发生率高于对照组,差异有统计学意义(P<0.05);研究组患者呼吸困难发生率高于对照组,差异有统计学意义(P<0.05)。结论替格瑞洛用于ACS患者行PCI术后的抗血小板治疗,临床疗效确切,但有一定出血风险和呼吸困难症状。     

替格瑞洛对非ST段抬高急性冠脉综合征患者预后及血小板聚集率的影响

目的：探讨替格瑞洛对非ST段抬高急性冠脉综合征(NSTE-ACS)患者预后及血小板聚集率的影响。方法选择2013年6月至2014年12月在东莞市常平医院心内科住院的NSTE-ACS患者170例,将其按照随机数表法随机分为氯吡格雷组(85例,氯吡格雷+阿司匹林)和替格瑞洛组(85例,替格瑞洛+阿司匹林),连续治疗24周。在治疗前及治疗后1周用比浊法测定两组患者的血小板聚集率。随访24周,观察两组患者的心血管事件发生率及出血事件发生率。结果治疗1周后,氯吡格雷组与替格瑞洛组患者的血小板聚集率分别为(54.8±5.2)%与(47.6±4.9)%,两组患者的血小板聚集率与治疗前[(60.4±5.8)%、(62.1±6.5)%]比较显著降低(P<0.05),且替普瑞洛组的血小板聚集率下降幅度明显大于氯吡格雷组,差异均有统计学意义(P<0.05;随访24周期间,氯吡格雷组与替格瑞洛组心血管事件发生率分别为27.1%(23/85)与12.9%(11/85),差异有统计学意义(P<0.05)。氯吡格雷出血事件发生率为3.53%(3/85),替格瑞洛组为5.88%(5/85),两组比较差异无统计学意义(P>0.05)。结论替格瑞洛可以明显降低血小板聚集率,具有比氯吡格雷更强的抗血小板聚集作用,能够降低NSTE-ACS患者心血管事件发生率,且出血并发症无明显增加。     

替格瑞洛在急性冠脉综合征患者介入治疗中的近期疗效评价

目的 探讨替格瑞洛对急性冠脉综合征(acute coronary syndrome,ACS)患者介入治疗近期临床疗效的影响.方法 将入选的拟行冠状动脉支架植人术(percutaneous coronary intervention,PCI)的ACS 283例患者随机分为对照组(氯吡格雷+常规治疗)和试验组(替格瑞洛+常规治疗).检测两组PCI治疗前后TIMI血流分级、血小板聚集率和血小板计数;随访30 d,记录心血管不良事件(MACE)发生率;观察治疗后出血并发症的发生率.结果 两组患者PCI术前TIMI血流分级比较,差异无统计学意义(P＞0.05),术后试验组TIMI血流3级例数明显高于对照组(P＜0.05);PCI术后试验组血小板聚集率为0.27±0.08,明显低于对照组的0.37±0.09(P＜0.05);术后随访30 d,与对照组比较,试验组MACE发生率明显低于对照组(P＜0.05);而对照组与试验组出血并发症发生率无明显差异(P＞0.05).结论 对于行PCI的ACS患者,替格瑞洛能有效改善患者术后TIMI血流分级,降低血小板聚集率,改善近期临床疗效,且不增加出血风险.     

替格瑞洛在在急性ST段抬高型心肌梗死合并糖尿病患者行经皮冠状动脉介入术上的临床疗效及安全性

目的 探究替格瑞洛在急性ST段抬高型心肌梗死（STEMI）合并糖尿病患者行经皮冠状动脉介入术（PCI）上的临床疗效及安全性。方法 将我院于2011年10月~2015年9月收治的124例急性STEMI合并糖尿病患者纳入本次研究,所有入选患者均行急诊PCI治疗,按照用药种类的不同上述患者均分为替格瑞洛组和氯吡格雷组。对比用药前后两组患者的血小板聚集率及PCI手术前后两组患者的心功能水平变化。并在PCI术后1年对两组患者的TIMI血流情况进行分级比较,同时对两组患者的心血管事件发生情况及出血风险发生情况进行比较。结果 用药前,两组患者在血小板聚集率上无明显差异（P〉0.05）,用药后1 h、24 h、48 h,替格瑞洛组的血小板聚集率明显低于氯吡格雷组（P〈0.05）;术后1年,替格瑞洛组的TIMI血流分级优于氯吡格雷组,同时替格瑞洛组的LVEF及LVEDD水平与氯吡格雷组比较也存在显著性差异,组间差异有统计学意义（P〈0.05）;1年后,替格瑞洛组的心血管事件发生率为4.48%,氯吡格雷组为16.13%,两组比较差异显著（P〈0.05）,而两组患者出血风险发生上比较无显著性差异（P〉0.05）。结论在急性STEMI合并糖尿病患者行急诊PCI治疗上,替格瑞洛的临床疗效优于氯吡格雷,其抗血小板聚集效果优于氯吡格雷,安全性良好。     

抗凝血药替卡格雷

替卡格雷（Ticagrelor；曾用代号：ADZ6140，ARC126532）属于环戊基三唑并嘧啶类化合物，化学名为（1S，2S，3R，5s）-3-[7-[（1R，2S）-2-（3，4-二氟苯基）环丙氨基]-5-（硫丙基）-3H-[1，2，3]三唑[4，5-d]嘧啶-3-基]-5-（2-羟基乙氧基）环戊烷-1，2-二醇，是由美国阿斯利康（AstraZeneca）公司研发的一种新型的、具有选择性的小分子抗凝血药。该药能可逆性地作用于血管平滑肌细胞（VSMC）上的嘌呤2受体（purinoceptor 2，P2）亚型P2Y12，对ADP引起的血小板聚集有明显的抑制作用，且口服使用后起效迅速，因此能有效改善急性冠心病患者的症状。