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.     

Limited early antiplatelet effect of 300 mg clopidogrel in patients with aspirin therapy undergoing percutaneous coronary interventions

Aim Our aim was to evaluate the early efficacy and variabilityof the platelet inhibition exerted by 300 mg clopidogrel forthe purpose of acute percutaneous coronary interventions usingplatelet function tests. Methods and results Elective percutaneous coronary interventionwas used as a timely model in which clopidogrel was added toongoing acetylsalicylic acid (aspirin) (100 mg/day) at 2.5 hprior to procedure. Blood samples were collected before administrationof clopidogrel and immediately before the intervention from50 patients. Platelet functions were assessed with traditionalaggregation and PFA-100^®. At baseline, 14 (28%) patients were poor responders to aspirinaccording to PFA and 9 (18%) continued to show arachidonic acid-inducedaggregation. After clopidogrel ADP-triggered aggregation wasonly modestly inhibited in 40% of the patients. Eight percentof the study population was left without any measurable antiplateleteffect. The patients with modest response to clopidogrel hadhigher levels of c-peptide (1.5 nmol/L) than the ones respondingwell (0.9 nmol/L, ). Conclusion Neither ongoing aspirin treatment nor added clopidogreldid reach an expected extent of platelet inhibition. This studyshows that aspirin-treated patients undergoing PCI gain highlyvariable levels of platelet inhibition with short-term clopidogrel300 mg. At 2 h after adding clopidogrel it failed to enhance platelet inhibition in 40% of the patients.In future, targeted platelet function tests may be helpful toindividually select an effective antiplatelet medication forthese patients. This study suggests that for acute PTCA clopidogreldoes not reach the optimal antithrombotic efficacy in all patients.     

Optimizing Platelet P2Y12 Inhibition for Patients Undergoing PCI

Guidelines recommend that dual antiplatelet therapy using aspirin and clopidogrel should be administered to the majority of patients with acute coronary syndromes, including those undergoing percutaneous coronary intervention (PCI). However, the results of a large randomized, placebo‐controlled study suggest that a 300‐mg loading dose of clopidogrel must be administered at least 15 h prior to PCI in order to achieve a significant reduction in peri‐PCI thrombotic events. Other data suggest that 2 h of pretreatment may be sufficient if a 600‐mg loading dose is used. Since it is often difficult to achieve an adequate pretreatment goal with clopidogrel in clinical practice, more rapid achievement of platelet P2Y₁₂ inhibition may improve patient outcomes. Prasugrel, [6‐[2‐(3,4‐diflurophenyl) cyclopropyl1‐1‐y1] amino‐2‐propylthio‐9?‐D‐ribofuranosyl‐9H‐purine (AZD6140), and cangrelor are platelet P2Y₁₂ receptor antagonists currently in development that offer faster acting inhibition of adenosine diphosphate (ADP)—induced platelet aggregation. These agents act upon the same platelet receptor as clopidogrel, but are distinguished by their routes of administration, reversibility, and pharmacodynamic properties. Prasugrel is an orally administered agent that provides faster, higher, and more consistent inhibition of platelet aggregation than clopidogrel. The results of Phase II testing suggest that the risk of bleeding is similar in prasugrel‐ and clopidogrel‐treated patients. AZD6140 is another orally administered platelet inhibitor with rapid and reversible action. Again, Phase II testing suggests similar bleeding risk for clopidogrel. Preliminary evidence suggests that clinical outcomes may be better in prasugrel‐ and AZD6140‐treated patients than in clopidogrel‐treated patients. Cangrelor is an intravenously administered, reversible, short‐acting agent with a rapid onset of activity. Bleeding risk and clinical outcomes data are similar in cangrelor‐ and abciximab‐treated patients. The results of ongoing Phase III clinical trials involving more than 40,000 patients will demonstrate whether these agents fulfill their potential to improve outcomes in PCI‐treated patients by providing faster, higher, and more consistent inhibition of platelet aggregation.     

Clopidogrel and thrombopenia. A case report

We report our experience with a case of isolated profound thrombocytopenia after clopidogrel (thienopyridine) administration. No adverse event such as bleeding or thrombotic event had occurred, although clopidogrel has been discontinued two weeks after the coronary artery stenting. Despite the safety of clopidogrel, this case demonstrates that clopidogrel can be associated not only with thrombotic thrombocytopenic purpura but also with isolated thrombocytopenia.     

阿司匹林联合氯吡格雷治疗脑梗死的效果分析

目的探讨阿司匹林联合氯吡格雷治疗脑梗死的有效性和安全性。方法选择68例新发脑梗死患者,分为阿司匹林组（对照组）、氯吡格雷联合阿斯匹林组（治疗组）,持续治疗21 d,患者治疗前后分别进行NIHSS评分,并监测治疗前后血清hs-CRP水平。结果治疗组总有效率与对照组比较,差异有统计学意义（P〈0.05）;治疗组治疗前后血清hs-CRP水平降低程度差异有统计学意义（P〈0.05）,而对照组差异无统计学意义（P〉0.05）。结论阿司匹林联合氯吡格雷治疗急性脑梗死的效果明显,临床不良反应少,未见严重出血事件,安全性较高。     

阿司匹林联合氯吡格雷治疗大脑中动脉狭窄脑梗死的临床研究

目的分析阿司匹林联合氯吡格雷治疗大脑中动脉狭窄脑梗死的临床效果及用药安全性。方法将本院神经内科收治的90例急性大脑中动脉狭窄脑梗死患者根据入院顺序随机分为对照组和治疗组,每组各45例,其中对照组口服阿司匹林,治疗组在对照组治疗方案的基础上加用氯吡格雷,均以2个月为1个疗程,1个疗程结束后比较两组患者改良Fugl-Meyer上肢体综合功能评分、改良Barthel指数评分以及脑梗死进展率、复发率。结果两组患者VAS、Fugl-Meyer、Barthel指数评分比较,差异有统计学意义（P〈0.05）,治疗组优于对照组;治疗组脑梗死进展率、复发率低于对照组（P〈0.05）。结论阿司匹林联合氯吡格雷治疗急性大脑中动脉狭窄脑梗死的效果明显,可提高患者的生活质量,缩短患者重返社会的时间。     

药物基因组学与抗血小板药物抵抗研究进展

阿司匹林和氯吡格雷是急性冠状动脉综合征和经皮冠状动脉介入术后的基础抗栓药物,但其疗效存在明显个体差异,部分患者出现药物抵抗。本文综述基因多态性与上述药物反应变异性的关联,以促进基因检测有助于治疗方案的决策。     

阿托伐他汀与瑞舒伐他汀分别联合波立维治疗不稳定型心绞痛的疗效观察

目的：对比观察阿托伐他汀与瑞舒伐他汀分别联合波立维（硫酸氢氯吡格雷）治疗不稳定型心绞痛的疗效。方法将122例不稳定型心绞痛患者随机分为研究组和对照组各61例。研究组采用阿托伐他汀联合波立维治疗,对照组采用瑞舒伐他汀联合波立维治疗。比较2组临床疗效、心电图改善和不良反应发生率。结果2组临床疗效、心电图改善情况、不良反应比较差异均无统计学意义（P＞0．05）。结论阿托伐他汀联合波立维与瑞舒伐他汀联合波立维治疗不稳定型心绞痛均能够有效改善患者的症状,临床疗效较好,不良反应率低,安全有效,值得临床推广和应用。     

氯吡格雷联合速效救心丸治疗急性冠状动脉综合征的临床效果观察

目的：观察氯吡格雷联合速效救心丸治疗急性冠状动脉综合征的临床效果,以探讨其临床适用性。方法选择2012年3月~2013年12月于本院就诊的88例急性冠状动脉综合征患者,简单随机分为试验组45例和对照组43例,对照组给予氯吡格雷治疗,试验组则采用氯吡格雷联合速效救心丸治疗。观察两组患者的治疗效果及血液流变学的改善情况。结果试验组患者的心电图治疗有效率为93.33%,对照组为76.74%,两组比较差异有统计学意义（χ2=4.8063,P=0.0284）。试验组患者的治疗有效率为95.56%,对照组为81.40%,两组比较差异有统计学意义（字2=4.3773,P=0.0364）。患者服药后均未出现明显出血等不良反应;试验组患者的全血黏度和血浆黏度的改善情况均优于对照组,差异均有统计学意义（P〈0.05）,试验组患者的血小板黏附率与对照组相当,差异无统计学意义（P〉0.05）。结论氯吡格雷联合速效救心丸治疗急性冠状动脉综合征更有效、安全,适合临床推广应用。