替格瑞洛对比氯吡格雷治疗东亚ACS患者有效性和安全性的Meta分析

目的:系统性评价替格瑞洛对比氯吡格雷治疗东亚急性冠状动脉综合征(ACS)患者的有效性和安全性,旨在为临床用药提供循证参考。方法:计算机检索Cochrane图书馆、PubMed、Embase、中国知网、万方数据库等,收集替格瑞洛(试验组)对比氯吡格雷(对照组)治疗东亚ACS患者的随机对照试验(RCT)。筛选文献、提取数据后采用Cochrane系统评价员手册5.1.0推荐的偏倚风险评估工具对纳入文献进行质量评价,采用Rev Man 5.3统计软件进行Meta分析。结果:共纳入5项RCT,共计4511例患者。Meta分析结果显示,两组患者主要心血管不良事件发生率[OR=0.85,95%CI(0.68,1.04),P=0.12]、心血管原因死亡率[OR=0.76,95%CI(0.57,1.03),P=0.08]、脑卒中发生率[OR=0.77,95%CI(0.48,1.24),P=0.28]比较,差异均无统计学意义;试验组患者主要出血事件发生率[OR=1.54,95%CI(1.19,1.99),P=0.001]、次要出血事件发生率[OR=1.80,95%CI(1.40,2.32),P<0.00001]均显著高于对照组。结论:替格瑞洛在降低东亚ACS患者的主要心血管不良事件、心血管原因死亡以及脑卒中的发生风险等方面的作用与氯吡格雷相当,但该药会增加患者主要出血、次要出血事件的发生风险。     

Therapeutic experience of ticagrelor in Indian patients with acute coronary syndrome: A non-interventional,prospective, and observational study

ObjectiveThis observational study was designed to understand the usage pattern of ticagrelor in real-life clinical practice among a large number of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), or medical management (MM). The study also recorded clinical events, i.e., bleeding, dyspnea, and cardiovascular (CV) events, reported by the investigator during the follow-up period.MethodsThe ACS patients aged ≥18 years hospitalized for ACS and were prescribed ticagrelor upon discharge or ≤1 month and patients who underwent PCI, CABG, or MM for ACS were enrolled. The subjects were followed up for a period of up to 12 months. The data were collected on a case report form.ResultThe study recruited 2997 subjects from 49 sites in India. Approximately half of the ACS subjects had ST segment elevation myocardial infarction (48.9%), and PCI was used as management in 92.4% subjects. The mean (±SD) duration of use of ticagrelor was 314 (±110.2) days over a period of 12 months. Of 136 subjects (4.5%) who experienced any clinical events, CV deaths were reported in 20 (0.7%), myocardial infraction in 19 (0.6) subjects and ischemic stroke in 23 (0.8%) subjects, and severe dyspnea was reported in 68 (2.2%) subjects. Out of 33 bleeding cases, 25 (0.8%) subjects had thrombolysis in myocardial infarction (TIMI) minimal, seven (0.2%) had TIMI minor, and one TIMI major. Platelet inhibition and patient outcomes (PLATO) major was reported in two subjects and CABG bleed in one subject. The incidence of PLATO defined major and minimal bleeding were lower in subjects undergoing fibrinolysis than overall population.ConclusionTicagrelor has been used across ACS types and in different management strategies in real world settings in India. The incidence of clinical events was lower as compared with data in literature. ClinicalTrials.gov Identifier: NCT02408224     

替格瑞洛对急性冠状动脉综合征患者血小板聚集的影响

目的比较替格瑞洛和氯吡格雷对急性冠状动脉综合征(ACS)患者血小板聚集的影响。方法 81例ACS患者被随机分为替格瑞洛组(A组,41例)和氯吡格雷组(B组,40例),比较两组服药前和服药后1、2、4、8、24h及治疗第7天的血小板最大聚集率(PMAR)、血小板聚集抑制率(IPA)及出血事件。结果两组服药前PMAR水平相近(P>0.05)。A组患者服药期间的PMAR均低于B组(P<0.01),IPA及IPA≥50%的患者比例均高于B组(P<0.01)。B组服药后2h的IPA低于服药后8h(P<0.01),而A组两个时间段IPA差异无统计学意义(P>0.05)。两组均只有轻微出血事件。结论在ACS患者,替格瑞洛较氯吡格雷更能有效地抑制血小板聚集;两药短期的安全性相仿。     

经皮冠脉介入法围术期替格瑞洛联合替罗非班抗血小板出血风险临床观察

目的:观察经皮冠脉介入法(percutaneous coronary intervention,PCI)围术期替格瑞洛联合替罗非班抗血小板出血风险。方法:回顾性分析我院急性冠脉综合征并成功完成PCI手术的患者328例,其中替格瑞洛组172例,氢氯吡格雷组156例,所有患者均在术后给予替罗非班11.5 h,并长期口服阿司匹林100 mg,1次/d。分析患者临床资料观察PCI术后30 d内出血情况。结果:两组患者间一般情况、危险因素、临床资料、临床用药及PCI数据等均无统计学意义。替格瑞洛联合替罗非班组和氢氯吡格雷联合替罗非班组,两组均未见致命性出血患者。替格瑞洛组发生非致命性出血发生率为9.30%;氯吡格雷组为7.05%,两组比较差异无统计学意义(χ2=0.157,P>0.05)。结论:与氢氯吡格雷相比,PCI术后替格瑞洛联合替罗非班不会增加患者的出血风险。     

急性ST段抬高型心肌梗死急救治疗中应用替格瑞洛与阿司匹林的临床价值

目的研究替格瑞洛联合阿司匹林治疗急性ST段抬高型心肌梗死(STEMI)患者的临床价值。方法选择2014年2月至2017年2月期间我院收治的68例急性STEMI患者,随机分为两组各34例。对照组采用氯吡格雷联合阿司匹林治疗,观察组采用替格瑞洛联合阿司匹林治疗。观察两组患者的心功能情况以及血常规指标。结果治疗前,两组的LVEF、 WMSI、 cTnI水平比较无统计学差异(P>0.05);治疗后,观察组的LVEF水平高于对照组, WMSI、 cTnI水平均低于对照组(P均<0.05)。治疗前,两组患者的PLT、 MPV、 HCT、 WBC水平比较无统计学差异(P>0.05);治疗后,观察组的PLT水平高于对照组(P <0.05),但两组的MPV、 HCT、 WBC水平比较无统计学差异(P>0.05)。结论替格瑞洛联合阿司匹林治疗急性STEMI患者的效果较好,能明显改善患者的心功能,抑制血小板,值得临床应用推广。     

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。     

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.     

替格瑞洛对急性冠状动脉综合征患者经皮冠状动脉介入治疗后QT离散度及高敏C反应蛋白与可溶性CD40配体的影响

目的 探讨替格瑞洛对急性冠状动脉综合征(ACS)患者在经皮冠状动脉介入治疗(PCI)后QT离散度(QTd)以及对炎性因子高敏C反应蛋白(hs-CRP)、可溶性CD40配体(sCD40L)的影响.方法 抽取本院2017年1~12月接受PCI的ACS患者69例,随机分为对照组34例(口服氯吡格雷)、试验组35例(口服替格瑞洛),两组均使用阿司匹林行双联抗血小板聚集(DAPT)治疗1年.测量两组治疗前及术后24 h、1个月、1年QTd值以及静脉血hs-CRP、sCD40L值.术后6个月随访恶性心律失常的发生情况.结果 术后24 h,试验组QTd值及hs-CRP、sCD40L水平均低于对照组[(42.66±4.32)比(46.61±4.86),(3.73±0.39)mg/L比(4.06±0.42)mg/L,(593.94±61.69)ng/ml比(640.35±66.21)ng/ml](P<0.05);术后1个月,试验组QTd值及hs-CRP、sCD40L水平均低于对照组[(37.86±3.89)比(41.00±4.32),(1.87±0.21)mg/L比(2.03±0.22)mg/L,(417.20±43.21)ng/ml比(457.15±48.25)ng/ml](P<0.05);术后1年,试验组QTd值及hs-CRP、sCD40L水平均低于对照组[(32.19±3.35)比(37.36±3.81),(1.41±0.16)mg/L比(1.69±0.18)mg/L,(336.28±3.56)ng/ml比(387.96±3.91)ng/ml](P<0.05).术后6个月内,试验组恶性心律失常发生率(22.9%)小于对照组(47.1%)(P<0.05).结论 ACS患者PCI围术期应用替格瑞洛能显著缩短QTd,降低炎性因子hs-CRP、sCD40L水平,降低恶性心律失常发生率,显著改善预后.     

阿司匹林联合替格瑞洛或氯吡格雷对急性冠状动脉综合征患者高尿酸血症发生率影响的对比研究

目的 比较阿司匹林联合替格瑞洛或氯吡格雷对急性冠状动脉综合征(ACS)患者高尿酸血症发生率的影响.方法 选取2018年2~12月在中国医科大学盛京医院心内科住院的ACS患者476例.根据经皮冠状动脉介入治疗(PCI)术后患者应用抗血小板方案不同分为阿司匹林100 mg/d联合氯吡格雷75 mg/d组243例,阿司匹林100 mg/d联合替格瑞洛90 mg/bid组233例;以两组患者术前血尿酸值为基础对照,观察两组患者用药7天、1个月、3个月、6个月时的血尿酸水平及高尿酸血症发生率.结果 两组患者在性别、年龄等方面比较差异均无统计学意义(P>0.05).两组患者用药前血尿酸水平差异无统计学意义(P=0.238),用药1个月、3个月、6个月时,替格瑞洛组高尿酸血症发生率高于氯吡格雷组,差异有统计学意义(χ2值分别为7.623、20.367、14.018,P<0.05);多因素Logistic回归分析显示,在调整了混杂因素后,口服替格瑞洛与口服氯吡格雷对ACS患者高尿酸血症发生率影响仍有差异(β=-1.139,SE=0.249,Waldχ2=20.903,OR=0.320,95%CI 0.196~0.522);重复测量设计分析显示两组患者的血尿酸水平随着用药时间变化的趋势不同,用药组别与用药时间之间存在交互作用(F=6.201,P<0.05).结论 替格瑞洛组较氯吡格雷组对ACS患者血尿酸水平影响更大,导致高尿酸血症发生率更高,在用药3个月时血尿酸水平达高峰,需要临床医师重视血尿酸管理,建议患者至少要在用药1个月及3个月时复查血尿酸水平,便于及时调整用药与早期干预.