High-dose clopidogrel versus ticagrelor for treatment of acute coronary syndromes after percutaneous coronary intervention in CYP2C19 intermediate or poor metabolizers: a prospective, randomized, open-label, single-centre trial

Zhang, Yunmei; Zhao, Yan; Pang, Mingjie; Wu, Yu; Zhuang, Ke; Zhang, Hong; Bhat, Amit

doi:10.1080/ac.71.3.3152091

Cited by 23 publications

(12 citation statements)

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“…At last, a further 4 articles were eliminated since they were based on protocols of upcoming trials. Finally, only 16 studies [ 8 – 23 ] were selected for this analytical research (Fig. 1 ).…”

Section: Resultsmentioning

confidence: 99%

Choosing between ticagrelor and clopidogrel following percutaneous coronary intervention

Guan

Yang

2018

Medicine

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Background:Limitations have been observed with the use of clopidogrel following percutaneous coronary intervention (PCI) indicating the urgent need of a more potent anti-platelet agent. We aimed to compare the efficacy and safety of ticagrelor versus clopidogrel following PCI.Methods:Online databases were searched for relevant studies (published between the years 2007 and 2017) comparing ticagrelor versus clopidogrel following coronary stenting. Primary outcomes assessed efficacy whereas secondary outcomes assessed safety. Odds ratios (OR) with 95% confidence intervals (CIs) based on a random effect model were calculated and the analysis was carried out by the RevMan 5.3 software.Results:A total number of 25,632 patients with acute coronary syndrome (ACS) [12,992 patients with ST segment elevation myocardial infarction (STEMI) and 14,215 patients with non-ST segment elevation myocardial infarction (NSTEMI)] were included in this analysis, of whom 23,714 patients were revascularized by PCI. Results of this analysis did not show any significant difference in all-cause mortality, major adverse cardiac events (MACEs), myocardial infarction, stroke and stent thrombosis observed between ticagrelor and clopidogrel with (OR: 0.83, 95% CI: 0.67–1.03; P = .09), (OR: 0.64, 95% CI: 0.41–1.01; P = .06), (OR: 0.77, 95% CI: 0.57–1.03; P = .08), (OR: 0.85, 95% CI: 0.57–1.26; P = .42) and (OR: 0.70, 95% CI: 0.47–1.05; P =.09).However, ticagrelor was associated with a significantly higher minor and major bleeding with (OR: 1.57, 95% CI: 1.30–1.89; P = .00001) and (OR: 1.52, 95% CI: 1.01–2.29; P = 0.04) respectively. Dyspnea was also significantly higher in the ticagrelor group (OR: 2.64, 95% CI: 1.87–3.72; P = .00001).Conclusion:Ticagrelor and clopidogrel were comparable in terms of efficacy in these patients with ACS. However, the safety outcomes of ticagrelor should further be investigated.

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Section: Resultsmentioning

confidence: 99%

Choosing between ticagrelor and clopidogrel following percutaneous coronary intervention

Guan

Yang

2018

Medicine

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“…A total of 80 potential eligible studies were then reviewed for full‐text evaluations, of which 39 articles were excluded because they did not meet the inclusion criteria (Table S1). Finally, 41 RCTs were included in the meta‐analysis with 23 trials comparing ticagrelor with clopidogrel and 18 trials comparing prasugrel with clopidogrel, in which bleeding data from ClinicalTrial.gov were used for the study of Ge 2010 . The selection steps and specific excluding reasons were shown in Figure .…”

Section: Resultsmentioning

confidence: 99%

Systematic review with meta‐analysis: the risk of gastrointestinal bleeding in patients taking third‐generation P2Y₁₂ inhibitors compared with clopidogrel

Guo

Chen

Chan

et al. 2018

Aliment Pharmacol Ther

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Summary Background Ticagrelor and prasugrel are third‐generation oral P2Y12 receptor antagonists with rapid onset and pronounced platelet inhibition. However, higher overall bleeding rates have been reported for these agents when compared with clopidogrel. Aim To compare the risk of gastrointestinal bleeding (GIB) among users of third‐generation P2Y12 inhibitors with clopidogrel. Methods We systematically searched for published randomised controlled trials of ticagrelor or prasugrel versus clopidogrel until September 2018. The primary outcome was the risk of GIB among users of third‐generation P2Y12 inhibitors when compared to clopidogrel, expressed as risk ratio (RR) and 95% confidence interval (CI). The rates of non‐coronary artery bypass graft (CABG) major bleeding, life‐threatening bleeding, fatal bleeding, and intracranial bleeding were analysed as secondary outcomes. Results Forty‐one studies were included in the analysis of non‐CABG major bleeding, of which 12 were included in the analysis of GIB including 58 678 patients. Third‐generation P2Y12 inhibitors were associated with higher risk of GIB as compared with clopidogrel (RR 1.28, 95% CI 1.13‐1.46). The findings were consistent for upper (RR 1.32, 95% CI 1.05‐1.67) and unspecified GIB (RR 1.25, 95% CI 1.01‐1.53), but not lower GIB (RR 1.25, 95% CI 0.95‐1.65). Subgroup analysis showed higher GIB risk in prasugrel studies (RR 1.40, 95% CI 1.10‐1.77) than in ticagrelor studies (RR 1.15, 95% CI 0.94‐1.39). Third‐generation P2Y12 inhibitors also increased the risk of non‐CABG major bleeding (RR 1.18, 95% CI 1.08‐1.28). Conclusion Third‐generation P2Y12 inhibitors were associated with increased risk of GIB and non‐CABG major bleeding when compared with clopidogrel.

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“…Patients with genetic polymorphisms involving hypofunctional CYP2C19 alleles might benefit more from DAPT–PPI combination therapy with clopidogrel and rabeprazole rather than one of the other PPIs, [ 31 ] or from ticagrelor, a potent antiplatelet drug that is not affected by CYP2C19 polymorphisms. [ 34 ]…”

Section: Discussionmentioning

confidence: 99%

Influence of proton pump inhibitors on clinical outcomes in coronary heart disease patients receiving aspirin and clopidogrel

Jin²,

Kuang³

et al. 2018

Medicine

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Background:Proton pump inhibitors (PPIs) are usually prescribed to protect against gastrointestinal bleeding in patients on dual antiplatelet therapy. This meta-analysis reviewed clinical outcomes in patients taking aspirin and clopidogrel, with and without concomitant PPIs to address concerns of adverse reactions.Methods:We searched PubMed, Embase, and the Cochrane Library for articles published between January 1, 2010 and April 11, 2017. The primary end points were major adverse cardiovascular events and gastrointestinal bleeding. Secondary end points were myocardial infarction, stent thrombosis, revascularization, cardiogenic death, and all-cause mortality.Results:The meta-analysis included 33,492 patients in 4 randomized controlled trials and 8 controlled observational studies. Overall, patients taking PPIs had statistical differences in major adverse cardiovascular events [odds ratio (OR) 1.17 (95% confidence interval [CI] 1.07–1.28); P = .001; I2 = 28.3%], gastrointestinal bleeding [OR 0.58 (95% CI 0.36–0.92); P = .022; I2 = 80.6%], stent thrombosis [OR 1.30 (95% CI 1.01–1.68); P = .041; I2 = 0%], and revascularization [OR 1.20 (95% CI 1.04–1.38); P = .011; I2 = 5.1%], compared those not taking PPIs. There were no significant differences in myocardial infarction [OR 1.03 (95% CI 0.87–1.22); P = .742; I2 = 0%], cardiogenic death [OR 1.09 (95% CI 0.83–1.43); P = .526; I2 = 0%], or all-cause mortality [OR 1.08 (95% CI 0.93–1.25); P = .329; I2 = 0%).Conclusions:Among the patients taking aspirin and clopidogrel, the results indicated that the combined use of PPIs increased the rates of major adverse cardiovascular events, stent thrombosis, and revascularization.

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High-dose clopidogrel versus ticagrelor for treatment of acute coronary syndromes after percutaneous coronary intervention in CYP2C19 intermediate or poor metabolizers: a prospective, randomized, open-label, single-centre trial

Cited by 23 publications

References 0 publications

Choosing between ticagrelor and clopidogrel following percutaneous coronary intervention

Choosing between ticagrelor and clopidogrel following percutaneous coronary intervention

Systematic review with meta‐analysis: the risk of gastrointestinal bleeding in patients taking third‐generation P2Y₁₂ inhibitors compared with clopidogrel

Influence of proton pump inhibitors on clinical outcomes in coronary heart disease patients receiving aspirin and clopidogrel

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High-dose clopidogrel versus ticagrelor for treatment of acute coronary syndromes after percutaneous coronary intervention in CYP2C19 intermediate or poor metabolizers: a prospective, randomized, open-label, single-centre trial

Cited by 23 publications

References 0 publications

Choosing between ticagrelor and clopidogrel following percutaneous coronary intervention

Choosing between ticagrelor and clopidogrel following percutaneous coronary intervention

Systematic review with meta‐analysis: the risk of gastrointestinal bleeding in patients taking third‐generation P2Y12 inhibitors compared with clopidogrel

Influence of proton pump inhibitors on clinical outcomes in coronary heart disease patients receiving aspirin and clopidogrel

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Systematic review with meta‐analysis: the risk of gastrointestinal bleeding in patients taking third‐generation P2Y₁₂ inhibitors compared with clopidogrel