Increased Risk for Developing Major Adverse Cardiovascular Events in Stented Chinese Patients Treated with Dual Antiplatelet Therapy after Concomitant Use of the Proton Pump Inhibitor

Zou, Jianjun; Chen, Shao‐Liang; Tan, Jie; Lin, Ling; Zhao, Yingying; Xu, Hui; Lin, Song; Zhang, Juan; Fan, Hongwei; Xie, Hong‐Guang

doi:10.1371/journal.pone.0084985

Cited by 25 publications

(41 citation statements)

References 29 publications

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“…A retrospective cohort study from China, including about 6200 patients who received aspirin plus clopidogrel with a PPI, reported that PPI users had a 3% increase in MACE compared with non-users. 60 Another retrospective cohort from Italy reported an alarming 12% increase in MACE in patients receiving a PPI in conjunction with clopidogrel. 61 …”

Section: Consensus Statementsmentioning

confidence: 99%

Asia-Pacific working group consensus on non-variceal upper gastrointestinal bleeding: an update 2018

Sung

Chiu

Chan

et al. 2018

Gut

225

210

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Non-variceal upper gastrointestinal bleeding remains an important emergency condition, leading to significant morbidity and mortality. As endoscopic therapy is the ’gold standard' of management, treatment of these patients can be considered in three stages: pre-endoscopic treatment, endoscopic haemostasis and post-endoscopic management. Since publication of the Asia-Pacific consensus on non-variceal upper gastrointestinal bleeding (NVUGIB) 7 years ago, there have been significant advancements in the clinical management of patients in all three stages. These include pre-endoscopy risk stratification scores, blood and platelet transfusion, use of proton pump inhibitors; during endoscopy new haemostasis techniques (haemostatic powder spray and over-the-scope clips); and post-endoscopy management by second-look endoscopy and medication strategies. Emerging techniques, including capsule endoscopy and Doppler endoscopic probe in assessing adequacy of endoscopic therapy, and the pre-emptive use of angiographic embolisation, are attracting new attention. An emerging problem is the increasing use of dual antiplatelet agents and direct oral anticoagulants in patients with cardiac and cerebrovascular diseases. Guidelines on the discontinuation and then resumption of these agents in patients presenting with NVUGIB are very much needed. The Asia-Pacific Working Group examined recent evidence and recommends practical management guidelines in this updated consensus statement.

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Section: Consensus Statementsmentioning

confidence: 99%

Asia-Pacific working group consensus on non-variceal upper gastrointestinal bleeding: an update 2018

Sung

Chiu

Chan

et al. 2018

Gut

225

210

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“…Observational studies have also reported significant interaction between clopidogrel and PPIs, leading to an increased risk of adverse cardiovascular outcomes . Recent retrospective studies also reported that PPI users had a significantly higher incidence of MACE or stent thrombosis events than non‐users . Conversely, other studies, including four randomized clinical trials and two systematic reviews, have showed no clinically significant drug interaction between PPIs and clopidogrel.…”

Section: Proton Pump Inhibitors Impair the Antiplatelet Activity Of Cmentioning

confidence: 99%

“…10,23,[28][29][30] Recent retrospective studies also reported that PPI users had a significantly higher incidence of MACE or stent thrombosis events than non-users. 31,32 Conversely, other studies, including four randomized clinical trials [33][34][35][36] and two systematic reviews, 37,38 have showed no clinically significant drug interaction between PPIs and clopidogrel. However, the results from one randomized controlled trial, examining the potential interaction between clopidogrel and the PPI omeprazole with cardiovascular (CV) events as the outcome, could not exclude a clinically important increase in CV risk of up to 44%.…”

Section: Introductionmentioning

confidence: 99%

East Asian perspective on the interaction between proton pump inhibitors and clopidogrel

Zou

Goh

2017

J of Gastro and Hepatol

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Both proton pump inhibitors (PPIs) and clopidogrel are widely prescribed in the Asia-Pacific population. PPIs are the mainstay therapeutic agents for prophylaxis against aspirin gastropathy and for acid-related disorders including gastroesophageal reflux disease. They are also co-prescribed with oral anticoagulant agents and with dual-antiplatelet therapy for the treatment and prevention of gastrointestinal bleeding. Clopidogrel belongs to the drug class of thienopyridines and is currently the most widely prescribed oral anticoagulant agent either alone or in combination with aspirin. Platelet inhibition by clopidogrel is prone to significant inter-individual variability and is believed to be affected by several factors such as genetics and drug-drug interactions. Since it was first reported in 2009, the potential for drug-drug interactions between PPIs and clopidogrel has remained headline news, and its significance in clinical practice is the subject of an ongoing debate. For East Asian patients in particular, the clinical relevance of the interaction between PPIs and clopidogrel remains unclear because of conflicting data, as well as underrepresentation of East Asian subjects in landmark trials. Increased CYP2C19 genetic polymorphisms in individuals from Asia-Pacific countries only fuel the confusion. Recent studies in East Asian cohorts suggests that the potential of PPIs to attenuate the efficacy of clopidogrel could be minimized by the use of newer PPIs with weaker affinity for the CYP2C19 isoenzyme, namely, pantoprazole, dexlansoprazole, and rabeprazole. This review aims to help clinicians choose the most appropriate PPI for co-prescription with clopidogrel in patients from Asia-Pacific countries.

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“…[ 3 , 4 ] Proton pump inhibitors (PPIs) are usually prescribed for patients on DAPT to attenuate the side effects, [ 5 – 7 ] but there are concerns of adverse interactions of antiplatelet drugs and PPIs. [ 8 , 9 ] Current guidelines do not recommend the routine use of PPIs by patients with a low risk of GI bleeding [ 1 ] and advise that combination therapy with DAPT and PPIs has the potential of adverse drug interactions. [ 7 – 9 ]…”

Section: Introductionmentioning

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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Increased Risk for Developing Major Adverse Cardiovascular Events in Stented Chinese Patients Treated with Dual Antiplatelet Therapy after Concomitant Use of the Proton Pump Inhibitor

Cited by 25 publications

References 29 publications

Asia-Pacific working group consensus on non-variceal upper gastrointestinal bleeding: an update 2018

Asia-Pacific working group consensus on non-variceal upper gastrointestinal bleeding: an update 2018

East Asian perspective on the interaction between proton pump inhibitors and clopidogrel

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

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