Concomitant use of clopidogrel and proton pump inhibitors: impact on platelet function and clinical outcome- a systematic review

Focks, Jeroen Jaspers; Brouwer, Marc A.; van Oijen, Martijn G. H.; Lanas, Angel; Bhatt, Deepak L.; Verheugt, Freek W. A.
April 2013
Heart;Apr2013, Vol. 99 Issue 8, p520
Academic Journal
Background Clopidogrel as an adjunct to aspirin has improved outcomes after acute coronary syndromes, but laboratory studies suggest a reduced antiplatelet effect when proton pump inhibitors (PPIs) are co-administered. Despite corroborating data from retrospective studies, new clinical data fuel the controversy on this issue. Purpose Systematic review of the impact of the addition of PPIs to clopidogrel on platelet function and cardiovascular outcome. Data sources PubMed, Web-of-Science, Cochrane Database and reference lists of related articles. Study selection Published articles on controlled studies addressing the addition of PPIs to clopidogrel. Platelet function studies describe patients as well as healthy volunteers. Clinical studies concern patients using clopidogrel for acute coronary syndromes or because of stent implantation for stable coronary disease. Data extraction Two investigators independently reviewed the identified articles for eligibility, and one author extracted the data. Data synthesis In 70% (7/10) of the laboratory studies examining healthy volunteers on clopidogrel, addition of PPIs resulted in a significant reduction in platelet inhibition. For patients, this was observed in 11/ 18 (61%) studies. The 33 clinical studies showed significant heterogeneity in observed outcomes, with risk ratios for major adverse cardiovascular events varying from 0.64 to 4.58 in the case of PPI use, which was randomly allocated in only two studies. Consequently, imbalances between prognosticators at baseline and PPI prescription bias markedly contributed to the variability in results. Conclusions Despite indications of reduced antiplatelet activity ex vivo in the case of PPI administration in clopidogrel users, data on the clinical consequences are controversial. With the accumulating evidence from better designed, prospective clinical studies, an adverse effect of PPI use on clinical outcome in patients on clopidogrel cannot be substantiated. This review challenges the validity of conclusions based on quantitative analyses of predominantly non-randomised data.


Related Articles

  • Outcomes, Health Costs and Use of Antiplatelet Agents in 7,082 Patients Admitted for an Acute Coronary Syndrome Occurring in a Large Community Setting. Maggioni, Aldo; Rossi, Elisa; Cinconze, Elisa; Roggeri, Daniela; Roggeri, Alessandro; Fabbri, Gianna; Rosa, Marisa // Cardiovascular Drugs & Therapy;Aug2013, Vol. 27 Issue 4, p333 

    Purpose: To assess the outcomes of patients admitted for ACS and the prescription pattern of antiplatelets of patients discharged alive. Methods: From the ARNO Observatory database, we performed a record linkage analysis of hospital discharge and prescription databases, which included 2,758,872...

  • The culprit lesion score on multi-detector computed tomography can detect vulnerable coronary artery plaque. Kim, So; Kim, Kee-Sik; Seung, Myeung; Chung, Jin; Kim, Jeung; Mun, Sung; Lee, Young; Lee, Jin; Ryu, Jae; Choi, Ji; Chang, Sung // International Journal of Cardiovascular Imaging;Dec2010, Vol. 26, p245 

    Vulnerable plaques are characterized by large lipid cores, positive remodeling and small coronary calcium deposits. Multi-detector computed tomography (MDCT) has recently been shown to be able to characterize coronary artery plaques. The aim of this study was to evaluate culprit coronary lesions...

  • Impaired myocardial oxidative metabolism in the remote normal region in patients in the chronic phase of myocardial infarction and left ventricular remodeling. Ohte, Nobuyuki; Narita, Hitomi; Iida, Akihiko; Wakami, Kazuaki; Asada, Kaoru; Fukuta, Hidekatsu; Kato, Takafumi; Hyano, Junichiro; Kimura, Genjiro // Journal of Nuclear Cardiology;Jan2009, Vol. 16 Issue 1, p73 

    Background: Left ventricular (LV) remodeling occurs in the remote normal region in the LVs after myocardial infarction (MI) and is closely involved in heart failure. Methods: We assessed myocardial oxygen consumption using a clearance rate constant K for the time activity curves of C-acetate in...

  • Incremental prognostic value of cardiac single-photon emission computed tomography after nitrate administration in patients with ischemic left ventricular dysfunction. Evangelista, Laura; Acampa, Wanda; Petretta, Mario; Ferro, Adele; Ricci, Francesca; Luongo, Luca; Daniele, Stefania; Punzo, Giorgio; Cuocolo, Alberto // Journal of Nuclear Cardiology;Jan2009, Vol. 16 Issue 1, p38 

    Background: We evaluated the incremental prognostic value of viability assessment by nitrate single-photon emission computed tomography (SPECT) in patients with ischemic left ventricular (LV) dysfunction. Methods and Results: One hundred and sixty-four patients with previous myocardial...

  • Nadir Akut Koroner Sendrom Nedeni: Spontan Koroner Arter Disseksiyonu. Ercan, Süleyman; Çakıcı, Musa; Oylumlu, Muhammed; Davutoğlu, Vedat // TAF Preventive Medicine Bulletin;Mar/Apr2013, Vol. 12 Issue 2, p213 

    Spontaneous coronary artery dissection is rare cause of acute coronary syndrome. It is diagnosed by coronary angiography which shows dissection flap and false lumen. Patients might be presented different clinical conditions from asymptomatic to sudden cardiac death. A 52 year-old man with acute...

  • Derivation and assessment of risk prediction models using case-cohort data. Sanderson, Jean; Thompson, Simon G.; White, Ian R.; Aspelund, Thor; Pennells, Lisa // BMC Medical Research Methodology;2013, Vol. 13 Issue 1, p1 

    Background: Case-cohort studies are increasingly used to quantify the association of novel factors with disease risk. Conventional measures of predictive ability need modification for this design. We show how Harrell's C-index, Royston's D, and the category-based and continuous versions of the...

  • Percutaneous coronary intervention in treatment of multivessel coronary artery disease in patients with non-ST-segment elevation acute coronary syndrome. Gąsior, Paweł; Desperak, Piotr; Gierlaszyńska, Karolina; Hawranek, Michał; Gierlotka, Marek; Gąsior, Mariusz; Poloński, Lech // Advances in Interventional Cardiology;2013, Vol. 9 Issue 2, p136 

    Among patients with non-ST-elevated acute coronary syndromes (NSTE-ACS) the estimated percentage of single vessel coronary artery disease (SV-CAD) observed during coronarography is about 20-40%, while multivessel coronary artery disease (MV-CAD) is found in about 40-60%. Further treatment in...

  • Implications of C1q/TNF-related protein-3 (CTRP-3) and progranulin in patients with acute coronary syndrome and stable angina pectoris. Kyung Mook Choi; Soon Young Hwang; Ho Chel Hong; Hae Yoon Choi; Hye Jin Yoo; Byung-Soo Youn; Sei Hyun Baik; Hong Seog Seo // Cardiovascular Diabetology;2014, Vol. 13 Issue 1, p2 

    Background C1q/TNF-related protein-3 (CTRP-3), an adiponectin paralog, and progranulin were recently identified as novel adipokines which may link obesity with glucose dysregulation and subclinical inflammation. We analyzed the relationship between CTRP-3, progranulin and coronary artery disease...

  • Clinical: The Basics - Stable angina. Thakkar, Raj // GP: General Practitioner;11/5/2010, p27 

    The article focuses on the causes, symptoms, treatment required for managing angina pectoris. It mentions that angina is a common condition is caused by occlusion of a coronary artery or arteries by a stable plaque. It highlights the symptoms of angina and mentions that any condition causing...


Read the Article


Sign out of this library

Other Topics