Individual Proton Pump Inhibitors and Outcomes in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy: A Systematic Review.

Abstract

BACKGROUND: Observational studies evaluating the possible interaction between proton pump inhibitors (PPIs) and clopidogrel have shown mixed results. We conducted a systematic review comparing the safety of individual PPIs in patients with coronary artery disease taking clopidogrel. METHODS AND RESULTS: Studies performed from January 1995 to December 2013 were screened for inclusion. Data were extracted, and study quality was graded for 34 potential studies. For those studies in which follow-up period, outcomes, and multivariable adjustment were comparable, meta-analysis was performed.The adjusted odds or hazard ratios for the composite of cardiovascular or all-cause death, myocardial infarction, and stroke at 1 year were reported in 6 observational studies with data on individual PPIs. Random-effects meta-analyses of the 6 studies revealed an increased risk for adverse cardiovascular events for those taking pantoprazole (hazard ratio 1.38; 95% CI 1.12-1.70), lansoprazole (hazard ratio 1.29; 95% CI 1.09-1.52), or esomeprazole (hazard ratio 1.27; 95% CI 1.02-1.58) compared with patients on no PPI. This association was not significant for omeprazole (hazard ratio 1.16; 95% CI 0.93-1.44). Sensitivity analyses for the coronary artery disease population (acute coronary syndrome versus mixed) and exclusion of a single study due to heterogeneity of reported results did not have significant influence on the effect estimates for any PPIs. CONCLUSIONS: Several frequently used PPIs previously thought to be safe for concomitant use with clopidogrel were associated with greater risk of adverse cardiovascular events. Although the data are observational, they highlight the need for randomized controlled trials to evaluate the safety of concomitant PPI and clopidogrel use in patients with coronary artery disease.

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Citation

Published Version (Please cite this version)

10.1161/JAHA.115.002245

Publication Info

Sherwood, Matthew W, Chiara Melloni, W Schuyler Jones, Jeffrey B Washam, Vic Hasselblad and Rowena J Dolor (2015). Individual Proton Pump Inhibitors and Outcomes in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy: A Systematic Review. J Am Heart Assoc, 4(11). 10.1161/JAHA.115.002245 Retrieved from https://hdl.handle.net/10161/12646.

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Scholars@Duke

Sherwood

Matthew William Sherwood

Adjunct Assistant Professor in the Department of Medicine

I am striving to become a clinical and research leader in structural heart disease and complex coronary disease, specifically in the use of antithrombotic agents after structural heart interventions.  I will also explore the significance of bleeding/vascular complications and stroke in these patients as well as potential therapies such as transfusion, and embolic protection devices.

Melloni

Chiara Melloni

Adjunct Associate Professor in the Department of Medicine
Jones

William Schuyler Jones

Associate Professor of Medicine

I am an interventional cardiologist with a specific focus on the diagnosis and treatment of patients with cardiovascular disease. As a clinician, I see patients in the office and do coronary and peripheral vascular procedures (angiography and interventions) in the Duke Cardiac Catheterization Laboratory. I have served as the Medical Director of the cath lab at Duke since 2016. Alongside my partners in the cath lab, we collaborate with our cardiothoracic surgeons to hold Heart Team meetings each week, and we frequently are asked to address complex cardiovascular issues as a multidisciplinary team.

I also have a broad background in cardiovascular site-based research, multicenter clinical trials, clinical event classification, and observational analyses. I have helped to lead clinical trial efforts at the Duke Clinical Research Institute (DCRI) by designing and conducting studies evaluating new and existing treatments for patients with coronary artery disease and peripheral artery disease. My specific research interests include examining access to care and disparities in care for patients with peripheral artery disease and the design and conduct of pragmatic clinical trials in cardiovascular disease.

Hasselblad

Victor Hasselblad

Professor Emeritus of Biostatistics & Bioinformatics

The research interests of Vic Hasselblad include distribution fitting, sample size and power calculations, dose-response estimation, meta-analysis, and non-inferiority designs.

Dolor

Rowena Joy Dolor

Professor of Medicine

Rowena J. Dolor, MD, MHS did her medical training and internal medicine residency at Duke University Medical Center. She completed the Ambulatory Care/Health Services Research fellowship at the Durham VA Medical Center in 1996 and obtained her Masters in Health Sciences degree in Biometry (renamed MHS in Clinical Research) from the Duke University School of Medicine in 1998. Dr. Dolor was a staff physician in the Ambulatory Care Service at the Durham VA Medical Center and Research Associate at the Center for Health Services Research in Primary Care at the Durham VAMC from 1995-2012.  She is currently an investigator of several federally-funded projects conducted in the community-based setting. Dr. Dolor served as a member of the AHRQ PBRN Resource Center Steering Committee and co-chaired the NAPCRG PBRN conference from 2012-2016.

Since 1996, Dr. Dolor has been the director of the Primary Care Research Consortium (PCRC), a network of primary care practices in the Duke University Health System and outlying communities. The PCRC has participated in over 100 industry- and investigator-initiated studies on hypertension, hyperlipidemia, asthma, otitis, obesity, diabetes, depression, anticoagulation, and vaccines. In 2002, the Duke PCRC received grant funding from the Agency for Healthcare Research and Quality (AHRQ) for Primary Care Practice-based Research Networks (PBRNs). The focus of her research pertains to primary care clinical and outcomes research. She has helped lead a number of comparative effectiveness studies and large, pragmatic trials in the primary care setting.   In addition, Dr. Dolor has led or co-led networks in otolaryngology and integrative medicine.

Dr. Dolor has contributed to the development and methodology of Practice-based Research Networks (PBRNs). She has served as a co-investigator on three online resources to help researchers conduct multi-center research in the primary care practice-based setting – (1) A toolkit for building and sustaining health research partnership with practices and communities, http://www.researchtoolkit.org/index.php (2) Toolkit for Developing and Conducting Multi-site Clinical Trials in Practice Based Research Networks, http://www.dartnet.info/ClinicalTrialsPBRNToolkit.htm ; and (3) PBRN Research Good Practices (PRGP), http://www.napcrg.org/PBRNResearchGoodPractice

From July 2009-June 2012, she served as the Associate Director for the Duke EPC. She worked closely with the Director, Gillian Sanders PhD, in overseeing the day-to-day functioning of EPC projects and supervising EPC personnel.  The Duke EPC was awarded a contract entitled “American Recovery and Reinvestment Act of 2009: Comprehensive EPC Comparative Effectiveness Reviews for Effective Health Care” to serve within a core group of EPCs to focus on a comprehensive approach to comparative effectiveness review (CER) and evidence synthesis. The Duke EPC area of concentration was cardiovascular and pulmonary disorders.

She previously served as the principal investigator for the systematic literature review for the AHA Scientific Statement: Evidence-based guidelines for cardiovascular disease prevention in women published in 2004 and updated in 2007. She was the PI of four CER projects on “Noninvasive Technologies for the Diagnosis of Coronary Artery Disease in Women” and “Treatment Strategies for Women with CAD”, “PAD”, and “UA/NSTEMI” as well as upcoming CER topics on pulmonary arterial hypertension, peripheral artery disease and unstable angina/non-ST elevation myocardial infarction. 

Within the Duke Clinical and Translational Institute (CTSI), Dr. Dolor directs the collaboration with CTSI researchers on community-based PBRN projects. From 2011- 2014, she was co-chair of the CTSA PBRN Collaboration Workgroup, and a member of the Community Engagement Key Function Committee, the CTSA Strategic Goal 4 Combined Networking Group committee, and the CTSA Comparative Effectiveness Research Key Function Committee (CER KFC). Since September 2016, she serves as a Co-chair of the Dissemination, Implementation and Knowledge Transfer Workgroup within the Collaboration Engagement Domain Task Force.

In the fall of 2014, Dr. Dolor joined Vanderbilt part-time as a Consultant/Adjunct Associate Professor of Medicine within the Division of General Internal Medicine. Her role is to assist in the formation of the Meharry-Vanderbilt Clinical Research Network, a PBRN in the mid-Tennessee region.  In addition, she is a co-investigator on the Mid-South Clinical Data Research Network, a PCORnet awardee, to build the partnership with the community practices for comparative effectiveness studies that will utilize the electronic health records/information system infrastructure of the CDRN. 




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