Abstract
Background There are increasing concerns about clinically significant interactions between proton pump inhibitors (PPIs) and clopidogrel, resulting in adverse cardiovascular outcomes in patients with acute coronary syndromes (ACS). However, published evidence on the prevalence and predictors of PPI use with dual antiplatelet therapy (DAPT) is scarce. Objective This study investigated the prevalence of PPI use among patients with ACS receiving DAPT and possible predictors of co-prescribing the PPIs with the DAPT. Setting Heart Hospital, a specialized tertiary care center in Qatar. Methodology A retrospective observational study of a prescription database was conducted. Subjects included 626 patients admitted between January and December 2012 with the diagnosis of ACS who received DAPT and discharged with or without a PPI. Univariate analysis and multivariate binary logistic regression analysis were performed to determine the predictors of PPI–DAPT co-prescription. Main outcome measures Prevalence of PPI co-prescribing with DAPT in proportions and percentages and odd ratios for the predictors of PPI–DAPT co-prescribing. Results A total of 626 patients were analyzed for PPI prevalence, with 200 patients (32 %) being prescribed PPI with DAPT upon discharge. After controlling for confounders, PPI use on admission (aOR 14.5; 95 % CI 7.6–27.6, p < 0.001), nationality (aOR 3.2; 95 % CI 1.1–9.9, p = 0.041), and having a history of diabetes (aOR 0.5; 95 % CI 0.24–0.99, p = 0.046) significantly influenced PPI–DAPT co-prescribing. Users of PPI on admission compared to nonusers were about 15 times more likely to be prescribed PPI with DAPT upon discharge; likewise, having Qatari nationality increased the likelihood of co-prescribing PPI with DAPT upon discharge by three folds. Lastly, patients with a history of diabetes were 50 % less likely to be prescribed PPIs upon discharge compared to those with no history of diabetes. Conclusion The rate of PPI co-prescribing with DAPT in the population studied was relatively high. The strongest predictor of PPI co-prescription with DAPT upon discharge was PPI use on admission. Furthermore, PPI prescribing was significantly predicted by nationality and not having diabetes. Further studies are warranted to better predict the factors associated with PPI–DAPT co-prescription and to investigate rational prescribing of PPIs among ACS patients.
Similar content being viewed by others
References
Amsterdam EA, Wenger NK, Brindis RG, Casey JDE, Ganiats TG, Holmes JDR, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;64(24):e139–228.
Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation. 2011;124(23):2574–609.
O’Gara PT, Kushner FG, Ascheim DD, Casey DE, Chung MK, de Lemos JA, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(4):e362–425.
Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Eng J Med. 2006;354(16):1706–17.
Diener H-C, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet. 2004;364(9431):331–7.
Sabatine MS, Cannon CP, Gibson CM, López-Sendón JL, Montalescot G, Theroux P, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Eng J Med. 2005;352(12):1179–89.
Wijns W, Kolh P, Danchin N, Di Mario C, Falk V, Folliguet T, et al. Guidelines on myocardial revascularization: the task force on myocardial revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2010;31(20):2501–55.
Yusuf S, Zhao F, Mehta S, Chrolavicius S, Tognoni G, Fox K, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345(7):494–502.
Abraham NS, Hlatky MA, Antman EM, Bhatt DL, Bjorkman DJ, Clark CB, et al. ACCF/ACG/AHA 2010 expert consensus document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. J Am Coll Cardiol. 2010;56(24):2051–66.
Abraham NS. Prescribing proton pump inhibitor and clopidogrel together: current state of recommendations. Curr Opin Gastroenterol. 2011;27(6):558–64.
Agewall S, Cattaneo M, Collet JP, Andreotti F, Lip GYH, Verheugt FWA, et al. Expert position paper on the use of proton pump inhibitors in patients with cardiovascular disease and antithrombotic therapy. Eur Heart J. 2013;34(23):1708–13.
Bhatt DL, Scheiman J, Abraham NS, Antman EM, Chan FKL, Furberg CD, et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Circulation. 2008;118(18):1894–909.
Ho P, Maddox TM, Wang L, Fihn SD, Jesse RL, Peterson ED, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA. 2009;301(9):937–44.
Bhurke SM, Martin BC, Li C, Franks AM, Bursac Z, Said Q. Effect of the clopidogrel–proton pump inhibitor drug interaction on adverse cardiovascular events in patients with acute coronary syndrome. Pharmacother. 2012;32(9):809–18.
Burkard T, Kaiser C, Rocca BL, Osswald S, Pfisterer M, Jeger R. Combined clopidogrel and proton pump inhibitor therapy is associated with higher cardiovascular event rates after percutaneous coronary intervention: a report from the BASKET trial. J Intern Med. 2012;271(3):257–63.
Gerson L. Proton pump inhibitors and potential interactions with clopidogrel: an update. Curr Gastroenterol Rep. 2013;15(6):1–8.
Gerson L, McMahon D, Olkin I, Stave C, Rockson S. Lack of significant interactions between clopidogrel and proton pump inhibitor therapy: meta-analysis of existing literature. Dig Dis Sci. 2012;57(5):1304–13.
Gilard M, Arnaud B, Cornily J-C, Le Gal G, Lacut K, Le Calvez G, et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study. J Am Coll Cardiol. 2008;51(3):256–60.
Harrison R, Mahaffey K. Clopidogrel and PPI interaction: clinically relevant or not? Curr Cardiol Rep. 2012;14(1):49–58.
Hsiao F-Y, Mullins CD, Wen Y-W, Huang W-F, Chen P-F, Tsai Y-W. Relationship between cardiovascular outcomes and proton pump inhibitor use in patients receiving dual antiplatelet therapy after acute coronary syndrome. Pharmacoepidemiol Drug Saf. 2011;20(10):1043–9.
Kwok CS, Jeevanantham V, Dawn B, Loke YK. No consistent evidence of differential cardiovascular risk amongst proton-pump inhibitors when used with clopidogrel: meta-analysis. Int J Cardiol. 2013;167(3):965–74.
Gaspar A, Ribeiro S, Nabais S, Rocha S, Azevedo P, Pereira M, et al. Proton pump inhibitors in patients treated with aspirin and clopidogrel after acute coronary syndrome. Rev Port Cardiol. 2010;29(10):1511–20.
Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009;180(7):713–8.
O’Donoghue ML, Braunwald E, Antman EM, Murphy SA, Bates ER, Rozenman Y, et al. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. Lancet. 2009;374(9694):989–97.
Bursac Z, Gauss CH, Williams DK, Hosmer D. Purposeful selection of variables in logistic regression. Source Code Biol Med. 2008;3(1):17.
Hosmer DW, Lemeshow S, Sturdivant RX. Applied logistic regression. New York: Wiley; 2013.
Haroon M, Yasin F, Gardezi SKM, Adeeb F, Walker F. Inappropriate use of proton pump inhibitors among medical inpatients: a questionnaire-based observational study. J R Soc Med Sh Rep. 2013;4(8):36.
Tran M, Tafreshi J, Pai RG. Combination of clopidogrel and proton pump inhibitors: implications for clinicians. J Cardiovasc Pharmacol Ther. 2010;15(4):326–37.
Blume H, Donath F, Warnke A, et al. Pharmacokinetic drug interaction profiles of proton pump inhibitors. Drug Saf. 2006;29(9):769–84.
Wedemeyer R-S, Blume H. Pharmacokinetic drug interaction profiles of proton pump inhibitors: an update. Drug Saf. 2014;37(4):201–11.
Bhatt DL, Cryer BL, Contant CF, Cohen M, Lanas A, Schnitzer TJ, et al. Clopidogrel with or without omeprazole in coronary artery disease. N Eng J Med. 2010;363(20):1909–17.
Acknowledgments
The authors would like to thank the staff at the medical record unit of the Heart Hospital in Qatar who provided access to the required data.
Funding
This study was supported by Qatar University under the Undergraduate Research Fund (Grant Number: QUST-CPH-SPR-12/13-13). The content of this paper is the sole responsibility of the authors.
Conflicts of interest
The authors declare no conflict of interest in this study.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Awaisu, A., Hamou, F., Mekideche, L. et al. Proton pump inhibitor co-prescription with dual antiplatelet therapy among patients with acute coronary syndrome in Qatar. Int J Clin Pharm 38, 353–361 (2016). https://doi.org/10.1007/s11096-016-0250-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11096-016-0250-4