Subscribe to RSS
DOI: 10.1160/TH13-07-0542
Use of proton pump inhibitors and the risk of coronary events in new users of low-dose acetylsalicylic acid in UK primary care
Financial support: The study was funded in part with financial research support from AstraZeneca R&D, Mölndal, Sweden.Publication History
Received:
05 July 2013
Accepted after major revision:
23 September 2013
Publication Date:
29 November 2017 (online)
Summary
This study evaluated the risk of cardiovascular events associated with the use of proton pump inhibitors (PPIs) in new users of acetylsalicylic acid (ASA) for the secondary prevention of cardiovascular events. Two cohorts of patients aged 50–84 years were identified from UK primary care databases: individuals with a first prescription for ASA (75−300 mg/day) for secondary prevention of cardiovascular events (n = 39,513; CVD cohort) or with a record of hospitalisation for an acute coronary event (n = 42,542; ACS cohort) in 2000–2007. Cases of nonfatal myocardial infarction (MI) and coronary death were identified: 1,222 in the CVD cohort and 604 among new users of ASA in the ACS cohort. A nested case–control analysis estimated the relative risk (RR) of non-fatal MI or coronary death associated with use vs non-use of PPI therapy. Current continuous use of PPI therapy was not associated with a significant increase in RR overall: in the CVD cohort (RR = 1.14 [95% confidence interval = 0.91−1.43]); in the ACS cohort (0.88 [0.66−1.18]); or among current continuous users of ASA as antiplatelet monotherapy (CVD cohort: 1.15 [0.80−1.66]; ACS cohort: 0.73 [0.43−1.23]; pooled analysis of both cohorts: 0.96 [0.62−1.48]). In conclusion, among first-time users of ASA for the secondary prevention of cardiovascular events, PPI use was not shown to be associated with an increased risk of non-fatal MI or coronary death.
-
References
- 1 Perk J, De Backer G, Gohlke H. et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J 2012; 33: 1635-1701.
- 2 Steg PG, James SK, Atar D. et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). Eur Heart J 2012; 33: 2569-2619.
- 3 Jneid H, Anderson JL, Wright RS. et al. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elev-ation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. J Am Coll Car-diol 2012; 60: 645-681.
- 4 García Rodríguez LA, Lin KJ, Hernández-Díaz S. et al. Risk of upper gastrointestinal bleeding with low-dose acetylsalicylic acid alone and in combination with clopidogrel and other medications. Circulation 2011; 123: 1108-1115.
- 5 Lanas A, Wu P, Medin J. et al. Low doses of acetylsalicylic acid increase risk of gastrointestinal bleeding in a meta-analysis. Clin Gastroenterol Hepatol 2011; 9: 762-768.
- 6 Bhatt DL, Scheiman J, Abraham NS. 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: 1894-1909.
- 7 Cea Soriano L, García Rodríguez LA. Risk of upper gastrointestinal bleeding in a cohort of new users of low-dose ASA for secondary prevention of cardiovascular outcomes. Front Pharmacol 2010; 1: 126-135.
- 8 Hernández-Díaz S, García Rodríguez LA. Cardioprotective aspirin users and their excess risk of upper gastrointestinal complications. BMC Med 2006; 4: 22.
- 9 Serrano P, Lanas A, Arroyo MT. et al. Risk of upper gastrointestinal bleeding in patients taking low-dose aspirin for the prevention of cardiovascular diseases. Aliment Pharmacol Ther 2002; 16: 1945-1953.
- 10 Giraud MN, Sanduja SK, Felder TB. et al. Effect of omeprazole on the bioavail-ability of unmodified and phospholipid-complexed aspirin in rats. Aliment Pharmacol Ther 1997; 11: 899-906.
- 11 Fernandez-Fernandez FJ. Might proton pump inhibitors prevent the antiplatelet effects of low- or very low-dose aspirin?. Arch Intern Med 2002; 162: 2248.
- 12 Andersson T, Morrison D, Nagy P. et al. Evaluation of the pharmacodynamics of acetylsalicylic acid 81 mg with or without esomeprazole 20 mg in healthy volunteers. Am J Cardiovasc Drugs 2012; 12: 217-224.
- 13 Wurtz M, Grove EL, Kristensen SD. et al. The antiplatelet effect of aspirin is reduced by proton pump inhibitors in patients with coronary artery disease. Heart 2010; 96: 368-371.
- 14 Adamopoulos AB, Sakizlis GN, Nasothimiou EG. et al. Do proton pump inhibitors attenuate the effect of aspirin on platelet aggregation? A randomized crossover study. J Cardiovasc Pharmacol 2009; 54: 163-168.
- 15 Kasprzak M, Kozinski M, Bielis L. et al. Pantoprazole may enhance antiplatelet effect of enteric-coated aspirin in patients with acute coronary syndrome. Car-diol J 2009; 16: 535-544.
- 16 Charlot M, Grove EL, Hansen PR. et al. Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myo- cardial infarction: nationwide propensity score matched study. Br Med J 2011; 342: d2690
- 17 Stuart-Buttle CD, Read JD, Sanderson HF. et al. A language of health in action: Read codes, classifications and groupings. Proc AMIA Annu Fall Symp 1996: 75-79.
- 18 First Databank. MULTILEX for primary care. Available at: http://www.fdbhealth.co.uk/multilex-overview Accessed December 4, 2012.
- 19 García Rodriguez LA, Cea-Soriano L, Martin-Merino E. et al. Discontinuation of low dose aspirin and risk of myocardial infarction: case-control study in UK primary care. Br Med J 2011; 343: d4094
- 20 García Rodríguez LA, Cea Soriano L, Hill C. et al. Increased risk of stroke after discontinuation of acetylsalicylic acid: a UK primary care study. Neurology 2011; 76: 740-746.
- 21 Walker AM. Case-control studies: # sampling the source population. In: Observation and inference: An introduction to the methods of epidemiology. Epidemiology Resources Inc.; 1991: 75-80.
- 22 Charlson ME, Pompei P, Ales KL. et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40: 373-383.
- 23 Niazi M, Andersson T, Naucler E. et al. Evaluation of the pharmacokinetic interaction between esomeprazole (40 mg) and acetylsalicylic acid (325 mg) in healthy volunteers. Int J Clin Pharmacol Ther 2009; 47: 564-569.
- 24 Bourke A, Dattani H, Robinson M. Feasibility study and methodology to create a quality-evaluated database of primary care data. Inform Prim Care 2004; 12: 171-177.
- 25 Lewis JD, Schinnar R, Bilker WB. et al. Validation studies of the health improvement network (THIN) database for pharmacoepidemiology research. Pharma-coepidemiol Drug Saf 2007; 16: 393-401.
- 26 Herrett E, Thomas SL, Schoonen WM. et al. Validation and validity of diagnoses in the General Practice Research Database: a systematic review. Br J Clin Pharmacol 2010; 69: 4-14.
- 27 Jick SS, Kaye JA, Vasilakis-Scaramozza C. et al. Validity of the general practice research database. Pharmacotherapy 2003; 23: 686-689.
- 28 García Rodríguez LA, Pérez Gutthann S. Use of the UK general practice research database for pharmacoepidemiology. Br J Clin Pharmacol 1998; 45: 419-425.
- 29 García Rodríguez LA, Tacconelli S, Patrignani P. Role of dose potency in the prediction of risk of myocardial infarction associated with nonsteroidal anti-inflammatory drugs in the general population. J Am Coll Cardiol 2008; 52: 1628-1636.
- 30 García Rodríguez LA, Varas-Lorenzo C, Maguire A. et al. Nonsteroidal antiin-flammatory drugs and the risk of myocardial infarction in the general population. Circulation 2004; 109: 3000-3006.
- 31 Garcia Rodriguez LA, Johansson S, Cea Soriano L. Use of clopidogrel and proton pump inhibitors after a serious acute coronary event: Risk of coronary events and peptic ulcer bleeding. Thromb Haemost 2013; 110: 1014-1024.
- 32 Blackburn DF, Lamb DA, McLeod MM. et al. Increased use of acid-suppressing drugs before the occurrence of ischemic events: a potential source of confounding in recent observational studies. Pharmacotherapy 2010; 30: 985-993.
- 33 van Boxel OS, van Oijen MG, Hagenaars MP. et al. Cardiovascular and gastrointestinal outcomes in clopidogrel users on proton pump inhibitors: results of a large Dutch cohort study. Am J Gastroenterol 2010; 105: 2430-2436.
- 34 Banerjee S, Weideman RA, Weideman MW. et al. Effect of concomitant use of clopidogrel and proton pump inhibitors after percutaneous coronary intervention. Am J Cardiol 2011; 107: 871-878.
- 35 Goodman SG, Clare R, Pieper KS. et al. Association of proton pump inhibitor use on cardiovascular outcomes with clopidogrel and ticagrelor: insights from the platelet inhibition and patient outcomes trial. Circulation 2012; 125: 978-986.
- 36 Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Br Med J 2002; 324: 71-86.
- 37 Antithrombotic Trialists’ Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009; 373: 1849-1860.