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Impact of Gastrointestinal Problems on Adherence to Low-Dose Acetylsalicylic Acid

A Quantitative Study in Patients with Cardiovascular Risk

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Abstract

Background: Low-dose acetylsalicylic acid (ASA; 75–325 mg) is a mainstay of therapy for patients at high risk of cardiovascular (CV) events. However, in some patients, such treatment is associated with upper gastrointestinal (GI) adverse effects, e.g. dyspeptic symptoms, peptic ulceration, and GI bleeding, that may interfere with adequate adherence to, and continuation of, low-dose ASA for CV protection.

Objective: The objective of this study was to explore the extent of, and drivers for, poor adherence to, and discontinuation of, low-dose ASA treatment for CV protection among a representative sample of patients in the US with GI problems.

Methods: An online questionnaire was completed by eligible US adult patients (aged ≥20 years) who had been recommended low-dose ASA by a healthcare professional for secondary CV prevention or high-risk primary CV prevention (defined as diabetes mellitus or three or more risk factors for CV disease) and had experience of upper GI problems. Participants were asked questions about their demographic profile, general health, and attitudes towards low-dose ASA use. Patients were classified as ‘lapsers’ if they reported no longer regularly taking low-dose ASA; patients were also asked if they ever took deliberate, short-term breaks from their low-dose ASA regimen (‘breakers’). Statistical analysis was descriptive.

Results: From 56 296 invitation emails that were sent out, 1007 questionnaires were completed in full and were eligible for the analysis. The main reason for ineligible responses was unread emails. Respondents had a mean age of 52 years and 59% were women. Some 57% of patients were categorized as being at high primary CV risk and 43% were categorized as secondary CV prevention patients. A total of 67% of all patients used ASA at a daily dose of 81 mg.

Overall, 28% of patients were considered to be poorly adherent through lapsing and/or taking deliberate, short-term breaks, and those receiving low-dose ASA for secondary CV prevention were more likely to be poorly adherent than were high-risk primary CV prevention patients (32% vs 25%).

Of the overall population, 15% were lapsers (12% of secondary and 18% of high-risk primary CV prevention patients). The most common spontaneously reported reasons for lapse of low-dose ASA therapy were contraindicated combinations of medications and ‘stomach problems’.

Deliberate, short-term breaks from treatment were reported by 19% of all patients (24% of secondary and 15% of high-risk primary CV prevention). The most common spontaneously reported reasons for breaks were ‘stomach problems’ and preparation for surgery.

Overall, 88% of patients reported experiencing heartburn or acid reflux symptoms. Self-reported rates of GI problems were greater in secondary than in high-risk primary CV prevention patients.

Conclusion: Among the US cohort studied (i.e. low-dose ASA users with experience of upper GI problems), poor adherence to low-dose ASA treatment for both secondary and high-risk primary CV prevention was common.

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References

  1. Baigent C, Blackwell L, Collins R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009 May 30; 373(9678): 1849–60

    Article  PubMed  Google Scholar 

  2. Patrono C, Bachmann F, Baigent C, et al. Expert consensus document on the use of antiplatelet agents: the task force on the use of antiplatelet agents in patients with atherosclerotic cardiovascular disease of the European society of cardiology. Eur Heart J 2004 Jan; 25(2): 166–81

    Article  PubMed  Google Scholar 

  3. Patrono C, Garcia Rodriguez LA, Landolfi R, et al. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med 2005 Dec 1; 353(22): 2373–83

    Article  PubMed  CAS  Google Scholar 

  4. Ong G, Davis TM, Davis WA. Aspirin is associated with reduced cardiovascular and all-cause mortality in type 2 diabetes in a primary prevention setting: the Fremantle Diabetes study. Diabetes care 2010 Feb; 33(2): 317–21

    Article  PubMed  CAS  Google Scholar 

  5. Zhang C, Sun A, Zhang P, et al. Aspirin for primary prevention of cardiovascular events in patients with diabetes: a meta-analysis. Diabetes Res Clin Pract 2010; 87(2): 211–8

    Article  PubMed  CAS  Google Scholar 

  6. De Berardis G, Sacco M, Strippoli GF, et al. Aspirin for primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled trials. BMJ 2009; 339: b4531

    Article  Google Scholar 

  7. US Preventive Services Task Force. Aspirin for the prevention of cardiovascular disease: US Preventive Services Task Force recommendation statement. Ann Intern Med 2009 Mar 17; 150(6): 396–404

    Google Scholar 

  8. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996 Nov 16; 348(9038): 1329–39

    Article  Google Scholar 

  9. Cryer B, Feldman M. Effects of very low dose daily, long-term aspirin therapy on gastric, duodenal, and rectal prostaglandin levels and on mucosal injury in healthy humans. Gastroenterology 1999 Jul; 117(1): 17–25

    Article  PubMed  CAS  Google Scholar 

  10. Derry S, Loke YK. Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis. BMJ 2000 Nov 11; 321(7270): 1183–7

    Article  PubMed  CAS  Google Scholar 

  11. Garcia Rodriguez LA, Hernandez-Diaz S. Risk of uncomplicated peptic ulcer among users of aspirin and nonaspirin nonsteroidal antiinflammatory drugs. Am J Epidemiol 2004 Jan 1; 159(1): 23–31

    Article  Google Scholar 

  12. Garcia Rodriguez LA, Hernandez-Diaz S, de Abajo FJ. Association between aspirin and upper gastrointestinal complications: systematic review of epidemiologic studies. Br J Clin Pharmacol 2001 Nov; 52(5): 563–71

    Article  Google Scholar 

  13. Laheij RJ, Jansen JB, Verbeek AL, et al. Helicobacter pylori infection as a risk factor for gastrointestinal symptoms in patients using aspirin to prevent ischaemic heart disease. Aliment Pharmacol Ther 2001 Jul; 15(7): 1055–9

    Article  PubMed  CAS  Google Scholar 

  14. Niv Y, Battler A, Abuksis G, et al. Endoscopy in asymptomatic minidose aspirin consumers. Dig Dis Sci 2005 Jan; 50(1): 78–80

    Article  PubMed  Google Scholar 

  15. Taha AS, Angerson WJ, Prasad R, et al. Upper gastrointestinal bleeding and the changing use of COX-2 nonsteroidal anti-inflammatory drugs and low-dose aspirin. Aliment Pharmacol Ther 2007 Oct 15; 26(8): 1171–8

    Article  PubMed  CAS  Google Scholar 

  16. Weil J, Colin-Jones D, Langman M, et al. Prophylactic aspirin and risk of peptic ulcer bleeding. BMJ 1995 Apr 1; 310(6983): 827–30

    Article  PubMed  CAS  Google Scholar 

  17. Yeomans ND, Lanas AI, Talley NJ, et al. Prevalence and incidence of gastroduodenal ulcers during treatment with vascular protective doses of aspirin. Aliment Pharmacol Ther 2005 Nov 1; 22(9): 795–801

    Article  PubMed  CAS  Google Scholar 

  18. Scheiman JM, Devereaux PJ, Herlitz J, et al. Prevention of peptic ulcers with esomeprazole in patients at risk for ulcer development treated with low-dose acetylsalicylic acid: a randomised, controlled trial (OBERON). Heart. Epub 2011 Mar 17

  19. Lanas A, Rodrigo L, Marquez JL, et al. Low frequency of upper gastrointestinal complications in a cohort of high-risk patients taking low-dose aspirin or NSAIDS and omeprazole. Scand J Gastroenterol 2003 Jul; 38(7): 693–700

    Article  PubMed  CAS  Google Scholar 

  20. Biondi-Zoccai GG, Lotrionte M, Agostoni P, et al. A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease. Eur Heart J 2006 Nov; 27(22): 2667–74

    Article  PubMed  Google Scholar 

  21. Glynn RJ, Buring JE, Manson JE, et al. Adherence to aspirin in the prevention of myocardial infarction. The Physicians’ Health Study. Arch Intern Med 1994 Dec 12–26; 154(23): 2649–57

    Article  PubMed  CAS  Google Scholar 

  22. Pratt S, Thompson VJ, Elkin EP, et al. The impact of upper gastrointestinal symptoms on nonadherence to, and discontinuation of, low-dose acetylsalicylic acid in patients with cardiovascular risk. Am J Cardiovasc Drugs 2010; 10(5): 281–8

    Article  PubMed  CAS  Google Scholar 

  23. Collet JP, Himbet F, Steg PG. Myocardial infarction after aspirin cessation in stable coronary artery disease patients. Int J Cardiol 2000 Nov–Dec; 76(2–3): 257–8

    Article  PubMed  CAS  Google Scholar 

  24. Collet JP, Montalescot G, Blanch et B, et al. Impact of prior use or recent withdrawal of oral antiplatelet agents on acute coronary syndromes. Circulation 2004 Oct 19; 110(16): 2361–7

    Article  PubMed  CAS  Google Scholar 

  25. Sibon I, Orgogozo JM. Antiplatelet drug discontinuation is a risk factor for ischemic stroke. Neurology 2004 Apr 13; 62(7): 1187–9

    Article  PubMed  Google Scholar 

  26. Cotter G, Shemesh E, Zehavi M, et al. Lack of aspirin effect: aspirin resistance or resistance to taking aspirin? Am Heart J 2004 Feb; 147(2): 293–300

    Article  PubMed  CAS  Google Scholar 

  27. Ferrari E, Benhamou M, Cerboni P, et al. Coronary syndromes following aspirin withdrawal: a special risk for late stent thrombosis. J Am Coll Cardiol 2005 Feb 1; 45(3): 456–9

    Article  PubMed  CAS  Google Scholar 

  28. Ho PM, Spertus JA, Masoudi FA, et al. Impact of medication therapy discontinuation on mortality after myocardial infarction. Arch Intern Med 2006 Sep 25; 166(17): 1842–7

    Article  PubMed  Google Scholar 

  29. Burger W, Chemnitius JM, Kneissl GD, et al. Low-dose aspirin for secondary cardiovascular prevention: cardiovascular risks after its perioperative withdrawal versus bleeding risks with its continuation. Review and meta-analysis. J Intern Med 2005 May; 257(5): 399–414

    Article  PubMed  CAS  Google Scholar 

  30. Herlitz J, Tóth PP, Naesdal J. Low-dose acetylsalicylic acid therapy for CV prevention: quantification and consequences of poor compliance or discontinuation. Am J Cardiovasc Drugs 2010; 10: 125–41

    Article  PubMed  Google Scholar 

  31. Tournoij E, Peters RJ, Langenberg M, et al. The prevalence of intolerance for low-dose acetylsalicylacid in the secondary prevention of atherothrombosis. Eur J Vasc Endovasc Surg 2009 May; 37(5): 597–603

    Article  PubMed  CAS  Google Scholar 

  32. Nema H, Kato M, Katsurada T, et al. Investigation of gastric and duodenal mucosal defects caused by low-dose aspirin in patients with ischemic heart disease. J Clin Gastroenterol 2009 Feb; 43(2): 130–2

    Article  PubMed  Google Scholar 

  33. Chen WH, Cheng X, Lee PY, et al. Aspirin resistance and adverse clinical events in patients with coronary artery disease. Am J Med 2007 Jul; 120(7): 631–5

    Article  PubMed  CAS  Google Scholar 

  34. Krasopoulos G, Brister SJ, Beattie WS, et al. Aspirin ‘resistance’ and risk of cardiovascular morbidity: systematic review and meta-analysis. BMJ 2008 Jan 26; 336(7637): 195–8

    Article  PubMed  Google Scholar 

  35. Chan FK, Chung SC, Suen BY, et al. Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. N Engl J Med 2001 Mar 29; 344(13): 967–73

    Article  PubMed  CAS  Google Scholar 

  36. Lai KC, Lam SK, Chu KM, et al. Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use. N Engl J Med 2002 Jun 27; 346(26): 2033–8

    Article  PubMed  CAS  Google Scholar 

  37. Yeomans N, Lanas A, Labenz J, et al. Efficacy of esomeprazole (20 mg once daily) for reducing the risk of gastro-duodenal ulcers associated with continuous use of low-dose aspirin. Am J Gastroenterol 2008 Oct; 103(10): 2465–73

    Article  PubMed  CAS  Google Scholar 

  38. Abraham NS, Hlatky MA, Antman EM, 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. Am J Gastroenterol 2010; 105(12): 2533–49

    Article  PubMed  Google Scholar 

  39. Smith SR, Wahed AS, Kelley SS, et al. Assessing the validity of self-reported medication adherence in hepatitis C treatment. Ann Pharmacother 2007 Jul; 41(7): 1116–23

    Article  PubMed  Google Scholar 

  40. King A, MacDonald C, Orn C. Understanding gastro-oesophageal reflux disease: a patient-cluster analysis. Int J Clin Pract 2008 Dec; 62(12): 1838–43

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This study was supported by AstraZeneca, the manufacturers of esomeprazole. The authors thank Anna Mett of inScience Communications, a Wolters Kluwer business, who provided medical writing support funded by AstraZeneca. Christina Moberg, Jørgen Naesdal, and Lars-Erik Svedberg are employees of AstraZeneca. The remaining authors declare no conflicts of interest directly relevant to this study.

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Authors and Affiliations

  1. AstraZeneca R&D, Pepparedsleden 1, SE-431 83, Mölndal, Sweden

    Christina Moberg, Jørgen Naesdal & Lars-Erik Svedberg

  2. Hall & Partners Europe, London, UK

    Delphine Duchateau & Nicola Harte

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  1. Christina Moberg
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  2. Jørgen Naesdal
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  3. Lars-Erik Svedberg
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Correspondence to Christina Moberg.

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Moberg, C., Naesdal, J., Svedberg, LE. et al. Impact of Gastrointestinal Problems on Adherence to Low-Dose Acetylsalicylic Acid. Patient-Patient-Centered-Outcome-Res 4, 103–113 (2011). https://doi.org/10.2165/11589200-000000000-00000

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