Skip to main content

Advertisement

Log in

Underutilization of gastrointestinal prophylaxis in high-risk chronic nonsteroidal anti-inflammatory drug users in Korea

  • Research Article
  • Published:
International Journal of Clinical Pharmacy Aims and scope Submit manuscript

Abstract

Background The increasing use of antithrombotic therapies in older patients has led to an increased risk of gastrointestinal (GI) bleeding in chronic nonsteroidal anti-inflammatory drug (NSAID) users. Therefore, there is a pressing need for GI prophylaxis in these high-risk patients. Objective To analyze prescribing patterns and factors associated with the use of gastroprotective agents (GPAs) among high-risk, chronic NSAID users. Setting National claims database including 20% of the total Korean population aged ≥ 65 years. Method In this cross-sectional study, we identified older adults prescribed traditional NSAIDs for > 90 days and classified them into high- and ultra-high-risk groups if they had one or two or more GI risk factors, respectively. Proton pump inhibitors or misoprostol prescribed for more than 80% of traditional NSAID treatment days was regarded as appropriate GI prophylaxis. Main outcome measure Prevalence and associated factors with appropriate GI prophylaxis. Results Among 69,992 chronic traditional NSAID users, 38.8% and 9.4% belonged to the high and ultra-high-risk groups; 13.2% and 19.9% received appropriate GI prophylaxis, respectively. The most frequently used GPA was histamine H2 antagonists. Multiple NSAID use, concomitant antiplatelets and anticoagulants, and prior GI ulcer history increased the likelihood of receiving appropriate GI prophylaxis. Advanced age (≥ 85 years), indications other than arthritis, and neurology specialists negatively affected appropriate GI prophylaxis use. Conclusion Approximately one in five chronic NSAID users, considered ultra-high risk, are prescribed appropriate GI prophylaxis in Korea. Advanced age, indications, and specialties of the prescriber all need to be considered when selecting target populations for interventions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

The database used in this study was provided by HIRA in South Korea and is prohibited to transfer, rent or sale to any third party other than the researcher who have been officially approved for database use. However, it is possible for other researchers to request access to the data directly from the HIRA via instruction at following URLs: https://opendata.hira.or.kr/op/opc/selectPatDataAplInfoView.do.

Code availability

Not applicable.

References

  1. Day RO, Graham GG. Non-steroidal anti-inflammatory drugs (NSAIDs). BMJ. 2013;346:f3195.

    PubMed  Google Scholar 

  2. Bhala N, Emberson J, Merhi A, Abramson S, Arber N, Baron JA, et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382(9894):769–79.

    Article  CAS  Google Scholar 

  3. Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2010;24(2):121–32.

    Article  CAS  Google Scholar 

  4. Choi DW, Park SC, Chun HJ. Update on NSAIDs related peptic ulcers. Korean J Med. 2014;86(6):664–72.

    Article  Google Scholar 

  5. Sabzwari SR, Qidwai W, Bhanji S. Polypharmacy in elderly: a cautious trail to tread. J Pak Med Assoc. 2013;63(5):624–7.

    PubMed  Google Scholar 

  6. Griffin MR, Ray WA, Schaffner W. Nonsteroidal anti-inflammatory drug use and death from peptic ulcer in elderly persons. Ann Intern Med. 1988;109(5):359–63.

    Article  CAS  Google Scholar 

  7. Dregan A, Ravindrarajah R, Charlton J, Ashworth M, Molokhia M. Long-term trends in antithrombotic drug prescriptions among adults aged 80 years and over from primary care: a temporal trends analysis using electronic health records. Ann Epidemiol. 2018;28(7):440–6.

    Article  CAS  Google Scholar 

  8. Lanas A, Carrera-Lasfuentes P, Arguedas Y, Garcia S, Bujanda L, Calvet X, et al. Risk of upper and lower gastrointestinal bleeding in patients taking nonsteroidal anti-inflammatory drugs, antiplatelet agents, or anticoagulants. Clin Gastroenterol Hepatol. 2015;13(5):906-12.e2.

    Article  Google Scholar 

  9. Yang M, He M, Zhao M, Zou B, Liu J, Luo LM, et al. Proton pump inhibitors for preventing non-steroidal anti-inflammatory drug induced gastrointestinal toxicity: a systematic review. Curr Med Res Opin. 2017;33(6):973–80.

    Article  CAS  Google Scholar 

  10. Yuan J, Tsoi K, Yang M, Wang J, Threapleton D, Yang Z, et al. Systematic review with network meta-analysis: comparative effectiveness and safety of strategies for preventing NSAID-associated gastrointestinal toxicity. Aliment Pharmacol Ther. 2016;43(12):1262–75.

    Article  CAS  Google Scholar 

  11. Bello AE, Kent JD, Holt RJ. Gastroprotective efficacy and safety of single-tablet ibuprofen/famotidine vs ibuprofen in older persons. Phys Sportsmed. 2015;43(3):193–9.

    Article  Google Scholar 

  12. Szeto CC, Sugano K, Wang JG, Fujimoto K, Whittle S, Modi GK, et al. Non-steroidal anti-inflammatory drug (NSAID) therapy in patients with hypertension, cardiovascular, renal or gastrointestinal comorbidities: joint APAGE/APLAR/APSDE/APSH/APSN/PoA recommendations. Gut. 2020;69(4):617–29.

    Article  CAS  Google Scholar 

  13. Scarpignato C, Lanas A, Blandizzi C, Lems WF, Hermann M, Hunt RH. Safe prescribing of non-steroidal anti-inflammatory drugs in patients with osteoarthritis–an expert consensus addressing benefits as well as gastrointestinal and cardiovascular risks. BMC Med. 2015;19(13):55.

    Article  Google Scholar 

  14. Medlock S, Eslami S, Askari M, Taherzadeh Z, Opondo D, de Rooij SE, et al. Co-prescription of gastroprotective agents and their efficacy in elderly patients taking nonsteroidal anti-inflammatory drugs: a systematic review of observational studies. Clin Gastroenterol Hepatol. 2013;11(10):1259-69.e10.

    Article  Google Scholar 

  15. Dincer D, Ulukal Karanci E, Akin M, Adanir H. NSAID, antiaggregant, and/or anticoagulant-related upper gastrointestinal bleeding: Is there any change in prophylaxis rate after a 10-year period? Turk J Gastroenterol. 2019;30(6):505–10.

    PubMed  PubMed Central  Google Scholar 

  16. Kim TJ, Kim ER, Hong SN, Kim YH, Lee YC, Kim HS, et al. Effectiveness of acid suppressants and other mucoprotective agents in reducing the risk of occult gastrointestinal bleeding in nonsteroidal anti-inflammatory drug users. Sci Rep. 2019;9(1):11696.

    Article  Google Scholar 

  17. Kim L, Kim JA, Kim S. A guide for the utilization of health insurance review and assessment service national patient samples. Epidemiol Health. 2014;36:e2014008.

    Article  Google Scholar 

  18. van Soest EM, Sturkenboom M, Dieleman J, Verhamme KM, Siersema P, Kuipers E, et al. Adherence to gastroprotection and the risk of NSAID-related upper gastrointestinal ulcers and haemorrhage. Aliment Pharmacol Ther. 2007;26(2):265–75.

    Article  Google Scholar 

  19. Han MH, Noh E, Nam JH, Lee SW, Lee E-K. Prescribing pattern and safety analysis of nonsteroidal anti-inflammatory drug and gastro-protective agent following reimbursement guidelines relaxation. Korean J Clin Pharm. 2017;27(4):250–7.

    Article  Google Scholar 

  20. Warle-van Herwaarden MF, Koffeman AR, Valkhoff VE, t Jong GW, Kramers C, Sturkenboom MC, et al. Time-trends in the prescribing of gastroprotective agents to primary care patients initiating low-dose aspirin or non-steroidal anti-inflammatory drugs: a population-based cohort study. Br J Clin Pharmacol. 2015;80(3):589–98.

    Article  CAS  Google Scholar 

  21. Hoffmann F, Glaeske G, Schmiemann G. Underuse of proton-pump inhibitors in older patients newly starting NSAID treatment. Int J Clin Pract. 2015;69(7):791–5.

    Article  CAS  Google Scholar 

  22. Szabo IL, Matics R, Hegyi P, Garami A, Illes A, Sarlos P, et al. PPIs prevent aspirin-induced gastrointestinal bleeding better than H2RAs. a systematic review and meta-analysis. J Gastrointest Liver Dis. 2017;26(4):395–402.

    Article  Google Scholar 

  23. O’Mahony D, O’Sullivan D, Byrne S, O’Connor MN, Ryan C, Gallagher P, et al. STOPP/START criteria for potentially inappropriate prescribing in older people: version 2. Age Ageing. 2015;44(2):213–8.

    Article  Google Scholar 

  24. Tuskey A, Peura D. The use of H2 antagonists in treating and preventing NSAID-induced mucosal damage. Arthritis Res Ther. 2013;15(Suppl 3):S6.

    Article  Google Scholar 

  25. Kim JH, Park S-H, Cho C-S, Lee ST, Yoo W-H, Kim SK, et al. Preventive efficacy and safety of rebamipide in nonsteroidal anti-inflammatory drug-induced mucosal toxicity. Gut Liver. 2014;8(4):371.

    Article  CAS  Google Scholar 

  26. Lee OY, Kang DH, Lee DH, Chung IK, Jang JY, Kim JI, et al. A comparative study of DA-9601 and misoprostol for prevention of NSAID-associated gastroduodenal injury in patients undergoing chronic NSAID treatment. Arch Pharm Res. 2014;37(10):1308–16.

    Article  CAS  Google Scholar 

  27. Laine L, Connors L, Griffin MR, Curtis SP, Kaur A, Cannon CP. Prescription rates of protective co-therapy for NSAID users at high GI risk and results of attempts to improve adherence to guidelines. Aliment Pharmacol Ther. 2009;30(7):767–74.

    Article  CAS  Google Scholar 

  28. 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. Am J Gastroenterol. 2010;105(12):2533–49.

    Article  Google Scholar 

  29. Butler E, Moller MH, Cook O, Granholm A, Penketh J, Rygard SL, et al. The effect of systemic corticosteroids on the incidence of gastrointestinal bleeding in critically ill adults: a systematic review with meta-analysis. Intensive Care Med. 2019;45(11):1540–9.

    Article  Google Scholar 

  30. Chou CL, Perng DW, Lin TL, Lin AM, Chen TJ, Wu MS, et al. Analysis of prescription pattern and guideline adherence in the management of asthma among medical institutions and physician specialties in Taiwan between 2000 and 2010. Clin Ther. 2015;37(10):2275–85.

    Article  Google Scholar 

  31. Wilcox CM, Allison J, Benzuly K, Borum M, Cryer B, Grosser T, et al. Consensus development conference on the use of nonsteroidal anti-inflammatory agents, including cyclooxygenase-2 enzyme inhibitors and aspirin. Clin Gastroenterol Hepatol. 2006;4(9):1082–9.

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the Creative-Pioneering Researchers Program through Seoul National University (SNU).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ju-Yeun Lee.

Ethics declarations

Conflicts of interest

The authors declare no conflicts of interest.

Consent for publication

Not applicable.

Consent to participate

Participants informed consent was waived because the identification numbers of all the individuals in the HIRA claims database were encrypted to protect their privacy.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 17 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, WY., Lee, S., Jun, K. et al. Underutilization of gastrointestinal prophylaxis in high-risk chronic nonsteroidal anti-inflammatory drug users in Korea. Int J Clin Pharm 43, 645–653 (2021). https://doi.org/10.1007/s11096-020-01176-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11096-020-01176-0

Keywords

Navigation