J Korean Med Assoc.  2018 Jun;61(6):367-375. 10.5124/jkma.2018.61.6.367.

Strategies for the safe use of non-steroidal anti-inflammatory drugs

• Ahn GY
• Bae SC

• KMID: 2414145
• DOI: http://doi.org/10.5124/jkma.2018.61.6.367

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in various clinical situations, with excellent analgesic, anti-pyretic and anti-inflammatory effects. In addition to gastrointestinal bleeding, which was the first adverse effect to be reported, myriad adverse effects from the digestive system, cardiovascular system, renal system and hematology have been also reported. In early 2000s, a few new cyclooxygenase (COX)-2 selective inhibitors were developed with the expectation of better gastrointestinal safety profile, most of them were withdrawn from the market due to various adverse effects, and interest in safety of NSAIDs has been increased again. Over the past two decades, research on the safety and adverse effects of NSAIDs has accumulated. In brief, celecoxib is associated with fewer gastrointestinal adverse events compared to non-selective NSAIDs. In patients receiving aspirin, the use of non-selective NSAIDs should be avoided, and if an anti-inflammatory drug is required, a COX-2 selective inhibitor should be considered. Celecoxib has been shown to have similar or better safety profile than other non-selective COX inhibitors. Additionally, the new COX-2 selective inhibitors of etorixocib and polmacoxib have been approved. Many factors should be considered when prescribing NSAIDs, as the safety profile of indivisual NSAIDs vary, and NSAIDs have a high risk of duplicate prescription because of the variety of indications and over-the-counter products. Physicians should comprehend the updated guidelines and the results of new clinical studies, and the risk factors for each individual patient should also be reviewed. Physicians should therefore contemplate new prescription strategies.

Keyword

Anti-inflammatory agents, non-steroidal; Drug-related side effects and adverse reactions; Medication therapy management

MeSH Terms

Anti-Inflammatory Agents, Non-Steroidal
Aspirin
Cardiovascular System
Celecoxib
Digestive System
Drug-Related Side Effects and Adverse Reactions
Hematology
Hemorrhage
Humans
Medication Therapy Management
Prescriptions
Prostaglandin-Endoperoxide Synthases
Risk Factors
Anti-Inflammatory Agents, Non-Steroidal
Aspirin
Celecoxib
Prostaglandin-Endoperoxide Synthases

Figure

• 

  Figure 1 Pathway of prostanoid formation and illustration of functions. NSAIDs, non-steroidal antiinflammatory drugs; COX, cyclooxygenase.

Reference

1. Pirlamarla P, Bond RM. FDA labeling of NSAIDs: review of nonsteroidal anti-inflammatory drugs in cardiovascular disease. Trends Cardiovasc Med. 2016; 26:675–680.

2. Coxib and traditional NSAID Trialists' (CNT) Collaboration. Bhala N, Emberson J, Merhi A, Abramson S, Arber N, Baron JA, Bombardier C, Cannon C, Farkouh ME, FitzGerald GA, Goss P, Halls H, Hawk E, Hawkey C, Hennekens C, Hochberg M, Holland LE, Kearney PM, Laine L, Lanas A, Lance P, Laupacis A, Oates J, Patrono C, Schnitzer TJ, Solomon S, Tugwell P, Wilson K, Wittes J, Baigent C. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013; 382:769–779.

3. Bell AD, Roussin A, Cartier R, Chan WS, Douketis JD, Gupta A, Kraw ME, Lindsay TF, Love MP, Pannu N, Rabasa-Lhoret R, Shuaib A, Teal P, Theroux P, Turpie AG, Welsh RC, Tanguay JF. Canadian Cardiovascular Society. The use of antiplatelet therapy in the outpatient setting: Canadian Cardiovascular Society guidelines. Can J Cardiol. 2011; 27:Suppl A. S1–S59.

4. Sostres C, Gargallo CJ, Lanas A. Nonsteroidal anti-inflammatory drugs and upper and lower gastrointestinal mucosal damage. Arthritis Res Ther. 2013; 15:Suppl 3. S3.

5. Shorr RI, Ray WA, Daugherty JR, Griffin MR. Concurrent use of nonsteroidal anti-inflammatory drugs and oral anticoagulants places elderly persons at high risk for hemorrhagic peptic ulcer disease. Arch Intern Med. 1993; 153:1665–1670.

6. Chi TY, Zhu HM, Zhang M. Risk factors associated with nonsteroidal anti-inflammatory drugs (NSAIDs)-induced gastrointestinal bleeding resulting on people over 60 years old in Beijing. Medicine (Baltimore). 2018; 97:e0665.

7. Scarpignato C, Hunt RH. Nonsteroidal antiinflammatory drug-related injury to the gastrointestinal tract: clinical picture, pathogenesis, and prevention. Gastroenterol Clin North Am. 2010; 39:433–464.

8. Lee W, Suh JW, Yang HM, Kwon DA, Cho HJ, Kang HJ, Kim HS, Oh BH. Celecoxib does not attenuate the antiplatelet effects of aspirin and clopidogrel in healthy volunteers. Korean Circ J. 2010; 40:321–327.

9. Li S, Liu B, Luo W, Zhang Y, Li H, Huang D, Zhou Y. Role of cyclooxygenase-1 and -2 in endothelium-dependent contraction of atherosclerotic mouse abdominal aortas. Clin Exp Pharmacol Physiol. 2016; 43:67–74.

10. Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, Lines C, Riddell R, Morton D, Lanas A, Konstam MA, Baron JA. Adenomatous Polyp Prevention on Vioxx (APPROVe) Trial Investigators. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005; 352:1092–1102.

11. Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P, Anderson WF, Zauber A, Hawk E, Bertagnolli M. Adenoma Prevention with Celecoxib (APC) Study Investigators. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005; 352:1071–1080.

12. Arber N, Eagle CJ, Spicak J, Racz I, Dite P, Hajer J, Zavoral M, Lechuga MJ, Gerletti P, Tang J, Rosenstein RB, Macdonald K, Bhadra P, Fowler R, Wittes J, Zauber AG, Solomon SD, Levin B. PreSAP Trial Investigators. Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med. 2006; 355:885–895.

13. ADAPT Research Group. Cardiovascular and cerebrovascular events in the randomized, controlled Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT). PLoS Clin Trials. 2006; 1:e33.

14. White WB, Faich G, Whelton A, Maurath C, Ridge NJ, Verburg KM, Geis GS, Lefkowith JB. Comparison of thromboembolic events in patients treated with celecoxib, a cyclooxygenase-2 specific inhibitor, versus ibuprofen or diclofenac. Am J Cardiol. 2002; 89:425–430.

15. Cannon CP, Curtis SP, FitzGerald GA, Krum H, Kaur A, Bolognese JA, Reicin AS, Bombardier C, Weinblatt ME, van der Heijde D, Erdmann E, Laine L. MEDAL Steering Committee. Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet. 2006; 368:1771–1781.

16. Cho SK, Kim D, Won S, Lee J, Park B, Jang EJ, Bae SC, Sung YK. Impact of anti-rheumatic treatment on cardiovascular risk in Asian patients with rheumatoid arthritis. Semin Arthritis Rheu. 2018; 47:501–506.

17. Chen YR, Hsieh FI, Chang CC, Chi NF, Wu HC, Chiou HY. Effect on risk of stroke and acute myocardial infarction of nonselective nonsteroidal anti-inflammatory drugs in patients with rheumatoid arthritis. Am J Cardiol. 2018; 121:1271–1277.

18. Sica DS, Schoolwerth AC, Gehr TW. Pharmacotherapy in congestive heart failure: COX-2 inhibition: a cautionary note in congestive heart failure. Congest Heart Fail. 2000; 6:272–276.

19. Whelton A, Schulman G, Wallemark C, Drower EJ, Isakson PC, Verburg KM, Geis GS. Effects of celecoxib and naproxen on renal function in the elderly. Arch Intern Med. 2000; 160:1465–1470.

20. Whelton A, Lefkowith JL, West CR, Verburg KM. Cardiorenal effects of celecoxib as compared with the nonsteroidal anti-inflammatory drugs diclofenac and ibuprofen. Kidney Int. 2006; 70:1495–1502.

21. Zhang J, Ding EL, Song Y. Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events: meta-analysis of randomized trials. JAMA. 2006; 296:1619–1632.

22. Chan CC, Reid CM, Aw TJ, Liew D, Haas SJ, Krum H. Do COX-2 inhibitors raise blood pressure more than nonselective NSAIDs and placebo? An updated meta-analysis. J Hypertens. 2009; 27:2332–2341.

23. Rostom A, Goldkind L, Laine L. Nonsteroidal anti-inflammatory drugs and hepatic toxicity: a systematic review of randomized controlled trials in arthritis patients. Clin Gastroenterol Hepatol. 2005; 3:489–498.

24. Lapeyre-Mestre M, Grolleau S, Montastruc JL. Association Francaise des Centres Regionaux de Pharmacovigilance (CRPV). Adverse drug reactions associated with the use of NSAIDs: a case/noncase analysis of spontaneous reports from the French pharmacovigilance database 2002-2006. Fundam Clin Pharmacol. 2013; 27:223–230.

25. Bessone F, Hernandez N, Roma MG, Ridruejo E, Mendizabal M, Medina-Caliz I, Robles-Diaz M, Lucena MI, Andrade RJ. Hepatotoxicity induced by coxibs: how concerned should we be? Expert Opin Drug Saf. 2016; 15:1463–1475.

26. Knowles S, Shapiro L, Shear NH. Should celecoxib be con-traindicated in patients who are allergic to sulfonamides? Revisiting the meaning of ‘sulfa’ allergy. Drug Saf. 2001; 24:239–247.

27. Lanza FL, Chan FK, Quigley EM. Practice Parameters Committee of the American College of Gastroenterology. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol. 2009; 104:728–738.

28. Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, Gisbert JP, Graham DY, Rokkas T, El-Omar EM, Kuipers EJ. European Helicobacter Study Group. Management of helicobacter pylori infection: the Maastricht IV/ Florence Consensus Report. Gut. 2012; 61:646–664.

29. Scarpignato C, Lanas A, Blandizzi C, Lems WF, Hermann M, Hunt RH. International NSAID Consensus Group. 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; 13:55.

30. Bruyere O, Cooper C, Pelletier JP, Maheu E, Rannou F, Branco J, Luisa Brandi M, Kanis JA, Altman RD, Hochberg MC, Martel-Pelletier J, Reginster JY. A consensus statement on the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) algorithm for the management of knee osteoarthritis-from evidence-based medicine to the real-life setting. Semin Arthritis Rheum. 2016; 45:4 Suppl. S3–S11.