Impact of adherence to concomitant gastroprotective therapy on nonsteroidal-related gastroduodenal ulcer complications.

BACKGROUND & AIMS The clinical impact of nonadherence to gastroprotective agents (GPAs) coprescribed with anti-inflammatory therapies has not been evaluated. In a large, commercial, managed-care database, we retrospectively characterized the use of GPAs among patients receiving nonselective nonsteroidal anti-inflammatory drugs (ns-NSAIDs) or cyclooxygenase-2-selective inhibitors (coxibs) and determined the impact of nonadherence on the likelihood of gastroduodenal ulcer complications. METHODS Analyses identified the populations of patients with concomitant histamine-2 receptor antagonist or proton pump inhibitor (PPI) therapy and determined adherence with the prescribed therapy with respect to the duration of anti-inflammatory treatment. Multivariate regression analyses modeled the association between adherence with concomitant protective therapy and the likelihood of upper gastrointestinal (GI) complications including peptic ulcer disease, ulcer, and/or upper-GI bleed. RESULTS Among 144,203 patients newly prescribed anti-inflammatory therapies, 1.8% received concomitant GPA treatment (ns-NSAIDs, 1.4% vs coxibs, 2.6%; P < .0001). The likelihood of GPA use increased with the presence of risk factors: age older than 65 years (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.3-1.5) and prior history of peptic ulcer disease (OR, 2.5; 95% CI, 1.8-3.3), esophagitis/gastroesophageal reflux (OR, 3.8; 95% CI, 3.5-4.1), ulcer/upper-GI bleed (OR, 1.4; 95% CI, 1.2-1.5), or gastritis (OR, 2.5; 95% CI, 2.2-2.8). Of patients receiving concomitant PPI therapy, 68% had adherence rates of 80% or more. A significantly higher risk of upper-GI ulcers/complications was observed in ns-NSAID patients with adherence rates of less than 80% compared with adherence rates of 80% or more (OR, 2.4; 95% CI, 1.0-5.6), but no such relationship was observed among patients who took coxibs. CONCLUSIONS Few patients receive concomitant GPA therapy when prescribed anti-inflammatory treatment, although use increased with the presence of risk factors. Adherence to concomitant therapy is paramount to reducing GI events among ns-NSAID users and educational efforts should be undertaken to promote use of and adherence to GPA therapy among these patients.

[1]  J. W. Griffin,et al.  Effect of ranitidine gastroduodenal mucosal damage induced by nonsteroidal antiinflammatory drugs , 1989, Digestive Diseases and Sciences.

[2]  V. Wong,et al.  Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. , 2002, The New England journal of medicine.

[3]  R Day,et al.  Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. , 2000, The New England journal of medicine.

[4]  Peter J. Richardson,et al.  National adherence to evidence-based guidelines for the prescription of nonsteroidal anti-inflammatory drugs. , 2005, Gastroenterology.

[5]  E H Wagner,et al.  A chronic disease score from automated pharmacy data. , 1992, Journal of clinical epidemiology.

[6]  M. Wolfe,et al.  Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. , 1999, The New England journal of medicine.

[7]  C. Tilquin,et al.  Risk Adjustment in Outcome Assessment: the Charlson Comorbidity Index , 1993, Methods of Information in Medicine.

[8]  A. Weaver,et al.  Comparison of the upper gastrointestinal safety of Arthrotec 75 and nabumetone in osteoarthritis patients at high risk for developing nonsteroidal anti-inflammatory drug-induced gastrointestinal ulcers. , 1999, Clinical therapeutics.

[9]  A. Barkun,et al.  Omeprazole Compared with Misoprostol for Ulcers Associated with Nonsteroidal Antiinflammatory Drugs , 1998 .

[10]  Thomas J. Schnitzer,et al.  Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update , 2000 .

[11]  R. Makuch,et al.  Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. , 2000, JAMA.

[12]  V. Fuster,et al.  Platelet-active drugs: the relationships among dose, effectiveness, and side effects. , 2004, Chest.

[13]  E. Rosenow Patients' understanding of and compliance with medications: the sixth vital sign? , 2005, Mayo Clinic proceedings.

[14]  L. Laine,et al.  Guidelines for the appropriate use of non‐steroidal anti‐inflammatory drugs, cyclo‐oxygenase‐2‐specific inhibitors and proton pump inhibitors in patients requiring chronic anti‐inflammatory therapy , 2004, Alimentary pharmacology & therapeutics.

[15]  C. Bombardier,et al.  Stratifying the risk of NSAID-related upper gastrointestinal clinical events: results of a double-blind outcomes study in patients with rheumatoid arthritis. , 2002, Gastroenterology.

[16]  E. Friedman,et al.  Patients' understanding of their treatment plans and diagnosis at discharge. , 2005, Mayo Clinic proceedings.

[17]  C. Hawkey,et al.  Famotidine for the prevention of gastric and duodenal ulcers caused by nonsteroidal antiinflammatory drugs. , 1996, The New England journal of medicine.

[18]  T. Schnitzer,et al.  Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: randomised controlled trial , 2004, The Lancet.

[19]  A. Fendrick,et al.  PPI use in the OTC era: who to treat, with what, and for how long? , 2005, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[20]  S. Gabriel,et al.  Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. A meta-analysis. , 1991, Annals of internal medicine.

[21]  V. Wong,et al.  Celecoxib versus diclofenac plus omeprazole in high-risk arthritis patients: results of a randomized double-blind trial. , 2004, Gastroenterology.

[22]  A. Mattioli,et al.  Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients , 2002, BMJ : British Medical Journal.

[23]  W. Ray,et al.  Concurrent use of nonsteroidal anti-inflammatory drugs and oral anticoagulants places elderly persons at high risk for hemorrhagic peptic ulcer disease. , 1993, Archives of internal medicine.

[24]  L. Osterberg,et al.  Adherence to medication. , 2005, The New England journal of medicine.

[25]  J. Senior,et al.  Misoprostol Reduces Serious Gastrointestinal Complications in Patients with Rheumatoid Arthritis Receiving Nonsteroidal Anti-Inflammatory Drugs , 1995, Annals of Internal Medicine.

[26]  F. Lanza A guideline for the treatment and prevention of NSAID-induced ulcers , 1998, American Journal of Gastroenterology.

[27]  G. Singh,et al.  Recent considerations in nonsteroidal anti-inflammatory drug gastropathy. , 1998, The American journal of medicine.

[28]  Colin Baigent,et al.  Low-dose aspirin for the prevention of atherothrombosis. , 2005, The New England journal of medicine.

[29]  K. Chu,et al.  Celecoxib compared with lansoprazole and naproxen to prevent gastrointestinal ulcer complications. , 2005, The American journal of medicine.

[30]  R. Yood,et al.  Guidelines for the management of rheumatoid arthritis: 2002 Update. , 2002, Arthritis and rheumatism.

[31]  F. Silverstein,et al.  Reduced risk of upper gastrointestinal ulcer complications with celecoxib, a novel COX-2 inhibitor , 2000, American Journal of Gastroenterology.

[32]  D. Graham,et al.  Ulcer prevention in long-term users of nonsteroidal anti-inflammatory drugs: results of a double-blind, randomized, multicenter, active- and placebo-controlled study of misoprostol vs lansoprazole. , 2002, Archives of internal medicine.

[33]  G. Singh,et al.  NSAID induced gastrointestinal complications: the ARAMIS perspective--1997. Arthritis, Rheumatism, and Aging Medical Information System. , 1998, The Journal of rheumatology. Supplement.

[34]  G. Newsome Guidelines for the management of rheumatoid arthritis: 2002 update. , 2002, Journal of the American Academy of Nurse Practitioners.

[35]  G. Tildesley,et al.  Prevention of gastroduodenal damage induced by non-steroidal anti-inflammatory drugs: controlled trial of ranitidine. , 1988, BMJ.

[36]  A. Fendrick,et al.  NSAIDs without a prescription: over-the-counter access, under-counted risks , 2002, American Journal of Gastroenterology.

[37]  P. Unge,et al.  Prevention of peptic ulcer and dyspeptic symptoms with omeprazole in patients receiving continuous non-steroidal anti-inflammatory drug therapy. A Nordic multicentre study. , 1996, Scandinavian journal of gastroenterology.

[38]  R. de Caterina,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. , 2004, European heart journal.

[39]  J. Dieleman,et al.  Underutilization of preventive strategies in patients receiving NSAIDs. , 2003, Rheumatology.

[40]  J. Scheiman Gastrointestinal outcomes: evidence for risk reduction in patients using coxibs. , 2002, The American journal of managed care.

[41]  Catherine Sudlow,et al.  Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients , 2002, BMJ : British Medical Journal.

[42]  J. Dieleman,et al.  Adherence to proton pump inhibitors or H2‐receptor antagonists during the use of non‐steroidal anti‐inflammatory drugs , 2003, Alimentary pharmacology & therapeutics.

[43]  H. Sørensen,et al.  Outcome of upper gastro-intestinal bleeding and use of ibuprofen versus paracetamol , 2004, Pharmacy World and Science.

[44]  W A Ray,et al.  Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. , 1991, Annals of internal medicine.

[45]  M. Safdi,et al.  Superiority of lansoprazole vs ranitidine in healing nonsteroidal anti-inflammatory drug-associated gastric ulcers: results of a double-blind, randomized, multicenter study. NSAID-Associated Gastric Ulcer Study Group. , 2000, Archives of internal medicine.

[46]  V. Fuster,et al.  Platelet-active drugs : the relationships among dose, effectiveness, and side effects. , 2004, Chest.

[47]  C. Hawkey,et al.  A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment (ASTRONAUT) Study Group. , 1998, The New England journal of medicine.