Gastrointestinal and cardiovascular risk of non-selective NSAIDs and COX-2 inhibitors in elderly patients with knee osteoarthritis

Abstract

Objective: To evaluate the incidence and risk profiles for gastrointestinal (GI) events and cardiovascular (CV) events in elderly patients (aged > or =60 years) with knee osteoarthritis using tNSAIDs (traditional non-steroidal anti-inflammatory drugs) or coxibs users in patients with knee osteoarthritis aged > or =60 years.

Material and method: A hospital-based retrospective cohort study was applied. Data on prescription drug (NSAIDs, celecoxib, etoricoxib) was obtained from hospital database. Data on CV events and GI adverse events was obtained from the registry of the Cardiology Unit and Gastroesophagoscope Diagnosis Center, GI Center, Department of Internal medicine, Police General Hospital. Patients visiting the hospitals' outpatient clinics from June 2004 to June 2007 were included if they were aged > or =60 years and received at least one follow-up visit on the prescription of a tNSAIDNSAID or coxibs (etoricoxib or celecoxib). Patients with a history of gastrointestinal disease or heart disease were excluded. All patients were followed-up from their first visit to the date of their earliest event or to the end of the study period. The interested event was assumed to be attributed to the last prescription shown in the study period.

Results: A total 12,591 prescriptions from 1030 patients, an average of 4 prescriptions/patient/year, were screened -3,982 (31.6%) prescriptions were for NSAIDs, 4426 (35.2%) were for celecoxib, and 4183 (33.2%) were for etoricoxib. The most common traditional NSAID prescribed was meloxicam (24%), followed by nimesulide (21.4%) and naproxen (13.1%). The mean age of cohort was 69.6 years, with the majority being female (74%). We found a comparable dose of celecoxib (200 mg OD) and etoricoxib (90 mg OD) prescribed in the respective patients. A total of 78 gastrointestinal events occurred and Esophagogastroscopy indicated that 37 (47.4%) were dyspepsia, 22 (28.2%) were anemia (28.2%), 17 (21.7%) were upper GI bleeding, and 2 (2.6%) were others. Forty (40) of these events were attributed to NSAIDs, 21 to celecoxib and 17 to etoricoxib. Observed GI events included gastritis (50, 64.1%), gastric ulcer (14, 17.9%), duodenal ulcer (3, 3.8%), and normal (11, 14.1%). Patients receiving traditional NSAIDs, celecoxib and etoricoxib had 20, 18, and 11 CV events respectively. Of these 49 CV events, the most common was heart failure (20), followed by chronic heart failure (9), angina pectoris (9), unstable angina (6), and myocardial infarction (5). Comparing celecoxib with NSAID use in logistic regression analysis, patients who received celecoxib were significantly less likely to suffer GI events than those who received NSAIDs; OR = 0.36 (95% CI 0.21-0.63, p = 0.00.). Similarly, etoricoxib was less likely to cause GI events than NSAIDs; OR = 0.52 (95% CI 0.28-0.98, p = 0.04). Comparing to patients aged under 60 years, patients aged >70 years had a significantly higher chance of developing GI events, OR = 1.79 (95% CI 1.13-2.4) for patients aged 70-80 years and 3.36 (95% CI 1.78-5.81) for those aged > 80 years. Drug exposure time, which was defined as the number of days of medication supplied significantly increased the GI risks. For CV event, there were only 3 significantly associated with CV events -female (OR = 0.29, 95% CI 0.16-0.59, p = 0.00), age >80 years (OR = 2.98, 95% CI 1.57-4.23, p = 0.00), and drug exposure time (OR = 1.05, 95% CI 1.02-1.54, p = 0.00).

Conclusion: Incidence of GI and CV events was lower for coxibs than for NSAIDs and celecoxib had a lower incidence than etoricoxib. Patients with advanced age and higher drug exposure time had a significantly increased risk ofGI; the use of gastroprotective agents significantly decreased GI risks. Being female, advanced age, and drug exposure time significantly affected CV events.