Evaluation of Risk Profiles for Gastrointestinal and Cardiovascular Adverse Effects in Nonselective NSAID and COX-2 Inhibitor Users: A Cohort Study Using Pharmacy Dispensing Data in The Netherlands

• Published in: Drug safety 2008-01, Vol.31 (2), p.143-158
• Main Authors: Layton, Deborah, Souverein, Patrick C., Heerdink, Eibert R., Shakir, Saad A. W., Egberts, Antoine C. G.
• Format: Article
• Language: English
• Subjects: Age Factors; Aged; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Biological and medical sciences; Cardiovascular Diseases - chemically induced; Cohort Studies; Cyclooxygenase 2 Inhibitors - adverse effects; Drug Prescriptions - statistics & numerical data; Drug Safety and Pharmacovigilance; Drug toxicity and drugs side effects treatment; Drug Utilization Review - methods; Drug Utilization Review - statistics & numerical data; Female; Gastrointestinal Diseases - chemically induced; Humans; Insurance Claim Review - statistics & numerical data; Male; Medical sciences; Medicine; Medicine & Public Health; Netherlands; Original Research Article; Pharmaceutical Services - statistics & numerical data; Pharmacology. Drug treatments; Pharmacology/Toxicology; Product Surveillance, Postmarketing; Risk Assessment; Risk Factors; Time Factors; Toxicity: cardiovascular system; Toxicity: digestive system
• ISSN: 0114-5916; 1179-1942
• DOI: 10.2165/00002018-200831020-00004

Background : Newly approved drugs, in comparison with older drugs, are more often prescribed to patients who have not responded satisfactorily to established related drugs or as first-line therapy to patients with a high baseline risk for adverse outcomes (i.e. channelling). However, these patients are less likely to benefit from the prescribed drug and/or are more prone to adverse drug reactions. Therefore, it is difficult to unravel whether observed risks or increases in risk of new drugs are real, i.e. related to the pharmacology, or whether these are related to selective prescribing to patients who are more susceptible to adverse events because of some underlying risk factor(s). The channelling paradox may exist for cyclo-oxygenase (COX)-2 selective inhibitors (‘coxibs’) instead of traditional nonselective NSAIDs in relation to both gastrointestinal (GI) and cardiovascular (CV) safety. Objective : To evaluate the risk profiles for GI and CV adverse effects in nonselective NSAID and coxib new-user populations over time, in terms of a quantitative measure since the introduction of coxibs. Methods : This was a population-based cohort study using the Dutch pharmaceutical claims database (Foundation for Pharmaceutical Statistics). Eligible patients (≥18 years) were those where the date of their first prescription (index date) of an NSAID (first-line [e.g. ibuprofen] or second-line [e.g. piroxicam] nonselective NSAID, COX-2 preferential NSAID or coxib) was between January 1999 and December 2003. For each patient, GI and CV risk profiles at index date were defined by a cumulative score derived from dispensing data (patient age, sex and history of medication use within 6 months of index date). Risk scores were categorized as low (score = 0), medium (1) or high (2+). Patients were recorded as switchers based on other NSAID use prior to the index date. Other information collected included the Chronic Disease Score (CDS). Crude odds ratios (ORs) were calculated for risk factors for each NSAID group versus first-line nonselective NSAID users as the reference cohort. The effect of calendar time was examined by plotting mean CV or GI risk score by quarter-year. Correlation between GI and CV scores was examined using the Pearson correlation coefficient (R). Data were stratified by patients’ history of switching. Results : The four cohorts comprised patients using: first-line nonselective NSAIDs (n = 42 750); second-line nonselective NSAIDs (n = 1771); COX-2 preferent