Table 2.
Characteristics of Cohort Studies in the Meta‐analysis
| Feenstra et al12 | Mamdani et al14 | Bäck et al16 | |
|---|---|---|---|
| Country | The Netherlands | Canada | Sweden |
| Study design | Prospective cohort | Retrospective cohort | Retrospective cohort |
| Year | 2002 | 2004 | 2012 |
| Cases | All residents of Ommoord, a suburb city of Rotterdam, age ≥55 y, were invited to participate in this study. 78% of eligible residents agreed to participate. The first cross‐sectional study started in June 1990. Participants with prevalent HF at study entrance were excluded from the analyses. Cross‐sectional survey was conducted periodically by home interviews and participant visits to the research center. | All residents of Ontario, Canada, age ≥66 y and who were prescribed NSAIDs from April 17, 2000, to March 31, 2001, with a supply that lasted ≥30 days. Cases were identified from an administrative health care database that covered 1.3 million individuals ≥65 y. The study included patients with and without prior diagnosis of HF but provided separate analysis for each category. | All Swedish residents age ≥18 y. Medical information was retrieved from Swedish patient register, prescribed drug register, and cause of death register. Follow‐up started on July 1, 2005, and ended on December 31, 2008. Residents with history of MI, stroke, HF, and AF prior to the start date were excluded. |
| NSAIDs assessed in the study | Nonselective NSAIDs | Celecoxib, rofecoxib, and nonselective NSAIDs | Celecoxib, etoricoxib |
| Definition of NSAID exposure | Period of exposure was defined as duration of prescription plus a carryover period of 7 days | ≥2 prescriptions for NSAIDs from April 17, 2000, to March 31, 2001, with a supply that lasted ≥30 days | Period of exposure was defined as duration of prescription plus a carryover period of 30 days |
| Verification of NSAID exposure | Verified with the pharmacy database of the study, which comprehensively covered all prescriptions dispensed to participants | Verified with pharmacy records that were linked to the administrative health care database | Verified with the Swedish national prescribed drug register |
| Control | NSAID use was analyzed as a time‐dependent variable (ie, duration of nonexposure to NSAIDs served as control) | Residents age ≥66 y with no history of NSAID exposure, randomly selected from the same database | NSAID use was analyzed as a time‐dependent variable (ie, duration of nonexposure to NSAIDs served as control) |
| Diagnosis of HF | HF was of special interest in the study. The continuous follow‐up of all participants was aimed at identifying all events of interest, including HF. It was part of the routine follow‐up procedure that all available data on the events of interest, such as hospital discharge note and outpatient visit note, were analyzed. Two research physicians independently evaluated and verified the HF diagnosis. | The primary outcome was admission with primary diagnosis of HF, which was identified from the Canadian Institute for Health Information discharge abstract database. | Diagnostic code from the database. No further verification was performed. |
| Follow‐up | Until a diagnosis of incident HF, death, emigration out of system, or December 31, 1998 | Until occurrence of study endpoint, death, or March 31, 2001 | Until occurrence of study endpoint, death, or December 31, 2008 |
| Cases, n | 7277 | 44 258 (32 834 COXIBs and 11 424 nonselective NSAIDs) | 6 991 645 |
| Controls, n | 7277 | 98 409 | 6 991 645 |
| Average age, y, cases/controls | 70.0/70.0 | 75.4/76.3 | 50.0/50.0 |
| Female sex, %, cases/controls | 62.0/62.0 | 55.0/68.0 | 50.8/50.8 |
| Average follow‐up, y, cases/controls | 6.0/6.0 | 0.5/0.5 | NA/NA |
| Confounders adjusted for | Age, sex; sCr ≥1.1 mg/dL; HTN, history of MI, AF; concomitant cardiovascular and pulmonary medication | Age, sex; medications used; hospitalization; socioeconomic status | Age, sex; medications used; socioeconomic status, educational level; RA |
| Newcastle‐Ottawa scale | Selection, 4 stars; comparability, 2 stars; outcome, 3 stars | Selection, 4 stars; comparability, 1 star; outcome, 3 stars | Selection, 4 stars; comparability, 2 stars; outcome, 3 stars |
Abbreviations: AF, atrial fibrillation; COXIB, highly selective cyclooxygenase‐2 inhibitor; HF, heart failure; HTN, hypertension; MI, myocardial infarction; NA, not available; NSAID, nonsteroidal anti‐inflammatory drug; RA, rheumatoid arthritis; sCr, serum creatinine.