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BACKGROUND:Use of selective COX-2 non-steroidal anti-inflammatory drugs (NSAIDs) (coxibs) has been associated with an increased risk of acute myocardial infarction (AMI). However, the risk of AMI has only been studied for very few NSAIDs that are frequently used. OBJECTIVES:To estimate the risk of AMI for individual NSAIDs. METHODS:A nested case-control study was performed from a cohort of new NSAID users ≥18 years (1999-2011) matching cases to a maximum of 100 controls on database, sex, age, and calendar time. Data were retrieved from six healthcare databases. Adjusted odds ratios (ORs) of current use of individual NSAIDs compared to past use were estimated per database. Pooling was done by two-stage pooling using a random effects model (ORmeta) and by one-stage pooling (ORpool). RESULTS:Among 8.5 million new NSAID users, 79,553 AMI cases were identified. The risk was elevated for current use of ketorolac (ORmeta 2.06;95%CI 1.83-2.32, ORpool 1.80; 1.49-2.18) followed, in descending order of point estimate, by indometacin, etoricoxib, rofecoxib, diclofenac, fixed combination of diclofenac with misoprostol, piroxicam, ibuprofen, naproxen, celecoxib, meloxicam, nimesulide and ketoprofen (ORmeta 1.12; 1.03-1.22, ORpool 1.00;0.86-1.16). Higher doses showed higher risk estimates than lower doses. CONCLUSIONS:The relative risk estimates of AMI differed slightly between 28 individual NSAIDs. The relative risk was highest for ketorolac and was correlated with COX-2 potency, but not restricted to coxibs.

BACKGROUND AND PURPOSE:A multi-country European study using data from six healthcare databases from four countries was performed to evaluate in a large study population (>32 million) the risk of ischemic stroke (IS) associated with individual NSAIDs and to assess the impact of risk factors of IS and co-medication. METHODS:Case-control study nested in a cohort of new NSAID users. For each case, up to 100 sex- and age-matched controls were selected and confounder-adjusted odds ratios for current use of individual NSAIDs compared to past use calculated. RESULTS:49,170 cases of IS were observed among 4,593,778 new NSAID users. Use of coxibs (odds ratio 1.08, 95%-confidence interval 1.02-1.15) and use of traditional NSAIDs (1.16, 1.12-1.19) were associated with an increased risk of IS. Among 32 individual NSAIDs evaluated, the highest significant risk of IS was observed for ketorolac (1.46, 1.19-1.78), but significantly increased risks (in decreasing order) were also found for diclofenac, indomethacin, rofecoxib, ibuprofen, nimesulide, diclofenac with misoprostol, and piroxicam. IS risk associated with NSAID use was generally higher in persons of younger age, males, and those with a prior history of IS. CONCLUSIONS:Risk of IS differs between individual NSAIDs and appears to be higher in patients with a prior history of IS or transient ischemic attack (TIA), in younger or male patients. Co-medication with aspirin, other antiplatelets or anticoagulants might mitigate this risk. The small to moderate observed risk increase (by 13-46%) associated with NSAIDs use represents a public health concern due to widespread NSAID usage.

Fundamento: Estudio de la morbimortalidad coronaria y mortalidad total asociadas a los denominados factores de riesgo coronario de una cohorte industrial de varones seguida durante 28 años. Métodos: Población laboral de 1.059 varones de 30-59 años libres de cardiopatía en el examen inicial (1968), reexaminados cada cinco años hasta 1988 y con el examen final en 1996. Durante el tiempo de seguimiento se obtuvo información del 96,4% del total de participantes. Resultados: Las tasas de incidencia de enfermedad coronaria, mortalidad coronaria y muerte total por 105 (personas-años de observación) fueron: 499,80; 235,80 y 925,33, respectivamente. Los niveles elevados de colesterol y el consumo habitual de cigarrillos se asociaron independientemente con la incidencia de cardiopatía coronaria y la mortalidad coronaria ajustado por edad, presión arterial, glucemia e índice de masa corporal. Los niveles elevados de colesterol sérico, glucemia y consumo de cigarrillos se asociaron independientemente con el riesgo de muerte por todas las causas. Conclusiones: En esta población, con incidencia relativamente baja de enfermedad coronaria, el tabaco y el colesterol sérico mantuvieron el valor predictivo independiente, durante los 28 años de seguimiento.