Stroke risk and NSAIDs: A systematic review of observational studies

Aims: To perform a quantitative systematic review of observational studies on the risk of stroke associated with the use of individual NSAIDs. Methods and results: Searches were conducted using the Medline database within PubMed (1990-2008). Observational cohort or case-control studies were eligible if reported on the risk of cardiovascular events associated with individual NSAIDs versus the nonuse of NSAIDs. We found 3193 articles, in which 75 were eligible for review and abstraction. Of the 75 articles, 6 reported relative risk (RR) of stroke. Data were abstracted into a database using a standardized entry form. Two authors assessed study quality, and discrepancies were resolved by consensus. The pooled RR of all subtypes of incident stroke was increased with the current use of rofecoxib (RR=1.64, 95% CI=1.15-2.33) and diclofenac (RR=1.27, 95% CI=1.08-1.48). The pooled estimates for naproxen, ibuprofen, and celecoxib were close to unity. The risk of ischemic stroke was also increased with rofecoxib (RR=1.82, 95% CI=1.09-3.04) and diclofenac (RR=1.20, 95% CI=0.99-1.45). Data were inadequate to estimate the pooled RR by dose and duration, for other individual NSAIDs or nonischemic stroke subtypes. Conclusion: This meta-analysis supports an increased risk of ischemic stroke with the current use of rofecoxib and diclofenac. Additional studies are required to evaluate most individual NSAIDS, the effect of dose and duration, and the subtypes of stroke

Risk of acute myocardial infarction during use of individual NSAIDs: A nested case-control study from the SOS project

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) match

Patrones de mortalidad en una cohorte de trabajadores seguida durante 28 años: estudio Manresa

Introducción y objetivos. Describir los patrones de mortalidad de una cohorte de trabajadores seguida durante 28 años, estimar posibles tendencias y compararlas con las observadas en la población general. Sujetos y método. La cohorte estudiada incluye a 1.059 trabajadores varones sanos de 30 a 59 años seguidos durante 28 años. Cada 5 años se realizaron exámenes de salud a la población estudiada. La información acerca de los fallecimientos se obtuvo a partir de los certificados de defunción. La razón de mortalidad estandarizada (RME) se calculó utilizando las tasas específicas por sexo y edad del registro de mortalidad poblacional de Cataluña para el mismo período. Resultados. El número de defunciones observadas en esta cohorte fue de 259 (24%). Las primeras causas de mortalidad fueron las enfermedades cardiovasculares (ECV) (n = 90; 35%) y las neoplasias (n = 90; 35%). No se observó ningún exceso de mortalidad en esta cohorte con respecto a la observada en la población general; la mortalidad total y las tasas por causas específicas fueron inferiores o similares a las de la población general. El número de fallecimientos esperados fue de 382. La RME fue significativamente inferior: 67,7% (intervalo de confianza [IC] del 95%, 59,7%-76,5%). Conclusiones. Los patrones de mortalidad de este estudio son similares a los de la población general; la mortalidad total es inferior a la esperada; se describe por tanto el «efecto del trabajador sano» que afecta a la mortalidad total, especialmente durante los primeros períodos de seguimiento

Factores de riesgo y morbi-mortalidad coronaria a los 28 años de seguimiento de una cohorte con baja incidencia de la enfermedad: el estudio de Manresa

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

Cardiovascular risk associated with the use of glitazones, metformin and sufonylureas: meta-analysis of published observational studies

BACKGROUND: The results of observational studies evaluating and comparing the cardiovascular safety of glitazones, metformin and sufonylureas are inconsistent.To conduct and evaluate heterogeneity in a meta-analysis of observational studies on the risk of acute myocardial infarction (AMI) or stroke in patients with type 2 diabetes using non-insulin blood glucose-lowering drugs (NIBGLD). METHODS: We systematically identified and reviewed studies evaluating NIBGLD in patients with type 2 diabetes indexed in Medline, Embase, or the Cochrane Library that met prespecified criteria. The quality of included studies was assessed with the RTI item bank. Results were combined using fixed- and random-effects models, and the Higgins I(2) statistic was used to evaluate heterogeneity. Sensitivity analyses by study quality were conducted. RESULTS: The summary relative risk (sRR) (95% CI) of AMI for rosiglitazone versus pioglitazone was 1.13 (1.04-1.24) [I(2) = 55%]. In the sensitivity analysis, heterogeneity was reduced [I(2) = 16%]. The sRR (95% CI) of stroke for rosiglitazone versus pioglitazone was 1.18 (1.02-1.36) [I(2)  = 42%]. There was strong evidence of heterogeneity related to study quality in the comparisons of rosiglitazone versus metformin and rosiglitazone versus sulfonylureas (I (2) ≥ 70%). The sRR (95% CI) of AMI for sulfonylurea versus metformin was 1.24 (1.14-1.34) [I(2) = 41%] and for pioglitazone versus metformin was 1.02 (0.75-1.38) [I(2) = 17%]. Sensitivity analyses decreased heterogeneity in most comparisons. CONCLUSION/INTERPRETATION: Sulfonylureas increased the risk of AMI by 24% compared with metformin; an imprecise point estimate indicated no difference in risk of AMI when comparing pioglitazone with metformin. The presence of heterogeneity precluded any conclusions on the other comparisons. The quality assessment was valuable in identifying methodological problems in the individual studies and for analysing potential sources of heterogeneity

Myocardial infarction and individual nonsteroidal anti‐inflammatory drugs meta‐analysis of observational studies

OBJECTIVE: To conduct a systematic review of observational studies on the risk of acute myocardial infarction (AMI) with use of individual nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: A search of Medline (PubMed) for observational studies published from 1990 to 2011 identified 3829 articles; 31 reported relative risk (RR) of AMI with use of individual NSAIDs versus nonuse of NSAIDs. Information abstracted in a standardized form from 25 publications was used for the meta-analysis on 18 independent study populations. RESULTS: Random-effects RR (95% confidence interval (CI)) was lowest for naproxen 1.06 (0.94–1.20), followed by celecoxib 1.12 (1.00–1.24), ibuprofen 1.14 (0.98–1.31), meloxicam 1.25 (1.04–1.49), rofecoxib 1.34 (1.22–1.48), diclofenac 1.38 (1.26–1.52), indometacin 1.40 (1.21–1.62), etodolac 1.55 (1.16–2.06), and etoricoxib 1.97 (1.35–2.89). Heterogeneity between studies was present. For new users, RRs (95% CIs) were for naproxen, 0.85 (0.73–1.00); ibuprofen, 1.20 (0.97–1.48); celecoxib, 1.23 (1.00–1.52); diclofenac, 1.41 (1.08–1.86); and rofecoxib, 1.43 (1.21–1.66). Except for naproxen, higher risk was generally associated with higher doses, as defined in each study, overall and in patients with prior coronary heart disease. Low and high doses of diclofenac and rofecoxib were associated with high risk of AMI, with dose–response relationship for rofecoxib. In patients with prior coronary heart disease, except for naproxen, duration of use ≤3 months was associated with an increased risk of AMI. CONCLUSIONS: Most frequently NSAIDs used in clinical practice, except naproxen, are associated with an increased risk of AMI at high doses or in persons with diagnosed coronary heart disease. For diclofenac and rofecoxib, the risk was increased at low and high doses. Copyright © 2013 John Wiley & Sons, Ltd