Statins and intracerebral hemorrhage: collaborative systematic review and meta-analysis.

BACKGROUND: A recent large, randomized trial suggested that statins may increase the risk of intracerebral hemorrhage. Accordingly, we systematically reviewed the association of statins with intracerebral hemorrhage in randomized and observational data. METHODS AND RESULTS: We screened 17 electronic bibliographic databases to identify eligible studies and consulted with experts in the field. We used DerSimonian-Laird random-effects models to compute summary risk ratios with 95% confidence intervals. Randomized trials, cohort studies, and case-control studies were analyzed separately. Only adjusted risk estimates were used for pooling observational data. We included published and unpublished data from 23 randomized trials and 19 observational studies. The complete data set comprised 248 391 patients and 14 784 intracerebral hemorrhages. Statins were not associated with an increased risk of intracerebral hemorrhage in randomized trials (risk ratio, 1.10; 95% confidence interval, 0.86-1.41), cohort studies (risk ratio, 0.94; 95% confidence interval, 0.81-1.10), or case-control studies (risk ratio, 0.60; 95% confidence interval, 0.41-0.88). Substantial statistical heterogeneity was evident for the case-control studies (I(2)=66%, P=0.01), but not for the cohort studies (I(2)=0%, P=0.48) or randomized trials (I(2)=30%, P=0.09). Sensitivity analyses by study design features, patient characteristics, or magnitude of cholesterol lowering did not materially alter the results. CONCLUSIONS: We found no evidence that statins were associated with intracerebral hemorrhage; if such a risk is present, its absolute magnitude is likely to be small and outweighed by the other cardiovascular benefits of these drugs.

Difference in risks of allergic reaction to sulfonamide drugs based on chemical structure.

BACKGROUND: The chemical structure of sulfonamide antibiotics and sulfonamide nonantibiotics can affect the potential for adverse reactions. OBJECTIVE: To assess whether differences in chemical structure of the various sulfonamide drugs influence the risk of allergic events. METHODS: A case-control study was conducted among patients with diabetes mellitus (DM) using data from the General Practice Research Database. Cases were defined as patients with a diagnosis of hypersensitivity or allergic reaction. The date of the last event was the index date. Controls were matched on practice, type of DM, and index date. Current use of sulfonamides was defined as use in a 14 day time window before the index date. Sulfonamides were classified according to the presence/absence of an N1 substituent (N1(+)/(-)) and/or an arylamine (N4(+)/(-)). Conditional logistic regression was used to estimate strength of association and expressed as odds ratios and 95% confidence intervals. RESULTS: Overall, current use of N1(+) N4(+) sulfonamide drugs was associated with the outcome (adjusted OR 3.71; 95% CI 1.40 to 9.81). Current use of N1(+) N4(-) and N1(-) N4(-) sulfonamide drugs was also associated with the occurrence of allergic reactions, although not as strongly: adjusted OR 2.48 (95% CI 2.12 to 2.89) and 2.07 (95% CI 1.74 to 2.46), respectively. Sex and age seemed to be effect modifiers. There was no clear evidence for effect modification by immune disease state. CONCLUSIONS: Although we did not identify major differences between the groups, we believe that this approach is an innovative manner to examine adverse drug reactions by using chemical structure instead of therapeutic drug classes to classify exposure.