A multicenter case-control study of the effect of e-nos VNTR polymorphism on upper gastrointestinal hemorrhage in NSAID users.

Bleeding in non-steroidal anti-inflammatory drug (NSAID) users limited their prescription. This first multicenter full case-control study (325 cases and 744 controls), explored the association of e-NOS intron 4 variable number tandem repeat (VNTR) polymorphism with upper gastrointestinal hemorrhage (UGIH) in NSAID exposed and unexposed populations and assessed any interaction between this polymorphism and NSAIDs. NSAID users carrying e-NOS intron 4 wild type genotype or VNTR polymorphism have higher odds of UGIH than those unexposed to NSAIDs [Odds Ratio (OR): 6.62 (95% Confidence Interval (CI): 4.24, 10.36) and OR: 5.41 (95% CI 2.62, 11.51), respectively], with no effect modification from VNTR polymorphism-NSAIDs interaction [Relative Excess Risk due to Interaction (RERI): -1.35 (95% CI -5.73, 3.03); Synergism Index (S): 0.77 (95% CI 0.31, 1.94)]. Similar findings were obtained for aspirin exposure. Non-aspirin NSAID users who carry e-NOS intron 4 VNTR polymorphism have lower odds of UGIH [OR: 4.02 (95% CI 1.85, 8.75) than those users with wild type genotype [OR: 6.52 (95% CI 4.09, 10.38)]; though the interaction estimates are not statistically significant [RERI: -2.68 (95% CI -6.67, 1.31); S: 0.53 (95% CI 0.18, 1.55)]. This exploratory study suggests that the odds of UGIH in NSAID or aspirin users does not modify according to patient´s e-NOS intron 4 genotype.

Antipsychotics and cardiovascular risk: A case/non-case study.

Severe mental disorders have been reported to be associated with an increased cardiovascular risk. To measure the potential risk excess as compared, not with the baseline cardiovascular risk for the general population, but with the cardiovascular risk associated with drug iatrogenia. 197 reported cases of cardiovascular adverse reaction to antipsychotic drugs as compared to the reported cases of this type of adverse reactions to drugs other than antipsychotics entered in the Spanish Pharmacovigilance System database (FEDRA) (1995-2018) in an observational case/non-case study. Risk estimates of association were reporting odds ratio (ROR), and, chi-square test (χ2). Overall disproportionality for the whole drug class was found [ROR 2.3 (95% CI 2.0-2.7)], χ2 = 127.07]. When the two types of antipsychotics (typical and atypical) were analysed separately, we also found statistically significant disproportionality, and this disproportionality is similar between both groups, with disproportionality measures around 2.30, with the confidence intervals not including the 1. The disproportionality observed suggests a risk excess that might be greater than expected, which holds particularly true for torsade de pointes, sudden death and cardiac arrhythmias in patients treated with any of the two types of antipsychotics. There was no significant risk for ischaemic heart disease.