Proton-pump inhibitors seem to be associated with increased risk for adverse cardiovascular outcomes after discharge, regardless of clopidogrel use for myocardial infarction. Dual PPI and clopidogrel use was not associated with any additional risk for adverse cardiovascular events over that observed for patients prescribed a PPI alone.

Monotherapy with the most used ISs, including glimepiride, glibenclamide, glipizide, and tolbutamide, seems to be associated with increased mortality and cardiovascular risk compared with metformin. Gliclazide and repaglinide appear to be associated with a lower risk than other ISs.

Background:Data on the safety of selective serotonin-reuptake inhibitors (SSRIs) in pregnancy are inconsistent. We examined associations between SSRI use during early pregnancy and risk of congenital malformations in infants.Methods:Set in Northern Denmark, our population-based prevalence study included 216,042 women who had a live birth after the 20th week of gestation. We compared the prevalence of malformation in infants born to women who redeemed at least one SSRI prescription during early pregnancy with the prevalence in infants born to women who redeemed no SSRI prescriptions during their pregnancies. Drug use data were extracted from prescription databases, while data on congenital malformations were obtained from the National Registry of Patients.Results:The 2,062 women with SSRI prescriptions during early pregnancy gave birth to 105 (5.1%) infants with malformations, while the 213,712 women with no SSRI prescriptions gave birth to 7,449 (3.5%) infants with malformations. SSRI use was associated with an increased risk of malformations overall (odds ratio [OR] = 1.3; 95% confidence interval (CI): 1.1–1.6) and cardiac malformations (OR = 1.7; 95% CI: 1.1–2.5). For specific SSRIs, we found an increased risk for septal defects associated with sertraline.Conclusions:We found little overall association between use of SSRIs during pregnancy and congenital malformations, but our findings suggest an association between maternal SSRI use in early pregnancy and cardiac malformations which could be causal.

We found an increased risk of congenital malformations after exposure to SSRIs in early pregnancy. It is unclear whether the effects were causal or due to factors related to the underlying disease. There was no evidence that the association was specific to particular malformations.

Aims/hypothesis The safety of metformin in heart failure has been questioned because of a perceived risk of lifethreatening lactic acidosis, though recent studies have not supported this concern. We investigated the risk of all-cause mortality associated with individual glucose-lowering treatment regimens used in current clinical practice in Denmark.Methods All patients aged ≥30 years hospitalised for the first time for heart failure in 1997-2006 were identified and followed until the end of 2006. Patients who received treatment with metformin, a sulfonylurea and/or insulin were included and assigned to mono-, bi-or triple therapy groups. Multivariable Cox proportional hazard regression models were used to assess the risk of all-cause mortality. Results A total of 10,920 patients were included. The median observational time was 844 days (interquartile range 365-1,395 days). In total, 6,187 (57%) patients died. With sulfonylurea monotherapy used as the reference, adjusted hazard ratios for all-cause mortality associated with the different treatment groups were as follows: metformin 0.85 (95% CI 0.75-0.98, p=0.02), metformin+ sulfonylurea 0.89 (95% CI 0.82-0.96, p=0.003), metformin+ insulin 0.96 (95% CI 0.82-1.13, p=0.6), metformin+insulin+ sulfonylurea 0.94 (95% CI 0.77-1.15, p=0.5), sulfonylurea+ insulin 0.97 (95% CI 0.86-1.08, p=0.5) and insulin 1.14 (95% CI 1.06-1.20, p=0.0001). Conclusions/interpretation Treatment with metformin is associated with a low risk of mortality in diabetic patients with heart failure compared with treatment with a sulfonylurea or insulin.