Antidiabetic drugs and heart failure risk in patients with type 2 diabetes in the U.K. primary care setting.

OBJECTIVE: To assess the effects of antidiabetic drugs on the risk of heart failure in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study with a newly diagnosed diabetes cohort of 25,690 patients registered in the U.K. General Practice Research Database, 1988-1999. We categorized person-time drug exposures to monotherapies in insulin, sulfonylureas (SUs), metformins, and other oral hypoglycemic agents (i.e., acarbose, guar gum) and combination therapy including insulin, combination therapy without insulin, and triple combination therapy with or without insulin. A drug-free time interval served as a reference category. Cox interval-wise (piece-wise) regression analyses were used. The main outcome was incident heart failure. RESULTS: Among 43,390 drug exposure intervals for 25,690 patients who had a mean follow-up period of 2.5 years, 1,409 patients developed heart failure. Heart failure occurred most frequently in SU monotherapy exposure. After adjusting for duration of diabetes, the timing and order of treatments received, and known risk factors for heart failure, we found no differential effects among type-specific therapies. Patients with any drug use within the first year after diabetes diagnosis had a 4.75-fold higher risk (hazard ratio) for heart failure than those with drug-free status but had no increased risk during subsequent years. CONCLUSIONS: In conclusion, the use of any pharmacological therapy for type 2 diabetes appears to be associated with an increased risk of heart failure. This risk does not persist beyond the first year after diagnosis of diabetes and does not appear to differ among the types of drug therapy examined. This observation suggests that the severity of diabetes or the preclinical duration of diabetes and the need for drug therapy, and not the therapy itself, is an explanation for heart failure in patients with type 2 diabetes.

Pregnancy outcomes following systemic prenatal acyclovir exposure: Conclusions from the international acyclovir pregnancy registry, 1984-1999.

BACKGROUND: Oral acyclovir is commonly used for genital herpes and other herpesvirus infections. Data on potential fetal risk are extremely limited. From 1984 to 1998, the Acyclovir in Pregnancy Registry monitored birth outcomes of women exposed to oral or intravenous acyclovir during pregnancy. This report describes the final results. METHODS: The registry was publicized to health care providers most likely to diagnose pregnancy; providers called the registry telephone number, then mailed in a brief questionnaire. Pregnancy outcomes were categorized either as outcomes with birth defects or outcomes without birth defects, subcategorized as live births, spontaneous pregnancy losses (including stillbirths), and induced abortions. Birth defects were defined using a modification of the CDC definition for birth defects surveillance systems. Observed rates were compared to the rate (3.2%) of birth defects expected in the general population. RESULTS: Between June 1, 1984 and June 30, 1998, 1695 pregnancies exposed to oral or IV acyclovir were registered; 461 (27%) were lost to follow-up. A total of 1234 pregnancies in 24 countries were followed, with a total of 1246 outcomes. Among 1246 pregnancy outcomes, 756 involved acyclovir exposure in the first trimester, 197 in the second trimester, and 291 in the third trimester. Among live births with first trimester acyclovir exposure, risk of birth defects was 19 of 596 (3.2%; 95% CI, 2.0-5.0%). No unusual defects or pattern of defects were apparent. CONCLUSIONS: The observed rates and types of birth defects for pregnancies exposed to acyclovir did not differ significantly from those in the general population. Birth Defects Research (Part A), 2004. Published 2004 Wiley-Liss, Inc.