Comparative Safety of Sulfonylureas and the Risk of Sudden Cardiac Arrest and Ventricular Arrhythmia.

OBJECTIVE: To examine the association between individual antidiabetic sulfonylureas and outpatient-originating sudden cardiac arrest and ventricular arrhythmia (SCA/VA). RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study using 1999-2010 U.S. Medicaid claims from five large states. Exposures were determined by incident use of glyburide, glimepiride, or glipizide. Glipizide served as the reference exposure, as its effects are believed to be highly pancreas specific. Outcomes were ascertained by a validated ICD-9-based algorithm indicative of SCA/VA (positive predictive value ∼85%). Potential confounding was addressed by adjustment for multinomial high-dimensional propensity scores included as continuous variables in a Cox proportional hazards model. RESULTS: Of sulfonylurea users under study (N = 519,272), 60.3% were female and 34.9% non-Hispanic Caucasian, and the median age was 58.0 years. In 176,889 person-years of sulfonylurea exposure, we identified 632 SCA/VA events (50.5% were immediately fatal) for a crude incidence rate of 3.6 per 1,000 person-years. Compared with glipizide, propensity score-adjusted hazard ratios for SCA/VA were 0.82 (95% CI 0.69-0.98) for glyburide and 1.10 (0.89-1.36) for glimepiride. Numerous secondary analyses showed a very similar effect estimate for glyburide; yet, not all CIs excluded the null. CONCLUSIONS: Glyburide may be associated with a lower risk of SCA/VA than glipizide, consistent with a very small clinical trial suggesting that glyburide may reduce ventricular tachycardia and isolated ventricular premature complexes. This potential benefit must be contextualized by considering putative effects of different sulfonylureas on other cardiovascular end points, cerebrovascular end points, all-cause death, and hypoglycemia.

The quality of Medicaid and Medicare data obtained from CMS and its contractors: implications for pharmacoepidemiology.

BACKGROUND: Administrative claims of United States Centers for Medicare and Medicaid Services (CMS) beneficiaries have long been used in non-experimental research. While CMS performs in-house checks of these claims, little is known of their quality for conducting pharmacoepidemiologic research. We performed exploratory analyses of the quality of Medicaid and Medicare data obtained from CMS and its contractors. METHODS: Our study population consisted of Medicaid beneficiaries (with and without dual coverage by Medicare) from California, Florida, New York, Ohio, and Pennsylvania. We obtained and compiled 1999-2011 data from these state Medicaid programs (constituting about 38% of nationwide Medicaid enrollment), together with corresponding national Medicare data for dually-enrolled beneficiaries. This descriptive study examined longitudinal patterns in: dispensed prescriptions by state, by quarter; and inpatient hospitalizations by federal benefit, state, and age group. We further examined discrepancies between demographic characteristics and disease states, in particular frequencies of pregnancy complications among men and women beyond childbearing age, and prostate cancers among women. RESULTS: Dispensed prescriptions generally increased steadily and consistently over time, suggesting that these claims may be complete. A commercially-available National Drug Code lookup database was able to identify the dispensed drug for 95.2-99.4% of these claims. Because of co-coverage by Medicare, Medicaid data appeared to miss a substantial number of hospitalizations among beneficiaries ≥ 45 years of age. Pregnancy complication diagnoses were rare in males and in females ≥ 60 years of age, and prostate cancer diagnoses were rare in females. CONCLUSIONS: CMS claims from five large states obtained directly from CMS and its contractors appeared to be of high quality. Researchers using Medicaid data to study hospital outcomes should obtain supplemental Medicare data on dual enrollees, even for non-elders. TRIAL REGISTRATION: Not applicable.

Gastrointestinal bleeding and intracranial hemorrhage in concomitant users of warfarin and antihyperlipidemics.

BACKGROUND: Drug interactions, particularly those involving warfarin, are a major clinical and public health problem. Minimizing serious bleeding caused by anticoagulants is a recent major focus of the United States (US) Department of Health and Human Services. This study quantified the risk of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH) among concomitant users of warfarin and individual antihyperlipidemics. METHODS: The authors conducted a high-dimensional propensity score-adjusted cohort study of new concomitant users of warfarin and an antihyperlipidemic, among US Medicaid beneficiaries from five states during 1999-2011. Exposure was defined by concomitant use of warfarin plus one of eight antihyperlipidemics. The primary outcome measure was a composite of GIB/ICH within the first 30days of concomitant use. As a secondary outcome measure, GIB/ICH was examined within the first 180days of concomitant use. RESULTS: Among 236,691 persons newly-exposed to warfarin and an antihyperlipidemic, the crude incidence of GIB/ICH was 13.2 (95% confidence interval 12.7 to 13.8) per 100person-years. Users were predominantly older, female, and Caucasian. Adjusted hazard ratios (aHRs) for warfarin and individual statins were consistent with no association. Warfarin+gemfibrozil was associated with an 80% increased risk of GIB/ICH within the first month of concomitant use (aHR=1.8, 1.4 to 2.4). Warfarin+fenofibrate was associated with a similar increased risk (aHR=1.8, 1.2 to 2.7), yet with an onset during the second month of concomitant use. CONCLUSIONS: Among warfarin-treated persons, the use of fibrates-but not statins-increases the risk of hospital presentation for GIB/ICH.