Comparable long-term mortality risk associated with individual sulfonylureas in diabetes patients with heart failure.

AIMS: The aim was to investigate the outcomes of individual sulfonylureas in patients with heart failure (HF). METHODS: All patients hospitalized with HF for the first time in 1997-2006, alive 30 days after discharge, and who received anti-diabetic monotherapy with glimepiride (n=1097), glibenclamide (glyburide) (n=1031), glipizide (n=557), gliclazide (n=251), or tolbutamide (n=541) were identified from nationwide registers. Risk of all-cause mortality was assessed by multivariable Cox regression models. RESULTS: Over the median observational time of 744 (Inter Quartile Range 268-1451) days, 2242 patients (64%) died. The analysis demonstrated similar hazard ratio (HR) for mortality for treatment with glimepiride (1.10 [95% confidence interval 0.92-1.33]), glibenclamide (1.12 [0.93-1.34]), glipizide (1.14 [0.93-1.38]), tolbutamide (1.04 [0.85-1.26]), and gliclazide (reference). Grouped according to pancreatic specificity, i.e., with tolbutamide, glipizide, and gliclazide as specific, and glibenclamide, and glimepiride as non-specific agents, no differential prognosis was found between the two groups (HR 1.04 [0.96-1.14], for non-specific, compared to pancreas specific agents). The prognosis was not dependent on prior acute myocardial infarction or ischemic heart disease (p for interactions >0.3). CONCLUSIONS: In current clinical practice, it is unlikely that there are considerable differences in risk of mortality associated with individual sulfonylureas in patients with heart failure.

Temporal trends in the initiation of glucose-lowering medications after a first-time myocardial infarction - a nationwide study between 1997 and 2006.

BACKGROUND: Type 2 diabetes is a well-established risk factor for cardiovascular disease and is common among patients with acute myocardial infarction (MI). The extent to which patients with first-time MI develop diabetes requiring glucose-lowering medications (GLM) is largely unknown. The aim of the study was to investigate temporal trends in the initiation of GLM among patients discharged after first-time MI. METHODS: All Danish residents aged ≥ 30 years without prior diabetes hospitalized with first-time MI between 1997 and 2006 were identified by individual-level-linkage of nationwide registers. Initiation of GLM during follow-up was assessed by claimed prescriptions from pharmacies. Temporal trends in initiation of GLM were assessed by incidence rate calculations in the MI population as in the general population. Multivariable Cox proportional-hazard models were used to investigate the likelihood of initiating GLM within a year post-MI. RESULTS: The population comprised 66,788 patients. Among these patients 3962 patients initiated GLM, of whom 1567 started within one year post-MI. An increase in incidence rates of GLM initiation in the MI population from 19.6 per 1000 person years in 1997 to approximately 27.6 in 2001 was demonstrated. After 2001 the incidence rates stabilized. A similar trend was observed in the general population where the incidence rates increased from 2.8 in 1997 to 4.0 in 2004 and then stabilized. CONCLUSION: Our study demonstrated an increase in incidence rates of GLM initiation within the first year post- MI. A similar trend was observed in the general population suggesting that the increase in GLM among MI patients was primarily the effect of a general increased awareness of diabetes. From a public heath perspective, this study underscores a continuous need for diagnostic and therapeutic improvement in the care of MI patients that develop diabetes.

Heart failure severity, as determined by loop diuretic dosages, predicts the risk of developing diabetes after myocardial infarction: a nationwide cohort study.

AIMS: Heart failure (HF) is associated with increased insulin resistance, but the consequences of HF for development of diabetes are not well studied. The aim of the present study was to investigate the relationship between HF severity and risk of developing diabetes in a nationwide cohort of patients with myocardial infarction (MI). METHODS AND RESULTS: Patients discharged from first-time MI during 1997-2006 and not previously treated with glucose-lowering medications (GLM) or loop diuretics were identified from Danish nationwide registers. Heart failure severity was determined by loop diuretic dosage after discharge. Patients were followed until first claimed prescription of GLM, death, or until the end of 2006. The cohort comprised 50 874 patients. A total of 3006 (6%) had mild (loop-diuretic dosage≤40 mg/day), 5383 (11%) moderate (>40-120 mg/day), and 1127 (2%) severe (>120 mg/day) HF. During follow-up, 2531 (5%) patients developed diabetes. Increasing HF severity was associated with increased risk of diabetes, but the use of renin-angiotensin system inhibitors (RASi) attenuated the risk (P-value for interaction between the HF group and RASi<0.05). Compared with no HF, the adjusted hazard ratios (95% confidence interval) for the development of diabetes were 1.34 (1.11-1.63), 1.63 (1.40-1.90), and 1.68 (1.25-2.25) for mild, moderate, and severe HF with RASi treatment; and 1.45 (1.13-1.88), 1.90 (1.56-2.33), and 3.02 (2.01-4.54) for mild, moderate, and severe HF without RASi treatment. CONCLUSION: Heart failure predicts the development of diabetes in a severity-dependent manner among patients with MI. Focus on increased predisposition to diabetes is warranted and needs further investigations.