Impact of intensive glycemic control on the incidence of atrial fibrillation and associated cardiovascular outcomes in patients with type 2 diabetes mellitus (from the Action to Control Cardiovascular Risk in Diabetes Study).

Atrial fibrillation (AF) is prevalent in patients with type 2 diabetes mellitus (DM) and is associated with markers of poor glycemic control; however, the impact of glycemic control on incident AF and outcomes is unknown. The aims of this study were to prospectively evaluate if intensive glycemic control in patients with DM affects incident AF and to evaluate morbidity and mortality in patients with DM and incident AF. A total of 10,082 patients with DM from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) cohort were studied in a randomized, double-blind fashion. Participants were randomized to an intensive therapeutic strategy targeting a glycated hemoglobin level of <6.0% or a standard strategy targeting a glycated hemoglobin level of 7.0% to 7.9%. Incident AF occurred in 159 patients (1.58%) over the follow-up period, at a rate of 5.9 per 1,000 patient-years in the intensive-therapy group and a rate of 6.37 per 1,000 patient-years in the standard-therapy group (p = 0.52). In a multivariate model, predictors of incident AF were age, weight, diastolic blood pressure, heart rate, and heart failure history. Patients with DM and new-onset AF had a hazard ratio of 2.65 for all-cause mortality (95% confidence interval 1.8 to 3.86, p <0.0001), a hazard ratio of 2.1 for myocardial infarction (95% confidence interval 1.33 to 3.31, p = 0.0015), and a hazard ratio of 3.80 for the development of heart failure (95% confidence interval 2.48 to 5.84, p <0.0001). In conclusion, intensive glycemic control did not affect the rate of new-onset AF. Patients with DM and incident AF had an increased risk for morbidity and mortality compared with those without AF.

A combined anatomic and electrophysiologic substrate based approach for sudden cardiac death risk stratification.

BACKGROUND: Although left ventricular ejection fraction (LVEF) is the primary determinant for sudden cardiac death (SCD) risk stratification, in isolation, LVEF is a sub-optimal risk stratifier. We assessed whether a multi-marker strategy would provide more robust SCD risk stratification than LVEF alone. METHODS: We collected patient-level data (n = 3355) from 6 studies assessing the prognostic utility of microvolt T-wave alternans (MTWA) testing. Two thirds of the group was used for derivation (n = 2242) and one-third for validation (n = 1113). The discriminative capacity of the multivariable model was assessed using the area under the receiver-operating characteristic curve (c-index). The primary endpoint was SCD at 24 months. RESULTS: In the derivation cohort, 59 patients experienced SCD by 24 months. Stepwise selection suggested that a model based on 3 parameters (LVEF, coronary artery disease and MTWA status) provided optimal SCD risk prediction. In the derivation cohort, the c-index of the model was 0.817, which was significantly better than LVEF used as a single variable (0.637, P < .001). In the validation cohort, 36 patients experienced SCD by 24 months. The c-index of the model for predicting the primary endpoint was again significantly better than LVEF alone (0.774 vs 0.671, P = .020). CONCLUSIONS: A multivariable model based on presence of coronary artery disease, LVEF and MTWA status provides significantly more robust SCD risk prediction than LVEF as a single risk marker. These findings suggest that multi-marker strategies based on different aspects of the electro-anatomic substrate may be capable of improving primary prevention implantable cardioverter-defibrillator treatment algorithms.

Effect of intensive glycemic lowering on health-related quality of life in type 2 diabetes: ACCORD trial.

OBJECTIVE: To compare the effect of intensive versus standard glycemic control strategies on health-related quality of life (HRQL) in a substudy of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. RESEARCH DESIGN AND METHODS: A randomly selected subsample of 2,053 ACCORD participants enrolled in the HRQL substudy was assessed at baseline and 12-, 36-, and 48-month visits. HRQL assessment included general health status (the 36-Item Short Form Health Survey [SF-36]), diabetes symptoms (the Diabetes Symptom Distress Checklist), depression (Patient Health Questionnaire [PHQ]-9), and treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire [DTSQ]). Repeated-measures ANOVA models were used to estimate change in HRQL outcomes by treatment group over 48 months adjusting for model covariates. The effects of early discontinuation of the ACCORD intensive glycemic control arm on study results were explored. RESULTS: A total of 1,956 (95%) completed the self-report HRQL instrument(s) at baseline. The intensive arm had a larger decrease in SF-36 physical health component score than the standard arm (-1.6 vs. -1.1, P = 0.0345). Treatment satisfaction (DTSQ) showed larger improvement with intensive than standard (P = 0.0004). There were no differences in mean scores of the Diabetes Symptom Checklist and PHQ-9. Effects of participant transition following discontinuation of the intensive arm on HRQL were not significant. CONCLUSIONS: The ACCORD trial strategy of intensive glycemic control did not lead to benefits in HRQL and was associated with modest improvement in diabetes treatment satisfaction. Thus patient acceptability was apparently not compromised with intensive and complex interventions such as those used in ACCORD.