Effect of Intensive Glycemic and Blood Pressure Control on QT Prolongation in Diabetes: The ACCORD Trial

Matthew J Singleton, Elsayed Z Soliman, Alain G Bertoni, S Patrick Whalen, Prashant D Bhave, Joseph Yeboah, Matthew J Singleton, Elsayed Z Soliman, Alain G Bertoni, S Patrick Whalen, Prashant D Bhave, Joseph Yeboah

Abstract

Compared with standard glycemic control, intensive glycemic control caused increased mortality in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Preliminary data from several studies suggest that intensive glycemic control is associated with QT prolongation, which may lead to ventricular arrhythmias as a possible explanation of this increased mortality. We sought to assess the effects of intensive glycemic control and intensive blood pressure control on the risk of incident QT prolongation. Cox proportional hazards models were used to compare the risk of incident QT prolongation (>460 ms in women or >450 ms in men) in the intensive versus standard glycemic control arms. Over a combined 48,634 person-years of follow-up (mean 4.9), 634 participants (6.4%) developed a prolonged QTc. Participants in the intensive glycemic control arm did not have an increased risk of QT prolongation. Similarly, a strategy of intensive blood pressure control did not result in a significant change in risk of prolonged QTc. Sensitivity analyses using alternative QT correction formulas (Hodges and Bazett) yielded overall similar findings. In conclusion, the increased mortality observed in the intensive glycemic control arm in the ACCORD trial is not likely to be explained by QT prolongation leading to lethal ventricular arrhythmias.

Trial registration: ClinicalTrials.gov NCT00000620.

© 2020 by the American Diabetes Association.

Figures

Figure 1
Figure 1
Baseline QTc (Framingham) of the ACCORD study population (n = 10,205). Histogram of the baseline QTc of the study population in 10-ms bins (top) and separated into those with and without baseline prolonged QTc (bottom).
Figure 2
Figure 2
Kaplan-Meier curves of survival free of incident QT prolongation demonstrate that participants in the intensive glycemic control arm and those in the standard glycemic control arm had similar rates of incident QT prolongation (at left); similarly, those in the intensive blood pressure control arm and those in the standard blood pressure control arm had similar rates of incident QT prolongation (at right).

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