Background: Compared with standard glycemic control, intensive glycemic control caused increased mortality in the ACCORD trial. Preliminary data from several studies suggests that intensive glycemic control can precipitate QT prolongation, which may lead to ventricular arrhythmias as a possible explanation of this increased mortality.
Objective: We sought to assess the effect of intensive glycemic control on the risk of incident QT prolongation.
Methods: Participants with normal Bazett-corrected QT interval at baseline (n = 9,948) were included. Cox proportional hazards models were used to compare the risk of incident QT prolongation (>460 ms in women or >450 ms in men) in those randomized to intensive versus standard glycemic control.
Results: Participants in the intensive glycemic control arm did not have an increased risk of QT prolongation; in fact, there was suggestion of decreased risk (HR 0.89, 95% CI 0.79 - 1.01, p = 0.06). Sensitivity analysis using the Framingham-corrected QT interval yielded similar findings. As a secondary analysis, we found that a strategy of intensive blood pressure control yielded a 21% lower risk of QT prolongation (HR 0.79, 95% CI 0.66 - 0.95, p = 0.01).
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, as there was no evidence of an increased risk of QT prolongation from intensive glycemic control. In addition, intensive blood pressure control lowers the risk of incident QT prolongation. Further studies exploring the mechanisms of these effects and their contribution to cardiovascular outcomes are warranted.