Intensive glycemic control and the risk of heart failure in patients with type 2 diabetes

Intensive glycemic control and the risk of heart failure in patients with type 2 diabetes Castagno et al 1 conducted a timely meta-analysis of 7 randomized controlled trials to help determine if intensive blood glucose control has benefit in reducing the risk of congestive heart failure (CHF). The study revealed that there was no significant reduction in risk of CHF among individuals randomized to intensive versus standard blood glucose control groups. The authors rightly point out the presence of important heterogeneity among the trials with regard to the use of thiazolidinediones (TZDs). As expected, among the 4 trials that had a high rate of TZD use (ie, PROactive, ACCORD, VADT, and RECORD), the risk of CHF was elevated in individuals randomized to intensive blood glucose control. On the other hand, among the remaining 3 trials (ie, UKPDS, ADVANCE, and VA-CSDM), the risk ratio was close to null with a wide CI, highlighting the limitedness of the available data (risk ratio 0.96, 95% CI 0.81-1.13). We believe that combining these 2 groups of trials that are fundamentally different with respect to CHF outcomes can give the reader a false sense of adequate power because, in actuality, the 4 trials that used TZDs (agents known to cause heart failure) to lower blood glucose levels are confounded by the intervention itself and, hence, are not appropriate to answer the question whether intensive blood glucose control can reduce the risk of CHF. Therefore, although Castagno et al discussed the various aspects of the observed null finding, it would have been useful to point out that the most relevant data on the topic come from only 2 trials (ie, UKPDS and ADVANCE, not counting the pilot trial with a total of 9 events of interest) and are not sufficiently powered to

provide a conclusive answer. For instance, the combined risk ratio for the non–TZD-based trials has a 95% CI between 0.81 and 1.13, which is actually consistent with the findings of the observational study by Iribarren et al 2 that the authors cite. Iribarren et al reported an 8% reduction in risk of CHF for each 1% lower hemoglobin A1C level (approximately the same level of difference in hemoglobin A1C that was achieved between the treatment and control arms in these trials). Clearly, further large trials using non–TZD-based hypoglycemic agents as treatment intervention are needed to provide conclusive evidence on glycemic control and risk of CHF. Am Heart J 2012;163:e35. 0002-8703/$ - see front matter doi:10.1016/j.ahj.2012.02.021

Sebhat Erquo, MD, PhD Chee-Tin Christine Lee, PhD Amanda Adler, MD, PhD, FRCP Department of Internal Medicine University of Pittsburgh Medical Center Montefiore Hospital, Pittsburgh, PA E-mail: [email protected]

References 1. Castagno D, Baird-Gunning J, Jhund PS, et al. Intensive glycemic control has no impact on the risk of heart failure in type 2 diabetic patients: evidence from a 37,229 patient meta-analysis. Am Heart J 2011;162:938-48. 2. Iribarren C, Karter AJ, Go AS, et al. Glycemic control and heart failure among adult patients with diabetes. Circulation 2001;103: 2668-73.