Atacand is the first angiotensin receptor blocker (ARB) shown to reduce the risk of diabetes in heart failure patients compared to placebo. A reduction in the risk of developing diabetes has been shown in heart failure patients on Atacand® (candesartan cilexetil) therapy. New data from placebo controlled studies, has shown a reduction in new onset of diabetes mellitus in Atacand treated patients across varying degrees of heart failure severity, body mass index (BMI), and in those on concomitant heart failure treatments.1
Six percent of patients in the candesartan group were newly diagnosed with diabetes during the study period (median 3.1 year), compared to 7.4% in the placebo group (P =.020). The composite endpoint of new diabetes diagnosis or death occurred in 25.2% of patients in the active treatment group, compared to 28.6% in the placebo group (P =.004).
Consistent reduction rates of new onset of diabetes were observed in patient groups across varying severities of heart failure symptoms, and with concomitant drugs such as beta-blockers or diuretics for the treatment of heart failure. This effect was consistently observed in all subgroups examined with no evidence of heterogeneity among the 3 component trials in the CHARM Program (Candesartan in Heart Failure – Assessment of Reduction in Mortality and Morbidity), although it appears that the magnitude of the effect may have been smaller in those receiving concomitant ACE inhibitors.
In patients without concomitant ACE inhibitor therapy, a relative risk reduction in new-onset diabetes of approximately 29% by Atacand was seen across the entire CHARM program.
Lead investigator Professor Salim Yusuf, McMaster University, Hamilton, Canada, commented on this new data: "This finding that candesartan may prevent the development of diabetes in some patients could have important future implications for the treatment of certain patient populations, such as those with hypertension, previous myocardial infarction and heart failure, in whom such treatments have already been shown to reduce major vascular events."
Incidence of both diabetes and chronic heart failure is increasing, and treatments with the potential to prevent both conditions could have important clinical benefits. CHARM investigators prospectively specified a secondary analysis comparing Atacand to placebo to assess prevention of diabetes in a broad range of heart failure patients. Pre-specified outcomes for this analysis were the development of diabetes mellitus alone, or as a composite with all-cause mortality.
At baseline, 5436 of the 7601 patients in the overall CHARM population were not known to have diabetes. These patients (2715 on Atacand) were included in this new analysis. Patients were followed up at 2, 4, and 6 weeks, 6 months and then every 4 months until study end (median follow-up 3.1 years).
These results are consistent with those from previous trials which have indicated that ACE inhibitors or ARBs may reduce diabetes onset, though CHARM is the only study to date to provide evidence of the effect of an ARB in preventing diabetes in heart failure patients, compared to placebo.
Circulation, July 2005