Canagliflozin Reduces Heart Failure Risk in T2D With Preserved EF

Canagliflozin may reduce the risk for heart failure (HF) in patients with type 2 diabetes (T2D) and preserved or reduced ejection fraction (EF), according to study results presented at the American College of Cardiology’s Annual Scientific Session held March 16-18, 2019, in New Orleans, Louisiana.

Given the high risk for HF in T2D and known cardiovascular benefits of sodium-glucose cotransporter-2 inhibitors, researchers in the CANVAS (CANagliflozin cardioVascular Assessment Study) Program aimed to define the effects of treatment with canagliflozin in patients with T2D and preserved or reduced ejection fraction (EF).

The study cohort included patients aged ≥30 years with T2D and a history of atherosclerotic cardiovascular disease or patients aged ≥50 years with T2D and ≥2 cardiovascular disease risk factors. Patients were randomly assigned treatment with canagliflozin or placebo.

The study’s primary end point was a composite of nonfatal stroke, nonfatal myocardial infarction, or cardiovascular death. HF was considered to be in the context of preserved EF when EF was ≥50% at the time of HF admission. HF in the context of reduced EF was defined as cases of EF at <50% at admission or when there was prior evidence of reduced EF with no documented recovery.

In total, the researchers followed 10,412 patients (mean age, 63.3 years; 35.8% women) for a mean duration of 188.2 weeks. A history of HF was present in 14.4% of participants at baseline. During follow-up, 276 patients had a HF event that led to death or hospitalization, and 61 patients had multiple HF events. There were 101 participants who had their first HF event with preserved EF, and 122 who had their first HF event with reduced EF.

Compared with patients who had a HF event with reduced EF, patients with a HF event and preserved EF had higher baseline systolic blood pressure (P <.001), higher prevalence of microvascular disease (P =.041), lower prevalence of macrovascular disease (P =.038), and higher body mass index (P <.001), and were more likely to be female (P <.001) and have a history of hypertension (P =.014).

Canagliflozin reduced the risk for HF in the context of both reduced EF (hazard ratio [HR], 0.69; 95% CI, 0.48-1.00) and preserved EF (HR, 0.83; 95% CI, 0.55-1.25). In a sensitivity analysis that categorized all HF events with undefined EF (n = 61) as reduced or preserved EF, the HRs were updated to be 0.64 (95% CI, 0.48-0.86) and 0.71 (95% CI, 0.52-0.97), respectively.

The study was limited by its use of EF measurements at the time of HF event as opposed to EF data at baseline.

These results “may provide some hope for patients with diabetes and [HF with preserved EF], where no prior intervention has been shown to have clear clinical benefits,” wrote the investigators.

Disclosure: The CANVAS Program was supported by Janssen Research & Development, LLC, which developed canagliflozin.

Reference

Figtree GA, Rådholm K, Barrett TD, et al. Effects of canagliflozin on heart failure outcomes associated with preserved and reduced ejection fraction in type 2 diabetes: results from the CANVAS Program. Presented at: American College of Cardiology’s 68th Annual Scientific Session. March 16-18, 2019; New Orleans, LA.