BASEL, Switzerland—Aiming straight to the heart of the matter, Novartis recently released the results of a new post-hoc analysis showing Entresto (sacubitril/valsartan) tablets improved glycemic control in patients with diabetes and reduced ejection fraction heart failure (HFrEF), suggesting that Entresto is indicated to reduce the risk of cardiovascular (CV) death and hospitalization for heart failure (HF) in patients with chronic HF and reduced ejection fraction.
Entresto, introduced to the market in 2015, is a twice-a-day medicine that reduces the strain on a failing heart. Novartis has established the largest global clinical program in the HF disease area across the pharma industry to date.
New analysis of the largest HF study was first presented March 18 at the American College of Cardiology Annual Scientific Session and later published in The Lancet Diabetes & Endocrinology.
“These results show that in addition to its compelling cardiovascular efficacy, Entresto may have important metabolic benefits for HFrEF patients with diabetes,” Vasant Narasimhan, global head of drug development and chief medical officer at Novartis, stated in a news release. “We are excited about these results and committed to improving our understanding of the benefits of Entresto in different heart failure patient populations.”
PARADIGM-HF is a randomized, double-blind, Phase 3 study evaluating the efficacy and safety profile of Entresto versus enalapril (a widely studied ACE inhibitor) in 8,442 patients with HfrEF. The baseline characteristics showed the patients enrolled in the study were typical HFrEF patients with NYHA Class II-IV heart failure. PARADIGM-HF was specifically designed to see if Entresto could decrease CV mortality by at least 15 percent. Patients received Entresto or enalapril in addition to current best treatment regimen. The primary endpoint was a composite of time to first occurrence of either CV death or HF hospitalization.
Novartis’ new post-hoc analysis of PARADIGM-HF data demonstrates Entresto lowered levels of HbA1c (a measure of glycemic control) by 0.26 percent vs. 0.16 percent for ACE-inhibitor enalapril in heart failure with reduced ejection fraction (HFrEF) patients who also had diabetes.
The use of insulin was also reduced by 29 percent among patients taking Entresto compared to enalapril-treated patients, the analysis shows. Up to 40 percent of HFrEF patients have diabetes, which is associated with worse cardiovascular outcomes.
Heart failure is a debilitating and life-threatening condition that impacts more than 60 million people worldwide, and is the leading cause of hospitalization in people over the age of 65. About half of people with HF have HfrEF, meaning the heart does not contract with enough force, so less blood is pumped out. HF presents a major and growing health-economic burden that currently costs the world economy $108 billion every year, accounting for both direct and indirect costs.
Also, diabetes “is a major risk factor in heart failure and is strongly linked to progression of the disease, putting heart failure patients at increased risk of hospitalization and death,” states Dr. Scott Solomon, director of noninvasive cardiology at Brigham and Women’s Hospital, a professor of medicine at Harvard Medical School and senior author of the publication. “This analysis suggests that, in addition to the proven heart failure benefits demonstrated in PARADIGM-HF, Entresto may also help tighten glycemic control among heart failure patients with diabetes.”
Eric Althoff, head of global media relations for Novartis, tells DDNews that the company has “established the largest global clinical program in heart failure (FortiHFy) with more than 40 active or planned clinical studies. These trials will improve our overall scientific understanding of heart failure and generate additional data on efficacy and real-world evidence with Entresto.”
“Diabetes is a major risk factor and a common comorbidity in heart failure,” he continues. “We are currently evaluating the results of this post-hoc analysis to determine whether additional studies would be beneficial to this patient population.”
An analysis was conducted of 3,778 HFrEF patients in the PARADIGM-HF trial who were diagnosed with diabetes or had a baseline HbA1c greater than or equal to 6.5 percent without a reported diagnosis at screening (98 percent of patients assessed had type 2 diabetes). The investigators compared the effects of Entresto vs. enalapril on glycemic factors.
Entresto lowered HbA1c levels—a measure of average blood glucose levels for two to three months after one year of treatment for HF—and this effect was sustained over three years of study follow-up. Also, new use of insulin therapy or oral diabetes agents was also reduced in the Entresto group.
The new analysis of the data suggest that cardiologists need to keep an eye on blood sugar levels in diabetic Entresto patients, in case their diabetes meds need adjusting.