Novartis announced new results from a 4-week extension of the landmark PIONEER-HF trial, presented as a late-breaker at the American College of Cardiology’s 68th Annual Scientific Session. Data from the 8-week double-blind PIONEER-HF trial, first presented in November 2018 at the American Heart Association Scientific Sessions, showed the benefits of in-hospital initiation in appropriate stabilized patients of Entresto tablets on a systolic heart failure (HF) biomarker, safety and clinical outcome. All patients received open-label Entresto during the 4-week extension period, and data showed reductions in both groups in the HF biomarker N-terminal pro–B-type natriuretic peptide (NT-proBNP) with use of Entresto, which was safe and well tolerated.1 Patients in the control group who were treated during the initial 8-week double-blind period with a HF therapy, enalapril, showed a substantial reduction in NT-proBNP when switched to Entresto for the open-label period.1 Further, patients who started on Entresto in the hospital had a greater overall reduction in NT-proBNP after 12 weeks, compared with patients started on enalapril in the hospital and switched to Entresto at the 8-week mark.
In addition, the greater improvement in a pre-specified, exploratory post-discharge outcome at 8 weeks with Entresto was maintained throughout 12 weeks, suggesting that initiating Entresto after stabilization following an acute systolic HF admission may result in a reduction in a composite of serious clinical events. The serious clinical composite occurred in a lower percentage of patients who initiated Entresto in the hospital compared with those who initiated enalapril in the hospital and switched to Entresto after 8 weeks post-discharge. The composite, which was explored as part of a pre-specified exploratory analysis, consisted of death, re-hospitalization for HF (hospital stay >24 hours), requirement for a left ventricular assist device (LVAD) insertion, or listing for a cardiac transplantation. “The evidence generated through the Entresto clinical trial program, which includes PIONEER-HF, TRANSITION-HF and PARADIGM-HF, contributes to the reimagining of heart failure treatment,” said Marcia Kayath, MD, Head, U.S. Medical Affairs, Novartis Pharmaceuticals. “Data from this 4-week extension of PIONEER-HF clearly support Entresto as a first-choice treatment upon systolic heart failure diagnosis or worsening of symptoms and underscore the importance of initiating Entresto in the hospital.”
Patients with systolic HF who need to be admitted to the hospital due to decompensation of their disease are at high short-term risk of death or being re-admitted to the hospital. PIONEER-HF showed that Entresto can be initiated in the hospital in these patients safely, once they have been stabilized, with a tolerability profile comparable to enalapril. The safety profile in PIONEER-HF was similar to that seen in the pivotal PARADIGM-HF trial. Rates of symptomatic hypotension (low blood pressure), hyperkalemia (elevated levels of potassium) or worsening renal (kidney) function were similar among treatment groups and there was a numerically lower incidence of angioedema in patients treated with Entresto. There were no new safety signals identified during the 4-week extension of PIONEER-HF. “This extension of the landmark PIONEER-HF study further demonstrates that starting appropriate patients on Entresto in the hospital is safe and provides important clinical benefit compared to starting patients on enalapril. We now know that initiating Entresto in the hospital, instead of waiting to switch post-discharge, can improve outcomes and can keep more of an especially vulnerable patient population out of the hospital longer,” said Eugene Braunwald, MD, Founding Chairman, TIMI Study Group, Brigham & Women’s Hospital; Distinguished Hershey Professor of Medicine, Harvard Medical School; and Chariman, PIONEER-HF. Entresto is indicated to reduce the risk of cardiovascular (CV) death or HF hospitalization in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction. – Medical Buyer Bureau