Conference Coverage
LCZ696 surpasses enalapril for heart failure
Key clinical point: Substituting LCZ696 for enalapril in heart failure patients was linked with significant improvements in survival, heart...
In an interview, Dr. Jessup said that she hopes that physicians approach this new drug with the same caution they have with other drugs for patients with systolic heart failure and encouraged clinicians to carefully read the study and familiarize themselves with the prescribing information. Patients should not be taken off an ACE inhibitor and immediately switched to Entresto, she said.
She referred to the “famous” Canadian study that identified a significant increase in spironolactone prescriptions and in the rates of hyperkalemia and hyperkalemia-associated deaths after the positive Randomized Aldactone Evaluation Study (RALES) results were published in 1999 (N. Engl. J. Med. 2004;351:543-51). After the study, which found significant improvements in morbidity and mortality in patients with severe heart failure, was published, “physicians immediately started to put their patients on spironolactone and there was a spike in hyperkalemia and in deaths,” she noted.
The Entresto label includes a boxed warning about the risk of fetal toxicity, and the FDA statement recommends that health care professionals counsel patients about the risks to an unborn baby. One of the company’s postmarketing requirements is to conduct an epidemiologic study evaluating the incidence of angioedema in black patients treated with the combination, compared with another drug, according to the FDA’s approval letter.
The PARADIGM-HF results were reported in August 2014 at the European Society of Cardiology annual meeting in Barcelona. Dr. Solomon said that a large international study evaluating Entresto in patients with heart failure and preserved ejection fraction is currently underway.
The cost per day of Entresto is $12.50 (the wholesale acquisition cost), and the company anticipates that the product will be available in most pharmacies within weeks of the approval date, according to a Novartis spokesperson.
Valsartan, approved in 2001, is marketed as Diovan by Novartis and is available in generic form from Ranbaxy.
The PARADIGM-HF trial was funded by Novartis. Dr. Solomon, a member of the executive committee for the study, has received research support from Novartis for the conduct of this and other studies, and has served as a consultant to the company. Dr. Jessup had no related disclosures.
