Treatment with sacubitril / valsartan, a mainstay of therapy for patients with chronic heart failure with a lower-than-normal ejection fraction, was suggestive of being effective in preventing cardiovascular death or heart failure events in newly diagnosed patients. have an IM but have no history of heart failure in a controlled trial with more than 5,600 patients.
Although sacubitril / valsartan (Entresto) did not achieve a significant benefit, it showed good safety similar to the comparative treatment of the study, ramipril, an agent of the class of enzyme inhibitor converting angiotensin which is a key point of treatment in these patients. .
“To say that, without intervention, sacubitril / valsartan is as well tolerated and as safe as one of the best-studied ACE inhibitors, ramipril, in patients with MI with acute disease, is an important statement,” he said. Marc A. Pfeffer, MD, at the annual scientific sessions of the American College of Cardiology. This high level of safety without gradual titration of sacubitril / valsartan (Entresto) “should reduce barriers” to a wider use of the dual drug formulation for its indication approved in patients with chronic heart failure, especially patients with a lower than normal left ventricular ejection fraction. In addition, the results of the PARADISE-MI trial suggested that “patients appeared to benefit before developing heart failure. We could not demonstrate this, but we should rely on this and make it easier for patients to use this treatment, ”said Dr. Pfeffer said during a press conference after his talk at the sessions.
Prevent heart failure
Sacubitril / valsartan treatment in patients with acute MI within a few days of their event “may be trying to prevent the coming heart failure,” he commented. Lynne W. Stevenson, MD, debtor appointed for the report and professor of medicine at Vanderbilt University Medical Center in Nashville. “Patients destined to develop heart failure begin treatment early. Subgroup analyzes suggest that it is the sickest patients who have benefited the most,” he said.
But Dr. Pfeffer has stressed that “I don’t think it’s a subgroup debate. I’d like to continue with that, but that depends on the sponsor,” Novartis, the company that sells sacubitril / valsartan.
“Extremely reassuring” security
The safety data reported by Dr. Pfeffer “are extremely reassuring. We didn’t see any signs of harm, and at some of the exploratory endpoints there was some evidence of benefits, so we should encourage you to continue.” Mary N. Walsh, MD, medical director of the Heart Failure and Heart Transplant Program at Ascension St. Vincent Heart Center of Indiana in Indianapolis.
He PARADISE ME The trial (Prospective ARNI vs. ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI) included 5,669 patients with no history of heart failure within an average of 4 days after a Acute IM in 495 sites in 41 countries during 2016-2020, with 8% of patients enrolled in the United States. Patients were on average 64 years old, approximately three-quarters were male, approximately 43% had a history of diabetes, and only 1% were black; Dr. Pfeffer noted that this is due to the fact that most patients came from countries with a low black population. The enrollment criteria require a left ventricular ejection fraction of no more than 40%, and among enrolled patients this average was approximately 37%.
A relative risk reduction of 10% not significant for the primary endpoint
The main endpoint of the study was the combined rate of early cardiovascular death events, hospitalization for heart failure, or outpatient visit for heart failure. During a mean follow-up of 23 months, there was a rate of 7.4 / 100 patient years in the ramipril arm and 6.7 / 100 patient years in the sacubitril / valsartan arm, a 10% reduction in relative risk with sacubitril / valsartan which was insignificant, meaning that all other efficacy analyzes were exploratory, Dr. Pfeffer stressed.
Several secondary efficacy analyzes showed significant benefits of sacubitril / valsartan, compared with ramipril, including the total number of events comprising the primary endpoint, with a 21% reduction in relative risk associated with sacubitril / valsartan, as well. as events reported by the researcher. The main endpoint value of sacubitril / valsartan was also significant in two subgroup analyzes: patients aged 65 years or older (approximately half of the study cohort), who had a relative risk reduction of 24%. of sacubitril / valsartan compared with ramipril and 88% of patients receiving treatment with percutaneous coronary intervention for their acute MI, who had a 19% reduction in the relative risk of sacubitril / valsartan, compared with patients receiving receive ramipril.
The safety data from the study showed almost identical rates in the two treatment arms for total adverse events, serious adverse events, adverse events that led to discontinuation of the study drug, as well as in laboratory measurements. The differences between larger treatments were a modest excess of hypotension in sacubitril valsartan, 28%, compared with 22% in ramipril, and a modest excess rate of cough in ramipril, 13%, compared with 9% in sacubitril / valsartan.
The added insight provided by the results on sacubitril / valsartan comes at a time when American patients continue to struggle to obtain health insurance coverage for an agent who has been approved for American use in the treatment of heart failure since 2015.
“Our patients do not have access to this important treatment,” Dr. Walsh during the press conference. “The pre-authorization process is amazing and some patients don’t have access unless they pay the full cost on their own. This is a major real-world problem we face with this drug.”
PARADISE-MI was sponsored by Novartis, the company that sells sacubitril / valsartan (Entresto). Dr. Pfeffer has received funding for research and is a consultant for Novartis. He is also a consultant to AstraZeneca, Boehringer Ingelheim, Corvidia, DalCor, Eli Lilly, GlaxoSmithKline, Novo Nordisk, Peerbridge and Sanofi, and has stakes in DalCor and Peerbridge. Dr. Stevenson has received fees from LivaNova and has received support from Abbott’s research. Dr. Walsh had no disclosure.
This article originally appeared on MDedge.com, which is part of the Medscape professional networkork.