This article is more than 5 years old. Information may no longer be current.
Sacubitril/valsartan beneficial in real-world HFrEF population
Click Here to Manage Email Alerts
PHILADELPHIA — In a real-world population of patients hospitalized for HF with reduced ejection fraction, sacubitril/valsartan was associated with reduced risk for mortality and rehospitalization at 12 months, according to findings presented at the Heart Failure Society of America Scientific Meeting.
“These findings suggest that the substantial benefits of sacubitril/valsartan observed in randomized trials extend to older patients hospitalized for HFrEF in real-world U.S. clinical practice,” Stephen J. Greene, MD, a fellow in the advanced training program in advanced heart failure and transplant cardiology at Duke University School of Medicine, said during a presentation.
Greene said sacubitril/valsartan (Entresto, Novartis) has been demonstrated to improve clinical outcomes in HFrEF, but its U.S. real-world use has been low and “uncertainty regarding the generalizability of clinical trial results to U.S. clinical practice may be a key contributor to slow adoption of sacubitril/valsartan. Uncertainty may particularly apply to populations generally underrepresented in clinical trials such as older patients, women, racial and ethnic minorities and patients with multiple comorbidities.”
To determine whether clinical trial results were translatable to a real-world population hospitalized for HF with EF of 40% or less, Greene and colleagues analyzed 9,212 patients (median age, 79 years; 39% women) from the Get With the Guidelines–Heart Failure registry between September 2015 and October 2017.
The researchers compared the patients who were prescribed sacubitril/valsartan at discharge with those who were eligible for sacubitril/valsartan but not prescribed it and those who were prescribed an ACE inhibitor or angiotensin receptor blocker. Only 8.1% of patients were prescribed sacubitril/valsartan at discharge, Greene said. Of those not prescribed sacubitril/valsartan, 62.4% were prescribed an ACE inhibitor or angiotensin receptor blocker and the rest were not prescribed any of those drugs, he noted.
The outcomes of interest, all at 12 months, were all-cause mortality, all-cause hospitalization, all-cause mortality/HF hospitalization and HF hospitalization. There were also two falsification endpoints to account for residual confounding, hospitalization for urinary tract infection and hospitalization for nutritional disorder.
The researchers used inverse probability of treatment weighting to balance groups across 24 patient characteristics, Greene said.
Compared with those who were not prescribed it, those who were prescribed sacubitril/valsartan had lower risk for all-cause mortality (adjusted HR = 0.68; 95% CI, 0.57-0.81), all-cause hospitalization (aHR = 0.79; 95% CI, 0.71-0.89) and all-cause mortality/HF hospitalization (aHR = 0.72; 95% CI, 0.64-0.82) at 12 months, according to the researchers. Unadjusted HF hospitalization at 12 months did not differ between the groups (P = .72), but after inverse probability of treatment weighting, risk was lower in the sacubitril/valsartan group (aHR = 0.8; 95% CI, 0.68-0.94).
When the sacubitril/valsartan group was compared with those prescribed an ACE inhibitor or angiotensin receptor blocker, an unadjusted analysis showed no difference in outcomes, but after inverse probability of treatment weighting, all outcomes except HF hospitalization favored the sacubitril/valsartan group, Greene said.
The falsification endpoints were not significant, meaning the results were not likely explained by residual confounding, he said.
“Significant benefits of sacubitril/valsartan were observed as compared with no sacubitril/valsartan and as compared with ACE inhibitor/angiotensin receptor blocker,” he said. – by Erik Swain
Reference:
Greene SJ, et al. Late-Breaking Clinical Trials and Insights with Angiotensin Receptor Neprilysin Inhibitors. Presented at: Heart Failure Society of America Scientific Meeting; Sept. 13-16, 2019; Philadelphia.
Disclosures: The analysis was sponsored by Novartis. The Get With the Guidelines–Heart Failure registry is sponsored by the American Heart Association. Greene reports he receives research support from Amgen, Bristol-Myers Squibb and Novartis and serves on an advisory board for Amgen.
Perspective
Back to Top
Mary Norine Walsh, MD, MACC
The data from the Get With the Guidelines–Heart Failure registry are very important because they concerned a real-world population of quite elderly patients and showed significant benefits from all the endpoints measured. This was a real-world population of patients who were ill and hospitalized. The evidence is no longer based on one single trial for which our guidelines were changed. We have compelling real-world evidence now.
One of the most important issues in clinical practice is the denial of this therapy in favor of ACE inhibitors or angiotensin receptor blockers. Many pharmacy benefits managers insist upon seeing patients “fail” ACE inhibitors or angiotensin receptor blockers prior to approving angiotensin receptor/neprilysin inhibitors. Therefore, initiation in the hospital for some patients is impossible, and even a switch for a symptomatic patient is not possible without prior authorization, which is often denied. Increasingly, these requests will not even be entertained by the medical director. I hope that with the publication of these data, we will have some movement in that regard.
Click Here to Manage Email Alerts