Study shows cost benefits associated with early use

Initiating treatment with the first-in-class heart failure drug combo sacubitril-valsartan (Entresto) during hospitalization was associated with reduced readmission and cost savings compared to no initiation or later initiation in heart failure patients with reduced ejection fraction in an economic modeling study and budget analysis.

The model-based analysis suggested that starting sacubitril-valsartan during hospitalization would be cost-effective compared with administration of the ACE-inhibitor enalapril, followed by sacubitril-valsartan 2 months after hospital discharge, or enalapril alone as long-term treatment.

Initiation of sacubitril-valsartan as an outpatient was found to be cost-effective, but not cost-saving, compared with continued use of enalapril, wrote researcher Thomas Gaziano, MD, of Brigham and Women’s Hospital, Harvard Medical School, Boston, and colleagues.

The study was published online August 12 in JAMA Cardiology.

Sacubitril-valsartan was the first angiotensin-receptor-neprilysin inhibitor (ARNI) approved by the FDA for the treatment of heart failure patients with reduced ejections fraction (HFrEF), and it was the first new drug to show a mortality benefit in these patients in more than a decade.

Treatment with sacubitril-valsartan was shown to be associated with reduced mortality and hospitalizations, compared to enalapril, in an earlier study. Gaziano and colleagues also previously reported that treatment with the ARNI-therapy was cost effective, compared to enalapril, in outpatients with HFrEF, based on findings from a similar modeling study.

But uptake of the drug has remained low, despite studies linking its use to a 20% reduction in cardiovascular death, compared to treatment with an ACE-inhibitor, and a 2019 cost analysis suggested that the drug’s price may be the cause.

The study by Colette DeJong, MD, of the UCSF Center for Healthcare Value, and colleagues, found that Medicare patients with HFrEF prescribed an ARNI could expect to pay $1,685 out-of-pocket annually for the drug, with monthly costs exceeding $160 during the Medicare coverage gap.

“Even with new legislation capping out-of-pocket costs at 25% during the coverage gap, cost sharing for an ARNI would exceed $100 a month,” DeJong et al. wrote. “This is concerning because high out-of-pocket costs have been associated with poorer adherence and worse health outcomes among patients with cardiovascular disease.”

In their latest cost analysis, Gaziano and colleagues developed a 5-state Markov model simulating heart failure based on data from the PIONEER-HF and the PARADIGM-HF studies, which both compared sacubitril-valsartan to enalapril. Quality of life was estimated using Euro-QoL-5D scores, and the researchers modeled the cost of hospitalization, long-term care and medication costs with a discount rate of 3%.

The mean age of the modeled patients was 64 (11.5) years, and inpatient treatment with sacubitril-valsartan ($5,628 per year) was associated with 62 fewer HF-related admissions per 1,000 patients compared with outpatient initiation or 116 fewer HF-related admissions compared with continuation of enalapril treatment.

The cost-effectiveness modelling also found:

  • Initiation of sacubitril-valsartan during hospitalization would save health care systems $452 per year compared with continuing enalapril and $811 per year compared with initiation at 2 months after hospitalization.
  • Initiation of sacubitril-valsartan during hospitalization was associated with an incremental cost-effectiveness ratio of $21,532 per quality-adjusted life-year compared with continued enalapril treatment over a lifetime.
  • From a societal perspective, inpatient initiation was estimated to save $460 per year per patient compared with no initiation of sacubitril-valsartan and $813 per year per patient compared with initiation after hospitalization.
  • In a budget analysis, inpatient initiation of sacubitril-valsartan was estimated to save up to $449 per person for 1 year or $2,550 per person over 5 years compared with continuation of enalapril.

“We found that for eligible patients with HFrEF, initiation of sacubitril-valsartan during hospitalization was cost saving compared with initiation 2 months after hospitalization and was cost saving or highly cost-effective compared with indefinite continuation of enalapril treatment,” Gaziano and colleagues wrote.

Study limitations included the short duration of the PIONEER-HF trial and its relatively small sample size, and the reliance on an exploratory secondary outcome of HF-related hospitalizations in the analysis of the PIONEER-HF data “with a relatively large 95% CI.”

But in an editorial published with the study, JAMA Cardiology editors Clyde Yancy, MD, and Robert O. Bonow, MD, of Northwestern University, Chicago; and Adrian Hernandez, MD, of Duke University characterized the cost-effectiveness studies by Gaziano and colleagues as “informative and actionable.”

“If the reduction in hospitalization after an episode of hospitalized heart failure seen in the secondary post hoc analyses from PIONEER HF is replicable, then early initiation of sacubitril/valsartan, preferably during hospitalization, meets a bar for cost-effectiveness in all but the most conservative estimates of efficacy and/or at the highest cost thresholds for sacubitril/valsartan,” they wrote.

“Given the prevailing assumptions, our interpretation is that use of sacubitril/valsartan for hospitalized heart failure is further enabled by these provocative cost-effectiveness data,” they noted, adding that “equitable access” remains a challenge for many patients with HFrEF.

“Careful ongoing analyses are required to further validate these assumptions in real-world applications, evaluate their generalizability, and consider the individual, health system, and societal value for this indication,” they concluded.

  1. Among eligible patients with HFrEF, initiation of sacubitril-valsartan during hospitalization was cost saving compared with initiation 2 months after hospitalization.

  2. Initiation of the angiotensin-converting enzyme inhibitor during hospitalization for HFrEF was cost saving or highly cost-effective compared with indefinite continuation of treatment with enalapril.

Salynn Boyles, Contributing Writer, BreakingMED

The research was funded by grants from Novartis AG.

Lead researcher Thomas Gaziano reported receiving grants from Novartis AG during the conduct of the study; receiving personal fees from Amgen Inc, Teva, and Takeda; and receiving research support from the National Institutes of Health and UnitedHealth Care outside the submitted work. Researcher Gregg C. Fonarow reported receiving research support from the National Institutes of Health; and being a consult for Abbott, Amgen Inc, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc, Janssen, Medtronic, and Novartis AG outside the submitted work. Researcher Eric Velazquez reported receiving research support from the National Institutes of Health, receiving grants from Novartis AG during the conduct of the study, and receiving consultancy fees from Novartis AG outside the submitted work.

Editorial writer Clyde Yancy reported his spouse being employed with Abbott Labs, Inc. Adrian Hernandez reported grants and personal fees from AstraZeneca, Merck, and Novartis and personal fees from Amgen and Bayer outside the submitted work.

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