Quadruple therapy borderline cost-effective for HFrEF; drug prices continue to rise
Key takeaways:
- Quadruple therapy for heart failure with reduced ejection fraction was narrowly cost-effective.
- Medicare discounts improve affordability of high drug prices.
Researchers reported quadruple therapy with SGLT2 and angiotensin receptor-neprilysin inhibition was narrowly cost-effective compared with standard care plus SGLT2 inhibition alone for patients with HF and reduced ejection fraction.
Quadruple therapy was estimated to provide intermediate value for patients with HFrEF, but clinicians may consider weighing the patient’s ability to afford the high cost of SGLT2 inhibitors and the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan (Entresto, Novartis), according to a cost-effectiveness analysis published in Circulation: Cardiovascular Quality and Outcomes.
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“A clinical trial demonstrated that the use of an angiotensin receptor-neprilysin inhibitor in place of an ACE inhibitor in management of heart failure with reduced ejection fraction lowered risk of death and heart failure hospitalization. ... Clinical trials have also shown that the addition of a sodium-glucose cotransporter-2 inhibitors to the previous standard of care for heart failure with reduced ejection fraction conferred a reduction in deaths and risk of heart failure hospitalization,” Brandon W. Yan, MPH, internal medicine resident physician at the University of California, San Francisco, and colleagues wrote. “Adding either an angiotensin receptor-neprilysin inhibitor or an sodium-glucose cotransporter-2 inhibitor to the previous standard of care has been shown to be cost-effective, but the cost-effectiveness of adding both to form a four-drug regimen known as quadruple therapy is not well-studied.”
For this cost-effectiveness analysis, Yan and colleagues compared four HFrEF treatment strategies:
- quadruple therapy with beta-blockers and mineralocorticoid receptor antagonist (MRA) plus angiotensin receptor-neprilysin inhibitor (ARNI) and SGLT2 inhibiton;
- triple therapy with beta-blockers and MRA plus ARNIs;
- beta-blockers and MRA plus SGLT2 inhibition on top of previous guideline-directed medical therapy with enalapril; and
- beta-blockers and MRA plus old guideline-directed medical therapy with enalapril.
The researchers estimate the expected lifetime discounted costs and quality-adjusted life-years within a simulated cohort of U.S. patients with HFrEF who underwent each treatment option and calculated their incremental cost-effectiveness ratios.
Cost-effectiveness of quadruple therapy for HFrEF
QALY less than $50,000 indicated high value, whereas $50,000 to $150,000 indicated intermediate value and more than $150,000 indicated low value. The cost-effectiveness threshold was set at a standard $100,000 per QALY.
The researchers reported that compared with the previous standard of care of beta-blocker, MRA and enalapril, the addition of an SGLT2 inhibitor was estimated to have an incremental cost-effectiveness ratio of $73,000 per QALY and slightly dominated the treatment option including the addition of ARNI.
Quadruple therapy offered 0.68 additional discounted QALYs compared with the addition of SGLT2 inhibition alone, with a lifetime discounted cost of $66,700, translating to an incremental cost-effectiveness ratio of $98,500 per QALY, according to the study.
Moreover, after conducting a sensitivity analysis that accounted for varying drug prices from those available to the U.S. Department of Veterans Affairs to drug list prices, the researchers estimated that the incremental cost-effectiveness ratio for quadruple therapy ranged from $73,500 to $110,000 QALYs.
“We found quadruple therapy to be of intermediate value, per American College of Cardiology/American Heart Association cost-effectiveness standards, compared with the +SGLT strategy and borderline cost-effective at the $100,000/QALY threshold,” the researchers wrote. “Consistent with prior studies, the +ARNI and +SGLT strategies were found to be cost-effective compared with old guideline-directed medical therapy.”
The rising cost of SGLT2 inhibition and ARNI
As the use of SGLT2 inhibitors expanded to more chronic conditions, from 2015 the average price per unit for the 30-day supply has increased 76% for dapagliflozin (Farxiga, AstraZeneca) and increased 90% for empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) from 2014. In addition, since 2015, the price has increased 70% for the only ARNI on the market, according to the study.
“Some of these drugs may be candidates for Medicare’s drug price negotiation under the Inflation Reduction Act (IRA) of 2022. While this provision does not enter effect until 2026, when negotiation is limited to just 10 drugs and generic SGLT2 inhibitors and ARNIs may or may not be available, the impact of lower ARNI and SGLT2 inhibitor drug prices on cost-effective management of HFrEF ought to be a consideration,” the researchers wrote. “Considering that the big four federal agencies have negotiated price ceilings that equal 37% and 34% off the lowest list price for the SGLT2 inhibitor and ARNI, respectively, we might expect Medicare drug price negotiations to achieve at least similarly sized discounts given Medicare’s collective market share.”
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