Medicare and Out-of-Pocket Costs of Quadruple Drug Therapy for HF

Quick Takes

  • In an analysis of 2020 Medicare beneficiaries, quadruple therapy with ARNI + BB + MRA and SGLT-2i was covered by nearly all plans but >98% restricted coverage for ARNI and SGLT-2i by cost sharing.
  • Eplerenone was not covered by 10% of plans.
  • Annual out-of-pocket cost associated with quadruple therapy was $2,217 as compared to $159 for generic triple therapy with ACEI/ARB + BB + spironolactone.

Study Questions:

What is the coverage and out-of-pocket (OOP) costs for combined quadruple therapy (beta-blockers [BB], angiotensin receptor-neprilysin inhibitors [ARNI], mineralocorticoid receptor antagonists [MRA], and sodium-glucose cotransporter-2 inhibitors [SGLT-2i]) among Medicare beneficiaries?


This was an analysis of the Medicare Prescription Drug Plan Formulary and Pricing Information Files for quarter 2 of 2020. Coverage in all Medicare Advantage and Medicare Part D plans for BB, ARNI, angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARB), SGLT-2i, and MRA. Drug costs were assessed for medications with the lowest price in their class (i.e., lisinopril, losartan, carvedilol, and spironolactone). First, whether coverage was present for any medication in a class was assessed. Next, requirement for prior authorization, step therapy, and/or cost sharing at tier level ≥3 was assessed. Presence of any of these was characterized as restrictive coverage.


A total of 4,068 Medicare beneficiaries were identified. All plans provided coverage for ≥1 medication in each of the classes. However, 99.1% of plans provided restrictive coverage for ARNI and 98.5% provided restrictive coverage for SGLT-2i. All plans covered ACEI, ARB, BB, and spironolactone. Eplerenone was not covered by 10% of plans. Restrictive coverage for quadruple therapy was usually due to cost sharing for ARNI, SGLT-2i, and eplerenone. Prior authorization for ARNI was needed for 24% of plans but not for SGLT-2i. Monthly median OOP cost of quadruple therapy was $94, mostly due to cost of ARNI and SGLT-2i. Median monthly total drug cost for ARNI was $552, for dapagliflozin $514, and empagliflozin $530. Median OOP cost for eplerenone was $43. Median monthly OOP cost for BB, ACEI, ARB, and spironolactone were $10. Total annual OOP cost for quadruple therapy was $2,217 with median annual OOP cost $976 for ARNI and $939 for SGLT-2i. Annual median OOP cost for BB + ACEI + spironolactone was $159.


While Medicare plans cover quadruple therapy for heart failure with reduced ejection fraction (HFrEF), this coverage is restricted for ARNI and SGLT-2i. Associated OOP cost annually for quadruple therapy comprised of ARNI + BB + MRA + SGLT-2i was estimated at a median of $2,217.


Therapy for HFrEF has had a revolution in the last decade with emergence of ARNI and SGLT-2i in addition to BB and MRA. While the combination of these four agents has significant mortality and morbidity benefit, widespread access to these drugs is limited due to associated costs. In this study, while Medicare plans provided coverage for all four agents, >98% of plans restricted coverage of the two newest classes—ARNI and SGLT-2i. Standard therapy with ACEI/ARB + BB and spironolactone had a median annual cost of $159, but median annual OOP cost for quadruple therapy was over $2,000—a price not affordable for some elderly Medicare beneficiaries. Although the cost benefit of these newer agents has been extensively proven, they remain widely unavailable for use. Legislation and other interventions to reduce medication prices, especially for newer agents, are urgently needed.

Clinical Topics: Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Adrenergic beta-Antagonists, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Cost-Benefit Analysis, Diabetes Mellitus, Type 2, Geriatrics, Health Expenditures, Heart Failure, Medicare, Mineralocorticoid Receptor Antagonists, Neprilysin, Prescription Drugs, Primary Prevention, Receptors, Angiotensin, Sodium-Glucose Transporter 2 Inhibitors, Spironolactone, Stroke Volume

< Back to Listings