A billion here, a billion there: it’s real money to Medicare

An economic analysis of the cost of dapagliflozin therapy for treatment of patients with reduced ejection fraction heart failure (HFrEF) combined with clinical evidence of benefit from the DAPA-HF trial found that the incremental cost-effectiveness per quality of life-year gained is $83,650, which by American College of Cardiology/American Heart Association standards means the drug has intermediate value, AKA is cost-effective.

But more data are needed to determine the “magnitude of the mortality reduction” to improve this cost-effectiveness estimate, wrote Justin T. Parizo, MD, of the division of cardiovascular medicine, Stanford University School of Medicine, Stanford, California, and colleagues in JAMA Cardiology.

And in the real world of clinical practice, cost-effectiveness models overlook a hard question that is likely to be more important: is this treatment affordable for individuals who need the wherewithal for out-of-pocket costs and for payers, such as Medicare and Medicaid, who will pick up the lion’s share of cost?

“Although clinicians have traditionally practiced using the principle that they should do everything possible to improve outcomes for their patients, modern medicine is also a health care business, and from the business perspective, cost (affordability and budget impact) issues are often critical determinants of which clinical and public health objectives receive adequate support. In the US, where drug prices are determined by a complex web of pharmaceutical companies, pharmacy benefits managers, and others, costs of new drugs for heart failure have typically approached list prices of $20 a day (>$7000/y),” wrote Derek S. Chow, MD MSc of Duke Clinical Research Institute, and Daniel B. Mark, MD, MPH, of Division of Cardiology, Department of Medicine, Duke University Medical Center, both in Durham, North Carolina in an editorial published with the study by Parizo et al.

Chow and Mark cited the example of sacubitril-valsartan, the ARNI that demonstrated superiority to enalapril in the PARADIGM trial, which received rapid approval by the FDA but has failed to gain wide use by clinicians. One barrier to sacubitril-valsartan uptake may be the affordability factor for patients and Uncle Sam.

“In recent studies of the cost of sacubitril-valsartan for Medicare patients with Part D coverage (approximately 70% of Medicare enrollees), the mean out-of-pocket costs were approximately $1630/y, while Medicare paid an additional $2500 (total, approximately $4130/y). If the payments for SGLT2 inhibitor therapy are comparable to those for sacubitril-valsartan, a large segment of the population with heart failure may now be strongly encouraged by their clinicians to spend $9000 or more a year on their 4-pillar therapy, including more than $3000 out of pocket for some. This out-of-pocket component appears to substantially exceed what many patients with heart failure can afford or are willing to spend.”

Parizo and colleagues used the Markow cohort cost-effectiveness model that factors in hospitalization costs, as well as costs for medications, estimates for costs of device therapies (left-ventricular assist devices), and ongoing clinical management costs for HFrEF for patients with or without type 2 diabetes.

“In the model, dapagliflozin therapy yielded a mean of 0.78 additional life-years and 0.46 additional QALYs compared with [standard of care] at an incremental cost of $38,212, resulting in a cost per QALY gained of $83,650. The cost per QALY was similar for patients with or without diabetes and for patients with mild or moderate impairment of health status due to heart failure. The cost-effectiveness was most sensitive to estimates of the effect on mortality and duration of therapy effectiveness. If the cost of dapagliflozin decreased from $474 to $270 (43% decline), the cost per QALY gained would drop below $50,000,” they wrote.

But duration of efficacy is also a consideration: “Dapagliflozin would need to remain effective for at least 44 months to have a cost per QALY of less than $150,000,” and the benefit of dapagliflozin “largely depends on the effect estimate on cardiovascular mortality… dapagliflozin must reduce cardiovascular mortality by at least 8% and 14% for the cost per QALY gained to remain below $150,000 and $100,000, respectively,” the study authors noted. In the DAPA-HF trial, the mortality reduction ranged from 2% to 31%.

These calculations are sobering for heart failure specialists who have been aggressively promoting the concept of 4-pillar HFrEF therapy, meaning use of four classes of drugs: beta-blockers, RAAS inhibitors (ACEi/ARBs/ARNI), mineralocorticoid receptor antagonists, and SGLT2 inhibitors (dapagliflozin, et al).

Compared to ACEi/beta-blocker therapy “the 4-pillar approach could improve the survival of 55-year-old patients with heart failure by more than 6 years (from 11.4 to 17.7 years) and that of 65-year-old patients by more than 4 years (from 10.6 to 15.0 years)… the possibility of such an impressive improvement over current practice has led some to call the 4-pillar approach the new standard of care,” Chow and Mark wrote.

But at what cost? The editorialists estimated that Medicare’s share of “full deployment” of dapagliflozin to eligible candidates would be $12 billion, and full deployment of sacubitril-valsartan would add another $12 billion.

Chow and Mark compared the challenges of heart failure treatment to the mythical 12 labors of Hercules, the original Herculean challenge. “With more emerging heart failure therapies on the horizon (e.g., vericiguat, omecamtiv mecarbil), clinicians and patients are faced with the possibility of even more (expensive) pillars to come. Hercules, for all his strength of purpose, did not have to contend with the cost consequences of what he did. Modern medicine does.”

  1. Markov model evaluation of the population in the DAPA-HF trial found that dapagliflozin had an incremental cost-effectiveness ratio of $83,650 per quality adjusted life year gained.

  2. The cost-effectiveness per quality adjusted life year gained meets the benchmarks for ACC/AHA intermediate value, thus the authors conclude that in HFrEF patients dapagliflozin therapy is both clinically beneficial and cost effective.

Peggy Peck, Editor-in-Chief, BreakingMED™

The research was supported by grants from the National Heart Lung and Blood Institute.

Parizo disclosed research support from a NHLBI award.

Mark reported receiving grants from Merck & Co, Inc, HeartFlow, and Mayo Clinic outside the submitted work.

Cat ID: 914

Topic ID: 74,914,730,914,192,925