Cost-effectiveness of SGLT2 Inhibitors in Patients with Heart Failure with Reduced Ejection Fraction

What is the cost-effectiveness of using SGLT2 inhibitors like dapagliflozin, which were created to treat diabetes, but noted to ameliorate cardiovascular events, in heart failure?

In the dapagliflozin population with heart failure and reduced ejection fraction experiment, adding dapagliflozin to guideline-directed medical treatment lowered the chances of cardiovascular death and heart failure hospitalization by 26% compared to that of medical therapy alone. Dapagliflozin is the primary SGLT2 inhibitor approved by the US Food and Drug Administration for heart failure therapy and reduced ejection fraction, including individuals without diabetes. 

Heart failure is the leading cause of hospitalization in the US, and dapagliflozin may ameliorate health outcomes and lower health care charges by averting hospitalization caused by heart failure downstream. However, the price of $6,188 per year of treatment could cause a significant increase in pharmaceutical expenditures. Therefore, a systemic cost-effectiveness analysis from the US health care sector perspective would evaluate the tradeoff between higher health care charges and improved health outcomes and aid in informing pricing and adoption methods. This analysis is specifically essential for SGLT2 inhibitors because diabetes treatment has factually seen significant manufacturer discounts, suggesting that patients’ actual prices may vary and be subject to negotiations with the manufacturers. Therefore, researchers analyzed the cost-effectiveness of adding dapagliflozin to guideline-directed medical treatment for the management of heart failure with reduced ejection fraction in population with and without diabetes at baseline, from a US health care sector point of view and a lifetime analytic horizon. 

Researchers created a Markov cohort model to compare two treatment methods among individuals with heart failure with reduced ejection fraction. The first method consisted of guideline-directed medical treatment comprised of an angiotensin-converting enzyme inhibitor, an angiotensin-receptor blocker, or an angiotensin receptor neprilysin inhibitor added to a B-blocker and a mineralocorticoid receptor antagonist. The second method consisted of dapagliflozin 10 mg once a day added to guideline-directed medical therapy. Due to the study relying on publicly available data sets, the study was not considered human participants research, and institutional review board approval was not necessary per the standard regulation. The study’s primary outcome is the incremental cost-effectiveness ratio of adding dapagliflozin to guideline-directed medical treatment compared with guideline-directed medical therapy alone. Researchers ran ten thousand simulations utilizing input parameter values at random to evaluate the number of simulations in which dapagliflozin would be cost-effective at different willingness to pay thresholds. The simulated cohort had a starting age of 66 years old, and almost half of the patients in the simulation had diabetes at baseline. The model reproduces all-cause mortality rates, heart failure with reduced ejection fraction, and emergency heart failure visits observed in the DAPA-heart failure experiment. The monitoring of dapagliflozin therapy was cost-effective in 94% of ten thousand probable simulations, suggesting that the findings are robust across a great range of estimates of key model parameters. Cost-effectiveness analysis delivered a formal mechanism to measure the gain or losses in population health as an outcome of a specific intervention.  

Despite total and out-of-pocket cost-reducing uptake of novel cardiovascular treatment in the recent past, three factors justify the researchers’ positivity that the experience with SGLT2 inhibitors will not be the same. First, diabetes treatment, including SGLT2 inhibitors, receives significant discounts in the US pharmaceutical markets. Second, SGLT2 inhibitors with guaranteed benefits in heart failure with reduced ejection therapies may allow payers to discuss better pricing in return for preferred formulary placement. Therefore, most US payers will have the ability to continue to access at least one SGLT2 inhibitor at an affordable price. Finally, recent administration reforms would force payers to give patients at least some manufacturer discounts. Thus, these changes would significantly reduce total costs for payers and out-of-pocket costs for patients and broaden access to this cost-effective treatment. To conclude, the addition of dapagliflozin to guideline-directed medical treatment is projected to ameliorate long-term clinical results in individuals with heart failure with reduced ejection fraction and be affordable at current US prices. 

Practice pearls  

• Dapagliflozin is the primary SGLT2 inhibitor approved by the US Food and Drug Administration for heart failure therapy and reduced ejection fraction. 
• Dapagliflozin may ameliorate health outcomes and lower health care charges by averting hospitalization caused by heart failure downstream. 
• The addition of dapagliflozin to guideline-directed medical treatment is projected to ameliorate long-term clinical results in a population with heart failure with reduced ejection fraction and be affordable at current US prices. 

References for “Cost-effectiveness of SGLT2 Inhibitors in Patients with Heart Failure with Reduced Ejection Fraction”:
Isaza, Nicolas et al. “Cost-effectiveness of Dapagliflozin for the Treatment of Heart Failure with Reduced Ejection Fraction.” JAMA network open vol. 4,7 e2114501. 1 Jul. 2021. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317009/ 

McEwan, Phil et al. “Cost-effectiveness of dapagliflozin as a treatment for heart failure with reduced ejection fraction: a multinational health-economic analysis of DAPA-HF.” European journal of heart failure vol. 22,11 (2020). https://pubmed.ncbi.nlm.nih.gov/32749733/ 

Emmanuella Louissaint, PharmD candidate, LECOM College of Pharmacy 

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