Early treatment with the diabetes and heart failure drug empagliflozin in patients recovering from a heart attack could deliver modest health gains at a steep price, according to a new model-based economic evaluation from Germany. The study, published in the journal Cost Effectiveness and Resource Allocation, is the first to estimate the long-term cost-effectiveness of starting empagliflozin soon after acute myocardial infarction, a strategy for which the drug is not currently licensed. From the perspective of the German statutory health insurance system, the analysis found an incremental cost-effectiveness ratio of approximately 45,100 euros per quality-adjusted life-year, a figure that sits near the boundary of what many health systems would consider acceptable and that hinges heavily on assumptions the underlying trial did not directly confirm.
The clinical foundation for the model comes from EMPACT-MI, a randomized trial that enrolled 6,522 patients hospitalized for acute myocardial infarction who were at increased risk of heart failure. In that trial, empagliflozin did not significantly reduce the primary composite endpoint of first heart failure hospitalization or all-cause death, and all-cause mortality was similar between the treatment and placebo groups. However, first and total heart failure hospitalizations were lower among patients receiving the drug. The researchers therefore built their base case around a hazard ratio of 0.77 for first heart failure hospitalization, deliberately assuming no direct mortality benefit, and modeled 24 months of treatment with monthly cycles over a lifetime horizon.
The model tracked patients through five health states, post-myocardial-infarction and post-stroke, each with and without heart failure, plus death, and included three acute events: heart failure hospitalization, recurrent myocardial infarction, and stroke. Background mortality was drawn from German life tables and calibrated so that first-year all-cause mortality matched the roughly 3.7 percent observed in contemporary German post-myocardial-infarction survivors. Costs were expressed in 2026 euros and discounted at 3 percent annually. In the base case, standard care generated 8.321 discounted quality-adjusted life-years at 47,520 euros per patient, while early empagliflozin generated 8.352 quality-adjusted life-years at 48,939 euros, an incremental gain of 0.0315 quality-adjusted life-years at an additional cost of 1,418 euros.
The projected clinical benefit was small in absolute terms. Early empagliflozin avoided 52.0 total heart failure hospitalizations per 1,000 patients treated over a lifetime, including 9.5 first and 42.5 recurrent hospitalizations. The reduction in recurrent hospitalizations arose indirectly, because preventing first hospitalizations left fewer patients in the chronic heart failure state where subsequent events occur, rather than from a directly modeled effect on recurrent events. Life-year gains were similarly modest at 0.028 years, since no direct mortality benefit was assumed and survival improvements emerged only through delayed progression to chronic heart failure and lower downstream event burden.
A critical structural assumption underpins the entire lifetime result: that preventing an early heart failure hospitalization prevents or delays entry into the chronic heart failure state. When the researchers varied the proportion of prevented first hospitalizations that avoid chronic heart failure entry, the incremental cost-effectiveness ratio ranged from more than 7.0 million euros per quality-adjusted life-year at 0 percent down to 45,100 euros at 100 percent, the base-case assumption. Because EMPACT-MI provides no direct evidence on this point, the authors emphasized that the lifetime cost-effectiveness is entirely contingent on this structural choice. In an analysis restricted to the trial’s 17.9-month follow-up horizon, the incremental cost was approximately 1,157 euros per patient with a negligible incremental quality-adjusted life-year gain of 0.001, making the trial-period evaluation a cost-consequence comparison rather than a cost-utility analysis.
Drug price emerged as a dominant lever on economic value. Price reductions of 25 percent and 50 percent lowered the incremental cost-effectiveness ratio to 32,300 and 19,500 euros per quality-adjusted life-year, respectively, while a 75 percent reduction brought it to 6,700 euros. At illustrative willingness-to-pay values of 30,000 and 50,000 euros per quality-adjusted life-year, the maximum compatible annual empagliflozin prices were approximately 607 and 944 euros per patient-year. Because confidential rebates and negotiated net prices are not publicly available in Germany, these threshold analyses identify the net-price range in which early post-myocardial-infarction use would become economically more attractive, rather than reflecting observed reimbursement prices.
Baseline heart failure risk also shaped the results substantially. In exploratory risk-based subgroup analyses, patients with type 2 diabetes or chronic kidney disease, whose placebo first-heart-failure-hospitalization incidence was 7.77 versus 4.05 per 100 patient-years in those without these conditions, showed a more favorable incremental cost-effectiveness ratio of approximately 39,000 euros per quality-adjusted life-year, while those without showed approximately 63,000 euros. These differences reflect greater absolute benefit at higher baseline risk rather than subgroup-specific treatment efficacy, as no credible treatment-effect heterogeneity was demonstrated in the trial. A German claims-based real-world scenario with higher absolute event burden yielded an even more favorable ratio of approximately 22,900 euros per quality-adjusted life-year.
Uncertainty around the findings was substantial. Probabilistic sensitivity analysis with 10,000 Monte Carlo simulations produced a mean incremental cost-effectiveness ratio of approximately 46,500 euros per quality-adjusted life-year, with the probability of cost-effectiveness at 16.2 percent, 55.2 percent, 79.7 percent, and 85.8 percent at willingness-to-pay values of 30,000, 50,000, 80,000, and 100,000 euros per quality-adjusted life-year, respectively. Per-patient expected value of perfect information peaked at 269 euros at 50,000 euros per quality-adjusted life-year, and population-level expected value of perfect information reached 52.9 million euros over a five-year decision horizon, indicating that further evidence generation could carry meaningful value. The treatment effect on first heart failure hospitalization was the dominant driver of uncertainty, shifting the ratio from approximately 23,200 euros at the lower bound of the trial’s confidence interval to 586,200 euros at the upper bound.
The authors framed the work as an early modelling exercise, or early health technology assessment, rather than evidence of established cost-effectiveness, noting that empagliflozin is authorized in the European Union for type 2 diabetes, symptomatic chronic heart failure, and chronic kidney disease but not specifically for heart failure prevention after acute myocardial infarction. Germany does not use a formal quality-adjusted life-year threshold within its AMNOG reimbursement process, so the willingness-to-pay values were treated as illustrative analytical reference points. The researchers also stressed that the reduction in heart failure hospitalizations anchoring the model derives from a component of a neutral primary endpoint and should be interpreted with caution, making the findings exploratory and hypothesis-generating rather than confirmatory.
Despite these caveats, the analysis offers a conditional map of where economic value could emerge. The clinical and economic case appears strongest in patients with clear heart failure risk markers, including reduced left ventricular ejection fraction, congestion during the index hospitalization, diabetes, renal dysfunction, elevated natriuretic peptides, previous myocardial infarction, atrial fibrillation, or incomplete revascularization. The findings should not be read as support for unselected post-myocardial-infarction use. The relevant comparison, the authors noted, is not lifelong sodium-glucose cotransporter 2 inhibitor use versus none, but early initiation versus delayed initiation after clinically manifest heart failure, since contemporary guidelines already recommend these drugs across much of the heart failure spectrum. Longer follow-up of EMPACT-MI, pooled analyses across post-myocardial-infarction trials, individual patient data meta-analysis, and German claims-based studies would help clarify absolute event reduction, long-term resource use, and subgroup-specific value before any reimbursement decision could rest on these projections.
Subject of Research: Model-based cost-effectiveness of early empagliflozin initiation after acute myocardial infarction from the German statutory health insurance perspective
Article Title: Cost-effectiveness of early empagliflozin initiation after acute myocardial infarction: a German statutory health insurance perspective
Article References: Boettger, P., Nakou, E., Kinsley, T., Buerke, M., Wild, E.-M., & Sossalla, S. (2026). Cost-effectiveness of early empagliflozin initiation after acute myocardial infarction: a German statutory health insurance perspective. Cost Effectiveness and Resource Allocation, 24(1), Article 123. https://doi.org/10.1186/s12962-026-00830-0
Image Credits: AI Generated
DOI: 10.1186/s12962-026-00830-0
Keywords: empagliflozin, acute myocardial infarction, heart failure prevention, cost-effectiveness, German statutory health insurance, EMPACT-MI, SGLT2 inhibitors, quality-adjusted life-years, incremental cost-effectiveness ratio, drug pricing, health technology assessment, decision uncertainty
News Source: Courtney Benton. (October 30, 2026). Empagliflozin After Heart Attack Shows Modest Value at High Price in German Model. Scienmag.
