Objectives

The clinical efficacy of lisinopril and carvedilol in reducing trastuzumab-induced cardiotoxicity (CTX) among patients with early-stage breast cancer (eBC) previously received anthracyclines has been demonstrated through the randomized controlled trial. This study aimed to assess the cost-effectiveness of lisinopril and carvedilol (Coreg CR) in US adults with eBC receiving trastuzumab, compared with no treatment.

Methods

We developed a Markov model to simulate trajectories for patients between 3 health states: CTX-free, asymptomatic CTX, and symptomatic CTX. The transition probabilities were derived from the original trial report. The utilities and costs were obtained from the published literature. Costs were standardized to the 2021 US dollars using the consumer price index for medical supply. The simulation time horizon was 2 years, with a cycle length of 3 months. The annual discount rate for the cost and utility was 3%. The model estimated the incremental cost-effectiveness ratio (ICER) of lisinopril and carvedilol versus no treatment, respectively, from a health system perspective. We performed one-way and probabilistic sensitivity analyses (PSA) to assess the robustness of the results.

Results

The incremental effectiveness and cost of lisinopril versus placebo were 0.09 QALY and $74, resulting in an ICER of $790/QALY. The incremental effectiveness and cost of carvedilol versus placebo were 0.05 QALY and $6,591, resulting in an ICER of $125,545/QALY. These results are sensitive to lisinopril’s and carvedilol’s price and the cost of treating symptomatic CTX for both lisinopril and carvedilol cohorts. At a willingness-to-pay threshold (WTP) of $50,000/QALY, lisinopril was cost-effective in 94% of 1,000 iterations and carvedilol (Coreg CR) was cost-effective in 43% of 1,000 iterations, compared with no prophylaxis.

Conclusions

Based on a WTP of $50,000/QALY, lisinopril is a cost-effective prophylaxis against trastuzumab-induced CTX for US eBC patients. The price is a major impact factor for carvedilol’s economic efficiency.