Ex Ante Economic Evaluations of Arg389 Genetic Testing and Bucindolol Treatment Decisions in Heart Failure Stage III/IV
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PublisherThe University of Arizona.
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EmbargoRelease after 1-May-2020
AbstractIntroduction: Beta-Blocker Evaluation Survival Trial (BEST) sub-analyses indicated a likely interaction between bucindolol and race disadvantaging black heart failure (HF) patients (Domanski J Cardiac Fail 2003); Arg389 homozygotes having adjusted reductions of 38% in mortality and 34% in mortality/hospitalization over other genotypes (Liggett PNAS 2006). Bucindolol is being evaluated in Arg389 genotype patients in the GENETIC-AF trial (NCT01970501). Objective: To conduct parallel (using Domanski et al and Liggett et al) ex ante economic evaluations of Arg389 genetic testing in stage III/IV HF to support bucindolol treatment decisions (if Arg389-positive) and carvedilol (if Arg389-negative) treatment versus no such testing and empirical bucindolol; using Domanski et al and Liggett et al BEST sub-analyses. Methods: In both Domanski et al and Liggett et al analyses, we used a decision tree model with time horizon of 18 months divided into 3 six-month cycles to estimate the cost-effectiveness and cost-utility of Arg389 genetic testing, considering overall survival (OS) from Domanski et al and Liggett et al BEST sub-analyses. Costs and utilities were retrieved from literature except for assumed cost for bucindolol treatment (1.5x cost of carvedilol) and genetic testing ($250). Discount rate was set at 3%/yr. Weibull distributions were fitted to OS data. Life-years (LY) and quality-adjusted life-years (QALY) were used to estimate incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR), and results were validated using probabilistic sensitivity analyses (PSA). Results: In the Domanski et-based analysis, Arg389 genetic testing versus no testing was associated with incremental gains of 0.29LYs and 0.27QALYs at incremental cost of $726; yielding ICER of US$2,503/LY and ICUR of US$2,688/QALY gained. In the Liggett et al-based analysis, Arg-389 genetic testing versus no testing was associated with incremental gains of 0.35LYs and 0.32QALYs at savings of -$1.081; for ICER of -US$3,089/LY and ICUR of -US$3,378/QALY gained. Both analyses were confirmed in PSAs. Conclusion: Arg389 genetic testing to support bucindolol treatment in stage III/IV HF patients prevails economically over bucindolol treatment without genetic testing due to superior OS. If bucindolol is priced at 1.5x the cost of carvedilol. this economic benefit is likely to disappear if bucindolol and/ or genetic testing are priced higher. The clinical and economic benefits of bucindolol treatment with versus without Arg389 genetic testing versus empiric carvedilol remains to be assessed.
Degree ProgramGraduate College