Cost-Effectiveness of Tafamidis Therapy for Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: In patients with transthyretin amyloid cardiomyopathy, tafamidis reduces all-cause mortality and cardiovascular hospitalizations and slows decline in quality of life compared with placebo. In May 2019, tafamidis received expedited approval from the US Food and Drug Administration as a breakthrough drug for a rare disease. However, at $225 000 per year, it is the most expensive cardiovascular drug ever launched in the United States, and its long-term cost-effectiveness and budget impact are uncertain. We therefore aimed to estimate the cost-effectiveness of tafamidis and its potential effect on US health care spending. METHODS: We developed a Markov model of patients with wild-type or variant transthyretin amyloid cardiomyopathy and heart failure (mean age, 74.5 years) using inputs from the ATTR-ACT trial (Transthyretin Amyloidosis Cardiomyopathy Clinical Trial), published literature, US Food and Drug Administration review documents, healthcare claims, and national survey data. We compared no disease-specific treatment ("usual care") with tafamidis therapy. The model reproduced 30-month survival, quality of life, and cardiovascular hospitalization rates observed in ATTR-ACT; future projections used a parametric survival model in the control arm, with constant hazards reduction in the tafamidis arm. We discounted future costs and quality-adjusted life-years by 3% annually and examined key parameter uncertainty using deterministic and probabilistic sensitivity analyses. The main outcomes were lifetime incremental cost-effectiveness ratio and annual budget impact, assessed from the US healthcare sector perspective. This study was independent of the ATTR-ACT trial sponsor. RESULTS: Compared with usual care, tafamidis was projected to add 1.29 (95% uncertainty interval, 0.47-1.75) quality-adjusted life-years at an incremental cost of $1 135 000 (872 000-1 377 000), resulting in an incremental cost-effectiveness ratio of $880 000 (697 000-1 564 000) per quality-adjusted life-year gained. Assuming a threshold of $100 000 per quality-adjusted life-year gained and current drug price, tafamidis was cost-effective in 0% of 10 000 probabilistic simulations. A 92.6% price reduction from $225 000 to $16 563 would be necessary to make tafamidis cost-effective at $100 000/quality-adjusted life-year. Results were sensitive to assumptions related to long-term effectiveness of tafamidis. Treating all eligible patients with transthyretin amyloid cardiomyopathy in the United States with tafamidis (n=120 000) was estimated to increase annual healthcare spending by $32.3 billion. CONCLUSIONS: Treatment with tafamidis is projected to produce substantial clinical benefit but would greatly exceed conventional cost-effectiveness thresholds at the current US list price. On the basis of recent US experience with high-cost cardiovascular medications, access to and uptake of this effective therapy may be limited unless there is a large reduction in drug costs.

Standardized Psychosocial Assessment Before Left Ventricular Assist Device Implantation.

BACKGROUND: Before consideration of advanced cardiac therapies, guidelines recommend a comprehensive multidisciplinary examination, including psychosocial assessment. The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) has emerged as a highly reproducible tool to assess for psychosocial impairment and is associated with negative medical and psychosocial outcomes after transplantation. We sought to assess the association between SIPAT and outcomes after left ventricular assist device. METHODS AND RESULTS: We evaluated 128 patients implanted with a first left ventricular assist device at the Cleveland Clinic from 2013 to 2017 who underwent a prospectively collected quantitative psychosocial assessment using SIPAT. Several survival analyses were performed testing the association between SIPAT score and mortality, first adverse event (defined as hospitalization, device exchange, or death), and recurring adverse events after multivariable adjustment. Median SIPAT score was 14 (interquartile range, 9.5-22.5), with higher values (representing more impairment) seen in patients implanted as destination therapy. After a median follow-up of 349 (interquartile range, 178-684) days, there were 319 adverse events (18 deaths, 10 device exchanges, and 291 readmissions) with 2.5±2.4 events per patient. Higher preimplant SIPAT scores were not associated with mortality ( P=0.764) or time to a first adverse event ( P=0.589) but were associated with cumulative adverse events (hazard ratio, 1.31; 95% CI, 1.09-1.58; P=0.005 per Δ10 in score). In addition, SIPAT was associated with days alive outside of the hospital ( P=0.016). CONCLUSIONS: A standardized assessment of psychosocial impairment after left ventricular assist device using the SIPAT score was not associated with mortality or time to first adverse event but was associated with cumulative adverse cardiac events. This score may provide insight when structuring mitigation strategies for high-risk patients and should be further tested in a prospective multicenter study.