Modelling Lifetime Survival Gain In Patients With Transthyretin Amyloid Cardiomyopathy And Baseline NYHA III: An Analysis Of ATTR-ACT And Long Term Extension Study

Abstract

Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underrecognized, underdiagnosed fatal disease associated with heart failure. Patients presenting in New York Heart Association (NYHA) class III have worse survival than patients presenting in earlier disease stages. These patients, therefore, represent a special group within ATTR-CM where effective therapies are urgently needed. Hypothesis Tafamidis will have higher mean survival and quality adjusted life years (QALYs) than placebo in baseline NYHA class III ATTR-CM patients. Methods A Markov model based on NYHA class health states was developed to simulate a hypothetical cohort of baseline NYHA class III receiving either 80 mg tafamidis or placebo over a lifetime horizon. Patient-level survival data from the ATTR-ACT and the preliminary data from long-term extension studies were extrapolated following technical best practices. For patients alive in each model cycle, transition probabilities derived from trial data were used to distribute these patients into NYHA class health states. In the model, patients can progress or improve to other NYHA class health states over time. Utility values were derived from ATTR-ACT. Results The mean survival was 4.31 years for 80 mg tafamidis and 2.36 years for placebo, resulting in an incremental survival of 1.95 years (95% confidence interval [CI] 0.49 to 3.56). Patients starting on tafamidis spent more time than placebo patients in earlier NYHA classes with higher utility scores, translating to mean QALY gains of 3.28 and 1.64, and 1.63 incremental QALYs (95% CI 0.56 to 2.90). Conclusions Based on the results of the disease simulation model, treatment with tafamidis is expected to extend the life expectancy by almost 2 years and improve the quality of life for patients with ATTR-CM in baseline NYHA class III compared to placebo. Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underrecognized, underdiagnosed fatal disease associated with heart failure. Patients presenting in New York Heart Association (NYHA) class III have worse survival than patients presenting in earlier disease stages. These patients, therefore, represent a special group within ATTR-CM where effective therapies are urgently needed. Tafamidis will have higher mean survival and quality adjusted life years (QALYs) than placebo in baseline NYHA class III ATTR-CM patients. A Markov model based on NYHA class health states was developed to simulate a hypothetical cohort of baseline NYHA class III receiving either 80 mg tafamidis or placebo over a lifetime horizon. Patient-level survival data from the ATTR-ACT and the preliminary data from long-term extension studies were extrapolated following technical best practices. For patients alive in each model cycle, transition probabilities derived from trial data were used to distribute these patients into NYHA class health states. In the model, patients can progress or improve to other NYHA class health states over time. Utility values were derived from ATTR-ACT. The mean survival was 4.31 years for 80 mg tafamidis and 2.36 years for placebo, resulting in an incremental survival of 1.95 years (95% confidence interval [CI] 0.49 to 3.56). Patients starting on tafamidis spent more time than placebo patients in earlier NYHA classes with higher utility scores, translating to mean QALY gains of 3.28 and 1.64, and 1.63 incremental QALYs (95% CI 0.56 to 2.90). Based on the results of the disease simulation model, treatment with tafamidis is expected to extend the life expectancy by almost 2 years and improve the quality of life for patients with ATTR-CM in baseline NYHA class III compared to placebo.