PRO5 Estimating the Health Benefits of Earlier Diagnosis and Treatment of Transthyretin Amyloid Cardiomyopathy

Abstract

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, fatal disease with significant morbidity and mortality, where patients commonly experience delayed diagnosis and misdiagnosis. Adoption of non-invasive diagnostic techniques and the approval of disease-modifying therapies are expected to increase disease awareness and reduce diagnostic delay. This study estimated the expected health benefits of earlier ATTR-CM diagnosis and treatment with tafamidis. A discrete time, cohort-level Markov state-transition model was developed, with health states based on New York Heart Association (NYHA) classification. Clinical efficacy was informed by the Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy (ATTR-ACT) study. Exemplar wild-type (wtATTR-CM) and hereditary (hATTR-CM) patients were simulated for early (younger age and earlier NYHA classification) and delayed diagnosis/treatment scenarios; delay durations were informed by a literature review and treatment with tafamidis was assumed to commence at diagnosis. Health outcomes were evaluated over a lifetime horizon. Exemplar patients were male, baseline NYHA class II, with baseline ages of 70 and 60 years for wtATTR-CM and hATTR-CM, respectively. For the wtATTR-CM patient, relative to a 3.42 (range 0.75-3.83) year delay, early diagnosis and treatment was estimated to result in 4.42 (1.56-4.79) additional life years (LYs) and 3.70 (1.33-4.00) additional quality-adjusted life years (QALYs); for the hATTR-CM patient, relative to a 2.50 (range 2.08-3.67) year delay, 5.43 (4.77-7.25) additional LYs and 4.45 (3.92-5.89) additional QALYs were predicted. Estimated benefits were greater for younger patients and females and attenuated for later baseline NYHA class. Tafamidis, the first disease-modifying treatment, is predicted to significantly improve survival and quality of life outcomes for both wtATTR-CM and hATTR-CM patients. This study demonstrates that lengthy diagnostic delays represent a foregone opportunity to further extend and improve life for ATTR-CM patients using tafamidis treatment.