ATTR-CM Incidence, Prevalence Rose Sharply in the US

The incidence and prevalence of transthyretin amyloid cardiomyopathy (ATTR-CM) increased markedly in the US between 2010 and 2023, according to a study published in the Journal of the American Heart Association.¹ The findings, drawn from 2 large claims databases, provide updated epidemiologic estimates from large US insurance claims databases.

“Advances in diagnosis and disease awareness have led to increased prevalence and incidence of transthyretin amyloid cardiomyopathy (ATTR‐CM), but current US population‐based epidemiologic data are lacking,” wrote the researchers of the study. “This study aimed to estimate temporal trends and current prevalence and incidence of ATTR‐CM in the United States and to describe patient characteristics and the clinical burden.”

Researchers conducted a cross-sectional analysis using the Merative MarketScan Medicare Database (2010-2021), which captures individuals 65 years and older enrolled in Medicare Supplement and, from 2020, Medicare Advantage, and the IQVIA PharMetrics Plus database (2016-2023), which includes commercially insured individuals 18 years and older. A subset of PharMetrics Plus data linked to IQVIA Ambulatory Electronic Medical Records was used to estimate prevalence by race.

ATTR-CM was identified using a claims-based algorithm requiring a diagnosis code for amyloidosis plus a cardiac manifestation (heart failure, atrial fibrillation, or cardiomyopathy), with individuals showing evidence of light chain amyloidosis excluded. The algorithm was not formally validated against confirmed diagnoses, identifying individuals with likely rather than confirmed ATTR-CM.

Incidence and Prevalence Climbed Across Both Databases

In the Medicare database, ATTR-CM incidence rose from 10.1 per 100,000 person-years in 2010 to 44.3 per 100,000 person-years in 2021—more than a 4-fold increase. Prevalence climbed from 15.8 to 95.8 per 100,000 individuals over a similar period, roughly a 6-fold rise.

In PharMetrics Plus, which captures a younger, commercially insured population, incidence rose from 2.0 per 100,000 person-years in 2016 to 5.4 in 2022, while prevalence increased from 1.5 to 11.3 per 100,000 individuals between 2016 and 2023.

Both incidence and prevalence increased across all age and sex subgroups, but rates were consistently higher and grew faster among men and older individuals. Among individuals 65 years and older in the Medicare Database, the mean age at diagnosis was 79.7 years, and 57.2% were men; in PharMetrics Plus, the mean age was 69.1 years, and 60.0% were men.

Race-stratified prevalence data, available only from 2019 to 2023 due to small sample sizes earlier in the study period, showed prevalence increased at a higher rate among Black individuals than White individuals, a gap the authors said was not explained by differences in age or sex between the 2 groups.

Comorbidity and Treatment Burden Grew More Complex Over Time

The proportion of individuals with more than 11 comorbidities before ATTR-CM diagnosis nearly tripled, from 8.3% in the 2010-2013 cohort to 23.8% in 2018-2021, an increase that held up after adjusting for age and sex. Hypertensive disease, atherosclerotic cardiovascular disease, and ischemic heart disease were the most common comorbidities throughout the study period.

Medication use in the year before diagnosis also rose. Lipid-lowering agent use increased from 42% to 68% of patients between the earliest and latest cohorts, whereas β-blocker use rose from 42% to 61%. The share of patients on no recorded medication fell from 35.9% to 8.6% over the same period.

The new estimates were higher than those reported in a frequently cited 2019 Medicare analysis among fee-for-service beneficiaries with cardiac amyloidosis broadly (not limited to ATTR-CM), which reported an incidence of 17 per 100,000 person-years and prevalence of 55 per 100,000 individuals in 2012.² The authors attributed the rise largely to improved diagnostic awareness, wider use of less invasive imaging techniques, and the availability of disease-specific treatment options, rather than necessarily reflecting a true rise in disease occurrence.

However, the researchers noted some limitations. The claims-based algorithm used to identify ATTR-CM was not formally validated and may have included false positives or missed true cases, and it could not distinguish hereditary from wild-type disease. Both databases capture only insured subpopulations, limiting generalizability.¹

Taken together, these findings suggest ATTR-CM is being recognized far more frequently than it was a decade ago, with newly diagnosed patients presenting with an increasing burden of comorbid conditions. As diagnostic tools and treatment options continue to expand, health systems, providers, and payers may need to prepare for a growing population of patients requiring specialized long-term management.

“The incidence and prevalence of ATTR‐CM diagnoses have increased in the United States from 2010 to 2023, and the clinical burden among newly diagnosed individuals has become more complex,” wrote the researchers.

References

1. Alexander KM, Dasgupta NR, Mathisen J, et al. Temporal trends in incidence and prevalence of transthyretin amyloid cardiomyopathy in the United States. J Am Heart Assoc. 2026;15:e047135. doi:10.1161/JAHA.125.047135
2. Gilstrap LG, Dominici F, Wang Y, et al. Epidemiology of cardiac amyloidosis-associated heart failure hospitalizations among fee-for-service Medicare beneficiaries in the United States. Circ Heart Fail. 2019;12(6):e005407. doi:10.1161/CIRCHEARTFAILURE.118.005407