Early diagnosis, treatment improves survival in ATTR-CM: Study
Fewer benefits seen in older patients, those with more advanced disease
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People with transthyretin amyloid cardiomyopathy (ATTR-CM) live longer when the disease is diagnosed and treated earlier, with treatment benefits being much smaller in older patients and in those with more advanced disease, according to a study.
The study analyzed patient data from five U.S. centers between 2001 and 2021. Notably, Pfizer’s tafamidis-based therapies Vyndaqel and Vyndamax were the only approved treatments for ATTR-CM during this time frame, having entered the market in 2019.
Vyndaqel and Vyndamax reduced the risk of death by nearly one-third, according to the data. However, these medications were used by just over half of the patients, and their benefits became less clear with increasing age and worsening prognosis.
“This suggests that there may be continued modifiable risk in patients treated with tafamidis in the real world, opening the door for clinical trials for novel treatment options,” researchers wrote.
The study, “Changing Patterns of Diagnosis and Survival in Transthyretin Cardiac Amyloidosis: A Multicenter Cohort Study,” was published in the Journal of the American Heart Association.
Disease-modifying treatments extend survival in ATTR-CM
ATTR-CM is marked by the production of an unstable and misfolded TTR protein that forms toxic clumps in the heart muscle, weakening it. The disease can be hereditary, caused by mutations in the TTR gene, or wild type, which develops sporadically with age, most often in older adults.
In recent years, ATTR-CM diagnosis has increased because of better awareness and noninvasive diagnostic tests. While the approval of disease-modifying treatments (DMTs) has extended survival in ATTR-CM, clinical studies mainly included patients with earlier disease, resulting in fewer serious events.
In this study, a team of researchers in the U.S. set out to understand how ATTR-CM patients and their outcomes have changed over time, including with DMTs. They retrospectively analyzed data from 1,165 people diagnosed with ATTR-CM between December 2001 and October 2021 at one of five U.S. referral centers, and followed up through May 2024.
Participants’ median age was 78, and most were men (85.9%), white (77%), and diagnosed with wild‐type ATTR-CM (71%).
For comparisons over time, the researchers defined four eras: pre‐2010, 2010 to 2013, 2014 to 2017, and 2018 to 2021. Data showed that over time, more patients were diagnosed each year, and patients were older at diagnosis. Those with a more recent diagnosis were also significantly more likely to be white, have wild-type ATTR-CM, be diagnosed noninvasively, and have a lower New York Heart Association (NYHA) class, indicating less severe functional limitations.
Simultaneous health conditions, including obesity and high blood pressure, were more common in the more recent eras.
More patients diagnosed with earlier-stage disease in recent years
The National Amyloidosis Center (NAC) stage, a measure of ATTR-CM severity based on blood markers of heart and kidney function, remained similar over time. The Columbia stage, which combines data from NAC stage, NYHA class, and furosemide dosage (a medication commonly used in ATTR-CM patients), was also assessed.
Columbia stage data showed that in more recent eras, more patients were diagnosed with earlier-stage disease, mainly because they had lower NYHA class and required lower doses of furosemide, which helps remove excess fluid.
Patients were followed up for a median of 44.5 months (a little over 3.5 years). During that time, over half of patients (54%) died or required surgical treatment for heart failure, an outcome that the researchers termed all-cause death.
“All‐cause death was highest in the pre‐2010 [era] and improved in more recent eras,” the team wrote.
All-cause death dropped steadily in more recent years, with patients diagnosed between 2018 and 2021 living more than five years on average.
Earlier recognition coupled with tafamidis treatment has changed the trajectory of patients diagnosed with ATTR‐CM.
Treatment with Vyndaqel or Vyndamax was significantly linked to a lower risk of all-cause death, by 29%. In contrast, having a higher NAC stage, which indicates worse prognosis, was significantly linked to a higher risk of all-cause death, which doubled in those with stage 2 and increased fourfold in stage 3 patients compared with those with stage 1.
Further statistical analyses showed that “the protective effect of tafamidis with respect to all‐cause death is attenuated at higher NAC stages” and “as age increased,” the team wrote. This meant that Vyndaqel or Vyndamax generally worked best in younger patients and in those with earlier-stage disease at diagnosis.
These medications worked similarly in wild-type or genetic forms of the disease and in both men and women.
“Earlier recognition coupled with tafamidis treatment has changed the trajectory of patients diagnosed with ATTR‐CM,” the researchers wrote. “These data are important to understand the real‐world outcomes in patients with ATTR‐CM to help guide future clinical trial development.”
