The U.S. Food and Drug Administration (FDA) has approved two TTR stabilizers for treating ATTR-CM:
acoramidis (Attruby)
tafamidis (Vyndaquel, Vyndamax)
Both medications are administered orally. Acoramidis doses are 712 milligrams (mg), taken twice daily. Tafamidis is available in two strengths. The dose for tafamidis free acid is 61 mg, taken once daily, while tafamidis meglumine is 80 mg (20 mg per capsule), taken once daily.
How They Work
TTR stabilizers help slow disease progression by preventing TTR proteins from misfolding and forming more amyloid deposits.
“Normally, TTR [proteins] are shaped like a group of four parts stuck together, called a tetramer,” says Ajay Vallakati, MBBS, an internal medicine physician who specializes in advanced heart failure at the Ohio State University Wexner Medical Center in Columbus. But in people with ATTR-CM, these proteins break apart into single pieces, creating clumps (called fibrils) that build up in the heart and make it stiff.
Medications like acoramidis and tafamidis attach to the thyroxine-binding sites of TTR proteins, helping them maintain their normal four-part shape and preventing them from breaking apart and forming amyloid fibrils, says Dr. Vallakati.
The Results
By slowing or preventing the accumulation of TTR proteins, TTR stabilizers reduce the risk of a heart health crisis and early death.
The FDA approved acoramidis in November 2024 based on the results of a 30-month randomized, controlled trial of over 600 people with wild-type or hereditary ATTR-CM. In this trial, people who received 800 mg of acoramidis twice daily experienced significantly better outcomes than those who received a placebo: 81 percent of participants who took acoramidis survived versus 74 percent in the placebo group, and those who took acoramidis were hospitalized for heart-related issues at half the rate of those in the placebo group.
Tafamidis was approved by the FDA in May 2019. In its 30-week clinical trial of 441 people with ATTR-CM, tafamidis was also associated with greater survival rates than the placebo (70.5 percent versus 57 percent) and fewer heart-related hospitalizations than the placebo (0.48 versus 0.7 per year).
These findings align with Vallakati’s practical experience: “We see that people need fewer hospital visits for worsening heart failure after a year [on these medications],” he says. Patients also notice improvements in their quality of life. They feel better and can do more physical activity around this same time, says Vallakati.
Side Effects and Considerations
TTR stabilizers have potential side effects, though they’re generally mild.
Common side effects associated with acoramidis include diarrhea and stomach pain. Meanwhile, tafamidis has no known side effects, according to prescribing information. That said, some research suggests it may cause diarrhea, stomach pain, headache, urinary tract infections, and swelling in the extremities.
TTR stabilizers are generally well tolerated, which makes them a practical option for many older patients, says Andrew Scott Rudin, MD, a board-certified cardiologist with Natural Heart Doctor, a holistic heart health clinic in Scottsdale, Arizona.
However, TTR stabilizers may be less effective in patients with more advanced or rapidly progressing disease. “In those cases, slowing new amyloid formation may not be enough to meaningfully change symptoms or outcomes,” says Dr. Rudin.