In cardiac ATTR amyloidosis, amyloid is deposited in the myocardium by monomers of the transthyretin (TTR) protein (= pre-albumin). The TTR protein is normally a tetramer (four smaller proteins form a stable large protein). In this disease, these tetramers break down into four small proteins (monomers) that precipitate as amyloid fibrils.

Read more: Specific cardiomyopathies – cardiac amyloidosis .

These drugs stabilize these unstable TTR proteins so that they no longer break down into monomers and then precipitate much less in the myocardium to amyloid. The already present amyloidosis will therefore not or only minimally disappear with this treatment. That is why it is very important that this therapy is started at an early stage of the disease.

Medicines:

• Tafamidis (Vyndaqel): partial selective stabilization of the TTR proteins.
• Acoramidis (Beyonttra): more potent, almost complete selective stabilization of the TTR proteins.

Slowing disease progression by preventing further deposition of TTR monomers in the myocardium.

Trials:

• Tafamidis (Vyndaqel): ATTR-ACT trial (NEJM, 2018), ATTR-ACT LTE (Circulation Heart Failure, 2022).
• Acoramidis (Beyonttra): ATTRibute-CM trial (NEJM, 2024).

Similar beneficial effects were demonstrated with both products in the studies, especially in NYHA I-II patients:

• Stabilization and slower decline in exercise capacity and quality of life.
• A less increasing NT-proBNP.
• Reduction in hospital admissions for heart failure after several months of treatment.
• With a longer treatment duration > 1.5 years, there is also a reduction in mortality.

These effects are maintained and increase after almost 5 years of treatment with tafamidis ( ATTR-ACT LTE).

These effects were not present in patients with more advanced disease and already NYHA class III.

There are no studies available yet with a direct comparison between tafamidis and acoramidis.

Treatment of both wild-type and hereditary forms of cardiac ATTR amyloidosis in early-stage disease, NYHA class I or II.

Available products:

• Tafamidis (Vyndaqel), oral, 61 mg per day.
• Acoramidis (Beyonttra), orally, 356 mg 2x 2 tablets per day. Not yet available in Belgium in May 2025. This is expected by the end of 2025.

Reimbursement for tafamidis (Vyndaqel), in Belgium since 10-2021:

• To be requested by a cardiologist.
• Conditions:
  • Few symptoms of dyspnea, NYHA class I or II.
  • Abnormal bone scintigraphy (Perugini score 2 or 3).
  • No evidence for an underlying gammopathy and therefore AL amyloidosis (after blood and urine tests).
  • Genetic research of the TTR gene.
• Medication can be collected from the hospital pharmacy.

No dosage adjustment is necessary in the elderly or with renal impairment.

Therapy should be started at the earliest possible stage of the disease. Patients who are already in NYHA class III at the start are no longer eligible for reimbursement. In the event of signs of progressive heart failure (evolution to permanent NYHA class III or IV), therapy should be stopped and reimbursement will lapse.

This is a very expensive treatment. Rational use is needed. Given that this is mainly a long-term treatment with only prognostic benefits after a treatment period of more than 1.5 years, this therapy may only be given to patients with:

• A still sufficiently good functional and cognitive condition.
• Not too many other comorbidities that negatively affect life expectancy in the short to medium term.
• Not too old an age. This is a relative criterion, whereby the general and functional condition (biological age) must be taken into account.

Little to none.

Sometimes mild gastrointestinal discomfort (flatulence, diarrhea).

Acoramidis: gout.

• Progressive heart failure, NYHA III-IV.
• However, this disease does not occur at a younger age.