Personalizing Treatment in ATTR-CM

Summary for Physicians: Selecting Treatment for Patients With ATTR-CM

With several disease-modifying therapies now available for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM), selecting the appropriate treatment for individual patients is a crucial decision. Dr Soman discusses factors to consider when choosing between available options:

1. Disease Severity and Progression:
   1. Early vs late-stage disease: For patients with early-stage ATTR-CM, transthyretin stabilizers such as tafamidis and acoramidis may be preferred, as they help stabilize the TTR protein and prevent further amyloid deposition. These are particularly useful in patients with minimal organ damage. In later stages, when significant cardiac involvement is present, transthyretin silencers such as patisiran, vutrisiran, and inotersen may be more beneficial, as they actively reduce the production of abnormal TTR proteins and help manage more advanced disease.
2. Treatment Goals:
   1. Symptom control: If the goal is to stabilize or prevent progression of symptoms (eg, reducing hospitalizations or improving heart failure symptoms), tafamidis or acoramidis may be appropriate options. These stabilizers have demonstrated efficacy in improving survival and reducing hospitalizations in patients with heart failure due to ATTR-CM.
   2. Disease modification: If reducing the production of misfolded TTR proteins is the primary goal, especially in patients with rapidly progressing disease, silencer therapies (eg, patisiran, vutrisiran, or inotersen) may be considered. These therapies lower TTR levels and can help slow disease progression in more advanced stages.
3. Patient Characteristics:
   1. Comorbidities: The presence of other health conditions, such as kidney disease, may influence the choice of therapy. For instance, vutrisiran has a favorable dosing schedule (subcutaneous every 3 months) and a potentially better safety profile, making it an appealing option for patients with comorbid conditions or those who have difficulty with more frequent injections.
   2. Age and tolerability: Some patients may have difficulty tolerating certain therapies due to adverse effects. For example, inotersen, although effective, may be associated with more frequent injection site reactions and requires careful monitoring due to its risk of thrombocytopenia. In contrast, vutrisiran, with its less-frequent dosing schedule, may be easier for patients to manage.
4. Patient Preferences:
   1. Administration: The frequency of administration is an important consideration. Vutrisiran, with its quarterly dosing, may be more convenient for patients than daily or weekly treatments such as inotersen and patisiran. In some cases, patient preference for less-frequent dosing can significantly impact adherence and quality of life.
5. Clinical Evidence:
   1. The selection of therapy also relies on the available clinical data. For example, tafamidis and vutrisiran have robust evidence supporting their use in reducing hospitalizations and improving survival, making them strong first-line options in many cases. Acoramidis, with positive results from the ATTRibute-CM trial, also demonstrates efficacy in stabilizing the disease, though its role in therapy will be better defined as more data become available.

Conclusion: When choosing a treatment for ATTR-CM, it is essential to consider disease stage, progression, patient comorbidities, and preferences. By tailoring treatment to these factors, physicians can optimize patient outcomes and manage this complex and progressive disease more effectively.