Fabian Aus dem Siepen, Teresa Trenkwalder, Birgit Aßmus, Ingrid Kindermann, Daniel Lavall, Sebastian Spethmann, Lars Michel, Timon Hansen, Sebastian Kruck, Christoph Rischpler, Fabian Knebel, Stéphanie K Schwarting, Udo Bavendiek, Maria Papathanasiou, Ute Hegenbart, Ali Yilmaz, Katrin Hahn, Alexander Carpinteiro, Roman Pfister, Caroline Morbach
This consensus provides a practical framework for the specific treatment of ATTR-CM in Germany, aiming for early treatment initiation. Local standards and shared decision-making remain essential for the establishment of ATTR-CM therapy in an individual patient.
BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure. Three disease-modifying agents are now approved for treatment in Germany: the transthyretin (TTR) stabilizers tafamidis and acoramidis, and the TTR gene silencer vutrisiran. In the absence of head-to-head trials, practical guidance for individual treatment decisions is lacking.
METHODS: A multidisciplinary expert panel appointed by the German Society of Amyloid Diseases (DGAK) and the German Cardiac Society (DGK) performed a comprehensive review of pivotal randomized controlled trials, open-label extension studies, real-world data, and the approved German summaries of product characteristics to develop evidence-based consensus recommendations.
RESULTS: All three agents have demonstrated significant reductions in all-cause mortality and cardiovascular hospitalizations in phase 3 trials with comparable efficacy and tolerability profiles. Due to the absence of direct comparative studies, the panel concludes that tafamidis, acoramidis, and vutrisiran, based on the current scientific data, are considered similarly effective for most patients with confirmed ATTR-CM. An exception applies to patients with hereditary ATTR-CM and a mixed phenotype (concurrent cardiomyopathy and polyneuropathy), for whom vutrisiran is recommended as first-line therapy. Combination therapy is safe but, lacking randomized data regarding efficacy, cannot be recommended at present. Treatment decisions should incorporate patient preferences, comorbidities, mode of administration, and local regulatory frameworks. Regular monitoring using clinical parameters, biomarkers including TTR serum levels, and cardiac imaging is recommended.
CONCLUSIONS: This consensus provides a practical framework for the specific treatment of ATTR-CM in Germany, aiming for early treatment initiation. Local standards and shared decision-making remain essential for the establishment of ATTR-CM therapy in an individual patient.