A SYSTEMATIC LITERATURE REVIEW OF STUDIES EVALUATING CLINICAL OUTCOMES IN TRANSTHYRETIN AMYLOID CARDIOMYOPATHY (ATTR-CM)
Author(s)
Jaydeep Das, BSc, MSc1, Robert Bauer, PhD2, Mamoona Javed, MSc, MPhil3, Palvi Gupta, M.Pharm4.
1Novo Nordisk A/S, Bangalore, India, 2Novo Nordisk A/S, Bagsvaerd, Denmark, 3Clarivate, London, United Kingdom, 4Clarivate, Bangalore, United Kingdom.
1Novo Nordisk A/S, Bangalore, India, 2Novo Nordisk A/S, Bagsvaerd, Denmark, 3Clarivate, London, United Kingdom, 4Clarivate, Bangalore, United Kingdom.
OBJECTIVES: Comparative efficacy and safety evidence across transthyretin amyloid cardiomyopathy (ATTR-CM) treatments remains fragmented and inconsistently reported. We conducted a systematic literature review to identify clinical trials in patients with ATTR-CM, to provide an overview of available evidence.
METHODS: Embase, MEDLINE®, and the Cochrane Library were searched in February 2026, from database inception, and grey literature from 2023, to identify relevant randomized clinical trials (RCTs) and single-arm studies reporting efficacy and/or safety outcomes of any intervention in patients with ATTR-CM.
RESULTS: Nine RCTs (49 publications) and 15 single-arm trials (16 publications) evaluating multiple disease-modifying therapies in patients with ATTR-CM were included. The most commonly evaluated treatments were tafamidis (n=5 studies), acoramidis (n=3) and doxycycline (n=3). Large-scale Phase III, double-blind RCTs showed significant benefits on composite clinical endpoints incorporating all-cause mortality and cardiovascular hospitalisations with acoramidis (hazard ratio 0.58, 95% confidence interval 0.43-0.79, p<0.0005) and vutrisiran (hazard ratio 0.72, 95% confidence interval 0.56-0.93, p=0.01). Similarly, tafamidis, in a hierarchical analysis of all-cause mortality and frequency of cardiovascular-related hospitalisation, demonstrated a win ratio of 1.70 (p=0.0006). Two RCTs for patisiran and revusiran, respectively, showed no such benefits. Acoramidis, tafamidis, and vutrisiran led to significantly better 6-minute walking test results at 30 months than placebo (by 26.5 to 75.8 m), which nevertheless was a decline from baseline (−30.46 to −64.65 m). Quality of life, primarily assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ), showed significantly better scores than placebo at 30 months for acoramidis, tafamidis, and vutrisiran, although decreased from baseline. While adverse events were common, treatments were generally well-tolerated, with safety profiles often comparable with placebo.
CONCLUSIONS: While the evidence demonstrates that some current disease-modifying therapies for ATTR‑CM provide benefits over placebo, there remains a high unmet need for treatments that halt or reverse disease progression.
METHODS: Embase, MEDLINE®, and the Cochrane Library were searched in February 2026, from database inception, and grey literature from 2023, to identify relevant randomized clinical trials (RCTs) and single-arm studies reporting efficacy and/or safety outcomes of any intervention in patients with ATTR-CM.
RESULTS: Nine RCTs (49 publications) and 15 single-arm trials (16 publications) evaluating multiple disease-modifying therapies in patients with ATTR-CM were included. The most commonly evaluated treatments were tafamidis (n=5 studies), acoramidis (n=3) and doxycycline (n=3). Large-scale Phase III, double-blind RCTs showed significant benefits on composite clinical endpoints incorporating all-cause mortality and cardiovascular hospitalisations with acoramidis (hazard ratio 0.58, 95% confidence interval 0.43-0.79, p<0.0005) and vutrisiran (hazard ratio 0.72, 95% confidence interval 0.56-0.93, p=0.01). Similarly, tafamidis, in a hierarchical analysis of all-cause mortality and frequency of cardiovascular-related hospitalisation, demonstrated a win ratio of 1.70 (p=0.0006). Two RCTs for patisiran and revusiran, respectively, showed no such benefits. Acoramidis, tafamidis, and vutrisiran led to significantly better 6-minute walking test results at 30 months than placebo (by 26.5 to 75.8 m), which nevertheless was a decline from baseline (−30.46 to −64.65 m). Quality of life, primarily assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ), showed significantly better scores than placebo at 30 months for acoramidis, tafamidis, and vutrisiran, although decreased from baseline. While adverse events were common, treatments were generally well-tolerated, with safety profiles often comparable with placebo.
CONCLUSIONS: While the evidence demonstrates that some current disease-modifying therapies for ATTR‑CM provide benefits over placebo, there remains a high unmet need for treatments that halt or reverse disease progression.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
CO48
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Cardiovascular Disorders (including MI, Stroke, Circulatory)