Recent advances in the diagnostic methods and therapeutic strategies of transthyretin cardiac amyloidosis

Table 1 Novel promising targeted medical therapies of transthyretin amyloidosis cardiac amyloidosis which are being investigated in large clinical trials

Clinical trial	Intervention per group	Duration	Endpoints	Outcomes
ATTR-ACT NCT01994889	I1: 80 mg of tafamidis; I2: 20 mg of tafamidis; C: Placebo	30 months	Primary: All-cause mortality; Frequency of CV-related hospitalizations. Secondary: 6MWT; KCCQ-OS; CV-related mortality; Stabilized TTR after 1 month	Tafamidis was associated with: (1) Lower all-cause mortality than placebo [78 of 264 (29.5%) vs 76 of 177 (42.9%); HR, 0.70; 95%CI: 0.51-0.96]; (2) Lower rate of cardiovascular-related hospitalizations [relative risk ratio of 0.68 (0.48 per year vs 0.70 per year; 95%CI: 0.56-0.81)]; (3) Lower rate of decline in distance for the 6-minute walk test (P < 0.001); (4) Lower rate of decline in KCCQ-OS score (P < 0.001); and (5) Similar incidence and types of adverse events between groups
ATTRIBUTE-CM NCT03860935	I: 800 mg of acoramidis BID; C: Placebo	30 months	Primary: (1) 6MWT after 12 months; (2) All-cause mortality; (3) CV-related hospitalizations; (4) NT-proBNP; (5) 6MWT after 30 months; and (6) KCCQ-OS	(1) All-cause mortality, cumulative frequency of CV-related hospitalization, change in NT-proBNP, and change in 6-6MWT, had an overall win ratio favoring acoramidis (win ratio 1.8, 95%CI: 1.4-2.2, P < 0.0001); (2) All-cause mortality: 25.7% vs 29.5%; HR: 0.77, 95%CI: 0.54-1.10 (P = 0.15); (3) Adjusted mean factor change in NT-proBNP from baseline: 0.529 (95%CI: 0.46-0.60, P < 0.05); (4) Improvement from baseline in 6-minute walk distance: 39.6 m (95%CI: 21.1-58.2, P < 0.001); (5) CV-related hospitalization: 26.7% vs 42.6% (P < 0.0001); (6) Least means square change in KCCQ-OS: 9.94 points (95%CI: 5.97-13.91, P < 0.001); and (7) Composite of all-cause mortality and CV-related hospitalization: HR: 0.65, 95%CI: 0.50-0.83 (P = 0.0008; number needed to treat = 7)
CARDIO-TTRansfor NCT04136171	I: Eplontersen (sc) once every 4 weeks; C: Placebo	140 weeks	Primary: CV mortality and recurrent CV clinical events up to week 140. Secondary: 6MWT at week 121; KCCQ at week 121; all-cause mortality up to week 140	The trial is estimated to be completed by 2025
HELIOS-B NCT04153149	I: 25 mg of vutrisiran (sc) once every 3 months C: Placebo	30-36 months	Primary: All-cause mortality and recurrent CV clinical events at 30-36 months. Secondary: (1) 6MWT at month 30; (2) KCCQ at month 30; (3) Mean (LV) wall thickness at month 30; (4) GLS at month 30; (5) All-cause mortality; (6) Recurrent all-cause hospitalizations and urgent HF visits; and (7) NTproBNP at month 30	The trial is estimated to be completed by 2026
APOLLO-B NCT03997383	I: 0.3 mg/kg of patisiran once every 3 weeks; C: Placebo	12 months	Primary: 6MWT. Secondary: (1) KCCQ-OS; (2) Composite of death from any cause, CV events, and 6MWT; and (3) Composite of death from any cause, hospitalizations for any cause, and urgent HF visits	Patisiran was associated with: (1) Lower decline in the 6MWT (Hodges-Lehmann estimate of median difference, 14.69 m; 95%CI: 0.69-28.69; P = 0.02); (2) Increase of the KCCQ-OS (least-squares mean difference, 3.7 points; 95%CI: 0.2-7.2; P = 0.04); and (3) Infusion-related reactions, arthralgia, and muscle spasms more often in the patisiran group compared to placebo
NI006 phase 1 NCT04360434	I: 0.3 to 60 mg/kg of NI006 IV every 4 weeks; C: Placebo	4 months	Safety and pharmacokinetic profile; Cardiac imaging studies	NI006 was associated with no apparent drug-related serious adverse events in this phase 1 trial

6MWT: 6-minute walk test; BID: Bis in die; C: Control group; CI: Confidence interval; CV: Cardiovascular; GLS: Global longitudinal strain; HF: Heart failure; HR: Hazard ratio; I: Intervention group; IV: Intravenous; KCCQ-OS: Kansas City Cardiomyopathy Questionnaire Overall Summary; LV: Left ventricular; NTproBNP: N-terminal prohormone B-type Natriuretic Peptide; SC: Subcutaneous; TTR: Transthyretin.