**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Amrut Ambardekar, University of Colorado Anschutz Medical Campus, Aurora, CO

**Main Body of the Abstract**
Background: Lower serum TTR levels are associated with greater cardiovascular mortality (CVM) risk in ATTR-CM. This interpretation is from retrospective analyses and has not been supported prospectively.
Methods: Acoramidis – a novel, potent, near-complete TTR stabilizer that increases serum TTR (prealbumin) – improved clinical outcomes in ATTRibute-CM. The relationship between change from baseline (CFB) in Day 28 serum TTR levels and CVM was analyzed with a multivariate stratified Cox proportional hazards model with baseline 6MWT and CFB in TTR level at Day 28 as covariates, and was stratified by treatment group, baseline TTR < or ≥ 20 mg/dL, and randomization stratification factors of genotype (variant vs. wild type), NT-proBNP level (≤ or >3000pg/mL) and eGFR level (< or  ≥45 mL/min).
Results: For subjects with Day 28 CFB TTR values, LS mean (95% CI) CFB was 9.09 (8.65, 9.54) and -0.52 (-1.15, 0.12) mg/dL in the acoramidis and placebo arms, respectively (p<0.0001); at Month 30, LS mean (95% CI) CFB was 5.78 (5.01, 6.54) and -1.32 (-2.38, -0.26) mg/dL, respectively (p<0.0001). Each 1 mg/dL CFB TTR increase at Day 28 post therapeutic intervention was associated with a 5.5% reduction in CVM risk over 30 months. These observations were independent of baseline TTR levels (Table).
Conclusion: To our knowledge, this is the first prospective demonstration of the relationship between CFB in TTR and subsequent risk of CVM in ATTR-CM. We demonstrate that a greater increase in TTR is significantly associated with lower risk of CVM.



**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Amrut Ambardekar, University of Colorado Anschutz Medical Campus, Aurora, CO

**Main Body of the Abstract**
**Background**: Lower serum TTR levels are associated with greater cardiovascular mortality (CVM) risk in ATTR-CM. This interpretation is from retrospective analyses and has not been supported prospectively.
**Methods**: Acoramidis – a novel, potent, near-complete TTR stabilizer that increases serum TTR (prealbumin) – improved clinical outcomes in ATTRibute-CM. The relationship between change from baseline (CFB) in Day 28 serum TTR levels and CVM was analyzed with a multivariate stratified Cox proportional hazards model with baseline 6MWT and CFB in TTR level at Day 28 as covariates, and was stratified by treatment group, baseline TTR < or ≥ 20 mg/dL, and randomization stratification factors of genotype (variant vs. wild type), NT-proBNP level (≤ or >3000pg/mL) and eGFR level (< or  ≥45 mL/min).
**Results**: For subjects with Day 28 CFB TTR values, LS mean (95% CI) CFB was 9.09 (8.65, 9.54) and -0.52 (-1.15, 0.12) mg/dL in the acoramidis and placebo arms, respectively (p<0.0001); at Month 30, LS mean (95% CI) CFB was 5.78 (5.01, 6.54) and -1.32 (-2.38, -0.26) mg/dL, respectively (p<0.0001). Each 1 mg/dL CFB TTR increase at Day 28 post therapeutic intervention was associated with a 5.5% reduction in CVM risk over 30 months. These observations were independent of baseline TTR levels (Table).
**Conclusion:** To our knowledge, this is the first prospective demonstration of the relationship between CFB in TTR and subsequent risk of CVM in ATTR-CM. We demonstrate that a greater increase in TTR is significantly associated with lower risk of CVM.



Treatment-related Early Increase in Serum TTR is Associated with Lower Cardiovascular Mortality in ATTR-CM: Insights from ATTRibute-CM PC124 (#292)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.