PMID- 36723935 OWN - NLM STAT- MEDLINE DCOM- 20230419 LR - 20240202 IS - 2380-6591 (Electronic) IS - 2380-6583 (Print) VI - 8 IP - 3 DP - 2023 Mar 1 TI - Association of Tafamidis With Health Status in Patients With ATTR Cardiac Amyloidosis: A Post Hoc Analysis of the ATTR-ACT Randomized Clinical Trial. PG - 275-280 LID - 10.1001/jamacardio.2022.5251 [doi] AB - IMPORTANCE: Tafamidis reduced all-cause mortality and cardiovascular-related hospitalizations and minimized patient-reported health status deterioration at 30 months in patients with transthyretin (ATTR) amyloidosis. However, the clinical significance of health status changes remains unclear, particularly in patients with New York Heart Association (NYHA) class III symptoms who experienced more cardiovascular-related hospitalizations than those with NYHA class I-II symptoms. OBJECTIVE: To evaluate the health status of patients taking tafamidis with baseline NYHA class III symptoms. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial post hoc analysis evaluated data for patients with transthyretin (ATTR) cardiac amyloidosis and NYHA class I-III symptoms at baseline who were enrolled in ATTR-ACT, a placebo-controlled study of tafamidis held at 48 sites in 13 countries. INTERVENTIONS: Tafamidis meglumine, 80 mg or 20 mg (pooled cohort), vs placebo. MAIN OUTCOMES AND MEASURES: Established thresholds for clinical benefit on the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) were used to define response groups (very large decline to very large improvement); the proportion of patients in each group was calculated within each baseline NYHA class. RESULTS: Among 441 patients (264 tafamidis, 177 placebo), the mean (SD) age was 74.3 (7.0) years; 398 (90%) were male and 43 (10%) were female. Mean (SD) baseline KCCQ-OS scores were 67.3 (21.4) in the tafamidis group and 65.9 (21.7) in the placebo group (range: 0-100, with 100 indicating the best health). There was a significant shift toward better KCCQ-OS scores in patients receiving tafamidis (odds ratio for 10-point improvement 2.4; 95% CI, 1.6-3.4; P < .001). More patients taking tafamidis were alive and not worse at all time points (37% vs 15% at month 30). These findings were similar in patients with NYHA class III symptoms. In patients with NYHA class III symptoms alive at 30 months, improvements in health status were more common (35% vs 10%) and declines were less common (38% vs 57%) with tafamidis vs placebo. CONCLUSIONS AND RELEVANCE: In ATTR-ACT, although patients with baseline NYHA class III symptoms had worse overall outcomes, treatment with tafamidis yielded better health status compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01994889. FAU - Sperry, Brett W AU - Sperry BW AD - Saint Luke's Mid America Heart Institute, Kansas City, Missouri. AD - University of Missouri-Kansas City, Kansas City. FAU - Hanna, Mazen AU - Hanna M AD - Cleveland Clinic, Cleveland, Ohio. FAU - Maurer, Mathew S AU - Maurer MS AD - Columbia University Irving Medical Center, New York, New York. FAU - Nativi-Nicolau, Jose AU - Nativi-Nicolau J AD - Mayo Clinic Jacksonville, Jacksonville, Florida. FAU - Floden, Lysbeth AU - Floden L AD - Clinical Outcomes Solutions, Chicago, Illinois. FAU - Stewart, Michelle AU - Stewart M AD - Pfizer, New York, New York. FAU - Wyrwich, Kathleen W AU - Wyrwich KW AD - Pfizer, New York, New York. FAU - Barsdorf, Alexandra I AU - Barsdorf AI AD - Clinical Outcomes Solutions, Chicago, Illinois. FAU - Kapadia, Heli AU - Kapadia H AD - Clinical Outcomes Solutions, Chicago, Illinois. FAU - Spertus, John A AU - Spertus JA AD - Saint Luke's Mid America Heart Institute, Kansas City, Missouri. AD - University of Missouri-Kansas City, Kansas City. LA - eng SI - ClinicalTrials.gov/NCT01994889 GR - R01 HL139671/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Cardiol JT - JAMA cardiology JID - 101676033 RN - 8FG9H9D31J (tafamidis) RN - 0 (Prealbumin) RN - 0 (Benzoxazoles) SB - IM MH - Humans MH - Male MH - Female MH - Aged MH - *Prealbumin MH - *Amyloidosis MH - Benzoxazoles/therapeutic use MH - Health Status PMC - PMC9996391 COIS- Conflict of Interest Disclosures: Dr Sperry reported consulting and/or speaking fees from Pfizer, Alnylam, and Eidos/BridgeBio outside the submitted work. Dr Hanna reported serving on an advisory board for Pfizer, Alnylam, Ionis, and Eidos outside the submitted work. Dr Maurer reported grant support from the National Institutes of Health (R01HL139671); consulting income from Eidos, Prothena, Ionis, Alnylam, Novo Nordisk, and Intellia; and institutional support in the form of clinical trial funding from Pfizer, Ionis, Eidos, and Alnylam. Dr Nativi-Nicolau reported funding for research from Akcea/Ionis, Pfizer, and Eidos Therapeutics and consulting fees from Alnylam Pharmaceuticals, Pfizer, and Akcea/Ionis. Dr Floden reported financial support for statistical analysis from Pfizer during the conduct of the study. Dr Stewart reported being an employee of and holding stock options in Pfizer during the conduct of the study. Dr Wyrwich reported being a former employee of Pfizer, holding stock and stock options in Pfizer and Eli Lilly, and being a current employee of Bristol Myers Squibb. Dr Barsdorf reported financial support for statistical analysis from Pfizer and owning stock in Pfizer. Dr Spertus reported a patent for copyright to the SAQ, KCCQ, and PAQ with royalties paid; grants from Abbott Vascular, Janssen, and Bristol Myers Squibb; consulting for Janssen, Bristol Myers Squibb, Terumo, Bayer, Merck, Imbria, UnitedHealthcare, and Sanofi; and serving on the board of directors of Blue Cross Blue Shield of Kansas City. No other disclosures were reported. EDAT- 2023/02/02 06:00 MHDA- 2023/04/19 06:41 PMCR- 2024/02/01 CRDT- 2023/02/01 11:33 PHST- 2023/04/19 06:41 [medline] PHST- 2023/02/02 06:00 [pubmed] PHST- 2023/02/01 11:33 [entrez] PHST- 2024/02/01 00:00 [pmc-release] AID - 2801004 [pii] AID - hbr220012 [pii] AID - 10.1001/jamacardio.2022.5251 [doi] PST - ppublish SO - JAMA Cardiol. 2023 Mar 1;8(3):275-280. doi: 10.1001/jamacardio.2022.5251.