{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T18:29:28Z","timestamp":1787077768430,"version":"build-2736575974"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Acoramidis achieves near-complete (\u226590%) transthyretin stabilization and is approved to reduce cardiovascular-related mortality and hospitalization in transthyretin amyloid cardiomyopathy. Its effects on kidney function are not well characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Data from randomized phase 2 (N=49) and phase 3 (N=632) studies in transthyretin amyloid cardiomyopathy were included. The estimated glomerular filtration rate (eGFR) slope was generated using a linear spline mixed-effects model. The urinary albumin-to-creatinine ratio was measured longitudinally. Relationships between changes in kidney function and clinical outcomes were explored using Cox proportional hazards models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Acoramidis initiation resulted in a modest acute dip in eGFR that was dose-dependent, reversible, and not associated with adverse kidney-related events. At Day 28, the mean (\u00b1SE) dip in eGFR from baseline with acoramidis was 8.5\u00b10.48 mL\/min per 1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      ; the placebo-corrected reduction in the urinary albumin-to-creatinine ratio was 15.5% (95% CI, 0.4%\u201328.4%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.044). The rate of decline in kidney function (chronic eGFR slope) was significantly improved with acoramidis versus placebo (\u22121.01 versus \u22123.48 mL\/min per 1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      per year;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001), and the reduction in the urinary albumin-to-creatinine ratio was sustained (13.7% [95% CI, 1.7%\u201324.2%];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.026) over time. Concomitant tafamidis use did not influence the chronic eGFR slope in either arm. Comparing acoramidis versus placebo subgroups with acute eGFR dips \u2265 the median (4.89 mL\/min per 1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      ) favored acoramidis for all-cause mortality or cardiovascular-related hospitalization (hazard ratio, 0.42 [95% CI, 0.22\u20130.78];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.006;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      interaction=0.043) and cardiovascular-related hospitalization (hazard ratio, 0.34 [95% CI, 0.17\u20130.66];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.002,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      interaction=0.025). Within the placebo arm, eGFR dips portended worse outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Acoramidis initiation resulted in an acute dip in eGFR and reductions in both the chronic eGFR slope and urinary albumin-to-creatinine ratio versus placebo without adverse kidney-related events. Acoramidis effects on kidney function may be mediated through direct kidney-protective hemodynamic effects. Importantly, the acute dip in eGFR was associated with a reduced risk of adverse clinical outcomes within the first year.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>REGISTRATION:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifiers: NCT03458130, NCT03536767, NCT03860935, NCT04988386.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circheartfailure.126.014656","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T09:02:19Z","timestamp":1782982939000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Acoramidis on Kidney Function in Transthyretin Amyloid Cardiomyopathy"],"prefix":"10.1161","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5285-0419","authenticated-orcid":true,"given":"Jeffrey M.","family":"Testani","sequence":"first","affiliation":[{"name":"Section of Cardiovascular Medicine, Yale University, New Haven, CT (J.M.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3407-0248","authenticated-orcid":true,"given":"Daniel P.","family":"Judge","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Medical University of South Carolina, Charleston (D.P.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9375-0596","authenticated-orcid":true,"given":"Barry A.","family":"Borlaug","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic and Foundation, Rochester, MN (B.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4164-0429","authenticated-orcid":true,"given":"David","family":"Cherney","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada (D.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4919-0146","authenticated-orcid":true,"given":"Zachary L.","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Lipscomb University College of Pharmacy, Nashville, TN (Z.L.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6174-9232","authenticated-orcid":true,"given":"Julian D.","family":"Gillmore","sequence":"additional","affiliation":[{"name":"National Amyloidosis Centre, Division of Medicine, University College London, Royal Free Hospital, United Kingdom (J.D.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1530-7115","authenticated-orcid":true,"given":"Julia B.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN (J.B.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2123-4964","authenticated-orcid":true,"given":"Scott H.","family":"Adler","sequence":"additional","affiliation":[{"name":"BridgeBio Pharma, Inc., San Francisco, CA (S.H.A., X.C., A.C., J.C.F., L.K., K.X.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0337-2069","authenticated-orcid":true,"given":"Xiaofan","family":"Cao","sequence":"additional","affiliation":[{"name":"BridgeBio Pharma, Inc., San Francisco, CA (S.H.A., X.C., A.C., J.C.F., L.K., 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