{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T09:40:15Z","timestamp":1793094015055,"version":"4.5.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T00:00:00Z","timestamp":1605139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Heart Fail"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Tafamidis is an effective treatment for transthyretin amyloid cardiomyopathy (ATTR\u2010CM) in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR\u2010ACT). While ATTR\u2010ACT was not designed for a dose\u2010specific assessment, further analysis from ATTR\u2010ACT and its long\u2010term extension study (LTE) can guide determination of the optimal dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      In ATTR\u2010ACT, patients were randomized (2:1:2) to tafamidis 80\u2009mg, 20\u2009mg, or placebo for 30\u2009months. Patients completing ATTR\u2010ACT could enrol in the LTE (with placebo\u2010treated patients randomized to tafamidis 80 or 20\u2009mg; 2:1) and all patients were subsequently switched to high\u2010dose tafamidis. All\u2010cause mortality was assessed in ATTR\u2010ACT combined with the LTE (median follow\u2010up 51\u2009months). In ATTR\u2010ACT, the combination of all\u2010cause mortality and cardiovascular\u2010related hospitalizations over 30\u2009months was significantly reduced with tafamidis 80\u2009mg (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0030) and 20\u2009mg (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0048) vs. placebo. All\u2010cause mortality vs. placebo was reduced with tafamidis 80\u2009mg [Cox hazards model (95% confidence interval): 0.690 (0.487\u20130.979),\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0378] and 20\u2009mg [0.715 (0.450\u20131.137),\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.1564]. The mean (standard error) change in N\u2010terminal pro\u2010B\u2010type natriuretic peptide from baseline to Month 30 was \u22121170.51 (587.31) (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0468) with tafamidis 80 vs. 20\u2009mg. In ATTR\u2010ACT combined with the LTE there was a significantly greater survival benefit with tafamidis 80 vs. 20\u2009mg [0.700 (0.501\u20130.979),\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0374]. Incidence of adverse events in both tafamidis doses were comparable to placebo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Tafamidis, both 80 and 20\u2009mg, effectively reduced mortality and cardiovascular\u2010related hospitalizations in patients with ATTR\u2010CM. The longer\u2010term survival data and the lack of dose\u2010related safety concerns support tafamidis 80\u2009mg as the optimal dose.<\/jats:p>\n                    <jats:p>\n                      Clinical Trial Registration:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      NCT01994889; NCT02791230.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2027","type":"journal-article","created":{"date-parts":[[2020,10,18]],"date-time":"2020-10-18T07:26:25Z","timestamp":1603005985000},"page":"277-285","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":213,"title":["Efficacy and safety of tafamidis doses in the\n                    <scp>Tafamidis in Transthyretin Cardiomyopathy Clinical Trial<\/scp>\n                    (\n                    <scp>ATTR\u2010ACT<\/scp>\n                    ) and long\u2010term extension study"],"prefix":"10.1093","volume":"23","author":[{"given":"Thibaud","family":"Damy","sequence":"first","affiliation":[{"name":"French Referral Center for Cardiac Amyloidosis, Amyloidosis Mondor Network, GRC Amyloid Research Institute and Department of Cardiology, all at APHP, CHU Henri Mondor; and INSERM U955, Clinical Investigation Center 006, and DHU ATVB  Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Garcia\u2010Pavia","sequence":"additional","affiliation":[{"name":"Hospital Universitario Puerta de Hierro Majadahonda, CIBERCV  Madrid Spain"},{"name":"Universidad Francisco de Vitoria, Pozuelo de Alarcon  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazen","family":"Hanna","sequence":"additional","affiliation":[{"name":"Amyloidosis Centre Cleveland Clinic  Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Judge","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina  Charleston SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giampaolo","family":"Merlini","sequence":"additional","affiliation":[{"name":"Amyloidosis Center IRCCS Policlinico San Matteo and University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balarama","family":"Gundapaneni","sequence":"additional","affiliation":[{"name":"Pfizer  Groton CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terrell A.","family":"Patterson","sequence":"additional","affiliation":[{"name":"Pfizer  Groton CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Riley","sequence":"additional","affiliation":[{"name":"Pfizer  Groton CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey H.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Pfizer Inc  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marla B.","family":"Sultan","sequence":"additional","affiliation":[{"name":"Pfizer Inc  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Witteles","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine  Stanford CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,11,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.078915"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2010.67"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02190707"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199702133360703"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(92)90672-X"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr383"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-015-9613-9"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/openhrt-2015-000289"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs123"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-016-0040-x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1121005109"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.113.000890"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.659912"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1805689"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.116.003815"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12561"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.789"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19990615)18:11<1341::AID-SIM129>3.0.CO;2-7"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.166.1.at1102"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(00)00531-3"},{"key":"e_1_2_7_22_1","unstructured":"Social Security Administration. 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