{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T14:01:21Z","timestamp":1794492081331,"version":"4.9.1"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Cardior Pharmaceuticals GmbH, a Novo Nordisk Company."},{"name":"Employee of Novo Nordisk A\/S"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    MicroRNA-132 (miR-132) is a central regulator of adverse cardiac remodeling. Here we evaluated CDR132L, a synthetic antisense oligonucleotide miR-132 inhibitor, in a multinational, randomized, double-blind, placebo-controlled phase 2 trial (HF-REVERT) in patients with recent myocardial infarction (MI) and left ventricular (LV) systolic dysfunction. Within 3\u201314\u2009days after MI, 294 patients were randomized to receive CDR132L 5\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    , CDR132L 10\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    or placebo as three intravenous doses at 4-week intervals plus guideline-directed therapy. In total, 280 patients (245 men and 35 women) who received at least one dose of the study drug were included in the modified intention-to-treat population. CDR132L was well tolerated, with no hepatic, renal, hematologic or cardiac toxicity signals. The primary endpoint\u2014the percentage change in LV end-systolic volume index at 6\u2009months\u2014improved in all groups but did not differ significantly between the CDR132L groups (5\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    and 10\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) and the placebo group. Secondary endpoints, including LV ejection fraction, global longitudinal strain and N-terminal pro B-type natriuretic peptide, were also not significantly different between the CDR132L and placebo groups. Prespecified exploratory analyses suggested potential benefits of CDR132L treatment in patients with advanced adverse remodeling at baseline, supporting further evaluation of CDR132L, including in chronic heart failure conditions. ClinicalTrials.gov:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\/study\/NCT05350969\" ext-link-type=\"uri\">NCT05350969<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41591-026-04408-4","type":"journal-article","created":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T11:02:10Z","timestamp":1778410930000},"page":"2654-2661","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The microRNA inhibitor CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: a randomized phase 2 trial"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9341-117X","authenticated-orcid":false,"given":"Johann","family":"Bauersachs","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3698-9597","authenticated-orcid":false,"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0805-8683","authenticated-orcid":false,"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9523-3787","authenticated-orcid":false,"given":"Isabel","family":"Antorrena-Miranda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4775-9140","authenticated-orcid":false,"given":"Rudolf A.","family":"de Boer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerasimos","family":"Filippatos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5347-7441","authenticated-orcid":false,"given":"Tim","family":"Friede","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfried","family":"Hauke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Ponikowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6387-1351","authenticated-orcid":false,"given":"Orly","family":"Vardeny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Altschul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gamborg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasper","family":"Vinther","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4360-1511","authenticated-orcid":false,"given":"Thomas","family":"Thum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,10]]},"reference":[{"key":"4408_CR1","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.1056\/NEJMra1606915","volume":"376","author":"JL Anderson","year":"2017","unstructured":"Anderson, J. L. & Morrow, D. A. Acute myocardial infarction. N. Engl. J. Med. 376, 2053\u20132064 (2017).","journal-title":"N. Engl. J. Med."},{"key":"4408_CR2","doi-asserted-by":"publisher","first-page":"2549","DOI":"10.1093\/eurheartj\/ehac223","volume":"43","author":"S Frantz","year":"2022","unstructured":"Frantz, S., Hundertmark, M. J., Schulz-Menger, J., Bengel, F. M. & Bauersachs, J. Left ventricular remodelling post-myocardial infarction: pathophysiology, imaging, and novel therapies. Eur. Heart J. 43, 2549\u20132561 (2022).","journal-title":"Eur. Heart J."},{"key":"4408_CR3","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1056\/NEJMra072139","volume":"358","author":"JA Hill","year":"2008","unstructured":"Hill, J. A. & Olson, E. N. Cardiac plasticity. N. Engl. J. Med. 358, 1370\u20131380 (2008).","journal-title":"N. Engl. J. Med."},{"key":"4408_CR4","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14349-2","volume":"11","author":"A Foinquinos","year":"2020","unstructured":"Foinquinos, A. et al. Preclinical development of a miR-132 inhibitor for heart failure treatment. Nat. Commun. 11, 633 (2020).","journal-title":"Nat. Commun."},{"key":"4408_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2090","volume":"3","author":"A Ucar","year":"2012","unstructured":"Ucar, A. et al. The miRNA-212\/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy. Nat. Commun. 3, 1078 (2012).","journal-title":"Nat. Commun."},{"key":"4408_CR6","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1093\/eurheartj\/ehaa791","volume":"42","author":"S Batkai","year":"2021","unstructured":"Batkai, S. et al. CDR132L improves systolic and diastolic function in a large animal model of chronic heart failure. Eur. Heart J. 42, 192\u2013201 (2021).","journal-title":"Eur. Heart J."},{"key":"4408_CR7","doi-asserted-by":"publisher","first-page":"2923","DOI":"10.1016\/j.jacc.2021.04.028","volume":"77","author":"R Hinkel","year":"2021","unstructured":"Hinkel, R. et al. AntimiR-132 attenuates myocardial hypertrophy in an animal model of percutaneous aortic constriction. J. Am. Coll. Cardiol. 77, 2923\u20132935 (2021).","journal-title":"J. Am. Coll. Cardiol."},{"key":"4408_CR8","doi-asserted-by":"publisher","first-page":"qyaf088","DOI":"10.1093\/ehjimp\/qyaf088","volume":"3","author":"S Batkai","year":"2025","unstructured":"Batkai, S. et al. MiR-132 inhibition improves myocardial strain in a large animal model of chronic left ventricular adverse remodelling. Eur. Heart J. Imaging Methods Pract. 3, qyaf088 (2025).","journal-title":"Eur. Heart J. Imaging Methods Pract."},{"key":"4408_CR9","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1093\/eurheartj\/ehaa898","volume":"42","author":"J T\u00e4ubel","year":"2021","unstructured":"T\u00e4ubel, J. et al. Novel antisense therapy targeting microRNA-132 in patients with heart failure: results of a first-in-human phase 1b randomized, double-blind, placebo-controlled study. Eur. Heart J. 42, 178\u2013188 (2021).","journal-title":"Eur. Heart J."},{"key":"4408_CR10","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1002\/ejhf.3139","volume":"26","author":"J Bauersachs","year":"2024","unstructured":"Bauersachs, J. et al. Efficacy and safety of CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: rationale and design of the HF-REVERT trial. Eur. J. Heart Fail. 26, 674\u2013682 (2024).","journal-title":"Eur. J. Heart Fail."},{"key":"4408_CR11","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.jacc.2020.11.008","volume":"77","author":"CG Santos-Gallego","year":"2021","unstructured":"Santos-Gallego, C. G. et al. Randomized trial of empagliflozin in nondiabetic patients with heart failure and reduced ejection fraction. J. Am. Coll. Cardiol. 77, 243\u2013255 (2021).","journal-title":"J. Am. Coll. Cardiol."},{"key":"4408_CR12","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1016\/j.jacbts.2023.09.006","volume":"8","author":"J Viereck","year":"2023","unstructured":"Viereck, J. & Thum, T. Development of a mechanism-based next-generation therapeutic for heart failure derived from the dark genome. JACC Basic Transl. Sci. 8, 1595\u20131598 (2023).","journal-title":"JACC Basic Transl. Sci."}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04408-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04408-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04408-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T14:02:09Z","timestamp":1784210529000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04408-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,10]]},"references-count":12,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["4408"],"URL":"https:\/\/doi.org\/10.1038\/s41591-026-04408-4","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,10]]},"assertion":[{"value":"19 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"J.B. received honoraria for lectures\/consulting from Abbott Laboratories, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Cardior Pharmaceuticals, CVRx, Edwards, Lilly, Novartis, Novo Nordisk, Pfizer, Roche and Zoll and research support for the department from Abiomed, CVRx, Norgine, Roche and Zoll. S.D.S. has received research grants from Alexion, Alnylam, Applied Therapeutics, AstraZeneca, Bayer, Bellerophon, Bristol Myers Squibb, Boston Scientific, BridgeBio, Cytokinetics, Edgewise, Gossamer, GlaxoSmithKline, Ionis, Intellia, Lexicon, Lilly, National Institutes of Health\/National Heart, Lung, and Blood Institute, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Tenaya, Theracos and US2.AI and has consulted for Abbott Laboratories, Action, Akros, Alexion, Alnylam, American Regent, Amgen, AnaCardio, Arena, AskBio, AstraZeneca, Bayer, Bristol Myers Squibb, BridgeBio, Cardior Pharmaceuticals, Cardurion, CellProthera, Corvia, Cytokinetics, DiNAQOR, GlaxoSmithKline, Intellia, Lilly, Moderna, Novartis, Novo Nordisk, Quantum Genomics, Recordati, Roche, Sanofi Pasteur, Sarepta, Synhale, Tenaya, Theracos, Tremeau and Valo. S.D.A. reports grants from Abbott Laboratories and CSL\/Vifor and personal fees for consultancies, trial committee work and\/or lectures from Actimed, Alleviant, AstraZeneca, Bayer, Berlin Heals, BiMyo, Boehringer Ingelheim, Brahms, Cardiac Dimensions, Cardior Pharmaceuticals, Cordio, Corvia, CSL\/Vifor, CVRx, Cytokinetics, Edwards, Impulse Dynamics, Lilly, Mankind Pharma, Novo Nordisk, Occlutech, Pfizer, Pulnovo, Regeneron, Relaxera, Repairon, Scirent, Sensible Medical, Vectorious, Veru, VisCardia, Vivus and V-Wave. S.D.A. is a named co-inventor of two patent applications regarding MR-proANP (DE 102007010834 and DE 102007022367) but does not benefit personally from the related issued patents. I.A.-M. reports honoraria for lectures, advisory board and\/or consulting from AstraZeneca, Boehringer Ingelheim, Cardior Pharmaceuticals and Daiichi Sankyo. R.A.d.B. reports research grants and\/or fees from Abbott Laboratories, Alnylam, AstraZeneca, Bristol Myers Squibb and Novo Nordisk; speaker engagements with and\/or received fees from and\/or service on an advisory board for Abbott Laboratories, AstraZeneca and Novo Nordisk. G.F. reports lecture fees and\/or advisory and\/or trial committee membership for Bayer, Boehringer Ingelheim, Cardior Pharmaceuticals, Impulse Dynamics, Medtronic, Merck Sharp & Dohme, Novartis, Novo Nordisk, Servier and Vifor and research grants from the European Union. T.F. reports receiving institutional grants from the European Commission, the Federal Joint Committee and the German Research Foundation and personal fees for statistical consultancies, including data monitoring committees, from Actimed Therapeutics, Apellis, argenx, Aslan, AstraZeneca, Bayer, Berlin Heals, Boehringer Ingelheim, Biogen, Biosense Webster, Bristol Myers Squibb, Cardior Pharmaceuticals, CSL Behring, CVRx, Daiichi Sankyo, eCovery, Enanta Pharmaceuticals, Fresenius Kabi, Galapagos, IQVIA, Johnson & Johnson, Novartis, PINK! Aktiv gegen Brustkrebs, PPD, Priothera, Recardio, Recordati, Relaxera, Roche, Sarfez, Upstream Bio, Viatris, VICO Therapeutics and Vifor. W.H. is an employee of Cardior Pharmaceuticals, a Novo Nordisk Company. P.P. received consultancy fees and speakers\u2019 honoraria from Abbott Vascular, AstraZeneca, Bayer, Boehringer Ingelheim, Moderna, Novartis, Novo Nordisk, Pharmacosmos, Relaxera, Servier, Vifor and WhiteSwell. O.V. received honoraria for consulting from AstraZeneca, Bayer, Cardior Pharmaceuticals, Cytokinetics and Novo Nordisk and research support to her institution from AstraZeneca, Bayer and Cardurion. R.A., M.G. and K.V. are employees of Novo Nordisk A\/S. T.T. is the founder, CSO, CMO and Managing Director of Cardior Pharmaceuticals, a Novo Nordisk company.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}