{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T11:13:25Z","timestamp":1789902805985,"version":"4.0.1"},"reference-count":26,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T00:00:00Z","timestamp":1700697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Vericiguat, a novel soluble guanylate cyclase (sGC) stimulator, is approved for the treatment of heart failure (HF) with reduced ejection fraction (HFrEF). Decreased nitric oxide (NO) availability, sGC desensitization to NO, sGC deficiency, and reduced cyclic guanosine monophosphate (cGMP) signaling are potential contributing factors for HF disease progression. Vericiguat works via stimulation of sGC in the critical NO\u2010sGC\u2010cGMP pathway. Vericiguat is primarily metabolized by glucuronidation via uridine diphosphate\u2010glucuronosyltransferase (UGT) isoforms UGT1A1 and UGT1A9. Urinary excretion and renal clearance of vericiguat are low. No intrinsic factor had a clinically relevant effect on vericiguat exposure. Vericiguat has low drug\u2013drug interaction potential with no clinically relevant pharmacokinetic or pharmacodynamic interactions observed with warfarin, digoxin, aspirin, or sacubitril\/valsartan. The global phase III study VICTORIA included patients with HFrEF who had a recent HF hospitalization or intravenous diuretic treatment for HF. Treatment with vericiguat on top of standard of care resulted in a 10% relative reduction in the primary composite outcome of death from cardiovascular causes or first hospitalization for HF. Vericiguat was well\u2010tolerated with low incidence of symptomatic hypotension and syncope compared to placebo. Given its positive benefit\u2013risk profile, vericiguat is an important option for high\u2010risk patients with HFrEF who are already on guideline\u2010directed medical therapy and had recent worsening of HF. Future efforts to develop additional effective therapies are needed to further reduce morbidity and mortality in patients with HF.<\/jats:p>","DOI":"10.1111\/cts.13677","type":"journal-article","created":{"date-parts":[[2023,11,25]],"date-time":"2023-11-25T01:01:39Z","timestamp":1700874099000},"page":"2458-2466","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Vericiguat, a novel <scp>sGC<\/scp> stimulator: Mechanism of action, clinical, and translational science"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9358-5532","authenticated-orcid":false,"given":"Maria E.","family":"Trujillo","sequence":"first","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5917-9397","authenticated-orcid":false,"given":"Surya","family":"Ayalasomayajula","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8609-3508","authenticated-orcid":false,"given":"Robert O.","family":"Blaustein","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5114-3572","authenticated-orcid":false,"given":"Ferdous","family":"Gheyas","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,23]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"Food and Drug Administration.Verquvo\u2122 (vericiguat) tablets. Highlights of prescribing information. Accessed May 11 2022.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/214377s000lbl.pdf"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32279-7"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2020.7472"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.117.004873"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l223"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/HHF.0b013e318291329a"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.10262"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/cir.0000000000001063"},{"key":"e_1_2_8_10_1","unstructured":"European Medicines Agency.Verquvo summary of product characteristics. Accessed July 31 2023.https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/verquvo\u2010epar\u2010product\u2010information_en.pdf"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/164_2016_100"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2017.08.013"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2022.10.431"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-021-01024-y"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2712"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2222"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.15734"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2574"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw593"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.15922"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1915928"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2020.08.008931-939"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.121.021094"},{"key":"e_1_2_8_24_1","unstructured":"ClinicalTrials.gov.A study of vericiguat (MK\u20101242) in participants with chronic heart failure with reduced ejection fraction (HFrEF) (MK\u20101242\u2010035) (VICTOR). Accessed April 18 2023.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05093933"},{"key":"e_1_2_8_25_1","unstructured":"ClinicalTrials.gov.Efficacy safety and pharmacokinetics of vericiguat in pediatric participants with heart failure due to left ventricular systolic dysfunction (MK\u20101242\u2010036). Accessed April 18 2023.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05714085"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2021.04.065"},{"key":"e_1_2_8_27_1","unstructured":"Biocardia.BioCardia announces US patent on bone marrow derived neurokinin\u20101 receptor positive (NK1R+) mesenchymal stem cells for therapeutic applications. Accessed June 22 2023.https:\/\/www.globenewswire.com\/news\u2010release\/2023\/05\/09\/2664254\/0\/en\/BioCardia\u2010Announces\u2010US\u2010Patent\u2010on\u2010Bone\u2010Marrow\u2010Derived\u2010Neurokinin\u20101\u2010Receptor\u2010Positive\u2010NK1R\u2010Mesenchymal\u2010Stem\u2010Cells\u2010for\u2010Therapeutic\u2010Applications.html"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13677","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,21]],"date-time":"2024-01-21T12:32:15Z","timestamp":1705840335000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.13677"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,23]]},"references-count":26,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1111\/cts.13677"],"URL":"https:\/\/doi.org\/10.1111\/cts.13677","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,23]]},"assertion":[{"value":"2023-07-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}