{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:29:56Z","timestamp":1790872196387,"version":"4.1.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2012,9,1]],"date-time":"2012-09-01T00:00:00Z","timestamp":1346457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Cinaciguat (BAY 58-2667) is a soluble guanylate cyclase (sGC) activator that, in a previous study among patients with acute heart failure syndromes (AHFS), improved pulmonary capillary wedge pressure (PCWP) at the expense of significant hypotension at doses \u2265200 \u00b5g\/h. The aim of the COMPOSE programme was to investigate the safety and efficacy of fixed, low doses of intravenous cinaciguat (&amp;lt;200 \u00b5g\/h for 24\u201348 h) as add-on to standard therapy in adults hospitalized with AHFS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>COMPOSE comprised three randomized, double-blind, placebo-controlled studies in patients with [COMPOSE 1 and 2 (NCT01065077 and NCT01067859)] or without [COMPOSE EARLY (NCT01064037)] a requirement for invasive haemodynamic monitoring. COMPOSE 1 and COMPOSE EARLY assessed the effects of cinaciguat (50, 100, and 150 \u00b5g\/h) on haemodynamics and dyspnoea, respectively. COMPOSE 2 assessed the haemodynamic effects of 10 and 25 \u00b5g\/h cinaciguat. COMPOSE was terminated early due to an excess of non-fatal hypotension and recruitment difficulties. In COMPOSE 1 (n = 12), cinaciguat reduced PCWP at 8 h compared with placebo, but there was no relevant change in cardiac index. In COMPOSE EARLY (n = 62), no meaningful difference in dyspnoea was shown between cinaciguat and placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this limited database, short-term use of intravenous cinaciguat decreased blood pressure without improving dyspnoea or cardiac index. Given the lack of effect on dyspnoea and cardiac index and the hypotensive effect seen even with low doses, it is doubtful that further studies with intravenous cinaciguat would prove beneficial in this patient population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurjhf\/hfs093","type":"journal-article","created":{"date-parts":[[2012,6,23]],"date-time":"2012-06-23T03:27:09Z","timestamp":1340422029000},"page":"1056-1066","source":"Crossref","is-referenced-by-count":113,"title":["Cinaciguat, a Soluble Guanylate Cyclase Activator: Results from the Randomized, Controlled, Phase IIb COMPOSE Programme in Acute Heart Failure Syndromes"],"prefix":"10.1093","volume":"14","author":[{"given":"Mihai","family":"Gheorghiade","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine , 645 North Michigan Ave., Suite 1006, Chicago, IL, 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Greene","sequence":"additional","affiliation":[{"name":"Department of Medicine, Northwestern University Feinberg School of Medicine , Chicago, IL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerasimos","family":"Filippatos","sequence":"additional","affiliation":[{"name":"Heart Failure Unit, Department of Cardiology, Attikon University Hospital , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erland","family":"Erdmann","sequence":"additional","affiliation":[{"name":"Herzzentrum der Universit\u00e4t zu K\u00f6ln , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Department of Cardiology and LTTA Centre, University Hospital of Ferrara and Salvatore Maugeri Foundation , IRCCS, Lumezzane ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip D.","family":"Levy","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Wayne State University School of Medicine , Detroit, MI ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo","family":"Maggioni","sequence":"additional","affiliation":[{"name":"ANMCO Research Centre , Florence ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Nowack","sequence":"additional","affiliation":[{"name":"Global Clinical Development, Bayer Pharma AG , Wuppertal ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Mebazaa","sequence":"additional","affiliation":[{"name":"AP-HP, Department of Anaesthesiology and Critical Care Medicine, H\u00f4pital Lariboisi\u00e8re, Paris, Universit\u00e9 Paris Diderot, PRES Sorbonne-Paris-Cit\u00e9, and U942 INSERM \u00a0","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,2,27]]},"reference":[{"key":"2026011921172771600_ejhfhfs093-bib-0001","first-page":"2388","article-title":"Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM)","volume":"29","author":"Dickstein","year":"2008","journal-title":"Eur Heart J"},{"key":"2026011921172771600_ejhfhfs093-bib-0002","doi-asserted-by":"crossref","first-page":"3958","DOI":"10.1161\/CIRCULATIONAHA.105.590091","article-title":"Acute heart failure syndromes: current state and framework for future research","volume":"112","author":"Gheorghiade","year":"2005","journal-title":"Circulation"},{"key":"2026011921172771600_ejhfhfs093-bib-0003","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.jacc.2008.11.013","article-title":"2009 focused update incorporated into the ACC\/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults. 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