Cinaciguat, a soluble guanylate cyclase activator: Results from the randomized, controlled, phase IIb COMPOSE programme in acute heart failure syndromes

European Journal of Heart Failure

Volumn 14, Issue 9, 2012, Pages 1056-1066

  Gheorghiade, Mihai ^a   Greene, Stephen J ^a   Filippatos, Gerasimos ^b   Erdmann, Erland ^c   Ferrari, Roberto ^d   Levy, Phillip D ^e   Maggioni, Aldo ^f   Nowack, Christina ^g   Mebazaa, Alexandre ^h  

^a NORTHWESTERN UNIVERSITY   (United States)

^b NATIONAL AND KAPODISTRIAN UNIVERSITY OF ATHENS   (Greece)

^c UNIVERSITY OF COLOGNE   (Germany)

^d UNIVERSITY HOSPITAL OF FERRARA   (Italy)

^e WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^f ANMCO RESEARCH CENTER   (Italy)

^g BAYER PHARMA AG   (Germany)

^h UNIVERSITÉ PARIS DESCARTES   (France)

Author keywords

Cinaciguat; Clinical trial, phase II; Dyspnoea; Haemodynamics; Heart failure; Soluble guanylate cyclase

Indexed keywords

CINACIGUAT; PLACEBO;

ACUTE HEART FAILURE; ADD ON THERAPY; ADULT; AGED; ARTICLE; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DYSPNEA; FEMALE; HEART INDEX; HEMODYNAMIC MONITORING; HEMODYNAMIC PARAMETERS; HOSPITALIZATION; HUMAN; HYPOTENSION; LOW DRUG DOSE; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NAUSEA; PRIORITY JOURNAL; PULMONARY ARTERY OCCLUSION PRESSURE; RANDOMIZED CONTROLLED TRIAL;

ACUTE DISEASE; ADJUVANTS, PHARMACEUTIC; AGED; AGED, 80 AND OVER; BENZOATES; BLOOD PRESSURE; DOUBLE-BLIND METHOD; DYSPNEA; ENZYME ACTIVATION; FEMALE; GLOMERULAR FILTRATION RATE; GUANYLATE CYCLASE; HEART FAILURE; HEMODYNAMICS; HUMANS; INFUSIONS, INTRAVENOUS; MALE; MIDDLE AGED; SYNDROME;

EID: 84865445580     PISSN: 13889842     EISSN: 18790844     Source Type: Journal    
DOI: 10.1093/eurjhf/hfs093     Document Type: Article

References (23)

1. Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, Stromberg A, van Veldhuisen DJ, Atar D, Hoes AW, Keren A, Mebazaa A, Nieminen M, Priori SG, Swedberg K, Vahanian A, Camm J, De Caterina R, Dean V, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 2008;29:2388-2442.
2. Gheorghiade M, Zannad F, Sopko G, Klein L, Pina IL, Konstam MA, Massie BM, Roland E, Targum S, Collins SP, Filippatos G, Tavazzi L. Acute heart failure syndromes: current state and framework for future research. Circulation 2005;112: 3958-3968. (Pubitemid 43739494)
3. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW. 2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults. A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation. J Am Coll Cardiol 2009;53:e1-e90.
4. Felker GM, Pang PS, Adams KF, Cleland JG, Cotter G, Dickstein K, Filippatos GS, Fonarow GC, Greenberg BH, Hernandez AF, Khan S, Komajda M, Konstam MA, Liu PP, Maggioni AP, Massie BM, McMurray JJ, Mehra M, Metra M, O'Connell J, O'Connor CM, Pina IL, Ponikowski P, Sabbah HN, Teerlink JR, Udelson JE, Yancy CW, Zannad F, Gheorghiade M. Clinical trials of pharmacological therapies in acute heart failure syndromes: lessons learned and directions forward. Circ Heart Fail 2010;3:314-325.
5. Evgenov OV, Pacher P, Schmidt PM, Hasko G, Schmidt HH, Stasch JP. NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential. Nat Rev Drug Discov 2006;5:755-768. (Pubitemid 44323702)
6. Tamargo J, Duarte J, Caballero R, Delpon E. Cinaciguat, a soluble guanylate cyclase activator for the potential treatment of acute heart failure. Curr Opin Investig Drugs 2010;11:1039-1047.
7. Martin F, Baskaran P, Ma X, Dunten PW, Schaefer M, Stasch JP, Beuve A, van den Akker F. Structure of cinaciguat (BAY 58-2667) bound to nostoc H-NOX domain reveals insights into heme-mimetic activation of the soluble guanylyl cyclase. J Biol Chem 2010;285:22651-22657.
8. Boerrigter G, Costello-Boerrigter LC, Cataliotti A, Lapp H, Stasch JP, Burnett JC Jr. Targeting heme-oxidized soluble guanylate cyclase in experimental heart failure. Hypertension 2007;49:1128-1133. (Pubitemid 351664312)
9. Jones ES, Kemp-Harper B, Stasch JP, Schmidt H, Widdop RE. Cardioprotective effects in aged spontaneously hypertensive rats due to chronic stimulation/activation of sGC without hypotension. BMC Pharmacol 2009;9 Suppl 1:29.
10. Lapp H, Mitrovic V, Franz N, Heuer H, Buerke M, Wolfertz J, Mueck W, Unger S, Wensing G, Frey R. Cinaciguat (BAY 58-2667) improves cardiopulmonary hemodynamics in patients with acute decompensated heart failure. Circulation 2009;119: 2781-2788.
11. Roongsritong C,Warraich I, Bradley C. Common causes of troponin elevations in the absence of acute myocardial infarction: incidence and clinical significance. Chest 2004;125:1877-1884. (Pubitemid 38648423)
12. Gheorghiade M, Ruschitzka F. Beyond dyspnoea as an endpoint in acute heart failure trials. Eur Heart J 2011;32:1442-1445.
13. Pang PS, Konstam MA, Krasa HB, Swedberg K, Zannad F, Blair JE, Zimmer C, Teerlink JR, Maggioni AP, Burnett JC Jr, Grinfeld L, Ouyang J, Udelson JE, Gheorghiade M. Effects of tolvaptan on dyspnoea relief from the EVEREST trials. Eur Heart J 2009;30:2233-2240.
14. Mebazaa A, Pang PS, Tavares M, Collins SP, Storrow AB, Laribi S, Andre S, Mark Courtney D, Hasa J, Spinar J, Masip J, Frank Peacock W, Sliwa K, Gayat E, Filippatos G, Cleland JG, Gheorghiade M. The impact of early standard therapy on dyspnoea in patients with acute heart failure: the URGENT-dyspnoea study. Eur Heart J 2010;31:832-841.
15. Coletta AP, Cleland JG. Clinical trials update: highlights of the scientific sessions of the XXIII Congress of the European Society of Cardiology-WARIS II, ESCAMI, PAFAC, RITZ-1 and TIME. Eur J Heart Fail 2001;3:747-750. (Pubitemid 33123176)
16. Torre-Amione G, Young JB, Colucci WS, Lewis BS, Pratt C, Cotter G, Stangl K, Elkayam U, Teerlink JR, Frey A, Rainisio M, Kobrin I. Hemodynamic and clinical effects of tezosentan, an intravenous dual endothelin receptor antagonist, in patients hospitalized for acute decompensated heart failure. J Am Coll Cardiol 2003;42:140-147. (Pubitemid 36760775)
17. Binanay C, Califf RM, Hasselblad V, O'Connor CM, Shah MR, Sopko G, Stevenson LW, Francis GS, Leier CV, Miller LW. Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness: the ESCAPE trial. JAMA 2005;294:1625-1633. (Pubitemid 41407355)
18. Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA, Givertz MM, Katz SD, Klapholz M, Moser DK, Rogers JG, Starling RC, Stevenson WG, Tang WH, Teerlink JR, Walsh MN. HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail 2010;16:e1-e194.
19. O'ConnorCM, StarlingRC,HernandezAF, Armstrong PW, DicksteinK,HasselbladV, Heizer GM, Komajda M, Massie BM, McMurray JJ, Nieminen MS, Reist CJ, Rouleau JL, Swedberg K, Adams KF Jr,AnkerSD,AtarD, Battler A, Botero R, BohidarNR, Butler J, Clausell N, Corbalan R, Costanzo MR, Dahlstrom U, Deckelbaum LI, Diaz R, Dunlap ME, Ezekowitz JA, Feldman D, Felker GM, Fonarow GC, Gennevois D, Gottlieb SS, Hill JA, Hollander JE, Howlett JG, Hudson MP, Kociol RD, Krum H, Laucevicius A, Levy WC, Mendez GF, Metra M, Mittal S, Oh BH, Pereira NL, Ponikowski P, Wilson WH, Tanomsup S, Teerlink JR, Triposkiadis F, Troughton RW, Voors AA, Whellan DJ, Zannad F, Califf RM. Effect of nesiritide in patients with acute decompensated heart failure. N Engl J Med 2011;365:32-43.
20. Wang NC, Piccini JP, Gheorghiade M. Implantable cardioverter- defibrillator implementation in acute heart failure syndromes: unanswered questions. Heart Fail Rev 2011;16:477-480.
21. Pang PS, Cleland JG, Teerlink JR, Collins SP, Lindsell CJ, Sopko G, Peacock WF, Fonarow GC, Aldeen AZ, Kirk JD, Storrow AB, Tavares M, Mebazaa A, Roland E, Massie BM, Maisel AS, Komajda M, Filippatos G, Gheorghiade M. A proposal to standardize dyspnoea measurement in clinical trials of acute heart failure syndromes: the need for a uniform approach. Eur Heart J 2008;29: 816-824. (Pubitemid 351431028)
22. Benz K, Orth SR, Simonaviciene A, Linz W, Schindler U, Rutten H, Amann K. Blood pressure-independent effect of long-term treatment with the soluble heme-independent guanylyl cyclase activator HMR1766 on progression in a model of noninflammatory chronic renal damage. Kidney Blood Press Res 2007; 30:224-233. (Pubitemid 47076219)
23. Swedberg K, Held P, Kjekshus J, Rasmussen K, Ryden L, Wedel H. Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction. Results of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II). N Engl J Med 1992;327:678-684.