This Article Full Text Full Text (PDF) All Versions of this Article: 119/21/2781    most recent CIRCULATIONAHA.108.800292v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lapp, H. Articles by Frey, R. Search for Related Content PubMed PubMed Citation Articles by Lapp, H. Articles by Frey, R. Related Collections Congestive Cardiovascular Pharmacology Related Articles

(Circulation. 2009;119:2781-2788.)
© 2009 American Heart Association, Inc.

Heart Failure

Cinaciguat (BAY 58–2667) Improves Cardiopulmonary Hemodynamics in Patients With Acute Decompensated Heart Failure

Harald Lapp, MD; Veselin Mitrovic, MD; Norbert Franz, MD; Hubertus Heuer, MD; Michael Buerke, MD; Judith Wolfertz, MD; Wolfgang Mueck, PhD; Sigrun Unger, MSc; Georg Wensing, MD; Reiner Frey, MD

From HELIOS Clinic Erfurt, Erfurt, Germany (H.L.); Kerckhoff Clinic Nauheim, Bad Nauheim, Germany (V.M.); Schüchtermann Clinic Bad Rothenfelde, Bad Rothenfelde, Germany (N.F.); St Johannes Hospital Dortmund, Dortmund, Germany (H.H.); University of Halle, Halle, Germany (M.B.); HELIOS Clinic Wuppertal, Wuppertal, Germany (J.W.); and Clinical Pharmacology (W.M., G.W., R.F.) and Global Biostatistics (S.U.), Bayer HealthCare AG, Pharma Research Center, Wuppertal, Germany.

Correspondence to PD Dr Harald Lapp, HELIOS Clinic Erfurt, Nordhaeuserstraße 74, D-99089 Erfurt, Germany. E-mail harald.lapp{at}helios-kliniken.de

Received June 23, 2008; accepted February 23, 2009.

Background— Cinaciguat (BAY 58–2667) is the first of a new class of soluble guanylate cyclase activators in clinical development for acute decompensated heart failure. We aimed to assess the hemodynamic effects, safety, and tolerability of intravenous cinaciguat in patients with acute decompensated heart failure (pulmonary capillary wedge pressure 18 mm Hg).

Methods and Results— After initial dose finding (part A; n=27), cinaciguat was evaluated in the nonrandomized, uncontrolled proof-of-concept part of the study (part B; n=33) using a starting dose of 100 µg/h, which could be titrated depending on hemodynamic response. Patients were categorized as responders if their pulmonary capillary wedge pressure decreased by 4 mm Hg compared with baseline. Final doses of cinaciguat after 6 hours of infusion in part B were 50 µg/h (n=2), 200 µg/h (n=12), and 400 µg/h (n=16). Compared with baseline, a 6-hour infusion of cinaciguat led to significant reductions in pulmonary capillary wedge pressure (–7.9 mm Hg), mean right atrial pressure (–2.9 mm Hg), mean pulmonary artery pressure (–6.5 mm Hg), pulmonary vascular resistance (–43.4 dynes · s · cm^–5), and systemic vascular resistance (–597 dynes · s · cm^–5), while increasing heart rate by 4.4 bpm and cardiac output by 1.68 L/min. The responder rate was 53% after 2 hours, 83% after 4 hours, and 90% after 6 hours. Cinaciguat was well tolerated, with 13 of 60 patients reporting 14 drug-related treatment-emergent adverse events of mild to moderate intensity, most commonly hypotension.

Conclusions— Cinaciguat has potent preload- and afterload-reducing effects, increasing cardiac output. Further investigation of cinaciguat for acute decompensated heart failure is warranted.

---

 

CLINICAL PERSPECTIVE

Related Articles:

Circulation: Clinical Summaries
Circulation 2009 119: 2749-2751. [Extract] [Full Text]

Soluble Guanylate Cyclase: Not a Dull Enzyme

Guido Boerrigter and John C. Burnett, Jr
Circulation 2009 119: 2752-2754. [Extract] [Full Text]

This article has been cited by other articles:

				M. A. Sovershaev, E. M. Egorina, J.-B. Hansen, B. Osterud, P. Pacher, J.-P. Stasch, and O. V. Evgenov Soluble Guanylate Cyclase Agonists Inhibit Expression and Procoagulant Activity of Tissue Factor Arterioscler Thromb Vasc Biol, October 1, 2009; 29(10): 1578 - 1586. [Abstract] [Full Text] [PDF]