Abstract | BACKGROUND: 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 microg/h, which could be titrated depending on hemodynamic response. Patients were categorized as responders if their pulmonary capillary wedge pressure decreased by > or =4 mm Hg compared with baseline. Final doses of cinaciguat after 6 hours of infusion in part B were 50 microg/h (n=2), 200 microg/h (n=12), and 400 microg/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.
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Authors | Harald Lapp, Veselin Mitrovic, Norbert Franz, Hubertus Heuer, Michael Buerke, Judith Wolfertz, Wolfgang Mueck, Sigrun Unger, Georg Wensing, Reiner Frey |
Journal | Circulation
(Circulation)
Vol. 119
Issue 21
Pg. 2781-8
(Jun 02 2009)
ISSN: 1524-4539 [Electronic] United States |
PMID | 19451356
(Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Chemical References |
- Benzoates
- Receptors, Cytoplasmic and Nuclear
- Vasodilator Agents
- BAY 58-2667
- Guanylate Cyclase
- Soluble Guanylyl Cyclase
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Topics |
- Acute Disease
- Adult
- Aged
- Aged, 80 and over
- Benzoates
(administration & dosage, adverse effects, pharmacology, therapeutic use)
- Blood Pressure
(drug effects)
- Cardiac Output
(drug effects)
- Enzyme Activation
(drug effects)
- Female
- Guanylate Cyclase
(drug effects)
- Heart Failure
(drug therapy, physiopathology)
- Heart Rate
(drug effects)
- Hemodynamics
(drug effects)
- Humans
- Hypotension
(chemically induced)
- Infusions, Intravenous
- Male
- Middle Aged
- Pulmonary Wedge Pressure
(drug effects)
- Receptors, Cytoplasmic and Nuclear
(drug effects)
- Soluble Guanylyl Cyclase
- Vascular Resistance
(drug effects)
- Vasodilator Agents
(administration & dosage, adverse effects, pharmacology, therapeutic use)
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