title: Agents with vasodilator properties in acute heart failure: how to design successful trials.
abstract: Agents with vasodilator properties (AVDs) are frequently used in the treatment of acute heart failure (AHF). AVDs rapidly reduce preload and afterload, improve left ventricle to aorta and right ventricle to pulmonary artery coupling, and may improve symptoms. Early biomarker changes after AVD administration have suggested potentially beneficial effects on cardiac stretch, vascular tone, and renal function. AVDs that reduce haemodynamic congestion without causing hypoperfusion might be effective in preventing worsening organ dysfunction. Existing AVDs have been associated with different results on outcomes in randomized clinical trials, and observational studies have suggested that AVDs may be associated with a clinical outcome benefit. Lessons have been learned from past AVD trials in AHF regarding preventing hypotension, selecting the optimal endpoint, refining dyspnoea measurements, and achieving early randomization and treatment initiation. These lessons have been applied to the design of ongoing pivotal clinical trials, which aim to ascertain if AVDs improve clinical outcomes. The developing body of evidence suggests that AVDs may be a clinically effective therapy to reduce symptoms, but more importantly to prevent end-organ damage and improve clinical outcomes for specific patients with AHF. The results of ongoing trials will provide more clarity on the role of AVDs in the treatment of AHF.
authors.affiliation: University Paris Diderot, Sorbonne Paris Cité, Paris, France.|U942 INSERM, AP-HP, Paris, France.|APHP, Department of Anesthesia and Critical Care, Hôpitaux Universitaires Saint Louis-Lariboisière, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Mebazaa
authors.affiliation: Département d'Anesthésie-Réanimation, Hôpital Bichat-Claude Bernard, University Paris Diderot, Sorbonne Paris Cité, Paris, U1148 INSERM, Paris, France.
authors.forename: Dan
authors.initials: D
authors.lastname: Longrois
authors.affiliation: Cardiology, University of Brescia, Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
authors.affiliation: Department of Cardiology, University Hospital Basel, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Mueller
authors.affiliation: Cardiovascular Research Institute, National University of Singapore, Singapore.|Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Arthur Mark
authors.initials: AM
authors.lastname: Richards
authors.affiliation: Global Clinical Development, Bayer Pharma AG, Berlin, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Roessig
authors.affiliation: Department of Cardiology, University Hospital of Besançon, U942 INSERM, Besançon, France.
authors.forename: Marie France
authors.initials: MF
authors.lastname: Seronde
authors.affiliation: Internal Medicine, Cardiology, and Intensive Care Medicine, Nippon Medical School Musashi-Kosugi Hospital, Kanagawa, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sato
authors.affiliation: Division of Cardiovascular and Renal Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Norman L
authors.initials: NL
authors.lastname: Stockbridge
authors.affiliation: Campbell University College of Pharmacy and Health Sciences, NC, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Gattis Stough
authors.affiliation: Scientific Advice Working Party European Medicines Agency, Madrid, Spain.
authors.forename: Angeles
authors.initials: A
authors.lastname: Alonso
authors.affiliation: Janssen Research and Development, Raritan, NJ, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Cody
authors.affiliation: Global Clinical Development, Bayer Pharma AG, Berlin, Germany.
authors.forename: Nancy
authors.initials: N
authors.lastname: Cook Bruns
authors.affiliation: Department of Medicine, Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
authors.affiliation: Cardiorentis AG, Zug, Switzerland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Holzmeister
authors.affiliation: APHP, Department of Emergency Medicine, Hôpitaux Universitaires Saint Louis-Lariboisière, INSERM U942, Paris, France.
authors.forename: Said
authors.initials: S
authors.lastname: Laribi
authors.affiliation: INSERM, Centre d'Investigation Clinique 9501 and Unité 961, Centre Hospitalier Universitaire, and the Department of Cardiology, Nancy University, Université de Lorraine, Nancy, France.
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
mesh_terms: D001794:Blood Pressure / Q000502:physiology; D002986:Clinical Trials as Topic / Q000379:methods*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D014665:Vasodilator Agents
keywords: Acute heart failure; Clinical trials; Vasodilator