Pharmacological reasons that may explain why randomized clinical trials have failed in acute heart failure syndromes.
Acute heart failure (AHF) represents a clinical challenge as it encloses a heterogeneous group of syndromes (AHFS) with different pathophysiology, clinical presentations, prognosis and response to therapy. In the last 25years multiple therapeutic targets have been identified and numerous new drugs were evaluated but, up to now, all failed to demonstrate a consistent benefit on clinical outcomes. Moreover, a repeated finding has been the poor correlation between the encouraging results of preclinical and early clinical trials and the lack of effect on outcomes observed in phase III trials. We review several possible pharmacological reasons that may explain the lack of success to develop new drugs and the pharmacological challenges to overcome in the future to develop new more effective and safer drugs for the treatment of AHFS.
Department of Pharmacology, School of Medicine, Universidad Complutense, 28040 Madrid, Spain. Electronic address: jtamargo@med.ucm.es.
Juan
J
Tamargo
Cardiology Clinical Academic Group, St George's University Hospitals NHS Foundation Trust, United Kingdom. Electronic address: grosano@sgul.ac.uk.
Giuseppe M C
GM
Rosano
Department of Pharmacology, School of Medicine, Universidad Complutense, 28040 Madrid, Spain.
Eva
E
Delpón
Research Institute, Hospital 12 de, Madrid, Spain.
Luis
L
Ruilope
Department of Cardiology, Hospital Universitario La Paz (IDIPAZ), Paseo de la Castellana 261, 28046 Madrid, Spain.
Jose
J
López-Sendón
D000208:Acute Disease; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D013577:Syndrome
D002317:Cardiovascular Agents
Acute heart failure syndromes; Acute heart failure therapy; Clinical trials; Drug development; Pharmacology