Treatment of chronic heart failure with β-adrenergic receptor antagonists: a convergence of receptor pharmacology and clinical cardiology.
Despite the absence of a systematic development plan, β-blockers have reached the top tier of medical therapies for chronic heart failure. The successful outcome was due to the many dedicated investigators who produced, over a 30-year period, increasing evidence that β-blocking agents should or actually did improve the natural history of dilated cardiomyopathies and heart failure. It took 20 years for supportive evidence to become undeniable, at which time in 1993 the formidable drug development resources of large pharmaceutical companies were deployed into Phase 3 trials. Success then came relatively quickly, and within 8 years multiple agents were on the market in the United States and Europe. Importantly, there is ample room to improve antiadrenergic therapy, through novel approaches exploiting the nuances of receptor biology and/or intracellular signaling, as well as through pharmacogenetic targeting.
University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. michael.bristow@ucdenver.edu
Michael R
MR
Bristow
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D055808:Drug Discovery; D019317:Evidence-Based Medicine; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D057170:Translational Research, Biomedical; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D002317:Cardiovascular Agents; D011943:Receptors, Adrenergic, beta