[Selective I(f) channel inhibition: an alternative for treating coronary artery disease?].
Several clinical studies demonstrate the importance of the heart rate for the cardiovascular morbidity and mortality. Over the last 50 years, some thought has been given to those substances that selectively reduce the heart rate. It is now recognized that I(f) ion channels of the sinus node play a major role in the automatism and modulation of the heart rate. Substances that selectively reduce the heart rate should decrease myocardial oxygen consumption and increase oxygen delivery via the prolonged diastolic coronary perfusion. Direct inotropic effects, however, are unlikely. In principle, anti-anginal and anti-ischemic effects of specific bradycardic substances can be expected. The clinical experience with some of the former bradycardic substances has not been sufficiently convincing. The more recent ivabradine (Procoralan presents an exception to this, as it successfully completed a clinical program for the treatment of chronically stable angina pectoris. In this review article, specific bradycardic substances (= I(f) channel inhibitors) are presented together with the corresponding experimental and clinical studies. The studies were selected against the background of the efficacy of I(f) channel inhibitors in the therapy of cardiovascular disease. As only ivabradine has completed a study on 5,000 patients, the discussion on that particular I(f) channel inhibitor is somewhat extensive. In addition, prospective possibilities and limitations of bradycardic substances are presented.
Schipke
Jochen D
JD
Forschungsgruppe Experimentelle Chirurgie, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf. schipke@med.uni-duesseldorf.de
Büter
Indra
I
Hohlfeld
Thomas
T
Schmitz-Spanke
Simone
S
Gams
Emmeran
E
D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000188:drug therapy*; D001552:Benzazepines / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D003000:Clonidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D003324:Coronary Artery Disease / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D054833:Isoindoles; D000077550:Ivabradine; D010797:Phthalimides / Q000627:therapeutic use; D017410:Practice Guidelines as Topic; D010818:Practice Patterns, Physicians' / Q000639:trends
D000889:Anti-Arrhythmia Agents; D001552:Benzazepines; D002316:Cardiotonic Agents; D002317:Cardiovascular Agents; D054833:Isoindoles; D010797:Phthalimides; D000077550:Ivabradine; C022192:alinidine; D003000:Clonidine; C030532:falipamil; C043636:zatebradine