Ivabradine in chronic stable angina: Effects by and beyond heart rate reduction.
Heart rate plays a major role in myocardial ischemia. A high heart rate increases myocardial performance and oxygen demand and reduces diastolic time. Ivabradine reduces heart rate by inhibiting the If current of sinoatrial-node cells. In contrast to beta-blockers, ivabradine has no negative inotropic and lusitropic effect for a comparable heart rate reduction. Consequently, diastolic duration is increased with ivabradine compared to beta-blockers. This has potential consequences on coronary blood flow since compression of the vasculature by the surrounding myocardium during systole impedes flow and coronary blood flow is mainly diastolic. Moreover, ivabradine does not unmask alpha-adrenergic vasoconstriction and, unlike beta-blockers, maintains coronary dilation during exercise. In comparison with beta-blockers, ivabradine increases coronary flow reserve and collateral perfusion promoting the development of coronary collaterals. Ivabradine attenuates myocardial ischemia and its consequences even in the absence of heart rate reduction, possibly through reduced formation of reactive oxygen species. In conclusion, ivabradine differs from other anti-anginal agents by improving coronary blood flow and by additional pleiotropic effects. These properties make ivabradine an effective anti-anginal and anti-ischemic agent for the treatment of patients with coronary artery disease.
Vita Salute University, San Raffaele Hospital, Milan, Italy. Electronic address: camici.paolo@hsr.it.
Paolo G
PG
Camici
Cardiology, Cardiovascular Department, University Hospital Bern, Bern, Switzerland.
Steffen
S
Gloekler
PARCC, INSERM U970, Vessels and Blood Institute, Hôpital Lariboisière, Paris, France.
Bernard I
BI
Levy
Cardiology Department, University Hospital of Heraklion, Crete, Greece.
Emmanouil
E
Skalidis
Cardiology Division, "Umberto I" Hospital, Nocera Inferiore, SA, Italy.
Ercole
E
Tagliamonte
Cardiology Department, University Hospital of Heraklion, Greece.
Panos
P
Vardas
Institute for Pathophysiology, West German Heart and Vascular Centre Essen, University of Essen Medical School, Essen, Germany.
Gerd
G
Heusch
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D060050:Angina, Stable / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology* / Q000627:therapeutic use; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D000077550:Ivabradine; D016032:Randomized Controlled Trials as Topic; D012849:Sinoatrial Node / Q000187:drug effects / Q000503:physiopathology
D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D000077550:Ivabradine
Angina pectoris; Anti-anginal drug; Beta-blocker; Coronary artery disease; Coronary blood flow; Coronary collateral circulation