Review of the If selective channel inhibitor ivabradine in the treatment of chronic stable angina.
Coronary heart disease is the major cause of morbidity and mortality in industrialized countries, and its prevalence is predicted to grow as the population ages. Current drugs for chronic stable angina (such as beta-blockers, calcium-channel blockers, long- and short-acting nitrates, and potassium-channel activators) are often effective, either as monotherapy or in combination, but side effects and contraindications may limit their use. The "I(f)" (for "funny") channel, discovered in 1979, is expressed mainly in the membrane of pacemaker cells present in the sinus node, the atrioventricular node, the ventricular conduction pathways, and ventricular myocytes. By determining the slope of diastolic depolarization, which in turn controls action potential frequency, it is a key determinant of heart rate and so provides a new therapeutic target for controlling angina symptoms. A new antiangina drug, ivabradine, has been developed and licensed for clinical use. It exclusively reduces the heart rate by selectively blocking the I(f) channel of the sino-atrial node. As clinical trials have shown it to be remarkably well-tolerated, ivabradine offers an alternative for patients who cannot take, or are intolerant of, beta blockade. This review provides an insight into this new agent, its historical background, mechanism of action, and pathophysiologic basis, and provides up-to-date evidence-based information on its optimum use in stable angina.
Prasad
Usha K
UK
Nottingham University Hospitals NHS Trust (City Campus), Nottingham, UK.
Gray
David
D
Purcell
Henry
H
D000200:Action Potentials / Q000187:drug effects; D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology; D001552:Benzazepines / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors*; D005080:Exercise Test; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D000077550:Ivabradine; D049990:Membrane Transport Modulators / Q000494:pharmacology / Q000627:therapeutic use; D018579:Patient Selection; D011788:Quality of Life; D012449:Safety; D012849:Sinoatrial Node / Q000187:drug effects; D016896:Treatment Outcome
D001552:Benzazepines; D054815:Cyclic Nucleotide-Gated Cation Channels; D049990:Membrane Transport Modulators; D000077550:Ivabradine