Oral agent with 40% bioavailability.
Protein binding of 70%.
Hepatic metabolism by first-pass 50% and is CYP3A4-mediated.
Half-life of 2 hours.
Renal and fecal excretion.
Used for the symptomatic management of stable angina pectoris.
Trade name Procoralan.
Acts by reducing the heart rate via specific inhibition of the funny channel.
A cardiotonic agent.
Indicated for the symptomatic treatment of chronic stable angina pectoris in patients with normal sinus rhythm who cannot take beta blockers.
Ivabradine provides pure heart rate reduction leading to major anti-ischemic and antianginal efficacy.
Indicated in combination with beta-blockers in patients inadequately controlled by beta-blocker alone and whose heart rate exceeds 60 beats per minute.
As effective as the beta-blocker atenolol and comparable with amlodipine in the management of chronic stable angina.
Also used off-label in the treatment of sinus tachycardia as an Italian clinical study showed significant improvement of symptoms compared to placebo in individuals with inappropriate sinus tachycardia.
Can be used to reduce the heart rate in patients with sepsis or septic shock..
Use in heart failure decreases both cardiovascular death rate and risk of hospitalization for heart failure.
Inhibits the IF pacemaker current in the sinoatrial node and reduced heart rate without affecting blood pressure or left ventricular systolic function.
Lessens symptoms and reduces ischemia with stable angina pectoris.
Improves outcomes with systolic heart failure.
Contraindicated in sick sinus syndrome.
Cannot be used concomitantly with inhibitors of CYP3A4 such as azole antifungals, macrolide antibiotics, nefazodone and antiretroviral drugs nelfinavir and ritonavir.
14.5% of patients taking the drug experience sensations of enhanced brightness, and about 1% of patients discontinue the drug because of these phenomena , which occur on average 40 days after commencement of the drug.
Bradycardia occurs at 2%-5% of cases, and is dose dependent.
Other adverse effects include: headaches, first-degree AV block, ventricular extrasystoles, dizziness and blurred vision.
Acts on the If ion current, which is highly expressed in the sinoatrial node and is a mixed Na+–K+ inward current.
The If ionic current has a major role in regulating pacemaker activity in the sinoatrial (SA) node.
This agent selectively inhibits the pacemaker If current in a dose-dependent manner.
Blocking if channel reduces cardiac pacemaker activity, slowing the heart rate and allowing more time for blood to flow to the myocardium.
In the BEAUTIFUL study randomized over 10917 patients with stable coronary artery disease and left ventricle dysfunction: Ivabradine did not show a significant reduction in cardiovascular death, admission to hospital for acute myocardial infarction, or worsening heart failure.
In the BEAUTIFUL trial cardiovascular death and vascular events were not significantly reduced by ivabradine, however there was a significant reduction in need for revascularization and myocardial infarction in the subgroup of patients with a resting heart rate greater than 70 bpm.
In the above study patients with a heart rate of more than 70 bpm, ivabradine significantly reduced coronary events by 22%, fatal and nonfatal myocardial infarction by 36%, and coronary revascularization by 30%.
In the SHIFT study, ivabradine significantly reduced the risk of hospitalization for worsening heart failure or cardiovascular death by 18% compared with placebo, and also showed that administration to heart failure patients significantly reduced the risk of death from heart failure by 26% and hospitalization for heart failure by 26%.
The reduction of heart rate with ibravadine produces anti-anginal effects and improves heart failure.
Among patients with stable coronary artery disease without clinical heart failure the addition of this drug to standard therapy to reduce heart rate does not improve outcomes (SIGNIFY Investigators).