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Systematic (IUPAC) name
Clinical data
[[Regulation of therapeutic goods |Template:Engvar data]]
  • AU: D
Routes of
Legal status
Legal status
  • UK: POM (Prescription only)
Pharmacokinetic data
Bioavailability 40%
Protein binding 70%
Metabolism Hepatic (first-pass) >50%, CYP3A4-mediated
Biological half-life 2 hours
Excretion Renal and fecal
CAS Number 155974-00-8
ATC code C01EB17 (WHO)
PubChem CID 132999
Chemical data
Formula C27H36N2O5
Molar mass 468.585 g/mol[[Script error: No such module "String".]]
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Ivabradine (INN) (pronounced /ɪˈvæbrədiːn/) is a novel medication used for the symptomatic management of stable angina pectoris. It is marketed under the trade name Procoralan (Servier), Coralan in India (Servier), Australia or such as in Italy Corlentor (Servier), and was also known as S-16257 during its development. Ivabradine acts by reducing the heart rate in a mechanism different from beta blockers and calcium channel blockers, two commonly prescribed antianginal drugs. It is classified as a cardiotonic agent.

Mode of action

Ivabradine acts on the If (f is for "funny", so called because it had unusual properties compared with other current systems known at the time of its discovery) ion current, which is highly expressed in the sinoatrial node. If is a mixed Na+–K+ inward current activated by hyperpolarization and modulated by the autonomic nervous system. It is one of the most important ionic currents for regulating pacemaker activity in the sinoatrial (SA) node. Ivabradine selectively inhibits the pacemaker If current in a dose-dependent manner. Blocking this channel reduces cardiac pacemaker activity, slowing the heart rate and allowing more time for blood to flow to the myocardium.[1][2]


Ivabradine was approved by the European Medicines Agency in 2005. It is indicated for the symptomatic treatment of chronic stable angina pectoris in patients with normal sinus rhythm, who have a contraindication to or intolerance to beta blockers. It is also indicated in combination with beta-blockers in patients inadequately controlled with an optimal beta-blocker dose and whose heart rate is superior to 60 bpm.

It has been shown to be non-inferior to the beta-blocker atenolol for this indication[3] and amlodipine.

Apart from angina, it is also being used off-label in the treatment of inappropriate sinus tachycardia.[4]


The usual recommended starting dose of ivabradine is 5 mg twice daily. After three to four weeks of treatment, the dose may be increased to 7.5 mg twice daily depending on the therapeutic response. If, during treatment, heart rate decreases persistently below 50 beats per minute (bpm) at rest or the patient experiences symptoms related to bradycardia such as dizziness, fatigue or hypotension, the dose must be titrated downward including the possible dose of 2.5 mg twice daily (one half 5 mg tablet twice daily). Treatment must be discontinued if heart rate below 50 bpm or symptoms of bradycardia persist.

Given limited experience in the elderly, the official Summary of Product Characteristics recommends a lower starting dose of 2.5 mg twice daily[5] before up-titration if necessary.


Ivabradine is contraindicated in sick sinus syndrome, and cannot be used concominantly with inhibitors of CYP3A4 such as azole antifungals (such as ketoconazole), macrolide antibiotics, nefazodone and the anti-HIV drugs nelfinavir and ritonavir[5].

Adverse effects

14.5% of all patients taking ivabradine experience luminous phenomena (by patients described as sensations of enhanced brightness in a fully maintained visual field). This is probably due to blockage of I h ion channels in the retina which are very similar to cardiac If. These symptoms are mild, transient, fully reversible and non-severe. In clinical studies about 1% of all patients had to discontinue the drug because of these sensations, which occurred on average 40 days after commencement of the drug.[3]

Bradycardia (unusually slow heart rate) occurs at 2% and 5% for doses of 7.5 and 10 mg respectively (compared to 4.3% in atenolol)[3]. 2.6-4.8% reported headaches[3]. Other common adverse drug reactions (1–10% of patients) include first-degree AV block, ventricular extrasystoles, dizziness and/or blurred vision.[6]

Clinical trials

Coronary artery disease

The BEAUTIFUL study has shown that in coronary patients with a heart rate more than 70 bpm, ivabradine significantly reduces the risk of[7]

  • Coronary events by 22% (P=0.023)
  • Fatal and nonfatal myocardial infarction by 36% (P=0.001)
  • Coronary revascularization by 30% (P=0.016).

Chronic heart failure

In the SHIFT study, ivabradine significantly reduced the risk of the primary composite endpoint of hospitalization for worsening heart failure or cardiovascular death by 18% (P<0.0001) compared with placebo on top of optimal therapy. These benefits were observed after 3 months of treatment. SHIFT also showed that administration of ivabradine to heart failure patients significantly reduced the risk of death from heart failure by 26% (P=0.014) and hospitalization for heart failure by 26% (P<0.0001). The improvements in outcomes were observed throughout all prespecified subgroups: female and male, with or without beta-blockers at randomization, patients below and over 65 years of age, with heart failure of ischemic or non-ischemic etiology, NYHA class II or class III, IV, with or without diabetes, and with or without hypertension.[8]


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External links

de:Ivabradin fr:Ivabradine

  1. Thollon C, Cambarrat C, Vian J, Prost JF, Peglion JL, Vilaine JP (1994). "Electrophysiological effects of S 16257, a novel sino-atrial node modulator, on rabbit and guinea-pig cardiac preparations: comparison with UL-FS 49". Br. J. Pharmacol. 112 (1): 37–42. PMC 1910295Freely accessible. PMID 8032660. 
  2. Sulfi S, Timmis AD (2006). "Ivabradine -- the first selective sinus node I(f) channel inhibitor in the treatment of stable angina". Int. J. Clin. Pract. 60 (2): 222–8. doi:10.1111/j.1742-1241.2006.00817.x. PMC 1448693Freely accessible. PMID 16451297. 
  3. 3.0 3.1 3.2 3.3 Tardif JC, Ford I, Tendera M, Bourassa MG, Fox K (2005). "Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina". Eur. Heart J. 26 (23): 2529–36. doi:10.1093/eurheartj/ehi586. PMID 16214830. 
  4. Yusuf S, Camm AJ (2003). "Sinus tachyarrhythmias and the specific bradycardic agents: a marriage made in heaven?". J. Cardiovasc. Pharmacol. Ther. 8 (2): 89–105. doi:10.1177/107424840300800202. PMID 12808482. 
  5. 5.0 5.1 "European Medicine Agency, Procoralan Summary of Product Characteristics" (PDF). Retrieved 2010-09-13. 
  6. Anonymous (2006). "New medicines: Procoralan". Pharmaceutical Journal. 276 (7386): 131. 
  7. Kim Fox, Ian Ford, P Gabriel Steg, Michal Tendera, Prof Roberto Ferrari (2008). "Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction: a randomised, double-blind, placebo-controlled trial". The Lancet. 372 (9641): 807–816. doi:10.1016/S0140-6736(08)61170-8. 
  8. Swedberg K, Komajda M, Böhm M, Borer JS, Ford I, Dubost-Brama A, Lerebours G, Tavazzi L; on behalf of the SHIFT Investigators (2010). "Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study". The Lancet. 376 (9744): 875–885. doi:10.1016/S0140-6736(10)61198-1.