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Rate Control with Ivabradine

Angina Pectoris and Beyond

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Abstract

The importance of heart rate in human health and disease has been well known to clinicians for quite some time. Recent epidemiologic studies have further strengthened this concept. Modulation of heart rate by pharmacologic as well as non-pharmacologic means has affected cardiovascular mortality and morbidity in various trials and observational studies. Conventional rate-control agents, such as β-adrenoceptor antagonists (β-blockers), calcium channel blockers, and digoxin, have contributed greatly to the management of various diseases where heart-rate reduction is required; however, these agents have effects beyond rate control that may be unacceptable.

Ivabradine has recently been recognized as a pure heart-rate-reducing agent and is being extensively studied. It is the latest addition to the class of drugs used to control angina. It is indicated in cases of β-blocker intolerance or when β-blockers fail to achieve a heart rate of <60 beats/min. The pure heart-rate-reducing effect of ivabradine has also been reported in smaller studies and anecdotal case reports. The theoretical possibilities of the utility of ivabradine are many and have opened up a whole new field of research for the future. The BEAUTIFUL trial enrolled approximately 10 000 patients with coronary artery disease (CAD) and left ventricular dysfunction, with the aim of assessing the effect of ivabradine versus atenolol on various cardiovascular outcomes. Although ivabradine failed to achieve favorable results for primary endpoints, it appeared effective in achieving a favorable secondary endpoint in a subgroup of patients who had a heart rate of >70 beats/min. Other large trials are also underway to assess the effects of ivabradine on heart failure, acute coronary syndromes, CAD, and other cardiovascular disorders. In this review, we discuss the pharmacologic basis of the action of ivabradine and its role in angina control, as well as in other conditions being actively studied or in which a role for ivabradine has been hypothesized.

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References

  1. Lad VD. Secrets of the pulse: the ancient art of the ayurvedic pulse diagnosis. 2nd ed. Delhi: Lotus Press, Motilal Banarasi Dass Publishers, 2005: 10–8.

    Google Scholar 

  2. Kannel WB, Kannel C, Paffenbarger Jr RS, et al. Heart rate and cardiovascular mortality: the Framingham Study. Am Heart J 1987 Jun; 113(6): 1489–94.

    Article  PubMed  CAS  Google Scholar 

  3. Gillum RF, Makuc DM, Feldman JJ. Pulse rate, coronary heart disease, and death: the NHANES I Epidemiologic Follow-Up Study? Am Heart J 1991 Jan; 121(1 Pt 1): 172–7.

    Article  PubMed  CAS  Google Scholar 

  4. Dyer AR, Persky V, Stamler J, et al. Heart rate as a prognostic factor for coronary heart disease and mortality: findings in three Chicago epidemiologic studies. Am J Epidemiol 1980 Dec; 112(6): 736–49.

    PubMed  CAS  Google Scholar 

  5. Wilhelmsen L, Berglund G, Elmfeldt D, et al. The multifactor primary prevention trial in Goteborg, Sweden. Eur Heart J 1986 Apr; 7(4): 279–88.

    PubMed  CAS  Google Scholar 

  6. Tverdal A, Hjellvik V, Selmer R. Heart rate and mortality from cardiovascular causes: a 12 year follow-up study of 379 843 men and women aged 40–45 years. Eur Heart J 2008 Nov; 29(22): 2772–81.

    Article  PubMed  Google Scholar 

  7. Hozawa A, Ohkubo T, Kikuya M, et al. Prognostic value of home heart rate for cardiovascular mortality in the general population: the Ohasama study? Am J Hypertens 2004 Nov; 17(11 Pt 1): 1005–10.

    PubMed  Google Scholar 

  8. Kristal-Boneh E, Silber H, Harari G, et al. The association of resting heart rate with cardiovascular, cancer and all-cause mortality: eight year follow-up of 3527 male Israeli employees (the CORDIS Study). Eur Heart J 2000 Jan; 21(2): 116–24.

    Article  PubMed  CAS  Google Scholar 

  9. Gillman MW, Kannel WB, Belanger A, et al. Influence of heart rate on mortality among persons with hypertension: the Framingham Study. Am Heart J 1993 Apr; 125: 1148–54.

    Google Scholar 

  10. Fox K, Ford I, Steg PG, et al. BEAUTIFUL investigators Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial. Lancet 2008 Sep; 372(9641): 817–21.

    Article  PubMed  Google Scholar 

  11. Palatini P, Benetos A, Grassi G, et al. Identification and management of the hypertensive patient with elevated heart rate: statement of a European Society of Hypertension Consensus Meeting. J Hypertens 2006 Apr; 24(4): 603–10.

    Article  PubMed  CAS  Google Scholar 

  12. Jouven X, Empana JP, Schwartz PJ, et al. Heart-rate profile during exercise as a predictor of sudden death. N Engl J Med 2005 May; 352(19): 1951–8.

    Article  PubMed  CAS  Google Scholar 

  13. Beere PA, Glagov S, Zarins CK. Experimental atherosclerosis at the carotid bifurcation of the cynomolgus monkey: localization, compensatory enlargement, and the sparing effect of lowered heart rate? Arterioscler Thromb 1992 Nov; 12(11): 1245–53.

    Article  PubMed  CAS  Google Scholar 

  14. Traub O, Berk BC. Laminar shear stress: mechanisms by which endothelial cells transduce an atheroprotective force. Arterioscler Thromb Vasc Biol 1998 May; 18(5): 677–85.

    Article  PubMed  CAS  Google Scholar 

  15. Kaplan JR, Manuck SB, Adams MR, et al. Inhibition of coronary atherosclerosis by propranolol in behaviorally predisposed monkeys fed an atherogenic diet. Circulation 1987 Dec; 76(6): 1364–72.

    Article  PubMed  CAS  Google Scholar 

  16. Bassiouny HS, Zarins CK, Kadowaki MH, et al. Hemodynamic stress and experimental aortoiliac atherosclerosis. J Vasc Surg 1994 Mar; 19(3): 426–34.

    Article  PubMed  CAS  Google Scholar 

  17. Brown HF, DiFrancesco D, Noble SJ. How does adrenaline accelerate the heart? Nature 1979 Jul; 280(57): 235–6.

    Article  PubMed  CAS  Google Scholar 

  18. Nerbonne JM, Kass RS. Molecular physiology of cardiac repolarization. Physiol Rev 2005 Oct; 85(4): 1205–53.

    Article  PubMed  CAS  Google Scholar 

  19. Baruscotti M, Bucchi A, DiFrancesco D. Physiology and pharmacology of the cardiac pacemaker (“funny”) current. Pharmacol Ther 2005 Jul; 107(1): 59–79.

    Article  PubMed  CAS  Google Scholar 

  20. Dobrzynski H, Nikolski VP, Sambelashvilli AT, et al. Site of origin and molecular substrate of atrioventricular junctional rhythm in the rabbit heart. Circ Res 2003 Nov; 93(11): 1102–10.

    Article  PubMed  CAS  Google Scholar 

  21. Munk AA, Adjemian RA, Zhao J, et al. Electrophysiological properties of morphologically distinct cells isolated from the rabbit atrioventricular node? J Physiol 1996 Jun; 493(Pt 3): 801–18.

    PubMed  CAS  Google Scholar 

  22. Shi W, Wymore R, Yu H, et al. Distribution and prevalence of hyperpolarization-activated cation channel (HCN) mRNA expression in cardiac tissue? Circ Res 1999 Jul; 85(1): e1–6.

    Article  PubMed  CAS  Google Scholar 

  23. Robinson RB, Siegelbaum SA. Hyperpolarization-activated cation currents: from molecules to physiological function. Annu Rev Physiol 2003; 65: 453–80.

    Article  PubMed  CAS  Google Scholar 

  24. Pape HC. Queer current and the pacemaker: hyperpolarization-activated cation current in neurons. Annu Rev Physiol 1996; 58: 299–327.

    Article  PubMed  CAS  Google Scholar 

  25. Snyders DJ, Van Bogaert PP. Alinidine modifies the pacemaker current in sheep Purkinje fibers? Pflügers Arch 1987 Sep; 410(1–2): 83–91.

    Article  PubMed  CAS  Google Scholar 

  26. Goethals M, Raes A, van Bogaert PP. Use-dependent block of the pacemaker current If in rabbit sinoatrial node cells by zatebradine (UL-FS 49): on the mode of action of sinus node inhibitors? Circulation 1993 Nov; 88(5 Pt 1): 2389–401.

    Article  PubMed  CAS  Google Scholar 

  27. Thollon C, Bidouard JP, Cambarrat C, et al. Stereospecific in vitro and in vivo effects of the new sinus node inhibitor (+)-S 16257. Eur J Pharmacol 1997 Nov; 339(19): 43–51.

    Article  PubMed  CAS  Google Scholar 

  28. Fox K, Ford I, Steg PG, et al. Ivabradine for patients with stable coronary artery disease and left ventricular dysfunction (BEAUTIFUL): a randomized, double-blind, placebo controlled trial. Lancet 2008 Sep; 372(9641): 807–16.

    Article  PubMed  CAS  Google Scholar 

  29. Tardif JC, Ford I, Tendera M, et al., for the INITIATIVE Investigators. Efficacy of ivabradine, a new selective If inhibitor, compared with atenolol in patients with chronic stable angina. Eur Heart J 2005 Dec; 26(23): 2529–36.

    Article  PubMed  CAS  Google Scholar 

  30. Tardif JC, Ponikowski P, Kahan T, ASSOCIATE Study Investigators. Efficacy of the I(f) current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy: a 4-month, randomized, placebo-controlled trial. Eur Heart J 2009 Mar; 30(5): 540–8.

    Article  PubMed  CAS  Google Scholar 

  31. Köster R, Kaehler J, Meinertz T. Treatment of stable angina pectoris by ivabradine in every day practice: The REDUCTION Study? Am Heart J 2009 Oct; 158(4): e51–7.

    Article  PubMed  Google Scholar 

  32. Ruzyllo W, Tendera M, Ford I, et al. Antianginal efficacy and safety of ivabradine compared with amlodipine in patients with stable effort angina pectoris: a 3-month randomised, double-blind, multicentre, noninferioriry trial. Drugs 2007; 67(3): 393–405.

    Article  PubMed  CAS  Google Scholar 

  33. Borer JS, Fox K, Jaillon P, et al., Ivabradine Investigators Group. Antianginal and antiischemic effects of ivabradine, an I(f) inhibitor, in stable angina: a randomized, double-blind, multicentered, placebo-controlled trial. Circulation 2003 Feb; 107(6): 817–23.

    Article  PubMed  Google Scholar 

  34. Lopez-Bescos L, Filipova S, Martos R. Long-term safety and efficacy of the If current inhibitor ivabradine in patients with chronic stable angina. Cardiology 2007; 108(4): 387–96.

    Article  PubMed  CAS  Google Scholar 

  35. Swedberg K, Komajda M, Bahm M, et al. Rationale and design of a randomized, double-blind, placebo-controlled outcome trial of ivabradine in chronic heart failure: the Systolic Heart Failure Treatment with the I(f) Inhibitor Ivabradine Trial (SHIFT). Eur J Heart Fail 2010 Jan; 12(1): 75–81.

    Article  PubMed  CAS  Google Scholar 

  36. ISRCTN (International Standard Randomised Controlled Trial Number). Evaluation versus placebo of the effects on heart rate, haemodynamic parameters, safety and tolerability of 5 mg bolus of ivabradine followed by 8-hour infusion of 5 mg of ivabradine, given to patients undergoing a percutaneous coronary intervention following a myocardial infarction with ST segment elevation (STEMI): a pilot, blind, randomised, placebo-controlled, international, multi-centre study including the ancillary sub-study to the clinical study protocol. VIVIFY trial [online]. Available from URL: http:// www.controlled-trials.com/ISRCTN66067800 [Accessed 2010 Apr 30].

  37. Dominguez-Rodriguez A, Fard SS, Abreu-Gonzalez P, et al. Randomised, double-blind, placebo-controlled trial of ivabradine in patients with acute coronary syndrome: effects of the If current inhibitor ivabradine on reduction of inflammation markers in patients with acute coronary syndrome. RIVIERA trial study design and rationale. Cardiovasc Drugs Ther 2009 Jun; 23(3): 243–7.

    Article  PubMed  CAS  Google Scholar 

  38. ISRCTN (International Standard Randomised Controlled Trial Number). Effects of ivabradine in patients with stable coronary artery disease without heart failure: SIGNIFY trial [online]. Available from URL: http:// www.controlled-trials.com/ISRCTN6157629 [Accessed 2010 Apr 30].

  39. Steg PG. Heart rate management in coronary artery disease: the CLARIFY registry. Eur Heart J 2009; 11 Suppl. D: D13–8.

    Article  Google Scholar 

  40. Bucchi A, Baruscotti M, DiFrancesco D. Current-dependent block of rabbit sino-atrial node If channels by ivabradine. J Gen Physiol 2002 Jul; 120(1): 1–13.

    Article  PubMed  CAS  Google Scholar 

  41. Thollon C, Cambarrat C, Vian J, et al. 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 1994 May; 112(1): 37–42.

    Article  PubMed  CAS  Google Scholar 

  42. Savelieva I, Camm AJ. Comparison of the effects of a selective If current inhibitor ivabradine and atenolol on the QT interval in patients with coronary artery disease [abstract no. P2–36]? Heart Rhythm 2005 May; 2(5): S145–6.

    Article  Google Scholar 

  43. Camm AJ, Lau CP. Electrophysiological effects of a single intravenous administration of ivabradine (S 16257) in adult patients with normal baseline electrophysiology. Drugs R D 2003; 4(2): 83–9.

    Article  PubMed  CAS  Google Scholar 

  44. Mulder P, Barbier S, Chagraoui A, et al. Long-term heart-rate reduction induced by the selective If current inhibitor ivabradine improves left ventricular function and intrinsic myocardial structure in congestive heart failure. Circulation 2004 Apr; 109(13): 1674–9.

    Article  PubMed  CAS  Google Scholar 

  45. Mulder P, Thuillez C. Heart rate slowing for myocardial dysfunction/heart failure: rationale and preclinical studies. In: Camm J, Tandera M, editors. Heart rate slowing by If current inhibition. Advances in Cardiology 43. Basel: Karger, 2006: 97–105.

    Google Scholar 

  46. European Public Assessment Report (EPAR). Ivabradine hydrochloridestable angina pectoris: scientific discussion. EMEA 2005 [online]. Available from URL: http://www.emea.europa.eu/humandocs/Humans/EPAR/pro coralan/procoralan.htn [Accessed 2010 Apr 30].

  47. Baumhakel M, Custodis F, Schlimmer N, et al. Heart-rate reduction with ivabradine improves erectile dysfunction in parallel to decrease in atherosclerotic plaque load in ApoE-knockout mice. Atherosclerosis. Epub 2010 Mar.

  48. Drouin A, Gendron ME, Thorin E, et al. Chronic heart-rate reduction by ivabradine prevents endothelial dysfunction in dyslipidaemic mice. Br J Pharmacol 2008 Jun; 154(4): 749–57.

    Article  PubMed  CAS  Google Scholar 

  49. Procoralan™ (ivabradine hydrochloride) [summary of product characteristics]. Servier Laboratories Ltd. Updated 13 November 2009 [online]. Available from URL: http://emc.medicines.org.uk/medicine/17188/SPC/Procoralan [Accessed 2010 Apr 30].

  50. Borer JS, Tardif JC. Efficacy of ivabradine, a selective I(f) inhibitor, in patients with chronic stable angina pectoris and diabetes mellitus. Am J Cardiol 2010 Jan; 105(1): 29–35.

    Article  PubMed  CAS  Google Scholar 

  51. Portolos A, Terleira A, Calvo A, et al. Effects of Hypericum perforatum on ivabradine pharmacokinetics in healthy volunteers: an open-label, pharmacokinetic interaction clinical trial. J Clin Pharmacol 2006 Oct; 46(10): 1188–94.

    Article  Google Scholar 

  52. Portoles A, Calvo A, Terleira A, et al. Lack of pharmacokinetic interaction between omeprazole or lansoprazole and ivabradine in healthy volunteers: an open-label, randomized, crossover, pharmacokinetic interaction clinical trial. J Clin Pharmacol 2006 Oct; 46(10): 1195–203.

    Article  PubMed  CAS  Google Scholar 

  53. Simon L, Ghaleh B, Puybasset L, et al. Coronary and hemodynamic effects of S 16257, a new bradycardic agent, in resting and exercising conscious dogs. J Pharmacol Exp Ther 1995 Nov; 275(2): 659–66.

    PubMed  CAS  Google Scholar 

  54. Fox K, Ford I, Steg PG, et al. Relationship between ivabradine treatment and cardiovascular outcomes in patients with stable coronary artery disease and left ventricular systolic dysfunction with limiting angina: a subgroup analysis of the randomized controlled BEAUTIFUL trial. Eur Heart J 2009 Oct; 30(19): 2337–45.

    Article  PubMed  CAS  Google Scholar 

  55. Köster R, Kaehler J, Meinertz T, for the REDUCTION Study. Ivabradine reduces angina pectoris in patients after PCI: results from the reduction study [abstract no. 1213–298]. J Am Coll Cardiol 2010 Mar; 55(10A): A121.E1132.

    Article  Google Scholar 

  56. Cerbai E, Barbieri M, Mugelli A. Characterization of the hyperpolarizationactivated current, If, in ventricular myocytes isolated from hypertensive rats? J Physiol 1994 Dec; 481(Pt 3): 585–91.

    PubMed  CAS  Google Scholar 

  57. Cerbai E, Barbieri M, Mugelli A. Occurrence and properties of the hyperpolarization-activated current If in ventricular myocytes from normotensive and hypertensive rats during aging. Circulation 1996 Oct; 94(7): 1674–81.

    Article  PubMed  CAS  Google Scholar 

  58. Stilli D, Sgoifo A, Macchi E, et al. Myocardial remodeling and arrhythmogenesis in moderate cardiac hypertrophy in rats? Am J Physiol Heart Circ Physiol 2001 Jan; 280(1): H142–50.

    PubMed  CAS  Google Scholar 

  59. Fernandez-Velasco M, Goren N, Benito G, et al. Regional distribution of hyperpolarization-activated current If and hyperpolarization-activated cyclic nucleotide-gated channel mRNA expression in ventricular cells from control and hypertrophied rat hearts? J Physiol 2003 Dec; 553(Pt 2): 395–405.

    Article  PubMed  CAS  Google Scholar 

  60. Cerbai E, Sartiani L, De Paoli P, et al. Isolated cardiac cells for electropharmacological studies. Pharmacol Res 2000 Jul; 42(1): 1–8.

    Article  PubMed  CAS  Google Scholar 

  61. Sartiani L, DePaoli P, Stillitano F, et al. Functional remodeling in postmyocardial infarcted rats: focus on beta-adrenoceptor subtypes. J Mol Cell Cardiol 2006 Feb; 40(2): 258–66.

    Article  PubMed  CAS  Google Scholar 

  62. Cerbai E, Pino R, Porciatti F, et al. Characterization of the hyperpolarization-activated current, If, in ventricular myocytes from human failing heart. Circulation 1997 Feb; 95(3): 568–71.

    Article  PubMed  CAS  Google Scholar 

  63. Hoppe UC, Jansen E, Sudkamp M, et al. Hyperpolarization activated inward current in ventricular myocytes from normal and failing human hearts. Circulation 1998 Jan; 97(1): 55–65.

    Article  PubMed  CAS  Google Scholar 

  64. Cerbai E, Sartiani L, DePaoli P, et al. The properties of the pacemaker current If in human ventricular myocytes are modulated by cardiac disease. J Mol Cell Cardiol 2001 Mar; 33(3): 441–8.

    Article  PubMed  CAS  Google Scholar 

  65. Couvreur N, Tissier R, Pons S, et al. Chronic heart-rate reduction with ivabradine improves systolic function of the reperfused heart through a dual mechanism involving a direct mechanical effect and a long-term increase in FKBP12/12.6 expression. Eur Heart J. Epub 2009 Dec.

  66. Fasullo S, Cannizzaro S, Maringhini G, et al. Comparison of ivabradine versus metoprolol in early phases of reperfused anterior myocardial infarction with impaired left ventricular function:preliminary findings. J Card Fail 2009 Dec; 15(10): 856–63.

    Article  PubMed  CAS  Google Scholar 

  67. Reil JC, Reil GH, Bohm M. Heart-rate reduction by I(f)-channel inhibition and its potential role in heart failure with reduced and preserved ejection fraction. Trends Cardiovasc Med 2009 Jul; 19(5): 152–7.

    Article  PubMed  CAS  Google Scholar 

  68. Colin P, Ghaleh B, Monnet X, et al. Effect of graded heart-rate reduction with ivabradine on myocardial oxygen consumption and diastolic time in exercising dogs. J Pharmacol Exp Ther 2004 Jan; 308(1): 236–40.

    Article  PubMed  CAS  Google Scholar 

  69. De Ferrari GM, Mazzuero A, Agnesina L, et al. Favourable effects of heartrate reduction with intravenous administration of ivabradine in patients with advanced heart failure. Eur J Heart Fail 2008 Jun; 10(6): 550–5.

    Article  PubMed  Google Scholar 

  70. Arutyunov GP, Arutyunov AG, Volkova AG. Study evaluating the impact of a combination of inotropic support and heart rate monitoring on prognosis and stabilization rate in patients with decompensated chronic heart failure (LEGION). Ter Arkh 2010; 82(3): 47–52.

    Google Scholar 

  71. Link A, Reil JC, Selejan S, et al. Effect of ivabradine in dobutamine induced sinus tachycardia in a case of acute heart failure. Clin Res Cardiol 2009 Aug; 98(8): 513–5.

    Article  PubMed  Google Scholar 

  72. Heidland UE, Stauer BE. Left ventricular muscle mass and elevated heart rate are associated with coronary plaque disruption. Circulation 2001 Sep; 104(13): 1477–82.

    Article  PubMed  CAS  Google Scholar 

  73. Custodis F, Baumhakel M, Schlimmer N, et al. Heart-rate reduction by ivabradine reduces oxidative stress, improves endothelial function, and prevents atherosclerosis in apolipoprotein E-deficient mice. Circulation 2008 May; 117(18): 2377–87.

    Article  PubMed  CAS  Google Scholar 

  74. Schulze-Bahr E, Neu A, Friederich P, et al. Pacemaker channel dysfunction in a patient with sinus node disease. J Clin Invest 2003 May; 111(10): 1537–45.

    PubMed  CAS  Google Scholar 

  75. Milanesi R, Baruscotti M, Gnecchi-Ruscone T, et al. Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel [published erratum appears in N Engl J Med 2006 Jun; 354 (23): 2520]. N Engl J Med 2006 Jan; 354(2): 151–7.

    Article  PubMed  CAS  Google Scholar 

  76. Nof E, Luria D, Brass D, et al. Point mutation in the HCN4 cardiac ion channel pore affecting synthesis, trafficking, and functional expression is associated with familial asymptomatic sinus bradycardia. Circulation 2007 Jul; 116(5): 463–70.

    Article  PubMed  CAS  Google Scholar 

  77. Plotnikov AN, Bucchi A, Shlapakova I, et al. HCN212-channel biological pacemakers manifesting ventricular tachyarrhythmias are responsive to treatment with If blockade. Heart Rhythm 2008 Feb; 5(2): 282–8.

    Article  PubMed  Google Scholar 

  78. Vaillant F, Tabib A, Chevalier P, et al. Heart-rate reduction with ivabradine protects against ventricular fibrillation during acute ischemia in pigs [abstract]. J Mol Cell Cardiol 2007 Jun; 42(6 Suppl. 1): S14.

    Article  Google Scholar 

  79. Zellerhoff S, Hinterseer M, Krull BF, et al. Selective inhibition of the ‘funny current’: a novel pharmacological intervention in patients with inadequate sinus tachycardia [abstract no. PO01–23]. Heart Rhythm 2009 May; 6(5) Suppl. 1: S103.

    Google Scholar 

  80. Winum PF, Cayla G, Rubini M, et al. A case of cardiomyopathy induced by inappropriate sinus tachycardia and cured by ivabradine. Pacing Clin Electrophysiol 2009 Jul; 32(7): 942–4.

    Article  PubMed  Google Scholar 

  81. Lai LP, Su MJ, Lin JL, et al. Measurement of funny current (If) channel mRNA in human atrial tissue: correlation with left atrial filling pressure and atrial fibrillation. J Cardiovasc Electrophysiol 1999 Jul; 10(7): 947–53.

    Article  PubMed  CAS  Google Scholar 

  82. Porciatti F, Pelzmann B, Cerbai E, et al. The pacemaker current If in single human atrial myocytes and the effect of beta-adrenoceptor and A1-adenosine receptor stimulation. Br J Pharmacol 1997 Nov; 122(5): 963–9.

    Article  PubMed  CAS  Google Scholar 

  83. Pino R, Cerbai E, Calamai G, et al. Effect of 5-HT4 receptor stimulation on the pacemaker current If in human isolated atrial myocytes. Cardiovasc Res 1998 Dec; 40(3): 516–22.

    Article  PubMed  CAS  Google Scholar 

  84. Opthof T. The membrane current (If) in human atrial cells: implications for atrial arrhythmias. Cardiovasc Res 1998 Jun; 38(3): 537–40.

    Article  PubMed  CAS  Google Scholar 

  85. Doesch AO, Celik S, Ehlermann P, et al. Heart-rate reduction after heart transplantation with beta-blocker versus the selective If channel antagonist ivabradine. Transplantation 2007 Oct; 84(8): 988–96.

    Article  PubMed  CAS  Google Scholar 

  86. Doesch AO, Ammon K, Konstandin M, et al. Heart-rate reduction for 12 months with ivabradine reduces left ventricular mass in cardiac allograft recipients. Transplantation 2009 Sep; 88(6): 835–41.

    Article  PubMed  Google Scholar 

  87. Pasceri E, Curcio A, Achille F, et al. Acute reduction of transmitral gradient after I(f) channel inhibition in patients with mitral valve stenosis or a mitral annuloplasty ring [abstract no. 974]. Europace 2009 Jun; 11 Suppl. 2: S6.

    Google Scholar 

  88. Bel A, Perrault LP, Faris B, et al. Inhibition of the pacemaker current: a bradycardic therapy for off-pump coronary operations. Ann Thorac Surg 1998 Jul; 66(1): 148–52.

    Article  PubMed  CAS  Google Scholar 

  89. Cervetto L, Demontis GC, Gargini C. Cellular mechanisms underlying the pharmacological induction of phosphenes. Br J Pharmacol 2007 Feb; 150(4): 383–90.

    Article  PubMed  CAS  Google Scholar 

  90. Babu KS, Gadzik F, Holgate ST. Absence of respiratory effects with ivabradine in patients with asthma. Br J Clin Pharmacol 2008 Jul; 66(1): 96–101.

    Article  PubMed  CAS  Google Scholar 

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No funding was used for the preparation of this review. The authors have no conflicts of interest that relate directly to the content of this review.

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  1. Govind Ballabh Pant Hospital, New Delhi, India

    Neeraj Parakh

  2. C.N. Center, Department of Cardiology, All India Institute of Medical Sciences, Suite #30, 7th Floor, Ansari Nagar, New Delhi, 110029, India

    Balram Bhargava

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Parakh, N., Bhargava, B. Rate Control with Ivabradine. Am J Cardiovasc Drugs 11, 1–12 (2011). https://doi.org/10.2165/11584840-000000000-00000

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