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Efficacy of Ivabradine in Combination with Beta-Blocker Versus Uptitration of Beta-Blocker in Patients with Stable Angina

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Abstract

Purpose

The antianginal and anti-ischemic efficacy of the selective I f inhibitor ivabradine is established in patients with stable angina in monotherapy and in combination with other antianginals, including beta-blocker. This pilot study compared the antianginal and anti-ischemic efficacy and hemodynamic profile of ivabradine plus 5 mg bisoprolol versus those of 10 mg bisoprolol in patients with stable angina.

Patients and methods

Twenty-nine patients with stable angina and moderate left ventricular systolic dysfunction already on bisoprolol 5 mg od were randomized into 2 groups. Group 1 (n = 17) received ivabradine (5–7.5 mg bid) in addition to bisoprolol 5 mg od, while in group 2 (n = 12) bisoprolol was uptitrated first to 7.5 mg and then 10 mg od. Patients underwent a treadmill test, 6-minute walking test, and echocardiography at baseline and after 2 months.

Results

Mean resting heart rate decreased in both groups, from 76.6 ± 4.6 bpm to 59.3 ± 2.5 bpm (P < 0.001) in group 1 and from 75.9 ± 3.0 bpm to 60.5 ± 2.3 bpm (P = 0.002) in group 2. The effect on resting heart rate did not differ significantly between the two groups. However, more patients became asymptomatic in group 1 than in group 2. Addition of ivabradine also improved exercise capacity, as shown by the results of the 6-minute walking and exercise tolerance tests, whereas in group 2 neither parameter was significantly affected. Chronotropic reserve significantly improved with ivabradine, but not with bisoprolol 10 mg.

Conclusions

These results suggest that combining ivabradine with low dose bisoprolol in stable angina patients produces additional antianginal and anti-ischemic benefits and improves chronotropic reserve.

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References

  1. Fox K, Borer JS, Camm AJ, et al. Resting heart rate in cardiovascular disease. J Am Coll Cardiol. 2007;50:823–30.

    Article  PubMed  Google Scholar 

  2. DiFrancesco D. Funny channels in the control of cardiac rhythm and mode of action of selective blockers. Pharmacol Res. 2006;53:399–406.

    Article  PubMed  CAS  Google Scholar 

  3. Borer JS, Fox K, Jaillon P, Lerebours G. Antianginal and antiischemic effects of ivabradine, an I(f) inhibitor, in stable angina: a randomized, double-blind, multicentered, placebo-controlled trial. Circulation. 2003;107:817–23.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  5. Tardif JC, Ford I, Tendera M, Bourassa MG, Fox K. Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina. Eur Heart J. 2005;26:2529–36.

    Article  PubMed  CAS  Google Scholar 

  6. Tardif JC, Ponikowski P, Kahan T. Efficacy of the If current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy: a 4 month, randomized, placebo-controlled trial. Eur Heart J. 2009;30:540–8.

    Article  PubMed  CAS  Google Scholar 

  7. Fox K, Ford I, Steg PG, Tendera M, Ferrari R. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:807–16.

    Article  PubMed  CAS  Google Scholar 

  8. Swedberg K, Komajda M, Bohm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled trial. Lancet. 2010;376:875–85.

    Article  PubMed  CAS  Google Scholar 

  9. Fox K, Ford I, Steg PG, Tendera M, Robertson M, Ferrari R. 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;30:2337–45.

    Article  PubMed  CAS  Google Scholar 

  10. Schiller NB, Shah PM, Crawford M, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr. 1989;2:358–67.

    PubMed  CAS  Google Scholar 

  11. Elhendy A, Mahoney DW, Khandheria BK, Burger K, Pellikka PA. Prognostic significance of impairment of heart rate response to exercise: impact of left ventricular function and myocardial ischemia. J Am Coll Cardiol. 2003;42:823–30.

    Article  PubMed  Google Scholar 

  12. Fox K, Garcia MA, Ardissino D, et al. Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. Eur Heart J. 2006;27:1341–81.

    Article  PubMed  Google Scholar 

  13. Witte KK, Cleland JG, Clark AL. Chronic heart failure, chronotropic incompetence, and the effects of beta blockade. Heart. 2006;92:481–6.

    Article  PubMed  CAS  Google Scholar 

  14. Villella M, Villella A, Barlera S, Franzosi MG, Maggioni AP. Prognostic significance of double product and inadequate double product response to maximal symptom-limited exercise stress testing after myocardial infarction in 6296 patients treated with thrombolytic agents. GISSI-2 Investigators. Grupo Italiano per lo Studio della Sopravvivenza nell-Infarto Miocardico. Am Heart J. 1999;137:443–52.

    Article  PubMed  CAS  Google Scholar 

  15. Simon L, Ghaleh B, Puybasset L, Giudicelli JF, Berdeaux A. Coronary and hemodynamic effects of S 16257, a new bradycardic agent, in resting and exercising conscious dogs. J Pharmacol Exp Ther. 1995;275:659–66.

    PubMed  CAS  Google Scholar 

  16. Baumgart D, Haude M, Gorge G, et al. Augmented alpha-adrenergic constriction of atherosclerotic human coronary arteries. Circulation. 1999;99:2090–7.

    PubMed  CAS  Google Scholar 

  17. Heusch G, Baumgart D, Camici P, et al. Alpha-adrenergic coronary vasoconstriction and myocardial ischemia in humans. Circulation. 2000;101:689–94.

    PubMed  CAS  Google Scholar 

  18. Ceconi C, Comini L, Suffredini S, et al. Heart rate reduction with ivabradine prevents the global phenotype of left ventricular remodeling. Am J Physiol Heart Circ Physiol. 2011;300:H366–73.

    Article  PubMed  CAS  Google Scholar 

  19. Manz M, Reuter M, Lauck G, Omran H, Jung W. A single intravenous dose of ivabradine, a novel I(f) inhibitor, lowers heart rate but does not depress left ventricular function in patients with left ventricular dysfunction. Cardiology. 2003;100:149–55.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  21. Ceconi C, Freedman SB, Tardif JC, et al. Effect of heart rate redution by ivabradine on left ventricular remodeling in the echocardiographic substudy of BEAUTIFUL. Int J Cardiol. 2011;146:408–14.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to R. Ferrari.

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Amosova, E., Andrejev, E., Zaderey, I. et al. Efficacy of Ivabradine in Combination with Beta-Blocker Versus Uptitration of Beta-Blocker in Patients with Stable Angina. Cardiovasc Drugs Ther 25, 531–537 (2011). https://doi.org/10.1007/s10557-011-6327-3

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  • DOI: https://doi.org/10.1007/s10557-011-6327-3

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