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Open Access 01-02-2015 | Original Research

Ivabradine in Combination with Beta-Blockers in Patients with Chronic Stable Angina After Percutaneous Coronary Intervention

Authors: Karl Werdan, Henning Ebelt, Sebastian Nuding, Florian Höpfner, Georg Stöckl, Ursula Müller-Werdan

Published in: Advances in Therapy | Issue 2/2015

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Abstract

Introduction

The anti-anginal efficacy of ivabradine is well established. We describe a post hoc analysis in the ADDITIONS database to investigate effectiveness and tolerability of ivabradine in combination with beta-blocker in patients with angina who have had a percutaneous coronary intervention (PCI).

Methods

ADDITIONS was a non-interventional, multicenter prospective study including 2,330 patients with stable angina. In addition to beta-blocker, patients were treated with ivabradine in approved dosages for 4 months. We divided the population according to whether they had previously had a PCI or not, and explored the effect of ivabradine on heart rate, number of weekly angina attacks, frequency of nitrate consumption, as well as quality of life (QoL) and tolerability.

Results

Data were available for 2,319 patients, of whom 51.4% had previously had a PCI. There was no difference in the effect of ivabradine on mean heart rate between patients with a previous PCI [64.4 ± 7.6 beats per minute (bpm)] than those without (66.8 ± 8.5 bpm) at 4 months (both P < 0.0001). Similarly, the number of angina attacks decreased from 1.9 ± 2.4 to 0.5 ± 1.5 per week in patients with a previous PCI and 1.5 ± 2.0 to 0.3 ± 1.0 per week in patients without a previous PCI (both P < 0.0001). The frequency of nitrate consumption fell from 2.7 ± 3.7 to 1.0 ± 1.9 per week and 1.8 ± 2.8 to 0.6 ± 1.5 per week (both P < 0.0001) in patients with and without a previous PCI, respectively. There was no difference in the improvements in Canadian Cardiovascular Society class of angina, QoL, and physicians’ assessment of effectiveness and tolerability between patients with a previous PCI and those without.

Conclusion

Ivabradine is an effective and well-tolerated anti-anginal treatment in patients with stable angina after PCI. Ivabradine reduced the frequency of weekly angina attacks and nitrate consumption, led to an improvement in Canadian Cardiovascular Society class and a substantial improvement in the QoL of stable angina patients.
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Literature
2.
go back to reference Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013;34(38):2949–3003.CrossRefPubMed Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013;34(38):2949–3003.CrossRefPubMed
3.
go back to reference Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012;126(25):e354–471.CrossRefPubMed Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012;126(25):e354–471.CrossRefPubMed
4.
go back to reference Steg PG, Greenlaw N, Tardif JC, et al. Women and men with stable coronary artery disease have similar clinical outcomes: insights from the international prospective CLARIFY registry. Eur Heart J. 2012;33(22):2831–40.CrossRefPubMedCentralPubMed Steg PG, Greenlaw N, Tardif JC, et al. Women and men with stable coronary artery disease have similar clinical outcomes: insights from the international prospective CLARIFY registry. Eur Heart J. 2012;33(22):2831–40.CrossRefPubMedCentralPubMed
5.
go back to reference Ferrari R, Ford I, Greenlaw N, et al. Geographical variations in the prevalence and management of cardiovascular risk factors in outpatients with CAD: data from the contemporary CLARIFY registry. Eur J Prev Cardiol. 2014. Epub ahead of print. Ferrari R, Ford I, Greenlaw N, et al. Geographical variations in the prevalence and management of cardiovascular risk factors in outpatients with CAD: data from the contemporary CLARIFY registry. Eur J Prev Cardiol. 2014. Epub ahead of print.
6.
go back to reference Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2163–96.CrossRefPubMed Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2163–96.CrossRefPubMed
7.
go back to reference Coronary angioplasty versus medical therapy for angina: the second Randomised Intervention Treatment of Angina (RITA-2) trial. RITA-2 trial participants. Lancet. 1997;350(9076):461–8. Coronary angioplasty versus medical therapy for angina: the second Randomised Intervention Treatment of Angina (RITA-2) trial. RITA-2 trial participants. Lancet. 1997;350(9076):461–8.
8.
go back to reference Henderson RA, Pocock SJ, Clayton TC, et al. Seven-year outcome in the RITA-2 trial: coronary angioplasty versus medical therapy. J Am Coll Cardiol. 2003;42(7):1161–70.CrossRefPubMed Henderson RA, Pocock SJ, Clayton TC, et al. Seven-year outcome in the RITA-2 trial: coronary angioplasty versus medical therapy. J Am Coll Cardiol. 2003;42(7):1161–70.CrossRefPubMed
9.
go back to reference Parisi AF, Folland ED, Hartigan P. A comparison of angioplasty with medical therapy in the treatment of single-vessel coronary artery disease. Veterans Affairs ACME Investigators. N Engl J Med. 1992;326(1):10–6.CrossRefPubMed Parisi AF, Folland ED, Hartigan P. A comparison of angioplasty with medical therapy in the treatment of single-vessel coronary artery disease. Veterans Affairs ACME Investigators. N Engl J Med. 1992;326(1):10–6.CrossRefPubMed
10.
go back to reference Weintraub WS, Spertus JA, Kolm P, et al. Effect of PCI on quality of life in patients with stable coronary disease. N Engl J Med. 2008;359(7):677–87.CrossRefPubMed Weintraub WS, Spertus JA, Kolm P, et al. Effect of PCI on quality of life in patients with stable coronary disease. N Engl J Med. 2008;359(7):677–87.CrossRefPubMed
11.
go back to reference Holubkov R, Laskey WK, Haviland A, et al. Angina 1 year after percutaneous coronary intervention: a report from the NHLBI Dynamic Registry. Am Heart J. 2002;144(5):826–33.CrossRefPubMed Holubkov R, Laskey WK, Haviland A, et al. Angina 1 year after percutaneous coronary intervention: a report from the NHLBI Dynamic Registry. Am Heart J. 2002;144(5):826–33.CrossRefPubMed
12.
go back to reference Brorsson B, Bernstein SJ, Brook RH, Werko L. Quality of life of patients with chronic stable angina before and four years after coronary revascularisation compared with a normal population. Heart. 2002;87(2):140–5.CrossRefPubMedCentralPubMed Brorsson B, Bernstein SJ, Brook RH, Werko L. Quality of life of patients with chronic stable angina before and four years after coronary revascularisation compared with a normal population. Heart. 2002;87(2):140–5.CrossRefPubMedCentralPubMed
13.
go back to reference Maddox TM, Reid KJ, Spertus JA, et al. Angina at 1 year after myocardial infarction: prevalence and associated findings. Arch Intern Med. 2008;168(12):1310–6.CrossRefPubMed Maddox TM, Reid KJ, Spertus JA, et al. Angina at 1 year after myocardial infarction: prevalence and associated findings. Arch Intern Med. 2008;168(12):1310–6.CrossRefPubMed
14.
go back to reference Boden WE, O’Rourke RA, Teo KK, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007;356(15):1503–16.CrossRefPubMed Boden WE, O’Rourke RA, Teo KK, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007;356(15):1503–16.CrossRefPubMed
15.
go back to reference Pursnani S, Korley F, Gopaul R, et al. Percutaneous coronary intervention versus optimal medical therapy in stable coronary artery disease: a systematic review and meta-analysis of randomized clinical trials. Circ Cardiovasc Interv. 2012;5(4):476–90.CrossRefPubMed Pursnani S, Korley F, Gopaul R, et al. Percutaneous coronary intervention versus optimal medical therapy in stable coronary artery disease: a systematic review and meta-analysis of randomized clinical trials. Circ Cardiovasc Interv. 2012;5(4):476–90.CrossRefPubMed
16.
go back to reference Stergiopoulos K, Brown DL. Initial coronary stent implantation with medical therapy vs medical therapy alone for stable coronary artery disease: meta-analysis of randomized controlled trials. Arch Intern Med. 2012;172(4):312–9.CrossRefPubMed Stergiopoulos K, Brown DL. Initial coronary stent implantation with medical therapy vs medical therapy alone for stable coronary artery disease: meta-analysis of randomized controlled trials. Arch Intern Med. 2012;172(4):312–9.CrossRefPubMed
17.
go back to reference De Bruyne B, Fearon WF, Pijls NH, et al. Fractional flow reserve-guided PCI for stable coronary artery disease. N Engl J Med. 2014;371(13):1208–17.CrossRefPubMed De Bruyne B, Fearon WF, Pijls NH, et al. Fractional flow reserve-guided PCI for stable coronary artery disease. N Engl J Med. 2014;371(13):1208–17.CrossRefPubMed
18.
go back to reference Borden WB, Redberg RF, Mushlin AI, Dai D, Kaltenbach LA, Spertus JA. Patterns and intensity of medical therapy in patients undergoing percutaneous coronary intervention. JAMA. 2011;305(18):1882–9.CrossRefPubMed Borden WB, Redberg RF, Mushlin AI, Dai D, Kaltenbach LA, Spertus JA. Patterns and intensity of medical therapy in patients undergoing percutaneous coronary intervention. JAMA. 2011;305(18):1882–9.CrossRefPubMed
20.
go back to reference 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(6):817–23.CrossRefPubMed 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(6):817–23.CrossRefPubMed
21.
go back to reference 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(23):2529–36.CrossRefPubMed 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(23):2529–36.CrossRefPubMed
22.
go back to reference 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(3):393–405.CrossRefPubMed 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(3):393–405.CrossRefPubMed
23.
go back to reference Koester R, Kaehler J, Ebelt H, Soeffker G, Werdan K, Meinertz T. Ivabradine in combination with beta-blocker therapy for the treatment of stable angina pectoris in every day clinical practice. Clin Res Cardiol. 2010;99(10):665–72.CrossRefPubMed Koester R, Kaehler J, Ebelt H, Soeffker G, Werdan K, Meinertz T. Ivabradine in combination with beta-blocker therapy for the treatment of stable angina pectoris in every day clinical practice. Clin Res Cardiol. 2010;99(10):665–72.CrossRefPubMed
24.
go back to reference Werdan K, Ebelt H, Nuding S, Hopfner F, Hack G, Muller-Werdan U. Ivabradine in combination with beta-blocker improves symptoms and quality of life in patients with stable angina pectoris: results from the ADDITIONS study. Clin Res Cardiol. 2012;101(5):365–73.CrossRefPubMed Werdan K, Ebelt H, Nuding S, Hopfner F, Hack G, Muller-Werdan U. Ivabradine in combination with beta-blocker improves symptoms and quality of life in patients with stable angina pectoris: results from the ADDITIONS study. Clin Res Cardiol. 2012;101(5):365–73.CrossRefPubMed
25.
26.
go back to reference Tendera M, Borer J, Tardif J. Efficacy of I(f) inhibition with ivabradine in different subpopulations with stable angina pectoris. Cardiology. 2009;114(2):116–25.CrossRefPubMed Tendera M, Borer J, Tardif J. Efficacy of I(f) inhibition with ivabradine in different subpopulations with stable angina pectoris. Cardiology. 2009;114(2):116–25.CrossRefPubMed
27.
go back to reference Holmes DR Jr, Gersh BJ, Whitlow P, King SB III, Dove JT. Percutaneous coronary intervention for chronic stable angina: a reassessment. JACC Cardiovasc Interv. 2008;1(1):34–43.CrossRefPubMed Holmes DR Jr, Gersh BJ, Whitlow P, King SB III, Dove JT. Percutaneous coronary intervention for chronic stable angina: a reassessment. JACC Cardiovasc Interv. 2008;1(1):34–43.CrossRefPubMed
28.
29.
go back to reference Trikalinos TA, Sheikh-Ali AA, Tatsioni A, Nallamothu BK, Kent DM. Percutaneous coronary interventions for non-acute coronary artery disease: a quantitative 20-year synopsis and a network meta-analysis. Lancet. 2009;373(9667):911–8.CrossRefPubMedCentralPubMed Trikalinos TA, Sheikh-Ali AA, Tatsioni A, Nallamothu BK, Kent DM. Percutaneous coronary interventions for non-acute coronary artery disease: a quantitative 20-year synopsis and a network meta-analysis. Lancet. 2009;373(9667):911–8.CrossRefPubMedCentralPubMed
30.
go back to reference Fang JC. Underestimating medical therapy for coronary disease… again. N Engl J Med. 2011;364(17):1671–3.CrossRefPubMed Fang JC. Underestimating medical therapy for coronary disease… again. N Engl J Med. 2011;364(17):1671–3.CrossRefPubMed
31.
go back to reference Fox KM, Ferrari R. Heart rate: a forgotten link in coronary artery disease? Nat Rev Cardiol. 2011;8(7):369–79.CrossRefPubMed Fox KM, Ferrari R. Heart rate: a forgotten link in coronary artery disease? Nat Rev Cardiol. 2011;8(7):369–79.CrossRefPubMed
32.
go back to reference Deedwania PC, Carbajal EV. Role of myocardial oxygen demand in the pathogenesis of silent ischemia during daily life. Am J Cardiol. 1992;70(16):19F–24F.CrossRefPubMed Deedwania PC, Carbajal EV. Role of myocardial oxygen demand in the pathogenesis of silent ischemia during daily life. Am J Cardiol. 1992;70(16):19F–24F.CrossRefPubMed
33.
go back to reference Hinderliter A, Miller P, Bragdon E, Ballenger M, Sheps D. Myocardial ischemia during daily activities: the importance of increased myocardial oxygen demand. J Am Coll Cardiol. 1991;18(2):405–12.CrossRefPubMed Hinderliter A, Miller P, Bragdon E, Ballenger M, Sheps D. Myocardial ischemia during daily activities: the importance of increased myocardial oxygen demand. J Am Coll Cardiol. 1991;18(2):405–12.CrossRefPubMed
34.
go back to reference McLenachan JM, Weidinger FF, Barry J, et al. Relations between heart rate, ischemia, and drug therapy during daily life in patients with coronary artery disease. Circulation. 1991;83(4):1263–70.CrossRefPubMed McLenachan JM, Weidinger FF, Barry J, et al. Relations between heart rate, ischemia, and drug therapy during daily life in patients with coronary artery disease. Circulation. 1991;83(4):1263–70.CrossRefPubMed
35.
go back to reference Daly CA, Clemens F, Sendon JL, et al. Inadequate control of heart rate in patients with stable angina: results from the European heart survey. Postgrad Med J. 2010;86(1014):212–7.CrossRefPubMed Daly CA, Clemens F, Sendon JL, et al. Inadequate control of heart rate in patients with stable angina: results from the European heart survey. Postgrad Med J. 2010;86(1014):212–7.CrossRefPubMed
36.
go back to reference Colin P, Ghaleh B, Monnet X, et al. Contributions of heart rate and contractility to myocardial oxygen balance during exercise. Am J Physiol Heart Circ Physiol. 2003;284(2):H676–82.CrossRefPubMed Colin P, Ghaleh B, Monnet X, et al. Contributions of heart rate and contractility to myocardial oxygen balance during exercise. Am J Physiol Heart Circ Physiol. 2003;284(2):H676–82.CrossRefPubMed
37.
go back to reference 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(2):659–66.PubMed 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(2):659–66.PubMed
38.
go back to reference Gloekler S, Traupe T, Stoller M, et al. The effect of heart rate reduction by ivabradine on collateral function in patients with chronic stable coronary artery disease. Heart. 2014;100(2):160–6.CrossRefPubMed Gloekler S, Traupe T, Stoller M, et al. The effect of heart rate reduction by ivabradine on collateral function in patients with chronic stable coronary artery disease. Heart. 2014;100(2):160–6.CrossRefPubMed
39.
go back to reference Heusch G. Heart rate in the pathophysiology of coronary blood flow and myocardial ischaemia: benefit from selective bradycardic agents. Br J Pharmacol. 2008;153(8):1589–601.CrossRefPubMedCentralPubMed Heusch G. Heart rate in the pathophysiology of coronary blood flow and myocardial ischaemia: benefit from selective bradycardic agents. Br J Pharmacol. 2008;153(8):1589–601.CrossRefPubMedCentralPubMed
40.
go back to reference Tardif JC, Ponikowski P, Kahan T. 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;30(5):540–8.CrossRefPubMedCentralPubMed Tardif JC, Ponikowski P, Kahan T. 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;30(5):540–8.CrossRefPubMedCentralPubMed
41.
42.
go back to reference Borer JS, Heuzey JY. Characterization of the heart rate-lowering action of ivabradine, a selective I(f) current inhibitor. Am J Ther. 2008;15(5):461–73.CrossRefPubMed Borer JS, Heuzey JY. Characterization of the heart rate-lowering action of ivabradine, a selective I(f) current inhibitor. Am J Ther. 2008;15(5):461–73.CrossRefPubMed
43.
go back to reference Gardner AW, Montgomery PS, Ritti-Dias RM, Thadani U. Exercise performance, physical activity, and health-related quality of life in participants with stable angina. Angiology. 2011;62(6):461–6.CrossRefPubMedCentralPubMed Gardner AW, Montgomery PS, Ritti-Dias RM, Thadani U. Exercise performance, physical activity, and health-related quality of life in participants with stable angina. Angiology. 2011;62(6):461–6.CrossRefPubMedCentralPubMed
44.
go back to reference Beltrame JF, Weekes AJ, Morgan C, Tavella R, Spertus JA. The prevalence of weekly angina among patients with chronic stable angina in primary care practices: the Coronary Artery Disease in General Practice (CADENCE) Study. Arch Intern Med. 2009;169(16):1491–9.CrossRefPubMed Beltrame JF, Weekes AJ, Morgan C, Tavella R, Spertus JA. The prevalence of weekly angina among patients with chronic stable angina in primary care practices: the Coronary Artery Disease in General Practice (CADENCE) Study. Arch Intern Med. 2009;169(16):1491–9.CrossRefPubMed
45.
go back to reference Blankenship JC, Marshall JJ, Pinto DS, et al. Effect of percutaneous coronary intervention on quality of life: a consensus statement from the Society for Cardiovascular Angiography and Interventions. Catheter Cardiovasc Interv. 2013;81(2):243–59.CrossRefPubMed Blankenship JC, Marshall JJ, Pinto DS, et al. Effect of percutaneous coronary intervention on quality of life: a consensus statement from the Society for Cardiovascular Angiography and Interventions. Catheter Cardiovasc Interv. 2013;81(2):243–59.CrossRefPubMed
46.
go back to reference Fox K, Ford I, Steg PG, Tardif JC, Tendera M, Ferrari R. Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med. 2014;371(12):1091–9.CrossRefPubMed Fox K, Ford I, Steg PG, Tardif JC, Tendera M, Ferrari R. Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med. 2014;371(12):1091–9.CrossRefPubMed
Metadata
Title
Ivabradine in Combination with Beta-Blockers in Patients with Chronic Stable Angina After Percutaneous Coronary Intervention
Authors
Karl Werdan
Henning Ebelt
Sebastian Nuding
Florian Höpfner
Georg Stöckl
Ursula Müller-Werdan
Publication date
01-02-2015
Publisher
Springer Healthcare
Published in
Advances in Therapy / Issue 2/2015
Print ISSN: 0741-238X
Electronic ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-015-0182-8