, Volume 67, Issue 3, pp 393–405 | Cite as

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
  • Witold Ruzyllo
  • Michal Tendera
  • Ian Ford
  • Kim M. Fox
Original Research Article


Background and objective: Current medical therapies for the symptoms of angina pectoris aim to improve oxygen supply and reduce oxygen demand in the myocardium. Not all patients respond to current antianginal monotherapy, or even combination therapy, and a new class of antianginal drug that complements existing therapies would be useful. This study was undertaken to compare the antianginal and anti-ischaemic effects of the novel heart-rate-lowering agent ivabradine and of the calcium channel antagonist amlodipine.

Patients and methods: Patients with a ≥3-month history of chronic, stable effortinduced angina were randomised to receive ivabradine 7.5mg (n = 400) or 10mg (n = 391) twice daily or amlodipine 10mg once daily (n = 404) for a 3-month, double-blind period. Bicycle exercise tolerance tests were performed at baseline and monthly intervals. The primary efficacy criterion was the change from baseline in total exercise duration after 3 months of treatment. Secondary efficacy criteria included changes in time to angina onset and time to lmm ST-segment depression, rate-pressure product at trough drug activity, as well as short-acting nitrate use and anginal attack frequency (as recorded in patient diaries).

Results: At 3 months, total exercise duration was improved by 27.6 ± 91.7, 21.7 ± 94.5 and 31.2 ± 92.0 seconds with ivabradine 7.5 and 10mg and amlodipine, respectively, both ivabradine groups were comparable to amlodipine (p-value for noninferiority < 0.001). Similar results were observed for time to angina onset and time to lmm ST-segment depression. Heart rate decreased significantly by 11–13 beats/min at rest and by 12–15 beats/min at peak of exercise with ivabradine but not amlodipine, and rate-pressure product decreased more with ivabradine than amlodipine (p-value vs amlodipine <0.001, at rest and at peak of exercise). Anginal attack frequency and short-acting nitrate use decreased substantially in all treatment groups with no significant difference between treatment groups. The most frequent adverse events were visual symptoms and sinus bradycardia with ivabradine (0.8% and 0.4% withdrawals, respectively) and peripheral oedema with amlodipine (1.5% withdrawals).

Conclusions: In patients with stable angina, ivabradine has comparable efficacy to amlodipine in improving exercise tolerance, a superior effect on the reduction of rate-pressure product (a surrogate marker of myocardial oxygen consumption) and similar safety.


Amlodipine Stable Angina Ivabradine Calcium Channel Antagonist Daily Group 
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This study was supported by Servier, France. Each of the authors has received an honorarium for committee membership in association with this study.

List of investigators:

Czech Republic: Dr J. Widimsky, Dr O. Jerabek, Dr J. Florian, Dr J. Ulman, Dr M. Rubacek, Dr Z. Lorenc, Dr O. Mayer, Dr I. Oral, Dr J. Nagel, Dr L. Berka, Dr H. Krejcova, Dr K. Kamenik, Dr T. Brabec, Dr J. Kost’ak

Denmark: Prof. J. Aldershvile, Dr P. Grande, Dr K. Egstrup, Dr H. Nielsen, Dr K.E. Pedersen, Dr T. Nielsen, Dr P. Hildebrandt, Dr L. Kober, Dr H. Ulriksen, Dr D.J. Markenvard, Dr K. Skagen, Dr H. Rickers

Finland: Dr J. Hartikainen, Dr K. Peuhkurinnen, Dr P.-E. Wingren, Dr J. Juvonan, Dr A. Karkkainen, Dr M. Huttunen, Dr H. Sodervik, Dr J. Melin, Dr A. Kokko, Dr T. Hamalainen, Dr P. Kettunen, Dr S. Pohjola-Sintonen, Dr J. Karmakoski, Dr M. Niemela

Hungary: Dr S. Timar, Dr F. Lakatos, Dr A. Papp, Dr C. Toth, Dr E. Kalo, Prof. J. Tenczer, Dr G. Veress, Prof. I. Preda, Prof. E. Kekes, Dr B. Barsi, Prof. I. Edes, Prof. C. Balazs, Dr J. Tomcsanyi, Dr A. Matoltsy, Dr A. Cziraki, Dr J. Tarjan, Dr D. Apro

Norway: Dr K. Gjesdal, Dr T. Indrebo, Dr D. Torvik, Dr A. Nesvold, Dr A. Andersen, Dr S. Njalla, Dr E. Hauge, Dr T. Holm, Dr K. Loland-Jacobsen, Dr O. Vikesdal, Dr J. Kjekshus, Dr H. Istad, Dr F. Kontny, Dr F. Wandel

Poland: Prof. Adamus, Prof. M. Krzeminska-Pakula, Prof. W. Ruzyllo, Dr Trojnar, Dr Chmielinski, Dr Kozlowski, Dr Sinkiewicz, Dr Achremczyk, Dr K. Janik, Dr T. Marczyk, Dr W. Piotrowski, Prof. K. Kawecka-Jaszcz, Prof. J. Dubiel, Dr S. Malinowski, Prof. A. Pluta, Prof. Cieslinski, Dr W. Pluta, Dr K. Jaworska, Dr M. Piepiorka, Prof. W. Banasiak, Dr Kleinrok, Dr Kurowski, Dr Malinski, Prof. M. Dluzniewski

Russia: Prof. V. Tsyrline, Prof. E. Kuleshova, Prof. Konstantinov, Prof. E. Shliakhto, Dr E. Nifontov, Dr B. Goloschekin, Dr S. Minkin, Prof. E. Zemtsovsky, Dr E. Varga, Dr M. Balyuzek, Dr A. Kuchinsky, Dr G. Katashkova, Dr E. Zhukova, Dr A. Ronzhin, Dr V. Kostenko, Prof. S. Churina, Prof. Y. Lukjanov, Prof. A. Obrezan, Dr D.A. Zverev, Dr A.V. Strekalovsky, Dr S. Dobrodeev, Prof. O.L. Barbarash, Dr P. Yakhontova, Dr A.A. Kolomiets, Dr V.I. Fialkovsky, Dr E. Pavlyukova, Dr G.A. Choumakova

Slovak Republic: Dr S. Filipova, Dr J. Sirotiakova, Dr G. Kamensky, Dr J. Mazur, Dr A. Banikova, Dr T. Duris

Sweden: Dr B. Karlson, Dr J. Herlitz, Dr B. Persson, Dr M. Dellborg, Dr G. Ulvenstam, Dr P. Hardhammer, Dr T. Johansson, Dr L. Kareld, Dr P. Pettersson, Dr A. Sjostrand, Dr T. Carlsson, Dr L. Erhardt, Dr P. Lofdahl, Dr J. Perk, Dr G. Stehn, Dr A. Tisell, Dr A. Torp, Dr U. Ahremark, Dr B. Petersson, Dr C. Hoglund, Dr J.E. Frisell, Dr H. Nilsson, Dr T. Fraser, Dr J. Ellstrom, Dr L. Juntti, Dr A. Andersson, Dr M. Henning, Dr V. Engblom

The Netherlands: Dr G.C.M. Linssen, Dr R. Dijkgraaf, Dr Kuijer, Dr A. Withagen, Dr P. Van Rossum, Dr R.F. Veldkamp.

Expert Committee: Prof. K. Fox, Royal Brompton Hospital (London, UK), Prof. M. Tendera, Silesian School of Medicine (Katowice, Poland), Prof. I. Ford, Robertson Centre for Biostatistics (Glasgow, UK).


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Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  • Witold Ruzyllo
    • 1
  • Michal Tendera
    • 2
  • Ian Ford
    • 3
  • Kim M. Fox
    • 4
  1. 1.Department of Coronary Artery Disease and Cardiac Catheterization LaboratoryNational Institute of CardiologyWarsawPoland
  2. 2.3rd Division of CardiologySilesian School of MedicineKatowicePoland
  3. 3.Robertson Centre for BiostatisticsUniversity of GlasgowGlasgowUK
  4. 4.Royal Brompton HospitalLondonUK

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