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European Heart Journal Advance Access originally published online on January 9, 2009
European Heart Journal 2009 30(5):540-548; doi:10.1093/eurheartj/ehn571
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Efficacy of the If current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy: a 4-month, randomized, placebo-controlled trial

Jean-Claude Tardif1,*, Piotr Ponikowski2,3, Thomas Kahan4 for the ASSOCIATE study Investigators

1 Montreal Heart Institute, Université de Montreal, 5000 Belanger Street, Montreal, Quebec, Canada H1T 1C8
2 Clinical Military Hospital, Wroclaw, Poland
3 Wroclaw Medical University (2nd Cardiology Department), Wroclaw, Poland
4 Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden

Received 25 July 2008; revised 18 November 2008; accepted 27 November 2008; online publish-ahead-of-print 9 January 2009.

* Corresponding author. Tel: +1 514 376 3330 ext. 3564, Fax: +1 514 376 1355, Email: jean-claude.tardif{at}icm-mhi.org

See page 524 for the editorial comment on this article (doi:10.1093/eurheartj/ehp027)

Aims: To evaluate the anti-anginal and anti-ischaemic efficacy of the selective If current inhibitor ivabradine in patients with chronic stable angina pectoris receiving beta-blocker therapy.

Methods and results: In this double-blinded trial, 889 patients with stable angina receiving atenolol 50 mg/day were randomized to receive ivabradine 5 mg b.i.d. for 2 months, increased to 7.5 mg b.i.d. for a further 2 months, or placebo. Patients underwent treadmill exercise tests at the trough of drug activity using the standard Bruce protocol for randomization and at 2 and 4 months. Total exercise duration at 4 months increased by 24.3 ± 65.3 s in the ivabradine group, compared with 7.7 ± 63.8 s with placebo (P < 0.001). Ivabradine was superior to placebo for all exercise test criteria at 4 months (P < 0.001 for all) and 2 months (P-values between <0.001 and 0.018). Ivabradine in combination with atenolol was well tolerated. Only 1.1% of patients withdrew owing to sinus bradycardia in the ivabradine group.

Conclusion: The combination of ivabradine 7.5 mg b.i.d. and atenolol at the commonly used dosage in clinical practice in patients with chronic stable angina pectoris produced additional efficacy with no untoward effect on safety or tolerability.

Key Words: Ivabradine • Myocardial ischaemia • Stable angina pectoris • Heart rate • If inhibition • Combination therapy


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