New Data Demonstrates Efficacy Of Procoralan(R) (ivabradine) And Beta-Blocker Combination In Chronic Stable Angina

Main Category: Cardiovascular / Cardiology
Article Date: 15 Aug 2008 - 0:00 PDT

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Primary results of a randomised, double-blind, placebo controlled trial demonstrate the anti-ischaemic efficacy of ivabradine given in combination with a commonly used dose of atenolol in patients with stable angina.1 These data demonstrate that ivabradine significantly improves all exercise tolerance test (ETT) parameters - total exercise duration (TED), time to onset of angina, time to ST depression and time to limiting angina - in patients already treated with a beta blocker.1 This significant increase from baseline of all ETT parameters was associated with a mean heart rate reduction of 9 beats per minute (bpm).1

The trial was designed to evaluate whether ivabradine provides additional anti-ischaemic and anti-anginal efficacy in patients taking atenolol 50 mg od monotherapy, over a four month period. 889 patients (84% men) with a mean age of 60 years, diagnosed with coronary artery disease (CAD) and with a history of stable angina, participated in the study. The baseline mean resting heart rate was 67 bpm.

Patients were randomised to receive either 5 mg bd of ivabradine (up-titrated to 7.5 mg bd in 87.5% of patients after two months), or placebo, in combination with atenolol 50 mg od‎1 - a dose that reflects the average UK dose in this patient group.3

Patients underwent treadmill ETT (Bruce protocol), to evaluate the time to objective myocardial ischaemia (1mm ST depression), time to anginal symptoms (angina onset and limiting angina), and total exercise duration, at the trough of drug activity. After four months of treatment, patients receiving the combination of ivabradine and atenolol had significant improvements in their treadmill ETT parameters. Patient withdrawal due to sinus bradycardia was 1.1%, compared with 0% in the placebo group.1

Previously published data suggests that in patients with CAD, a high resting heart rate is linked to a higher risk of cardiovascular mortality.4 In addition, the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of stable angina suggests it may be beneficial to adjust the dose of beta-blockers to reduce heart rate at rest to 55-60 bpm.5

Commenting on the study, Eve Knight from the British Cardiac Patients Association said, "The results of this study are very encouraging, with the potential to change the way stable angina is managed. Due to concerns regarding the tolerability of beta-blockers, patients tend to receive low doses which may not provide optimal heart rate reduction. The results of this study suggest that the combination of ivabradine and atenolol shows real promise in the treatment of patients with stable angina."

The use of ivabradine in combination with a beta blocker falls outside the current UK indication for ivabradine. Ivabradine is licensed for the symptomatic treatment of chronic stable angina pectoris in patients with normal sinus rhythm who have a contraindication or intolerance for beta-blockers.6

Full results of this study are due to be presented at the European Society of Cardiology (ESC) Congress, Munich (30 August - 3 September).

Ivabradine (Procoralan®) is a novel class of compound (the first selective sinus node If inhibitor), a specific heart-rate lowering agent, that reduces heart rate without affecting intracardiac conduction or myocardial contractility. It is an anti-ischaemic agent that is licensed for the symptomatic treatment of chronic stable angina pectoris in patients with normal sinus rhythm who have a contraindication or intolerance for beta-blockers. 5

The Bruce Protocol Stress Test was designed by Dr Robert Bruce in 1963 as a clinical test to evaluate patients with suspected coronary heart disease, though it can also be used to estimate cardiovascular fitness. Exercise is performed on a treadmill and at three minute intervals the incline and speed of the treadmill increases.

The British Cardiac Patients Association is a non profit making organisation run by volunteers and established to provide support to cardiac patients and their carers http://www.bcpa.co.uk

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Servier Laboratories Limited is the British subsidiary of the Servier Research Group, a leading French based organisation specialising in ethical pharmaceuticals. Servier is currently within the top 15 largest pharmaceutical companies in the UK.

Servier's product portfolio in the UK focuses on the therapeutic areas of cardiovascular disease, diabetes and osteoporosis. Servier's R&D pipeline is extremely healthy having the potential to submit one product for license every year for the next 8 to 10 years. http://www.servier.co.uk

References

1. Tardif et al. Fundam Clin Parmacol 2008 ; 22(suppl 1) : 96 (Abstract 475)
2. CSD Patient Data, Cegedim Strategic Data UK Ltd, December 2007
3. Diaz A et al; Eur Heart J 2005;26:967-974
4. Gibbons RJ et al;ACC/AHA Practice Guidelines 2002; 1-124. ACC - http://www.acc.org; AHA - http://www.americanheart.org last accessed March 2008.
5. Procoralan SmPC. http://emc.medicines.org.uk

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