New EU Drug Indication Allows Combination With Beta Blockers for Angina
December 15, 2009 - The European Medicines Agency (EMEA) recently approved a new indication for Procoralan (ivabradine) for chronic, stable angina patients, who remain inadequately controlled despite an optimal dose of beta blockers, and whose heart rate is above 60 beats per minute.
In October 2005, Procoralan was approved by the EMEA for clinical use in symptomatic treatment of chronic stable angina patients in sinus rhythm, unable to tolerate or with a contraindication to the use of beta blockers. Subsequently Servier, the drug’s manufacturer, said a great deal of new information concerning the clinical benefits of Procoralan has been published. In particular, the results of ASSOCIATE(1) and the BEAUTIFUL trial(2) have influenced the change in indication.
The results of the ASSOCIATE trial performed in 889 patients showed that Procoralan, given on top of atenolol 50 mg o.d, showed additional efficacy on all exercise tolerance test (ETT) parameters at trough of drug activity. The results of this trial have particular significance because despite the fact that combination therapy is widely used in clinical practice to achieve adequate control of angina, clinical trials evaluating combination therapy have yielded inconsistent results.
“The ASSOCIATE study, in terms of the size of the trial, the compliance with regulatory recommendations, and the consistency of significant improvements across all ETT criteria and time points, represents perhaps the most compelling single demonstration of the benefit of any combination of anti-anginal drugs published to date,” said the study lead investigator Dr Jean-Claude Tardif, from the Montreal Heart Institute in Canada.
BEAUTIFUL was a large outcome study done in 10,917 patients with coronary artery disease and left ventricular dysfunction (LVEF below 42 percent) on top of optimal background therapy with 86.9 percent of patients receiving beta-blockers. A specific analysis in patients with limiting angina showed that patients on Procoralan had a lesser risk of having a heart attack, of getting admitted to hospital for heart failure or cardiovascular death (Procoralan 12 percent versus placebo 15.5 percent).
Procoralan was well tolerated in both these studies. ASSOCIATE and BEAUTIFUL have been mentioned in the new updated summary of product characteristics.
“Procoralan has proven anti-anginal efficacy and may also prevent cardiovascular events in angina patients. This new indication will permit us to better treat the large number of chronic stable patients who remain uncontrolled despite receiving a beta blocker,” comments Prof K Fox from the Royal Brompton hospital, UK who has participated in several clinical trials on Procoralan.
For more information: www.servier.co.uk
(1) Tardif JC, Ponikowski P, Kahan T; ASSOCIATE study investigators. “Efficacy of the If current inhibitor ivabradine in patients with chronic stable angina receiving beta blocker therapy: a four month, randomized, placebo-controlled trial.” European Heart Journal. 2009;30:540-548.
(2) Fox K, Ford I, Steg PG, et al. on behalf of the BEAUTIFUL investigators. “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.” European Heart Journal, 2009;30, 2337-2345.