Source: DGNews  |  Posted 8 years ago

By Peggy Peck

VIENNA, AUSTRIA -- September 2, 2003 -- In a head-to-head study, escalating doses of the investigational agent ivabradine -- the first of a new class of drugs called I(f) inhibitors -- demonstrated comparable efficacy and safety to atenolol for treatment of stable angina.

According to Jean-Claude Tardif, MD, assistant professor of medicine, Montreal Heart Institute, Montreal, Canada, ivabradine has none of the side effects associated with beta blockers. Dr. Tardif presented results of the INITIATIVE study at the European Society of Cardiology Congress 2003 here on August 31st.

The study enrolled 939 patients who had stable angina for 3 months or longer and a documented history of coronary artery disease (CAD). Patients were randomized to either ivabradine 5 mg once a day or 7.5 mg bid or to atenolol 50 mg for 4 weeks. After a month, all groups were force titrated to higher doses: ivabradine 7.5 mg or 10 mg bid or atenolol 100 mg once a day. Patients underwent treadmill tests at randomization, at 1 month and again at 4 months.

In the study ivabradine demonstrated comparable efficacy for improving exercise capacity and increasing time to exercise-induced ischemia compared to atenolol. Total mean exercise duration at trough increased by 86.8 seconds with ivabradine 7.5 mg bid and by 91.7 seconds with ivabradine 10 mg bid compared with an increase of 78.8 with atenolol 100 mg, said Dr. Tardif.

In an interview he said the most impressive aspect of the new drug is its lack of side effects. "We didn't observe any of the sexual dysfunction, fatigue, bronchospasm or [atrioventricular] block seen with beta blockers."

Sidney Smith, Jr., MD, professor of medicine, University of North Carolina, Chapel Hill, said the study results "suggest that ivabradine has the potential to be a helpful addition to our therapies that can improve the lifestyle for patients with coronary disease. But it will be important to determine whether it does reduce mortality and cardiac events."

Dr. Smith said a particularly interesting finding from the INITIATIVE study is the lack of bronchospasm. "This is a problem for many patients on beta blockers and this drug could be useful for those patients," he said.

Ivabradine is being developed by Servier and will be marketed under the name Procoralan. It is the first of a new class of drugs called selective and specific I(f) inhibitors.

Vidal Benatar, MD, director cardio-respiratory unit, Servier, explained the class name this way: "the I stands for conduction and the f is for 'funny' because when these ions were first detected in the sodium/potassium channels they were called funny currents."

Dr. Tardif said the drug reduces heart rate by "specific action in the sinoatrial node."

Total exercise duration improved at 1 month, said Dr. Tardif and again at 4 months. He said time to exercise-induced ischemia and time to 1 mm ST segment depression also "consistently increased."

The only downside reported by ivabradine users was "mild visual symptoms that caused five patients to discontinue treatment.

Dr. Benatar said Servier plans to seek approval "first in Europe, then Canada and then the United States. We anticipate approval in Europe sometime next year."

[Study title: Anti-anginal and anti-ischaemic effects of the If current inhibitor ivabradine versus atenolol in stable angina. A 4-month randomised, double-blind, multicenter trial. Abstract 186]