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Heart rate-lowering efficacy and respiratory safety of ivabradine in patients with obstructive airway disease: a randomized, double-blind, placebo-controlled, crossover study
American Journal of Cardiovascular Drugs, 05/31/2012
Clinical Article
Majewski S et al. – This study demonstrated that selective heart rate (HR) reduction with ivabradine is effective in patients with asthma and chronic obstructive pulmonary disease (COPD), with no alteration in respiratory function or symptoms over the duration of the study. Ivabradine offers an interesting alternative, as an HR–lowering agent, in patients with respiratory disease and contraindications to β–blockers.
Methods- This was a randomized, single–center, double–blind, placebo–controlled, crossover trial.
- Enrolment began in May 2009, and the last patient completed the study in January 2011.
- The study was conducted in an ambulatory setting.
- A total of 40 patients completed the study (20 asthmatic patients and 20 COPD patients).
- Inclusion criteria were: documented diagnosis of asthma or COPD according to international guidelines, age 18–75 years, and mean HR on Holter ECG recording of ≥60beats/min.
- Exclusion criteria included disease exacerbation in a previous month or inability to understand instructions on the study procedures.
- All patients received ivabradine 7.5mg twice daily for 5 days and placebo twice daily for 5 days in a crossover manner, in one of the two arms of the study, with at least 2 days of washout between treatments.
- The main outcome measures included the difference in HR between ivabradine and placebo treatment and change in HR in comparison with baseline.
- Other evaluated outcomes were differences in the peak expiratory flow rate (PEFR), the daily symptom score, rescue medication consumption, and AEs.
- Ivabradine produced significantly lower mean HR than placebo in both groups of patients: asthma 67.4±8.38 versus 82.85±11.19beats/min (p<0.001) and COPD 69.75±8.9 versus 81.05±9.75beats/min (p<0.001).
- Similar results were observed for the minimal HR as well as for the maximal noted HR.
- In comparision with baseline, ivabradine significantly reduced HR in both groups of studied patients (all p<0.05), whereas placebo did not have such an effect.
- No significant difference, in either the asthma or the COPD group, was found between ivabradine and placebo in morning and evening peak expiratory flow rate, peak expiratory flow diurnal variability, daily symptom scores, and rescue medication usage (all p>0.05).
- Both treatments were well tolerated.
- The incidence of AEs was low and generally similar in both periods of treatment, except for visual symptoms during treatment with ivabradine, which was reported by 5% of the patients.