PMID- 22409211
OWN - NLM
STAT- MEDLINE
DCOM- 20120910
LR  - 20181201
IS  - 1179-187X (Electronic)
IS  - 1175-3277 (Linking)
VI  - 12
IP  - 3
DP  - 2012 Jun 1
TI  - Heart rate-lowering efficacy and respiratory safety of ivabradine in patients 
      with obstructive airway disease: a randomized, double-blind, placebo-controlled, 
      crossover study.
PG  - 179-88
LID - 10.2165/11597400-000000000-00000 [doi]
AB  - BACKGROUND: There is substantial evidence that heart rate (HR) is a powerful 
      predictor of mortality in both normal individuals and in patients with 
      cardiovascular disease. The use of beta-adrenoceptor antagonists (beta-blockers) has 
      confirmed the importance of lowering elevated HR in a patient's prognosis. 
      However, these agents can have undesirable adverse effects (AEs) and due to the 
      risk of bronchoconstriction are contraindicated in patients with obstructive 
      airway disease. A selective bradycardic agent, without such undesirable effects, 
      could be of therapeutic interest. Ivabradine, a new I(f) inhibitor that acts 
      specifically on the sino-atrial node, is a pure HR-lowering agent. OBJECTIVE: The 
      objective of this study was to assess HR-lowering efficacy and respiratory safety 
      of ivabradine in patients with asthma and chronic obstructive pulmonary disease 
      (COPD). 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 >/=60 beats/min. Exclusion criteria included disease 
      exacerbation in a previous month or inability to understand instructions on the 
      study procedures. All patients received ivabradine 7.5 mg 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. RESULTS: Ivabradine produced 
      significantly lower mean HR than placebo in both groups of patients: asthma 67.4 
      +/- 8.38 versus 82.85 +/- 11.19 beats/min (p < 0.001) and COPD 69.75 +/- 8.9 versus 
      81.05 +/- 9.75 beats/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. CONCLUSION: Our study 
      demonstrated that selective HR reduction with ivabradine is effective in patients 
      with asthma and 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 
      beta-blockers. CLINICAL TRIAL REGISTRATION: Registered at www.clinicaltrials.gov 
      (NCT01365286).
FAU - Majewski, Sebastian
AU  - Majewski S
AD  - Department of Pneumology and Allergy, Medical University of Lodz, Poland. 
      sebastian.majewski@umed.lodz.pl
FAU - Slomka, Sebastian
AU  - Slomka S
FAU - Zielinska-Wyderkiewicz, Ewa
AU  - Zielinska-Wyderkiewicz E
FAU - Ciebiada, Maciej
AU  - Ciebiada M
FAU - Gorski, Pawel
AU  - Gorski P
LA  - eng
SI  - ClinicalTrials.gov/NCT01365286
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - Am J Cardiovasc Drugs
JT  - American journal of cardiovascular drugs : drugs, devices, and other 
      interventions
JID - 100967755
RN  - 0 (Benzazepines)
RN  - 3H48L0LPZQ (Ivabradine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Asthma/*drug therapy
MH  - Benzazepines/adverse effects/pharmacology/*therapeutic use
MH  - Cross-Over Studies
MH  - Double-Blind Method
MH  - Female
MH  - Heart Rate/*drug effects
MH  - Humans
MH  - Ivabradine
MH  - Male
MH  - Middle Aged
MH  - Peak Expiratory Flow Rate/drug effects
MH  - Pulmonary Disease, Chronic Obstructive/*drug therapy
MH  - Treatment Outcome
EDAT- 2012/03/14 06:00
MHDA- 2012/09/11 06:00
CRDT- 2012/03/14 06:00
PHST- 2012/03/14 06:00 [entrez]
PHST- 2012/03/14 06:00 [pubmed]
PHST- 2012/09/11 06:00 [medline]
AID - 10.2165/11597400-000000000-00000 [doi]
PST - ppublish
SO  - Am J Cardiovasc Drugs. 2012 Jun 1;12(3):179-88. doi: 
      10.2165/11597400-000000000-00000.