Absence of respiratory effects with ivabradine in patients with asthma.

Babu, K. Suresh, Gadzik, Frantisek and Holgate, Stephen T. (2008) Absence of respiratory effects with ivabradine in patients with asthma. British Journal of Clinical Pharmacology, 66 (1), 96-101. (doi:10.1111/j.1365-2125.2008.03160.x).

Abstract

What is already known about this subject
* Ivabradine is a new heart rate-lowering agent that acts specifically on the sinoatrial node via the I(f) pacemaker channels. * Ivabradine has demonstrated similar efficacy to beta-blockers. * As beta-blockers are contraindicated in patients with obstructive airway disease, this study was conducted to assess the safety of ivabradine in patients with asthma.
What this study adds
* This study demonstrates that ivabradine has no effect on the pulmonary functions in patients with asthma and can be safely used a heart rate-lowering agent in patients with angina and coexistent airflow obstruction.
Aim
beta-Blockers are commonly prescribed for stable angina and are recommended as initial therapy. However, beta-blockers are contraindicated in patients with obstructive airway disease because of a risk of bronchoconstriction. Ivabradine is a specific heart rate-lowering agent that acts via I(f) pacemaker channels in the sinoatrial node with no beta-adrenoreceptor activity. Ivabradine has been recently approved for the treatment of stable angina. This study assessed the effects of repeated administration of ivabradine on lung function in patients with asthma.
Methods
In this double-blind, placebo-controlled, crossover study, 20 subjects with asthma received either oral ivabradine 10 mg b.i.d. or placebo for 4.5 days. Forced expiratory volume in 1 s (FEV(1)) and peak expiratory flow rate (PEFR) were designated as the main outcome variable. Diary cards were used to monitor asthma symptoms on a five-point scale, rescue medication usage, and adverse events.
Results
There were no significant differences in mean variation of FEV(1) (ivabradine P = 0.664; placebo P = 0.652) or PEFR (ivabradine P = 0.153; placebo P = 0.356) from baseline following administration of ivabradine. There was also no significant difference in maximum percent variation in FEV(1) or PEF between treatment groups (P = 0.994; FEV(1) and P = 0.704; PEF). On a similar note, there was no significant difference in asthma symptoms or rescue medication usage reported between the two groups. Adverse events were generally mild-to-moderate in intensity and no cardiovascular or serious adverse events were recorded.
Conclusions
This study confirms that ivabradine does not affect respiratory function or symptoms in patients with asthma and therefore represents a valuable therapeutic alternative to beta-blockers for treating patients with stable angina and asthma.

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