correspondence
Ivabradine in Stable Coronary Artery Disease To the Editor: In their article on the use of ivabradine in patients with stable coronary artery disease, Fox et al. (Sept. 18 issue)1 report significantly more cases of atrial fibrillation in the ivabradine group than in the placebo group (508 vs. 362); however, the authors do not address this finding in their report. The number of new cases of atrial fibrillation corresponds to 1.5% of patients who were treated with ivabradine and a 40% increase in relative risk. The observed increase in cases of atrial fibrillation was greater than the increase in primary end-point events, both in the total study population and in patients with limiting angina. Obviously, a finding of this nature is potentially significant. Moreover, the findings in this trial are consistent with those of the Ivabradine and Outcomes in Chronic Heart Failure (SHIFT) trial,2 as well as results from a recent meta-analysis that showed a significant increase (15%) in the risk of atrial fibrillation associated with ivabradine treatment.3 Therefore, it is quite clear that this arrhythmogenic effect warrants attention.4 Tomas Stulc, M.D. Richard Ceska, M.D. Charles University Prague, Czech Republic
[email protected] No potential conflict of interest relevant to this letter was reported. 1. Fox K, Ford I, Steg PG, Tardif JC, Tendera M, Ferrari R. Iva
bradine in stable coronary artery disease without clinical heart failure. N Engl J Med 2014;371:1091-9. 2. Swedberg K, Komajda M, Böhm M, et al. Ivabradine and Outcomes in Chronic Heart Failure (SHIFT): a randomised placebo-controlled study. Lancet 2010;376:875-85. 3. Martin RI, Pogoryelova O, Koref MS, Bourke JP, Teare MD, Keavney BD. Atrial fibrillation associated with ivabradine treatment: meta-analysis of randomised controlled trials. Heart 2014; 100:1506-10.
4. Stulc T, Ceška R. Ivabradine, coronary heart disease, and
heart failure: time for reappraisal. Curr Atheroscler Rep 2014; 16:463. DOI: 10.1056/NEJMc1413158
The Authors Reply: We agree that the issue of atrial fibrillation is an important question. In our opinion, it should be addressed alongside the increased rate of bradycardia, which was also a very frequent finding in our study. The bradycardia was most likely due to the relatively aggressive ivabradine regimen in the trial, which involved substantially higher initiation and maintenance doses than those that are currently authorized in clinical practice, or possibly an interaction with concurrent use of CYP3A4 inhibitors (including diltiazem and verapamil). We clearly stated the frequency of atrial fibrillation in our report (5.3% with ivabradine vs. 3.8% with placebo, P
Ivabradine in Stable Coronary Artery Disease To the Editor: In their article on the use of ivabradine in patients with stable coronary artery disease, Fox et al. (Sept. 18 issue)1 report significantly more cases of atrial fibrillation in the ivabradine group than in the placebo group (508 vs. 362); however, the authors do not address this finding in their report. The number of new cases of atrial fibrillation corresponds to 1.5% of patients who were treated with ivabradine and a 40% increase in relative risk. The observed increase in cases of atrial fibrillation was greater than the increase in primary end-point events, both in the total study population and in patients with limiting angina. Obviously, a finding of this nature is potentially significant. Moreover, the findings in this trial are consistent with those of the Ivabradine and Outcomes in Chronic Heart Failure (SHIFT) trial,2 as well as results from a recent meta-analysis that showed a significant increase (15%) in the risk of atrial fibrillation associated with ivabradine treatment.3 Therefore, it is quite clear that this arrhythmogenic effect warrants attention.4 Tomas Stulc, M.D. Richard Ceska, M.D. Charles University Prague, Czech Republic
[email protected] No potential conflict of interest relevant to this letter was reported. 1. Fox K, Ford I, Steg PG, Tardif JC, Tendera M, Ferrari R. Iva
bradine in stable coronary artery disease without clinical heart failure. N Engl J Med 2014;371:1091-9. 2. Swedberg K, Komajda M, Böhm M, et al. Ivabradine and Outcomes in Chronic Heart Failure (SHIFT): a randomised placebo-controlled study. Lancet 2010;376:875-85. 3. Martin RI, Pogoryelova O, Koref MS, Bourke JP, Teare MD, Keavney BD. Atrial fibrillation associated with ivabradine treatment: meta-analysis of randomised controlled trials. Heart 2014; 100:1506-10.
4. Stulc T, Ceška R. Ivabradine, coronary heart disease, and
heart failure: time for reappraisal. Curr Atheroscler Rep 2014; 16:463. DOI: 10.1056/NEJMc1413158
The Authors Reply: We agree that the issue of atrial fibrillation is an important question. In our opinion, it should be addressed alongside the increased rate of bradycardia, which was also a very frequent finding in our study. The bradycardia was most likely due to the relatively aggressive ivabradine regimen in the trial, which involved substantially higher initiation and maintenance doses than those that are currently authorized in clinical practice, or possibly an interaction with concurrent use of CYP3A4 inhibitors (including diltiazem and verapamil). We clearly stated the frequency of atrial fibrillation in our report (5.3% with ivabradine vs. 3.8% with placebo, P
