In the Journals

Bradycardia, AF did not affect outcomes of patients with stable CAD assigned ivabradine

In patients with stable CAD assigned ivabradine, bradycardia was common, new-onset atrial fibrillation was uncommon, and neither appeared to affect outcomes, according to new data from the SIGNIFY study.

In the main results from SIGNIFY, patients with stable CAD assigned ivabradine (Procoralan, Servier) had similar rates of CV death or nonfatal MI compared with patients assigned placebo. For the present study, researchers investigated whether bradycardia and AF, two of the most frequent adverse CV events in patients assigned ivabradine, were drivers of CV death or nonfatal MI in that group. The researchers analyzed those factors in the overall SIGNIFY population and in a subset of patients with angina because, in the main results, ivabradine users with angina had worse outcomes than those without angina but showed signs of angina symptom improvement.

A lower dose of ivabradine than used in SIGNIFY, marketed by Amgen as Corlanor, was approved by the FDA in April for reduction of hospitalization due to worsening HF.

Bradycardia results

Kim Fox, MD, from the National Heart and Lung Institute at Imperial College and Royal Brompton Hospital, London, and colleagues found that bradycardia (defined as fewer than 50 beats per minute on 12-lead ECG) occurred in 37.4% of those assigned ivabradine, as well as in 37.2% of those with Canadian Cardiovascular Society (CCS) angina class 2 or higher.

Kim Fox, MD

Kim Fox

The annual rates of the primary outcome of CV death or nonfatal MI were 2.5% in the ivabradine group with bradycardia (vs. 3.1% in the placebo group; HR = 0.78; 95% CI, 0.45-1.36) and 2.9% in the ivabradine group without bradycardia (vs. 2.5% in the placebo group; HR = 1.09; 95% CI, 0.95-1.26), Fox and colleagues reported.

In patients with CCS angina class 2 or higher, the annual rates of the primary outcome were 2.5% in those with bradycardia assigned ivabradine (vs. 3.1% in those assigned placebo; HR = 0.86; 95% CI, 0.45-1.67) and 3.2% in those without bradycardia assigned ivabradine (vs. 2.6% in those assigned placebo; HR = 1.2; 95% CI, 1.01-1.42), they found.

AF results

In the overall population, emergent AF occurred at a rate of 2.2% in the ivabradine group and 1.5% per year in the placebo group. In the angina population, emergent AF occurred at a rate of 2.2% per year in the ivabradine group and 1.5% per year in the placebo group, according to the researchers.

“The frequency of the primary composite endpoint and fatal and nonfatal stroke in the angina subgroup was greater following a recording of AF in both treatment groups than in those who did not have emergent AF,” Fox and colleagues wrote. “However, there was no difference in the frequency of the primary composite endpoint in the patients with limiting angina according to the treatment received and whether or not emergent AF occurred.”

They concluded that “neither the development of bradycardia nor the small increase in emergent AF appears to explain the increase in outcomes observed in the SIGNIFY patients with CCS class ≥ 2 angina.” – by Erik Swain

Disclosure: The SIGNIFY study was supported by Servier. Fox reports receiving personal fees and nonfinancial support from Broadview Ventures and Servier; nonfinancial support from Armgo; and personal fees from AstraZeneca, CellAegis, Director of Heart Research Ltd., TaurX and Vesalius Trials Ltd. See the full study for a list of the other researchers’ relevant financial disclosures.

In patients with stable CAD assigned ivabradine, bradycardia was common, new-onset atrial fibrillation was uncommon, and neither appeared to affect outcomes, according to new data from the SIGNIFY study.

In the main results from SIGNIFY, patients with stable CAD assigned ivabradine (Procoralan, Servier) had similar rates of CV death or nonfatal MI compared with patients assigned placebo. For the present study, researchers investigated whether bradycardia and AF, two of the most frequent adverse CV events in patients assigned ivabradine, were drivers of CV death or nonfatal MI in that group. The researchers analyzed those factors in the overall SIGNIFY population and in a subset of patients with angina because, in the main results, ivabradine users with angina had worse outcomes than those without angina but showed signs of angina symptom improvement.

A lower dose of ivabradine than used in SIGNIFY, marketed by Amgen as Corlanor, was approved by the FDA in April for reduction of hospitalization due to worsening HF.

Bradycardia results

Kim Fox, MD, from the National Heart and Lung Institute at Imperial College and Royal Brompton Hospital, London, and colleagues found that bradycardia (defined as fewer than 50 beats per minute on 12-lead ECG) occurred in 37.4% of those assigned ivabradine, as well as in 37.2% of those with Canadian Cardiovascular Society (CCS) angina class 2 or higher.

Kim Fox, MD

Kim Fox

The annual rates of the primary outcome of CV death or nonfatal MI were 2.5% in the ivabradine group with bradycardia (vs. 3.1% in the placebo group; HR = 0.78; 95% CI, 0.45-1.36) and 2.9% in the ivabradine group without bradycardia (vs. 2.5% in the placebo group; HR = 1.09; 95% CI, 0.95-1.26), Fox and colleagues reported.

In patients with CCS angina class 2 or higher, the annual rates of the primary outcome were 2.5% in those with bradycardia assigned ivabradine (vs. 3.1% in those assigned placebo; HR = 0.86; 95% CI, 0.45-1.67) and 3.2% in those without bradycardia assigned ivabradine (vs. 2.6% in those assigned placebo; HR = 1.2; 95% CI, 1.01-1.42), they found.

AF results

In the overall population, emergent AF occurred at a rate of 2.2% in the ivabradine group and 1.5% per year in the placebo group. In the angina population, emergent AF occurred at a rate of 2.2% per year in the ivabradine group and 1.5% per year in the placebo group, according to the researchers.

“The frequency of the primary composite endpoint and fatal and nonfatal stroke in the angina subgroup was greater following a recording of AF in both treatment groups than in those who did not have emergent AF,” Fox and colleagues wrote. “However, there was no difference in the frequency of the primary composite endpoint in the patients with limiting angina according to the treatment received and whether or not emergent AF occurred.”

They concluded that “neither the development of bradycardia nor the small increase in emergent AF appears to explain the increase in outcomes observed in the SIGNIFY patients with CCS class ≥ 2 angina.” – by Erik Swain

Disclosure: The SIGNIFY study was supported by Servier. Fox reports receiving personal fees and nonfinancial support from Broadview Ventures and Servier; nonfinancial support from Armgo; and personal fees from AstraZeneca, CellAegis, Director of Heart Research Ltd., TaurX and Vesalius Trials Ltd. See the full study for a list of the other researchers’ relevant financial disclosures.