Effect of ivabradine on heart rate reduction consistent regardless of comorbidities

Ivabradine reduced the heart rate of patients with HF, leading to reduced hospitalization for worsening HF, regardless of the number and presence of comorbidities, according to new data from the SHIFT trial.

In the main results of SHIFT, the addition of ivabradine (Corlanor, Amgen) to standard care reduced certain adverse outcomes related to HF. Based in part on those findings, ivabradine was approved by the FDA in April for reduction of worsening of HF.

In the present analysis, researchers investigated whether the impact of ivabradine differed based on comorbidities of patients in the SHIFT cohort. The cohort had moderate to severe HF, left ventricular dysfunction and sinus rhythm with heart rate of at least 70 bpm.

Patients were categorized based on presence of the following comorbidities: anemia, chronic obstructive pulmonary disease, diabetes, hypertension, impaired renal function, MI, peripheral artery disease and stroke.

Michael Böhm, MD, from Universitatsklinikum des Saarlandes, Klinik fur Innere Medizin III, Homburg (Saar), Germany, and colleagues found that the distribution of comorbidities was similar between those assigned ivabradine and those assigned placebo.

Patients with more comorbidities were likely to be older, female, have more advanced HF and not receive treatment with beta-blockers compared with those with fewer comorbidities.

The more comorbidities a patient had, the more likely he or she was to experience CV death or HF hospitalization (P < .0001). The most events occurred in patients with three or more comorbidities, regardless of whether they were assigned placebo or ivabradine, according to the researchers.

In all comorbidity groups, the HF hospitalization rate was lower among those assigned ivabradine (no comorbidities: HR = 0.64; 95% CI, 0.44-0.94; one or two comorbidities: HR = 0.72; 95% CI, 0.61-0.86; three or more comorbidities: HR = 0.81; 95% CI, 0.69-0.96).

In addition, there was no significant heterogeneity of ivabradine’s treatment effect for any of the comorbidity groups, or for any of the following outcomes: the primary endpoint (CV death or hospitalization for worsening HF), CV death, HF hospitalization, HF death, all-cause death, CV hospitalization, total hospitalization and non-CV hospitalization. The researchers also found no evidence that an increased number of comorbidities affected the size of ivabradine’s treatment effect.

“The treatment effect of heart rate lowering with ivabradine was maintained for all comorbidity loads,” Böhm and colleagues wrote. – by Erik Swain

Disclosure: The SHIFT trial was funded by Servier. All researchers report receiving honoraria and/or research support from Servier.