Ivabradine for Treatment of Heart Failure with Preserved Ejection Fraction

Aim      To evaluate the effect of combination ivabradine-containing therapy for chronic heart failure (CHF) with preserved ejection fraction on quality of life (QoL) and the primary composite endpoint during a one-year follow-up.Material and methods  This study included 160 patients aged 45 to 65 years with NYHA functional class (FC) II-III CHF with preserved left ventricular ejection fraction (CHF-PEF) and grade I and II diastolic dysfunction associated with FC III stable angina with sinus rhythm and a heart rate (HR) higher than 70 bpm. Presence of CHF-PEF was confirmed by results of echocardiography and myocardial tissue Doppler imaging. During one year of prospective observation, effects of bisoprolol and ivabradine as a part of the combination therapy on the primary composite endpoint, including death from cardiovascular complications (CVC) and hospitalizations for myocardial infarction (MI) or CHF, were evaluated in patients with CHF-PEF. Patients were randomized to three groups: A, bisoprolol with dose titration from 2.5 to 10 mg; В, combination of bisoprolol 2.5-10 mg and ivabradine 10-15 mg/day; and С, ivabradine 10-15 mg/day. All patients were on a chronic background therapy, including angiotensin-converting enzyme inhibitors (lisinopril) or, if not tolerated, angiotensin II receptor blockers (valsartan), antiaggregants, statins (atorvastatin, rosuvastatin), and short-acting nitrates as required. If edema developed diuretics were added. The follow-up duration was one year.Results After 12 weeks of follow-up, the achievement of goal HR in group A was associated with a tendency to increased distance in the 6-min walk test from 279±19 to 341±21 m (р>0,05); in group B the distance increased from 243±25 to 319±29 m (р<0.05); and in group C the distance increased from 268±21 to 323±22 m (р<0.05). In the combination ivabradine and bisoprolol treatment group, results of the 24-h electrocardiogram monitoring showed a more pronounced anti-ischemic effect associated with a decrease in the number of myocardial ischemic episodes (p<0.05). QoL was evaluated with the Minnesota questionnaire against the background of treatment. At 12 weeks of observation, the total score decreased from 44.5±2.6 to 38.4±2.1 in group A; from 45±2.9 to 38±2.2 in group B; and from 50.9±3.2 to 42.7±2.8 in group C (р<0.05). The risk of acute MI and repeated hospitalization for CHF during the year of observation, as evaluated according to the Kaplan-Meier method, decreased in both bisoprolol and ivabradine combination treatment groups.Conclusion      The inclusion of bisoprolol and ivabradine into the background therapy of CHF-PEF patients with stable IHD provided an improvement of QoL and a decrease in the risk of hospitalization for acute MI and CHF during the year of observation.