Efficacy and safety of beta-blockers and prolonged bronchodilators in patients with heart failure with coronary artery disease and moderate to severe COPD
Authors: Evdokimov V , Yushchuk E , Evdokimova A , Ivanova S , Sadulaeva I 
Published: November 2020

Abstract

Purpose
To compare clinical efficacy and safety of various treatment regimens with the inclusion of beta-blockers, RAAS antagonists (ACE inhibitors or ARBs), prolonged bronchodilators (LABA, LAMA) in heart failure patients with CAD and COPD.

Methods
385 patients (292 men and 93 women), aged 66.3±4.1 years, with CHF classes II to III (NYHA) combined with moderate to severe COPD (GOLD) and with LVEF less than 45% were randomized into nine groups: enalapril + LAMA (control group), nebivolol + enalapril + LAMA, nebivolol + losartan + LAMA, nebivolol + losartan + LABA, nebivolol + losartan + LAMA/LABA, carvedilol + enalapril + LAMA, carvedilol + losartan + LAMA, carvedilol + losartan + LABA, carvedilol + losartan + LAMA/LABA. Patients of all groups received complex CHF treatment comprising diuretics, nitrates, cardiac glycosides (if necessary). Clinical examination, TTE, 6-minute walk test (6MWT), 24-hour electrocardiogram and blood pressure monitoring, respiratory function test were assessed at baseline and after 6 months of treatment. The quality of life was evaluated by MYHFQ, SGRQ and mMRC scale.

Results
After 6 months of therapy the improvement of clinical condition and quality of life were marked in all groups. At the end of observation period there was a significant improvement of patients clinical condition, quality of life, reduction of mean CHF FC and dyspnea severity, increase of exercise tolerance, slowing of progression of CHF and COPD, improvement of the parameters of intracardiac hemodynamics, structural and functional parameters of the left and right heart (a decrease in the size of the atria, LV volumes and internal dimension at end-diastole and end-systole, cardiac index, LVMMI, an increase of LVEF, a significant decrease in systemic vascular resistance and the pulmonary hypertension grade, significant improvement in systolic and diastolic function of the ventricles, regression of pathological remodeling of the heart, reduction of heart rate, duration and frequency of myocardial ischemia episodes (including its “silent” form). The best results were obtained in groups using a beta-blocker (nebivolol or carvedilol), a RAAS antagonist, and a combination of long-acting bronchodilators (indacaterol and tiotropium) – group 5 and 9. It is worth noting that beta-blockers, LABA and LAMA were well tolerated in all observation groups and serious adverse events were absent.

Conclusions
The appointment of 3-generation beta-blockers to patients with CHF on the background of CAD and COPD can significantly increase the effectiveness of treatment and does not cause a deterioration in spirometry in patients with such cardiopulmonary pathology. In our opinion, the most important point in the appointment of beta blockers to patients with moderate to severe COPD is low start dose and slow titration of the dose at the beginning of the therapy. It is advisable to include in the complex therapy of such patients a combination of LABA and LAMA as a basic bronchodilator support.

Funding Acknowledgement
Type of funding source: None