Study of Cardiovascular Safety Profile of Budesonide/Formoterol Fixed Combination in Treatment of Chronic Obstructive Pulmonary Disease in Patients with Cardiovascular Diseases.

L. Bolieva. North-Ossetian State Madical Academy, Pharmacology and Clinical Pharmacology, Russia

Chronic Obstructive Pulmonary Disease (COPD) accounts for the 4th highest cause of global death. Patients with combination of COPD and cardiovascular diseases (CVD) have the most unfavorable prognosis for the disease, so working out the approaches to treatment of this category of patients is an important problem. The long-acting β2-agonists (LABA) and inhaled corticosteroids (ICS) fixed combinations recommended for treating severe and very severe stages of COPD have been shown to successfully improve pulmonary function. Budesonide/formoterol (320 μg/9 μg twice daily) was effective and well tolerated in adult patients with severe COPD participating in large, multicentre trials of up to 12 months\' duration.

The present study was carried out to evaluate cardiovascular safety of budesonide/formoterol (320 μg/9 μg twice daily) in patients with COPD and arterial hypertension (AH). The difficulties of treatment strategy choice are due to hypertensive effects of some medicines in the treatment of COPD (corticosteroids, β2-agonists) on the one hand and the respiratory side effects of β-blockers and ACE inhibitors on the other.

Patients with COPD and arterial hypertension (n=116, mean prebronchodilator forced expiratory volume in one second (FEV1) 47% predicted) received formoterol 9 μg twice daily during a two-week run-in period, and then received budesonide/formoterol 320 μg/9 μg twice daily. An equal number of control subjects with arterial hypertension without COPD were matched for gender, age and arterial hypertension severity. All patients received combination of calcium channel-blocking agent amlodipin and thiazide diuretic indapamid for arterial hypertension treatment. The study duration was 6 months. Study endpoints included cardiac arrhythmias, exacerbation of arterial hypertension, the risk of hospitalization for a cardiovascular event and cardiovascular mortality. All data analyses were performed using computer software (Statistica for Windows, Release 6.0 StatSoft, Inc.)

Budesonide/formoterol effectiveness was proved by post-dose FEV1 improvement by 0.19 L after six month treatment. Budesonide/formoterol also improved COPD total symptom scores, reduced reliever use from 2.42 ±0,34 at baseline to 0.95 ± 0.18 puffs/day (p < 0.01) and improved health-related quality-of-life.

Systolic blood pressure was 136±4 mm Hg, diastolic blood pressure was 86±2,1 mm HG at baseline. Repeated measurements didn’t reveal variations of pressure during study.

Safety monitoring confirmed data from other studies, that budesonide/formoterol was well tolerated. There were no treatment-related serious adverse events. The risk of hospitalization was equal in COPD case patients and in control subjects. Treatment-related cardiovascular adverse events were registered in 7 patients with COPD – mild or moderate sinus tachycardia (HR 95-110 beats per minute). The adverse events weren’t serious and resolved spontaneously without treatment.

Thus, in patients with severe COPD and arterial hypertension fixed combination treatment with budesonide/formoterol resulted in clinically meaningful improvements in lung function, health-related quality-of-life, COPD symptoms and reduction of reliever use and was generally well tolerated. There was no influence on blood pressure found. Thus we can conclude that budesonide/formoterol fixed combination is an effective and well-tolerated treatment for adult patients with COPD and arterial hypertension.