Approaches to the treatment of exacerbation of chronic obstructive pulmonary disease with comorbid hypertension

Aim. Аnalysis of the efficacy and safety of complex therapy including fixed-dose combinations of long-acting bronchodilators (FCLB) in comorbid patients with an exacerbation of chronic obstructive pulmonary disease (COPD) of the spirometry grades III – IV and hypertension.

Methods. A total of 232 patients with an exacerbation of COPD of the spirometry grades III – IV were examined. 174 (75%) patients were diagnosed with the third grade (GOLD III), 58 (25%) – with the fourth spirometry grade (GOLD IV). In the GOLD III group, a moderate exacerbation was diagnosed in 22 (12.6%), severe — in 152 (87.4%). In the GOLD IV group, a moderate exacerbation was diagnosed in 5 (8.5%), severe — in 53 (91.5%), respectively. The patients were divided into 4 groups. Group 1 included 50 patients with an exacerbation of COPD of the spirometry grades III – IV without hypertension; Group 2 – 56 patients with an exacerbation of COPD and concomitant hypertension; Group 3 – 64 patients with an exacerbation of COPD without hypertension, who received FCLB in addition to standard therapy from the 3rd day of hospitalization; Group 4 – 62 patients with an exacerbation of COPD of the spirometry grades III – IV and concomitant hypertension who received FCLB in addition to standard therapy from the 3rd day of hospitalization. The examination included clinical and instrumental methods: the changes in the clinical signs and symptoms, the dyspnea index (according to the mМRS scale), the saturation of hemoglobin with oxygen (SaO₂), spirometry, heart rate variability, the frequency and nature of arrhythmias, and systolic and diastolic blood pressure (BP).

Results. A sympathicotonic disorder of the autonomic balance was revealed in patients with exacerbation of COPD of the spirometry grades III – IV. This tendency intensified in the patients with concomitant hypertension, which indicated an additional negative effect of comorbid hypertension on the studied parameters. Aggravation of sympathicotonia could be a trigger for an increase in ectopic rhythm disturbances, including high-grade ventricular extrasystoles. In the groups with concomitant hypertension, rhythm disturbances were more frequent (p < 0.05). The inclusion of FCLB in the complex therapy of exacerbation of COPD of the spirometry grades III – IV made it possible to improve the condition of patients significantly: to reduce the dyspnea index on the mМRS scale, increase SaО₂ and FEV₁ (p < 0.05), achieve clinical improvement in COPD faster and shorten the hospitalization period. As a result of the rapid and effective relief of exacerbation of COPD, the influence of pathogenic factors on the cardiovascular system in the examined patients decreased. The addition of FCLB to the treatment COPD with and without comorbid hypertension did not have a negative effect on heart rate variability, did not aggravate rhythm disturbances, and did not destabilize the BP.

Conclusion. The positive clinical effects of the inclusion of FCLB in the complex therapy of exacerbation of COPD of the spirometry grades III – IV in patients with comorbid hypertension led to a decrease in shortness of breath, an improvement in respiratory functions, a decrease in tissue hypoxia and eliminated possible adverse events of this group of drugs.

1. Sing D., Agusti A., Anzueto A. et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019. Eur. Respir. J. 2019; 53 (5): 1900164. DOI: 10.1183/13993003.00164-2019.

2. Russian Respiratory Society. [Chronic Obstructive Pulmonary Disease: Federal Clinical Guidelines]. 2018. Available at: https://spulmo.ru/upload/federal_klinicheskie_rekomendaciy_hobl.pdf (in Russian).

3. Morgan A.D., Zakeri R., Quint J.K. Defining the relationship between COPD and CVD: what are the implications for clinical practice? Ther. Adv. Respir. Dis. 2018; 12: 1753465817750524. DOI: 10.1177/1753465817750524.

4. Ryabova A.Yu., Kozlova I.V., Agapov V.V., Zemlyanskaya O.V. [Comorbidal patients and revascularization of coronary arteries: frozen questions]. Sovremennye problemy nauki i obrazovaniya. 2018; (5): 197. DOI: 10.17513/spno.27995 (in Russian).

5. Hillas G., Perlikos F., Tsiligianni I., Tzanakis N. Managing comorbidities in COPD. Int. J. Chron. Obstruct. Pulmon. Dis. 2015; 10 (1): 95–109. DOI: 10.2147/COPD.S54473.

6. Agabiti N., Corbo G.M. COPD and bronchodilators: should the heart pay the bill for the lung? Eur. Respir. J. 2017; 49 (5): 1700370. DOI: 10.1183/13993003.00370-2017.

7. Suissa S., Dell’Aniello S., Ernst P. Concurrent use of long-acting bronchodilators in COPD and the risk of adverse cardiovascular events. Eur. Respir. J. 2017; 49 (5): 1602245. DOI: 10.1183/13993003.02245-2016.

8. Makarov L.M., Komolyatova V.N., Kupriyanova O.O. et al. [National Russian guidelines on application of the methods of holter monitoring in clinical practice]. Rossiyskiy kardiologicheskiy zhurnal. 2014; 19 (2): 6–71. Available at: https://scardio.ru/content/Guidelines/Rek_Holter_2013.pdf (in Russian).

9. Ernst G. Heart-rate variability-more than heart beats? Front. Public. Health. 2017; 5: 240. DOI: 10.3389/fpubh.2017.00240.

10. Chazova I.E., Nevzorova V.A., Ambatiello L.G. et al. [Clinical practice guidelines on the diagnosis and treatment of patients with arterial hypertension and chronic obstructive pulmonary disease]. Sistemnye gipertenzii. 2020; 17 (3): 7–34. DOI: 10.26442/2075082X.2020.3.200294 (in Russian).

11. Kobalava Zh.D., Konradi A.O., Nepogoda S.V. et al. [Arterial hypertension in adults. Clinical guidelines 2020]. Rossiyskiy kardiologicheskiy zhurnal. 2020; 25 (3): 149–218. DOI: 10.15829/1560-4071-2020-3-3786 (in Russian).

12. Mareev V.Yu., Fomin I.V., Ageev F.T.et al. [Russian Heart Failure Society, Russian Society of Cardiology. Russian Scientific Medical Society of Internal Medicine Guidelines for Heart failure: chronic (CHF) and acute decompensated (ADHF). Diagnosis, prevention and treatment]. Kardiologiya. 2018; 58 (Suppl. 6): 8–164 (in Russia).

13. Oba Y., Keeney E., Ghatehorde N., Dias S. Dual combination therapy versus long-acting bronchodilators alone for chronic obstructive pulmonary disease (COPD): a systematic review and network meta-analysis. Cochrane Database Syst. Rev. 2018; (12): CD012620. DOI: 10.1002/14651858.CD012620.pub2.

14. Corrao S., Brunori G., Lupo U., Perticone F. Effectiveness and safety of concurrent beta-blockers and inhaled bronchodilators in COPD with cardiovascular comorbidities. Eur. Respir. Rev. 2017; 26 (145): 160123. DOI: 10.1183/16000617.0123-2016.

15. Rogliani Р., Calzetta L., Matera M.G. et al. Inhaled therapies and cardiovascular risk in patients with chronic obstructive pulmonary disease. Expert Opin. Pharmacother. 2019; 20 (6): 737–750. DOI: 10.1080/14656566.2019.1570133.