medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2018-15-18-26medsovet-2667Research ArticleХроническая обструктивная болезнь легкихChronic obstructive pulmonary diseaseФиксированные комбинации длительно действующих бронходилататоров при хронической обструктивной болезни легких: безопасность, эффективность и сердечно-сосудистая системаFixed dose long-acting bronchodilator combinations in chronic obstructive pulmonary disease: safety, effectiveness and cardiovascular systemЛещенкоИ. В.LeshchenkoI. V.

Лещенко Игорь Викторович – доктор медицинских наук, профессор кафедры фтизиатрии, пульмонологии и торакальной хирургии УрГМУ, научный руководитель клиники ООО МО «Новая больница».

Екатеринбург

Ekaterinburg

ФГБОУ ВО «Уральский государственный медицинский университет» Минздрава России; ООО Медицинское объединение «Новая больницаРоссияUral State Medical University, Healthcare Ministry of Russia; LLC Medical Association New HospitalRussian Federation2018111020180151826Copyright © Лещенко И.В., 20182018Лещенко И.В.Leshchenko I.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/2667

В настоящее время длительно действующие бронходилататоры (ДДБД) представляют основной класс лекарственных средств (ЛС) для базисной терапии хронической обструктивной болезни легких (ХОБЛ). ХОБЛ сопровождается не только падением легочных функциональных параметров, но и снижением сердечной сократительной функции. В статье представлены результаты исследований 4 зарегистрированных в РФ фиксированных длительно действующих антихолинергических препаратов/длительно действующих бета2-агонистов (ДДАХП/ДДБА), отражающих их влияние на сердечно-сосудистую систему. Доказана не только безопасность фиксированных ДДАХП/ДДБА в отношении сердечно-сосудистой системы, но и положительное влияние препаратов на насосную функцию сердца у больных ХОБЛ, что подтверждает их незаменимое значение для лечения ХОБЛ.

At present time, long-acting bronchodilators are the main class of drugs for basis therapy of chronic obstructive pulmonary disease (COPD). COPD is characterized not only by a decrease in pulmonary function parameters, but also by a decline in cardiac contractility. The article presents the results of studies of four approved fixed long-acting anticholinergic drugs/long-acting beta2-agonists in the Russian Federation, according their effect on the cardiovascular system. The safety of LAMA/ LABA was proved in terms of relation to the cardiovascular system, additionally the positive effect on the pumping function of the heart was shown in patients with COPD, which confirms the value of dual bronchodilators for COPD treatment.

длительно действующие бронходилататорысердечно-сосудистая системабезопасностьэффективностьlong-acting bronchodilatorscardiovascular systemsafetyefficiencyReferencesGlobal Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO workshop report. Last updated 2018. www.goldcopd.org/.Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO workshop report. Last updated 2018. www.goldcopd.org/.Авдеев С.Н., Айсанов З.Р., Архипов В.В. и др. Национальные клинические рекомендации по диагностике и лечению хронической обструктивной болезни легких: алгоритмы принятия клинических решений. Пульмоно логия, 2017, 1: 13-20.Avdeev SN, Aysanov ZR, Arkhipov VV, et al. National clinical guidelines for the diagnosis and treatment of chronic obstructive pulmonary disease: clinical decision support algorithm. Pulmonologiya, 2017, 1: 13-20.Jones PW, Nadeau G, Small M, Adamek L. Metabolic and cardiovascular comorbidity in COPD patients classified using the GOLD 2011 assessment framework. Eur Resp J, 2012, 40: P988.Jones PW, Nadeau G, Small M, Adamek L. Metabolic and cardiovascular comorbidity in COPD patients classified using the GOLD 2011 assessment framework. Eur Resp J, 2012, 40: P988.Anthonisen NR, Connett JE, Kiley JP et al. Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1: the Lung Health Study. JAMA, 1994, 272: 1497–1505.Anthonisen NR, Connett JE, Kiley JP et al. Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1: the Lung Health Study. JAMA, 1994, 272: 1497–1505.Heindl S, Lehnert M, Criee CP et al. Marked sympathetic activation in patients with chronic respiratory failure. Am J Resp Crit Care Med, 2001, 164: 597–601.Heindl S, Lehnert M, Criee CP et al. Marked sympathetic activation in patients with chronic respiratory failure. Am J Resp Crit Care Med, 2001, 164: 597–601.Ridker PM, Buring JE, Cook NR, Rifai N. C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8 year follow up of 14 719 initially healthy American women. Circulation, 2003, 107: 391–397.Ridker PM, Buring JE, Cook NR, Rifai N. C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8 year follow up of 14 719 initially healthy American women. Circulation, 2003, 107: 391–397.Sin DD, Man SF. Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular diseases? The potential role of systemic inflammation in chronic obstructive pulmonary disease. Circulation, 2003, 107: 1514–1519.Sin DD, Man SF. Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular diseases? The potential role of systemic inflammation in chronic obstructive pulmonary disease. Circulation, 2003, 107: 1514–1519.Curkendall SM, DeLuise C, Jones JK et al. Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada cardiovascular disease in COPD patients. Am J Epid, 2006, 16: 63-70.Curkendall SM, DeLuise C, Jones JK et al. Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada cardiovascular disease in COPD patients. Am J Epid, 2006, 16: 63-70.Engstrom G, Wollmer P, Hedblad B et al. Occurrence and prognostic significance of ventricular arrhythmia is related to pulmonary function: a study from «men born in 1914», Malmo, Sweden. Circulation, 2001, 103: 3086–3091.Engstrom G, Wollmer P, Hedblad B et al. Occurrence and prognostic significance of ventricular arrhythmia is related to pulmonary function: a study from «men born in 1914», Malmo, Sweden. Circulation, 2001, 103: 3086–3091.Rosengren A, Wilhelmsen L. Respiratory symptoms and long term risk of death from cardiovascular disease, cancer and other causes in Swedish men Int J Epidemiol, 1998, 27: 962– 969.Rosengren A, Wilhelmsen L. Respiratory symptoms and long term risk of death from cardiovascular disease, cancer and other causes in Swedish men Int J Epidemiol, 1998, 27: 962– 969.Calverley PM, Anderson JA, Celli B et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med, 2007, 356: 775-789.Calverley PM, Anderson JA, Celli B et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med, 2007, 356: 775-789.Lange P, Marrott JL, Vestbo J et al. Prediction of the clinical course of chronic obstructive pulmonary disease, using the new GOLD classification: a study of the general population. AJRCCM, 2012, 186(10): 975-981.Lange P, Marrott JL, Vestbo J et al. Prediction of the clinical course of chronic obstructive pulmonary disease, using the new GOLD classification: a study of the general population. AJRCCM, 2012, 186(10): 975-981.Wouters EFM, Cells MPM, Breyer MK, Rutten EPA, Graat-Verboom L, Spruit MA. Co-morbid manifestations in COPD. Resp Med, 2007: 3(4): 135–151.Wouters EFM, Cells MPM, Breyer MK, Rutten EPA, Graat-Verboom L, Spruit MA. Co-morbid manifestations in COPD. Resp Med, 2007: 3(4): 135–151.Calzetta L, Rogliani P, Matera MG, Cazzola M. A systematic review with meta-analysis of dual bronchodilation with LAMA/LABA for the treatment of stable COPD. Chest, 2016, 149(5): 1181–1196.Calzetta L, Rogliani P, Matera MG, Cazzola M. A systematic review with meta-analysis of dual bronchodilation with LAMA/LABA for the treatment of stable COPD. Chest, 2016, 149(5): 1181–1196.Rogliani P, Matera MG, Ora J et al. The impact of dual bronchodilation on cardiovascular serious adverse events and mortality in COPD: a quantitative synthesis. Int J COPD, 2017, 12: 3469-3485.Rogliani P, Matera MG, Ora J et al. The impact of dual bronchodilation on cardiovascular serious adverse events and mortality in COPD: a quantitative synthesis. Int J COPD, 2017, 12: 3469-3485.Buhl R, Magder S, Bothner U et al. Long-term general and cardiovascular safety of tiotropium/olodaterol in patients with moderate to very severe chronic obstructive pulmonary disease. Resp Med, 2017, 122: 58-66.Buhl R, Magder S, Bothner U et al. Long-term general and cardiovascular safety of tiotropium/olodaterol in patients with moderate to very severe chronic obstructive pulmonary disease. Resp Med, 2017, 122: 58-66.Calverly P, AnzuetoA, Carter K, et al. Tiotropium and olodaterol in the prevention of chronic obstructive pulmonary disease exacerbations (DYNAGITO): a double-blind, randomised, parallel-group, active-controlled trial. Lancet Resp Med, 2018, 6(5): 337-344.Calverly P, AnzuetoA, Carter K, et al. Tiotropium and olodaterol in the prevention of chronic obstructive pulmonary disease exacerbations (DYNAGITO): a double-blind, randomised, parallel-group, active-controlled trial. Lancet Resp Med, 2018, 6(5): 337-344.Wedzicha JA, Decramer M, Ficker JH et al. Analysis of Chronic Obstructive Pulmonary Disease Exacerbations with the Dual Bronchodilator QVA149 Compared with Glycopyrronium and Tiotropium (SPARK): a Randomized, Double-blind, Parallel-group Study. Lancet Resp Med, 2013, 1: 199–209.Wedzicha JA, Decramer M, Ficker JH et al. Analysis of Chronic Obstructive Pulmonary Disease Exacerbations with the Dual Bronchodilator QVA149 Compared with Glycopyrronium and Tiotropium (SPARK): a Randomized, Double-blind, Parallel-group Study. Lancet Resp Med, 2013, 1: 199–209.Beeh K, Korn S, Beier J et al. Effect of QVA149 on lung volumes and exercise tolerance in COPD patients: The BRIGHT study. Resp Med, 2014, 108: 584-592.Beeh K, Korn S, Beier J et al. Effect of QVA149 on lung volumes and exercise tolerance in COPD patients: The BRIGHT study. Resp Med, 2014, 108: 584-592.Vogelmeier C, Bateman ED, Pallante J et al. Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol/ fluticasone in patients with COPD (ILLUMINATE): a randomized, double-blind, parallel group study. Lancet Resp Med, 2013, 1(1): 51-60.Vogelmeier C, Bateman ED, Pallante J et al. Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol/ fluticasone in patients with COPD (ILLUMINATE): a randomized, double-blind, parallel group study. Lancet Resp Med, 2013, 1(1): 51-60.Bateman ED, Ferguson GT, Barnes N et al. Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study. Eur Resp J, 2013, 42: 1484–1494.Bateman ED, Ferguson GT, Barnes N et al. Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study. Eur Resp J, 2013, 42: 1484–1494.Dahl R, Chapman KR, Rudolf M et al. Safety and efficacy of dual bronchodilation with QVA149 in COPD patients: the ENLIGHTEN study. Resp. Med. J. 2013, 107: 1558-1567.Dahl R, Chapman KR, Rudolf M et al. Safety and efficacy of dual bronchodilation with QVA149 in COPD patients: the ENLIGHTEN study. Resp. Med. J. 2013, 107: 1558-1567.Mahler D., Decramer M, D’Urzo A. et al. Dual bronchodilation with QVA149 reduces patientreported dyspnea in COPD: BLAZE study. Eur Resp J, 2014, 43: 1599–1609.Mahler D., Decramer M, D’Urzo A. et al. Dual bronchodilation with QVA149 reduces patientreported dyspnea in COPD: BLAZE study. Eur Resp J, 2014, 43: 1599–1609.Clinical Trials.gov, n.d. Long Term Safety and Tolerability of QVA149 versus Tiotropium in Japanese Patients with Chronic Obstructive Pulmonary Disease (COPD) (ARISE). [Online] Available at: http://www.clinicaltrials.gov/.Clinical Trials.gov, n.d. Long Term Safety and Tolerability of QVA149 versus Tiotropium in Japanese Patients with Chronic Obstructive Pulmonary Disease (COPD) (ARISE). [Online] Available at: http://www.clinicaltrials.gov/.Dahl R, Jadayel D, Alagappan VK et al. Efficacy and safety of QVA149 compared to the concurrent administration of its monocomponents indacaterol and glycopyrronium: the BEACON study. Int J COPD, 2013, 8: 501-508.Dahl R, Jadayel D, Alagappan VK et al. Efficacy and safety of QVA149 compared to the concurrent administration of its monocomponents indacaterol and glycopyrronium: the BEACON study. Int J COPD, 2013, 8: 501-508.ClinicalTrials.gov, n.d. Comparison of Long-term Safety of the Combination Product QVA149A against Placebo and Standard of Care Treatment in Chronic Obstructive Pulmonary Disease Patients with Moderate to Severe Airflow Limitation (RADIATE). [Online] www.clinicaltrials.gov/.ClinicalTrials.gov, n.d. Comparison of Long-term Safety of the Combination Product QVA149A against Placebo and Standard of Care Treatment in Chronic Obstructive Pulmonary Disease Patients with Moderate to Severe Airflow Limitation (RADIATE). [Online] www.clinicaltrials.gov/.Zhong N, Wang C, X et al. LANTERN: a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD. Int J Chron Obstruct Pulmon Dis, 2015, 10: 1015–1026.Zhong N, Wang C, X et al. LANTERN: a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD. Int J Chron Obstruct Pulmon Dis, 2015, 10: 1015–1026.Wedzicha JA, Banerji D, Chapman KR et al. FLAME Investigators. .FLAME: Indacaterol– Glycopyrronium versus Salmeterol–Fluticasone for COPD. N Engl J Med, 2016, 374: 2222–2234.Wedzicha JA, Banerji D, Chapman KR et al. FLAME Investigators. .FLAME: Indacaterol– Glycopyrronium versus Salmeterol–Fluticasone for COPD. N Engl J Med, 2016, 374: 2222–2234.Vogelmeier CF, Gaga M, Aalamian-Mattheis M et al. Efficacy and safety of direct switch to indacaterol/glycopyrronium in patients with moderate COPD: the CRYSTAL open-label randomised trial. Resp Res, 2017, 18(1): 140. Published online 2017 Jul 18. doi: 10.1186/s12931-017-0622-xVogelmeier CF, Gaga M, Aalamian-Mattheis M et al. Efficacy and safety of direct switch to indacaterol/glycopyrronium in patients with moderate COPD: the CRYSTAL open-label randomised trial. Resp Res, 2017, 18(1): 140. Published online 2017 Jul 18. doi: 10.1186/s12931-017-0622-xMatera MG, Rogliani P, Cazzola M. QVA149 (indacaterol/glycopyrronium) for the treatment of chronic obstructive pulmonary disease. Expert Opin Pharmacother, 2015, 16: 1079– 1090.Matera MG, Rogliani P, Cazzola M. QVA149 (indacaterol/glycopyrronium) for the treatment of chronic obstructive pulmonary disease. Expert Opin Pharmacother, 2015, 16: 1079– 1090.Rodrigo GJ, Plaza V. Efficacy and safety of a fixed-dose combination of indacaterol and glycopyrronium for the treatment of COPD: a systematic review. Chest, 2014, 146: 309–317.Rodrigo GJ, Plaza V. Efficacy and safety of a fixed-dose combination of indacaterol and glycopyrronium for the treatment of COPD: a systematic review. Chest, 2014, 146: 309–317.Drollmann A, Brown M, Sechaud R et al. Effect of dual bronchodilation with QVA149 on cardiac safety in healthy volunteers. Int J Clin Pharmacol Ther, 2014, 52: 369–380.Drollmann A, Brown M, Sechaud R et al. Effect of dual bronchodilation with QVA149 on cardiac safety in healthy volunteers. Int J Clin Pharmacol Ther, 2014, 52: 369–380.van de Maele B, Fabbri LM, Martin C et al. Cardiovascular safety of QVA149, a combination of Indacaterol and NVA237, in COPD patients. COPD, 2010, 7: 418–427.van de Maele B, Fabbri LM, Martin C et al. Cardiovascular safety of QVA149, a combination of Indacaterol and NVA237, in COPD patients. COPD, 2010, 7: 418–427.Hohlfeld JM, Claussen J V-C, Biller H et al. Effect of lung deflation with indacaterol plus glycopyrronium on ventricular filling in patients with hyperinflation and COPD (CLAIM). Lancet Resp Med, 2018, 6: 368-378.Hohlfeld JM, Claussen J V-C, Biller H et al. Effect of lung deflation with indacaterol plus glycopyrronium on ventricular filling in patients with hyperinflation and COPD (CLAIM). Lancet Resp Med, 2018, 6: 368-378.Barr RG, Bluemke DA, Ahmed FS et al. Percent Emphysema, Airflow Obstruction, and Impaired Left Ventricular Filling. New Engl J Med, 2010, 362: 217-227.Barr RG, Bluemke DA, Ahmed FS et al. Percent Emphysema, Airflow Obstruction, and Impaired Left Ventricular Filling. New Engl J Med, 2010, 362: 217-227.Watz H, Waschki B, Magnussen H et al. Decreasing Cardiac Chamber Sizes and Associated Heart Dysfunction in COPD. Chest, 2010, 138: 32-38.Watz H, Waschki B, Magnussen H et al. Decreasing Cardiac Chamber Sizes and Associated Heart Dysfunction in COPD. Chest, 2010, 138: 32-38.Donohue JF, Niewoehner D, Brooks J et al. Safety and tolerability of once-daily umeclidinium/vilanterol 125/25 mcg and umeclidinium 125 mcg in patients with chronic obstructive pulmonary disease: results from a 52-week, randomized, double blind, placebo-controlled study. Resp Res, 2014, 15(1): 78. doi: 10.1186/1465-9921-15-78.Donohue JF, Niewoehner D, Brooks J et al. Safety and tolerability of once-daily umeclidinium/vilanterol 125/25 mcg and umeclidinium 125 mcg in patients with chronic obstructive pulmonary disease: results from a 52-week, randomized, double blind, placebo-controlled study. Resp Res, 2014, 15(1): 78. doi: 10.1186/1465-9921-15-78.Naccarelli G, Finkle J, Chopra B et al. Cardiovascular safety of umeclidinium/vilanterol in COPD: results from eight randomized clinical trials [abstract]. Am J Resp Crit Care Med, 2014, 189: A3766.Naccarelli G, Finkle J, Chopra B et al. Cardiovascular safety of umeclidinium/vilanterol in COPD: results from eight randomized clinical trials [abstract]. Am J Resp Crit Care Med, 2014, 189: A3766.Donohue JF, Maleki-Yazdi MR, Kilbride S et al. Efficacy and safety of once-daily umeclidinium/ vilanterol 62.5/25 mcg in COPD. Resp Med, 2013, 107: 1538-1546.Donohue JF, Maleki-Yazdi MR, Kilbride S et al. Efficacy and safety of once-daily umeclidinium/ vilanterol 62.5/25 mcg in COPD. Resp Med, 2013, 107: 1538-1546.Donohue JF, Bateman ED, D’Urzo A et al. Cardiovascular (CV) safety of aclidinium bromide/formoterol fumarate fixed dose combination (FDC) in COPD: Pooled analyses of three Phase III studies [abstract]. Eur Resp J, 2014, 44(Suppl 58): P287.Donohue JF, Bateman ED, D’Urzo A et al. Cardiovascular (CV) safety of aclidinium bromide/formoterol fumarate fixed dose combination (FDC) in COPD: Pooled analyses of three Phase III studies [abstract]. Eur Resp J, 2014, 44(Suppl 58): P287.Baur F, Beattie D, Beer D, et al. The identification of indacaterol as an ultralong-acting inhaled b2-adrenoceptor agonist. J Med Chem, 2010, 53(9): 3675–84,Baur F, Beattie D, Beer D, et al. The identification of indacaterol as an ultralong-acting inhaled b2-adrenoceptor agonist. J Med Chem, 2010, 53(9): 3675–84,Handley D. The asthma-like pharmacology and toxicology of (S)-isomers of beta agonists. J Allergy Clin Immunol, 1999, 104(2 Pt 2): S69–76.Handley D. The asthma-like pharmacology and toxicology of (S)-isomers of beta agonists. J Allergy Clin Immunol, 1999, 104(2 Pt 2): S69–76.

The authors declare that there are no conflicts of interest present.