Optimising arterial-hypertension therapy in patients with chronic obstructive pulmonary disease

Aim. To assess the efficacy of a fixed-dose combination of an angiotensin II receptor blocker and a calcium-channel blocker within combination therapy in patients with arterial hypertension (AH) combined with chronic obstructive pulmonary disease (COPD).
Materials and methods. Thirty patients aged 61–75 years with AH and COPD were examined and allocated to two equal groups. Group 1 received a fixed combination of candesartan 16 mg and amlodipine 5 mg once daily (Hyposart A, Akrikhin) as antihypertensive therapy; Group 2 received amlodipine 5 mg/day and lisinopril 20 mg/day. A full clinical, instrumental and laboratory evaluation was performed before treatment and after six weeks; office blood pressure (BP) was measured after two weeks, and 24-hour ambulatory BP monitoring (ABPM) was used to analyse BP variability and circadian profile.
Results. By week 6, the target BP was achieved in 100 % of Group 1 and in 86.7 % of Group 2. ABPM showed more pronounced favourable changes in Group 1. In Group 2 the variability of systolic (SBP) and diastolic BP (DBP) fell significantly only in daytime (p < 0.05); at night the decrease was not significant (p > 0.05). The nocturnal dip percentage of SBP in Group 1 increased by 24.6 % and that of DBP by 21.4 % (p < 0.01); no significant change was recorded in Group 2. In Group 1 the proportion of dippers rose from 20.0 % to 73.3 % owing to a decline in non-dippers (from 53.0 % to 20.0 %) and night-peakers (from 26.7 % to 6.1 %). In Group 2 the numbers of non-dippers (from 46.7 % to 40.0 %) and night-peakers (from 26.7 % to 20.0 %) fell, resulting in an increase in dippers to 40.0 %. Spirometry revealed significant improvement in airway patency in both groups.
Conclusion. In patients with concomitant AH and COPD, the fixed-dose combination of candesartan and amlodipine provides potent antihypertensive action, markedly normalises nocturnal BP variability in non-dippers and night-peakers, and improves bronchial patency.

1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2023 Report. Available at: https://goldcopd.org

2. [Clinical recommendations «Chronic obstructive pulmonary disease». Russian respiratory society]. 2021 Available at: https://diseases.medelement.com/disease/хроническая-обструктивная-болезнь-легких-кр-рф-2024/18404 (in Russian).

3. Christenson S.A., Smith B.M., Bafadhel M., Putcha N. Chronic obstructive pulmonary disease. Lancet 2022; 99(10342):2227–2242. https://doi.org/10.1016/S0140-6736(22)00470-6

4. [Clinical guidelines "Chronic obstructive pulmonary disease". Russian Respiratory Society]. 2024. Available at: https://russjcardiol.elpub.ru/jour/article/view/6117/4464 (in Russian).

5. Klimova A.A., Ambatello L.G., Smolyakova E.V., Zykov K.A., Chazova I.E. [The frequency of detection of comorbid broncho-obstructive pathology in patients with arterial hypertension admitted to a specialized cardiological hospital]. Sistemnyye gipertenzii = Systemic Hypertension 2023; 20(1):35–43 (in Russian). https://doi.org/10.38109/2075-082X-2023-1-35-43

6. Balanova Yu.A., Drapkina O.M., Kutsenko V.A., Imaeva A.E., Koncevaja M.V., Maksimov S.A., Muromceva G.A., Kotova M.B., Karamnova N.S., Evstifeeva S.E., Kapustina A.V., Litinskaja O.A., Pokrovskaja M.S., Filichkina E.M., Ivlev O.E., Gomanova L.I., Doludin Ju.V., Efimova I.A., Borisova A.L., Nazarov B.M., Jarovaja E.B., Repkina T.V., Gonoshilova T.O., Kudrjavcev A.V., Belova N.M., Shagrov A.L., Samotrueva M.A., Jasenjavskaja A.L., Chernysheva E.N., Gluhovskaja S.V., Levina I.A., Shirshova E.A., Dorzhieva E.B., Urbanova E.Z., Borovkova Ju.N., Kurashin V.K., Tokareva A.S., Ragino Ju.I., Simonova G.I., Hudjakova A.D., Nikulin V.N., Asljamov O.R., Hohlova G.V., Solov'eva V.A., Rodionov A.A., Krjachkova O.V., Shamurova Ju.Ju., Tancyreva I.V., Baryshnikova I.N., Ataev M.G., Radzhabov M.O., Isahanova M.M., Umetov M.A., Jel'garova L.V., Hakuasheva I.A., Jamashkina E.I., Esina M.V., Kunjaeva T.A., Nikitina A.M., Savvina N.V., Spiridonova Ju.E., Naumova E.A., Keskinov A.A., Kashtanova D.A., Judin V.S., Judin S.M., Shal'nova S.A. [Hypertension in the Russian population during the COVID-19 pandemic: sex differences in prevalence, treatment and its effectiveness. Data from the ESSE-RF3 study]. Cardiovascular Therapy and Prevention 2023; 22(8S):3785 (in Russian). https://doi.org/10.15829/1728-8800-2023-3785

7. Greulich T., Weist B.J.D., Koczulla A.R., Janciauskiene S., Klemmer A., Lux W., Alter P., Vogelmeier C.F. Prevalence of comorbidities in COPD patients by disease severity in a German population. Respir. Med. 2017; 132:132–138. https://doi.org/10.1016/j.rmed.2017.10.0075

8. Chazova I.E., Nevzorova V.A., Ambatiello L.G., Brodskaya T.A., Oshchepkova E.V., Belevskiy A.S., Zhernakova J.V., Aysanov Z.R., Ovcharenko S.I., Chuchalin A.G. [Clinical practice guidelines on the diagnosis and treatment of patients with arterial hypertension and chronic obstructive pulmonary disease]. Sistemnyye gipertenzii = Systemic Hypertension 2020; 17(3):7–34 (in Russian). https://doi.org/10.26442/2075082X.2020.3.200294

9. Adasheva T.V., Samorukova E.I., Dolbin S.S., Li V.V., Zadionchenko V.S., Vysockaya N.V. [Chronic obstructive pulmonary disease and arterial hypertension: are there any specific patterns of patient management?] Rossiyskiy meditsinsniy zhurnal = Russian Medical Journal 2020; 3:32–38 (in Russian).

10. Sin D.D., Man S.F. Chronic obstructive pulmonary disease as a risk factor for cardiovascular morbidity and mortality. Proc. Am. Thorac. Soc. 2005; 2(1):2–11. https://doi.org/10.1513/pats.200404-032MS

11. Kunisaki K.M., Dransfield M.T., Anderson J.A., Brook R.D., Calverley P.M.A., Celli B.R., Crim C., Hartley B.F., Martinez F.J., Newby D.E., Pragman A.A., Vestbo J., Yates J.C., Niewoehner D.E., Investigators S. Exacerbations of chronic obstructive pulmonary disease and cardiac events: a post hoc cohort analysis from the SUMMIT randomized clinical trial. Am. J. Respir. Crit. Care Med. 2018; 1(98):51–57. https://doi.org/10.1164/rccm.201711-2239OC

12. Anthonisen N.R., Connett J.E., Enright P.L., Manfreda J. Hospitalizations and mortality in the lung health study. Am. J. Respir. Crit. Care Med. 2002; 166(3):333–339. https://doi.org/10.1164/rccm.2110093

13. Divo M., Cote C., de Torres J.P., Casanova C., Marin J.M., Pinto-Plata V., Zulueta J., Cabrera C., Zagaceta J., Hunninghake G., Celli B. Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2012; 186(2):155–161. https://doi.org/10.1164/rccm.201201-0034oc

14. Finks S.W., Rumbak M.J., Self T.H. Treating hypertension in chronic obstructive pulmonary disease. N. Engl. J. Med. 2020; 382(4):353–363. https://doi.org/10.1056/nejmra1805377

15. Mancia G., Kreutz R., Brunström M., Burnier М., Grassi G. 2023 ESH Guidelines for the management of arterial hypertension the task force for the management of arterial hypertension of the European Society of Hypertension: endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J. Hypertens. 2024; 42(1):194. https://doi.org/10.1097/HJH.0000000000003621

16. Leonova M.V. [Sartans in hypertension treatment: advantages of candesartan use]. Consilium Medicum 2019; 21 (1):25–30. https://doi.org/10.26442/20751753.2019.1.190280

17. Liefde I. Sartan-AT1 receptor interactions: in vitro evidence for insurmountable antagonism and inverse agonism. Mol. Cell. Endocrinol. 2009; 302(2):237–243. https://doi.org/10.1016/j.mce.2008.06.006

18. Chen R., Marc A., Harlan M., Schuemie M.J., Shea S., Duke J., Pratt N. Comparative first-line effectiveness and safety of ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers: a multinational cohort study. Hypertension 2021; 78(3):591–603. https://doi.org/10.1161/HYPERTENSIONAHA.120.16667

19. Yahontov D.A., Balabanova N.F. [Effects of calcium antagonists of the third generation in patients with arterial hypertension and concomitant chronic obstructive pulmonary disease]. Rational Pharmacotherapy in Cardiology 2010; 6(3):339–344 (in Russian). https://doi.org/10.20996/1819-6446-2010-6-3-339-344