The possibilities of using beta-blocker bisoprolol in patients with stable angina with concomitant bronchial asthma

Aim    To compare efficacy and safety of treatments with the calcium antagonist (CA) verapamil, the cardioselective β-blocker (BB) bisoprolol, and a combination therapy with bisoprolol and amlodipine in patients with stable angina (SA) with concurrent mild and moderate, persistent bronchial asthma (BA). 
Material and methods    This open, prospective, randomized, comparative study included 120 patients with an IHD+BA comorbidity. Of these patients, 60 had mild persistent BA and 60 had moderate persistent BA. Each group was divided into 3 subgroup, each including 20 patients, based on the used regimen of antianginal therapy. Stepwise dose titration was performed every 2 weeks (subgroup 1 received the BB bisoprolol 2.5 mg – 5 mg – 10 mg; subgroup 2 received the CA verapamil 240 mg – 240 mg – 240 mg; subgroup 3 received bisoprolol 2.5 mg followed by the combination treatment with bisoprolol and amlodipine as a fixed combination 5+5 mg). All patients underwent a complete clinical and instrumental examination at baseline and at 2, 4, and 6 weeks of treatment. The antianginal effectivity and the effect on bronchial patency were evaluated. 
Results    In patients with SA and mild persistent BA, the study of external respiration function (ERF) at 2, 4, and 6 weeks of treatment did not detect any significant difference in the forced expiratory volume in 1 second (FEV1) between the treatment subgroups. In patients with SA and moderate persistent BA receiving the treatment, a significant decrease in FEV1 (р=0.022) was observed in subgroup 1 receiving bisoprolol 10 mg at 6 weeks of treatment. In subgroups 2 and 3 during the treatment, significant differences were absent. In patients with SA and mild or moderate persistent BA, the heart rate was significantly decreased in all three subgroups; however, in subgroup 2 receiving verapamil, the changes were considerably smaller than in other subgroups.
Conclusion    The study results showed that the BB bisoprolol with dose titration every two weeks from 2.5 to 10 mg or the combination treatment with the BB bisoprolol and the CA amlodipine can be used as the antianginal therapy in patients with SA and mild persistent BA. The BB bisoprolol may be used in patients with SA and moderate persistent BA as the antianginal therapy, but only at doses not exceeding 5 mg to avoid the development of bronchial obstruction. The combination therapy with the BB bisoprolol 5 mg and the CA amlodipine 5 mg is indicated to enhance antianginal and vasoprotective effects.

1.

2. Cazzola M, Calzetta L, Bettoncelli G, Cricelli C, Romeo F, Matera MG et al. Cardiovascular disease in asthma and COPD: A population-based retrospective cross-sectional study. Respiratory Medicine. 2012;106(2):249–56. DOI: 10.1016/j.rmed.2011.07.021

3. Steppuhn H, Langen U, Keil T, Scheidt-Nave C. Chronic disease comorbidity of asthma and unscheduled asthma care among adults: results of the national telephone health interview survey German Health Update (GEDA) 2009 and 2010. Primary Care Respiratory Journal. 2014;23(1):22–9. DOI: 10.4104/pcrj.2013.00107

4. Girodet P-O, Dournes G, Thumerel M, Begueret H, Santos PD, Ozier A et al. Calcium Channel Blocker Reduces Airway Remodeling in Severe Asthma. A Proof-of-Concept Study. American Journal of Respiratory and Critical Care Medicine. 2015;191(8):876–83. DOI: 10.1164/rccm.201410-1874OC

5. Global Initiative for Asthma. 2019 GINA Report: Global Strategy for Asthma Management and Prevention. [Internet] Available at: https://ginasthma.org/reports/2019-gina-report-global-strategy-for-asthmamanagement-and-prevention/

6. Graudins A, Lee HM, Druda D. Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies. British Journal of Clinical Pharmacology. 2016;81(3):453–61. DOI: 10.1111/bcp.12763

7. Kotecha D, Flather MD, Altman DG, Holmes J, Rosano G, Wikstrand J et al. Heart Rate and Rhythm and the Benefit of Beta-Blockers in Patients with Heart Failure. Journal of the American College of Cardiology. 2017;69(24):2885–96. DOI: 10.1016/j.jacc.2017.04.001

8. Garcia-Araújo AS, Pires Di Lorenzo VA, Labadessa IG, Jürgensen SP, Di Thommazo-Luporini L, Garbim CL et al. Increased sympathetic modulation and decreased response of the heart rate variability in controlled asthma. Journal of Asthma. 2015;52(3):246–53. DOI: 10.3109/02770903.2014.957765

9. Morales DR, Dreischulte T, Lipworth BJ, Donnan PT, Jackson C, Guthrie B. Respiratory effect of beta‐blocker eye drops in asthma: population‐based study and meta‐analysis of clinical trials. British Journal of Clinical Pharmacology. 2016;82(3):814–22. DOI: 10.1111/bcp.13006

10. Sorbets E, Steg PG, Young R, Danchin N, Greenlaw N, Ford I et al. β-blockers, calcium antagonists, and mortality in stable coronary artery disease: an international cohort study. European Heart Journal. 2019;40(18):1399–407. DOI: 10.1093/eurheartj/ehy811

11. Barbarash O.L., Karpov Yu.A., Kashtalap V.V., Boshchenko A.A., Ruda M.Ya., Akchurin R.S. et al. 2020 Clinical practice guidelines for Stable coronary artery disease. Russian Journal of Cardiology. 2020;25(11):201–50. DOI: 10.15829/1560-4071-2020-4076

12. Ministry of Health of Russian Federation. Bronchial asthma. Av. at: https://spulmo.ru/upload/kr_bronhastma_2019.pdf. 2019.

13. Wang L, Gao S, Yu M, Sheng Z, Tan W. Association of asthma with coronary heart disease: A meta analysis of 11 trials. PLOS ONE. 2017;12(6):e0179335. DOI: 10.1371/journal.pone.0179335

14. Cepelis A, Brumpton BM, Malmo V, Laugsand LE, Loennechen JP, Ellekjær H et al. Associations of Asthma and Asthma Control With Atrial Fibrillation Risk: Results From the Nord-Trøndelag Health Study (HUNT). JAMA Cardiology. 2018;3(8):721–8. DOI: 10.1001/jamacardio.2018.1901

15. Strand LB, Tsai MK, Wen CP, Chang S-S, Brumpton BM. Is having asthma associated with an increased risk of dying from cardiovascular disease? A prospective cohort study of 446 346 Taiwanese adults. BMJ Open. 2018;8(5):e019992. DOI: 10.1136/bmjopen-2017-019992

16. Spanbroek R, Grabner R, Lotzer K, Hildner M, Urbach A, Ruhling K et al. Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis. Proceedings of the National Academy of Sciences. 2003;100(3):1238–43. DOI: 10.1073/pnas.242716099