Statins and Pulmonary Hypertension in Chronic Obstructive Lung Disease

Document Type: Narrative Review

Authors

Pulmonologist, Lung Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Chronic obstructive lung disease (COPD) is a chronic multisystem disease with a considerable burden. One of its most common complications is pulmonary artery hypertension (PAH). It has been demonstrated that the development of PAH is correlated with decreased quality of life and survival. Different medications have been proposed for the treatment of PAH, among which one can name statins. However, the same as other medications for the treatment of PAH, statins are still providing controversial results across different study settings. Moreover, the effect of statins on PAH in COPD patients has not been widely investigated so far. According to the present review, most of the available clinical trials demonstrated that the utilization of statins, including pravastatin, atorvastatin, and rosuvastatin may have beneficial effects on PAH in COPD patients. Nonetheless, it is necessary to conduct clinical trials with longer follow-up duration

Keywords


1. Young RP, Hopkins RJ. Update on the potential role of statins in chronic obstructive pulmonary disease and its co-morbidities. Expert Rev Respir Med. 2013;7:533-44.

2. Shujaat A, Bajwa AA, Cury JD. Pulmonary hypertension secondary to COPD. Pulm Med. 2012;2012:203952.

3. Arnaud C, Burger F, Steffens S, Veillard NR, Nguyen TH, Trono D, et al. Statins reduce interleukin-6-induced C-reactive protein in human hepatocytes: new evidence for direct antiinflammatory effects of statins. Arterioscler Thromb Vasc Biol. 2005;25:1231-6.

4.  Zakynthinos E, Daniil Z, Papanikolaou J, Makris D. Pulmonary hypertension in COPD: pathophysiology and therapeutic targets. Curr Drug Targets. 2011;12:501-13.

5. Ramkumar S, Raghunath A, Raghunath S. Statin therapy: review of safety and potential side effects. Acta Cardiol Sin. 2016;32:631-9.

6. Kim SW, Kang HJ, Jhon M, Kim JW, Lee JY, Walker AJ, et al. Statins and inflammation: new therapeutic opportunities in psychiatry. Front Psychiatry. 2019;10:103.

7. Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013; 1:Cd004816.

8. Pinal-Fernandez I, Casal-Dominguez M, Mammen AL. Statins: pros and cons. Med Clin (Barc). 2018;150:398-402.

9.  Yan J, Qiao L, Tian J, Liu A, Wu J, Huang J, et al. Effect of statins on Parkinson's disease: asystematic review and meta-analysis. Medicine (Baltimore). 2019;98:e14852.

10. Hothersall E, McSharry C, Thomson NC. Potential therapeutic role for statins in respiratory disease. Thorax. 2006;61:729-34.

11. Zaleska M, Mozenska O, Bil J. Statins use and cancer: an update. 2018;14(15):1497-509.

12. Cao C, Wu Y, Xu Z, Lv D, Zhang C, Lai T, et al. The effect of statins on chronic obstructive pulmonary disease exacerbation and mortality: a systematic review and meta-analysis of observational research. Sci Rep. 2015;5:16461.

13. Wilkins MR, Ali O, Bradlow W, Wharton J, Taegtmeyer A, Rhodes CJ, et al. Simvastatin as a treatment for pulmonary hypertension trial. Am J Respir Crit Care Med. 2010;181(10):1106-13.

14. Wright JL, Zhou S, Preobrazhenska O, Marshall C, Sin DD, Laher I, et al. Statin reverses smoke-induced pulmonary hypertension and prevents emphysema but not airway remodeling. 2011;183(1):50-8.

15. Lee JH, Lee DS, Kim EK, Choe KH, Oh YM, Shim TS, et al. Simvastatin inhibits cigarette smoking-induced emphysema and pulmonary hypertension in rat lungs. Am J Respir Crit Care Med. 2005;172(8):987-93.

16. Lee T-M, Chen C-C, Shen H-N, Chang N-CJCs. Effects of pravastatin on functional capacity in patients with chronic obstructive pulmonary disease and pulmonary hypertension. 2009;116(6):497-505.

17. Liu HF, Qi XW, Ma LL, Yao DK, Wang L. Atorvastatin improves endothelial progenitor cell function and reduces pulmonary hypertension in patients with chronic pulmonary heart disease. Experimental and clinical cardiology. 2013;18(1):e40-3.

18. Shahmiri S, Adeli S, Mousavi S, Mostafapour E, Fereshtehnejad S, Namegh B, et al. Evaluation of the simvastatin effects in the treatment of pulmonary hypertension (PH). 2009;131:12-5.

19. Zeng WJ, Xiong CM, Zhao L, Shan GL, Liu ZH, Xue F, et al. Atorvastatin in pulmonary arterial hypertension (APATH) study. The European respiratory journal. 2012;40(1):67-74.

20. Kawut SM, Bagiella E, Lederer DJ, Shimbo D, Horn EM, Roberts KE, et al. Randomized clinical trial of aspirin and simvastatin for pulmonary arterial hypertension: ASA-STAT. Circulation. 2011;123(25):2985-93.

21. Holzhauser L, Hovnanians N, Eshtehardi P, Mojadidi MK, Deng Y, Goodman-Meza D, et al. Statin therapy improves survival in patients with severe pulmonary hypertension: a propensity score matching study. 2017;32(8):969-76.

22. Reed RM, Iacono A, DeFilippis A, Jones S, Eberlein M, Lechtzin N, et al. Statin therapy is associated with decreased pulmonary vascular pressures in severe COPD. Copd. 2011;8(2):96-102.

23.     Moosavi SA, Raji H, Faghankhani M, Yazdani R, Esmaeili M. Evaluation of the effects of atorvastatin on the treatment of secondary pulmonary hypertension due to chronic obstructive pulmonary diseases: a randomized controlled trial. Iran Red Crescent Med J. 2013;15:649-54.

24. Arian A, Moghadam SG, Kazemi T, Hajihosseini M. The effects of statins on pulmonary artery pressure in patients with chronic obstructive pulmonary disease: a randomized controlled trial. J Res Pharm Pract. 2017;6:27-30  

25. Chogtu B, Kuriachan S, Magazine R, Shetty KR, Kamath A, George MM, Tripathy A, Kumar DM. A prospective, randomized study: Evaluation of the effect of rosuvastatin in patients with chronic obstructive pulmonary disease and pulmonary hypertension. Indian journal of pharmacology. 2016 Sep;48(5):503.