Skip to main content
Top
Published in: Cardiovascular Drugs and Therapy 6/2022

15-09-2021 | Statins | Original Article

Efficacy of Statin Therapy in Patients with Hospital Admission for COVID-19

Authors: Daein Choi, Qinzhong Chen, Sascha N. Goonewardena, Hannah Pacheco, Priscilla Mejia, Robin L. Smith, Robert S. Rosenson

Published in: Cardiovascular Drugs and Therapy | Issue 6/2022

Login to get access

Abstract

Purpose

COVID-19 is characterized by dysfunctional immune responses and metabolic derangements, which in some, lead to multi-organ failure and death. Statins are foundational lipid-lowering therapeutics for cardiovascular disease and also possess beneficial immune-modulating properties. Because of these immune-modulating properties, some have suggested their use in COVID-19. We sought to investigate the association between statin use and mortality in patients hospitalized with COVID-19.

Methods

Five thousand three hundred seventy-five COVID-19 patients admitted to Mount Sinai Health System hospitals in New York between February 27, 2020, and December 3, 2020, were included in this analysis. Statin use was classified as either non-user, low-to-moderate-intensity user, or high-intensity user. Multivariate Cox proportional hazards models were used to evaluate in-hospital mortality rate. Considered covariates were age, sex, race, and comorbidities.

Results

Compared to non-statin users, both low-to-moderate-intensity (adjusted hazard ratio; aHR 0.62, 95% confidential intervals; CI 0.51–0.76) and high-intensity statin users (aHR 0.53, 95% CI 0.43–0.65) had a reduced risk of death. Subgroup analysis of 723 coronary artery disease patients showed decreased mortality among high-intensity statin users compared to non-users (aHR 0.51, 95% CI 0.36–0.71).

Conclusions

Statin use in patients hospitalized with COVID-19 was associated with a reduced in-hospital mortality. The protective effect of statin was greater in those with coronary artery disease. These data support continued use of statin therapy in hospitalized patients with COVID-19. Clinical trials are needed to prospectively determine if statin use is effective in lowering the mortality in COVID-19 and other viral infections.
Appendix
Available only for authorised users
Literature
2.
go back to reference Pinney SP, Giustino G, Halperin JL, Mechanick JI, Neibart E, Olin JW, et al. Coronavirus historical perspective, disease mechanisms, and clinical outcomes: JACC focus seminar. J Am Coll Cardiol. 2020;76:1999–2010.CrossRefPubMedPubMedCentral Pinney SP, Giustino G, Halperin JL, Mechanick JI, Neibart E, Olin JW, et al. Coronavirus historical perspective, disease mechanisms, and clinical outcomes: JACC focus seminar. J Am Coll Cardiol. 2020;76:1999–2010.CrossRefPubMedPubMedCentral
3.
go back to reference Giustino G, Pinney SP, Lala A, Reddy VY, Johnston-Cox HA, Mechanick JI, et al. Coronavirus and cardiovascular disease, myocardial injury, and arrhythmia: JACC focus seminar. J Am Coll Cardiol. 2020;76:2011–23.CrossRefPubMedPubMedCentral Giustino G, Pinney SP, Lala A, Reddy VY, Johnston-Cox HA, Mechanick JI, et al. Coronavirus and cardiovascular disease, myocardial injury, and arrhythmia: JACC focus seminar. J Am Coll Cardiol. 2020;76:2011–23.CrossRefPubMedPubMedCentral
4.
go back to reference Bhatraju PK, Ghassemieh BJ, Nichols M, Kim R, Jerome KR, Nalla AK, et al. COVID-19 in critically ill patients in the Seattle region - case series. N Engl J Med. 2020;382:2012–22.CrossRefPubMed Bhatraju PK, Ghassemieh BJ, Nichols M, Kim R, Jerome KR, Nalla AK, et al. COVID-19 in critically ill patients in the Seattle region - case series. N Engl J Med. 2020;382:2012–22.CrossRefPubMed
5.
go back to reference Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020;5:802–10.CrossRefPubMedPubMedCentral Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020;5:802–10.CrossRefPubMedPubMedCentral
6.
go back to reference Colantonio LD, Shannon ED, Orroth KK, Zaha R, Jackson EA, Rosenson RS, Exter J, Mues KE, Muntner P. Ischemic event rates in very-high-risk adults. J Am Coll Cardiol. 2019;74:2496–507.CrossRefPubMed Colantonio LD, Shannon ED, Orroth KK, Zaha R, Jackson EA, Rosenson RS, Exter J, Mues KE, Muntner P. Ischemic event rates in very-high-risk adults. J Am Coll Cardiol. 2019;74:2496–507.CrossRefPubMed
7.
go back to reference Bikdeli B, Madhavan MV, Gupta A, Jimenez D, Burton JR, Der Nigoghossian C, et al. Pharmacological agents targeting thromboinflammation in COVID-19: review and implications for future research. Thromb Haemost. 2020;120:1004–24.CrossRefPubMedPubMedCentral Bikdeli B, Madhavan MV, Gupta A, Jimenez D, Burton JR, Der Nigoghossian C, et al. Pharmacological agents targeting thromboinflammation in COVID-19: review and implications for future research. Thromb Haemost. 2020;120:1004–24.CrossRefPubMedPubMedCentral
8.
go back to reference Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–207.CrossRefPubMed Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–207.CrossRefPubMed
10.
go back to reference Kong F, Ye B, Lin L, Cai X, Huang W, Huang Z. Atorvastatin suppresses NLRP3 inflammasome activation via TLR4/MyD88/NF-kappab signaling in PMA-stimulated THP-1 monocytes. Biomed Pharmacother. 2016;82:167–72.CrossRefPubMed Kong F, Ye B, Lin L, Cai X, Huang W, Huang Z. Atorvastatin suppresses NLRP3 inflammasome activation via TLR4/MyD88/NF-kappab signaling in PMA-stimulated THP-1 monocytes. Biomed Pharmacother. 2016;82:167–72.CrossRefPubMed
11.
go back to reference Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, et al. Sars-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271-280 e278.CrossRefPubMedPubMedCentral Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, et al. Sars-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271-280 e278.CrossRefPubMedPubMedCentral
12.
go back to reference Shin YH, Min JJ, Lee JH, Kim EH, Kim GE, Kim MH, et al. The effect of fluvastatin on cardiac fibrosis and angiotensin-converting enzyme-2 expression in glucose-controlled diabetic rat hearts. Heart Vessels. 2017;32:618–27.CrossRefPubMed Shin YH, Min JJ, Lee JH, Kim EH, Kim GE, Kim MH, et al. The effect of fluvastatin on cardiac fibrosis and angiotensin-converting enzyme-2 expression in glucose-controlled diabetic rat hearts. Heart Vessels. 2017;32:618–27.CrossRefPubMed
13.
go back to reference Tikoo K, Patel G, Kumar S, Karpe PA, Sanghavi M, Malek V, et al. Tissue specific up regulation of ACE2 in rabbit model of atherosclerosis by atorvastatin: role of epigenetic histone modifications. Biochem Pharmacol. 2015;93:343–51.CrossRefPubMed Tikoo K, Patel G, Kumar S, Karpe PA, Sanghavi M, Malek V, et al. Tissue specific up regulation of ACE2 in rabbit model of atherosclerosis by atorvastatin: role of epigenetic histone modifications. Biochem Pharmacol. 2015;93:343–51.CrossRefPubMed
14.
go back to reference Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, et al. Angiotensin-converting enzyme 2 is a functional receptor for the sars coronavirus. Nature. 2003;426:450–4.CrossRefPubMedPubMedCentral Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, et al. Angiotensin-converting enzyme 2 is a functional receptor for the sars coronavirus. Nature. 2003;426:450–4.CrossRefPubMedPubMedCentral
15.
go back to reference Rosenson RS, Baker S, Banach M, Borow KM, Braun LT, Bruckert E, et al. Optimizing cholesterol treatment in patients with muscle complaints. J Am Coll Cardiol. 2017;70:1290–301.CrossRefPubMed Rosenson RS, Baker S, Banach M, Borow KM, Braun LT, Bruckert E, et al. Optimizing cholesterol treatment in patients with muscle complaints. J Am Coll Cardiol. 2017;70:1290–301.CrossRefPubMed
16.
go back to reference Daniels LB, Sitapati AM, Zhang J, Zou J, Bui QM, Ren J, et al. Relation of statin use prior to admission to severity and recovery among COVID-19 inpatients. Am J Cardiol. 2020;136:149–55.CrossRefPubMedPubMedCentral Daniels LB, Sitapati AM, Zhang J, Zou J, Bui QM, Ren J, et al. Relation of statin use prior to admission to severity and recovery among COVID-19 inpatients. Am J Cardiol. 2020;136:149–55.CrossRefPubMedPubMedCentral
17.
go back to reference Gupta A, Madhavan MV, Poterucha TJ, DeFilippis EM, Hennessey JA, Redfors B, et al. Association between antecedent statin use and decreased mortality in hospitalized patients with COVID-19. Nat Commun. 2021;12:1325.CrossRefPubMedPubMedCentral Gupta A, Madhavan MV, Poterucha TJ, DeFilippis EM, Hennessey JA, Redfors B, et al. Association between antecedent statin use and decreased mortality in hospitalized patients with COVID-19. Nat Commun. 2021;12:1325.CrossRefPubMedPubMedCentral
18.
go back to reference Lohia P, Kapur S, Benjaram S, Mir T. Association between antecedent statin use and severe disease outcomes in COVID-19: a retrospective study with propensity score matching. J Clin Lipidol. 2021;15:451–9.CrossRefPubMedPubMedCentral Lohia P, Kapur S, Benjaram S, Mir T. Association between antecedent statin use and severe disease outcomes in COVID-19: a retrospective study with propensity score matching. J Clin Lipidol. 2021;15:451–9.CrossRefPubMedPubMedCentral
19.
go back to reference Daniels LB, Ren J, Kumar K, Bui QM, Zhang J, Zhang X, et al. Relation of prior statin and anti-hypertensive use to severity of disease among patients hospitalized with COVID-19: findings from the American Heart Association’s COVID-19 cardiovascular disease registry. PLoS One. 2021;16:e0254635.CrossRefPubMedPubMedCentral Daniels LB, Ren J, Kumar K, Bui QM, Zhang J, Zhang X, et al. Relation of prior statin and anti-hypertensive use to severity of disease among patients hospitalized with COVID-19: findings from the American Heart Association’s COVID-19 cardiovascular disease registry. PLoS One. 2021;16:e0254635.CrossRefPubMedPubMedCentral
20.
go back to reference Saeed O, Castagna F, Agalliu I, Xue X, Patel SR, Rochlani Y, et al. Statin use and in-hospital mortality in patients with diabetes mellitus and covid-19. J Am Heart Assoc. 2020;9:e018475.CrossRefPubMedPubMedCentral Saeed O, Castagna F, Agalliu I, Xue X, Patel SR, Rochlani Y, et al. Statin use and in-hospital mortality in patients with diabetes mellitus and covid-19. J Am Heart Assoc. 2020;9:e018475.CrossRefPubMedPubMedCentral
21.
go back to reference Zhang XJ, Qin JJ, Cheng X, Shen L, Zhao YC, Yuan Y, et al. In-hospital use of statins is associated with a reduced risk of mortality among individuals with covid-19. Cell Metab. 2020;32:176-187 e174.CrossRefPubMedPubMedCentral Zhang XJ, Qin JJ, Cheng X, Shen L, Zhao YC, Yuan Y, et al. In-hospital use of statins is associated with a reduced risk of mortality among individuals with covid-19. Cell Metab. 2020;32:176-187 e174.CrossRefPubMedPubMedCentral
23.
go back to reference Butt JH, Gerds TA, Schou M, Kragholm K, Phelps M, Havers-Borgersen E, et al. Association between statin use and outcomes in patients with coronavirus disease 2019 (covid-19): a nationwide cohort study. BMJ Open. 2020;10:e044421.CrossRefPubMed Butt JH, Gerds TA, Schou M, Kragholm K, Phelps M, Havers-Borgersen E, et al. Association between statin use and outcomes in patients with coronavirus disease 2019 (covid-19): a nationwide cohort study. BMJ Open. 2020;10:e044421.CrossRefPubMed
24.
go back to reference De Spiegeleer A, Bronselaer A, Teo JT, Byttebier G, De Tre G, Belmans L, et al. The effects of ARBs, ACEis, and statins on clinical outcomes of COVID-19 infection among nursing home residents. J Am Med Dir Assoc. 2020;21:909-914 e902.CrossRefPubMedPubMedCentral De Spiegeleer A, Bronselaer A, Teo JT, Byttebier G, De Tre G, Belmans L, et al. The effects of ARBs, ACEis, and statins on clinical outcomes of COVID-19 infection among nursing home residents. J Am Med Dir Assoc. 2020;21:909-914 e902.CrossRefPubMedPubMedCentral
25.
go back to reference Choi D, Choi S, Kim H, Kim K, Kim N, Ko A, et al. Impact of continuity of care on cardiovascular disease risk among newly-diagnosed hypertension patients. Sci Rep. 2020;10:19991.CrossRefPubMedPubMedCentral Choi D, Choi S, Kim H, Kim K, Kim N, Ko A, et al. Impact of continuity of care on cardiovascular disease risk among newly-diagnosed hypertension patients. Sci Rep. 2020;10:19991.CrossRefPubMedPubMedCentral
26.
go back to reference Kozma CM, Dickson M, Phillips AL, Meletiche DM. Medication possession ratio: Implications of using fixed and variable observation periods in assessing adherence with disease-modifying drugs in patients with multiple sclerosis. Patient Prefer Adherence. 2013;7:509–16.CrossRefPubMedPubMedCentral Kozma CM, Dickson M, Phillips AL, Meletiche DM. Medication possession ratio: Implications of using fixed and variable observation periods in assessing adherence with disease-modifying drugs in patients with multiple sclerosis. Patient Prefer Adherence. 2013;7:509–16.CrossRefPubMedPubMedCentral
27.
go back to reference Sikka R, Xia F, Aubert RE. Estimating medication persistency using administrative claims data. Am J Manag Care. 2005;11:449–57.PubMed Sikka R, Xia F, Aubert RE. Estimating medication persistency using administrative claims data. Am J Manag Care. 2005;11:449–57.PubMed
28.
go back to reference Prasad V, Jena AB. Prespecified falsification end points: can they validate true observational associations? JAMA. 2013;309:241–2.CrossRefPubMed Prasad V, Jena AB. Prespecified falsification end points: can they validate true observational associations? JAMA. 2013;309:241–2.CrossRefPubMed
29.
go back to reference Wimmer NJ, Resnic FS, Mauri L, Matheny ME, Yeh RW. Comparison of transradial versus transfemoral percutaneous coronary intervention in routine practice: evidence for the importance of “falsification hypotheses” in observational studies of comparative effectiveness. J Am Coll Cardiol. 2013;62:2147–8.CrossRefPubMed Wimmer NJ, Resnic FS, Mauri L, Matheny ME, Yeh RW. Comparison of transradial versus transfemoral percutaneous coronary intervention in routine practice: evidence for the importance of “falsification hypotheses” in observational studies of comparative effectiveness. J Am Coll Cardiol. 2013;62:2147–8.CrossRefPubMed
30.
go back to reference Oh TK, Song I, Jeon YT. Statin therapy and the risk of COVID-19: a cohort study of the national health insurance service in South Korea. J Pers Med. 2021;11(2):116.CrossRefPubMedPubMedCentral Oh TK, Song I, Jeon YT. Statin therapy and the risk of COVID-19: a cohort study of the national health insurance service in South Korea. J Pers Med. 2021;11(2):116.CrossRefPubMedPubMedCentral
31.
go back to reference Hariyanto TI, Kurniawan A. Statin therapy did not improve the in-hospital outcome of coronavirus disease 2019 (COVID-19) infection. Diabetes Metab Syndr. 2020;14:1613–5.CrossRefPubMedPubMedCentral Hariyanto TI, Kurniawan A. Statin therapy did not improve the in-hospital outcome of coronavirus disease 2019 (COVID-19) infection. Diabetes Metab Syndr. 2020;14:1613–5.CrossRefPubMedPubMedCentral
32.
go back to reference Hariyanto TI, Kurniawan A. Statin and outcomes of coronavirus disease 2019 (covid-19): a systematic review, meta-analysis, and meta-regression. Nutr Metab Cardiovasc Dis. 2021;31:1662–70.CrossRefPubMedPubMedCentral Hariyanto TI, Kurniawan A. Statin and outcomes of coronavirus disease 2019 (covid-19): a systematic review, meta-analysis, and meta-regression. Nutr Metab Cardiovasc Dis. 2021;31:1662–70.CrossRefPubMedPubMedCentral
33.
go back to reference Pal R, Banerjee M, Yadav U, Bhattacharjee S. Statin use and clinical outcomes in patients with COVID-19: an updated systematic review and meta-analysis. Postgrad Med J. 2021. postgradmedj-2020-139172. Pal R, Banerjee M, Yadav U, Bhattacharjee S. Statin use and clinical outcomes in patients with COVID-19: an updated systematic review and meta-analysis. Postgrad Med J. 2021. postgradmedj-2020-139172.
34.
go back to reference Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis. 2020;94:91–5.CrossRefPubMedPubMedCentral Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis. 2020;94:91–5.CrossRefPubMedPubMedCentral
35.
go back to reference Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–62.CrossRefPubMedPubMedCentral Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–62.CrossRefPubMedPubMedCentral
38.
go back to reference Totura AL, Whitmore A, Agnihothram S, Schafer A, Katze MG, Heise MT, et al. Toll-like receptor 3 signaling via TRIF contributes to a protective innate immune response to severe acute respiratory syndrome coronavirus infection. mBio. 2015;6:e00638-00615.CrossRefPubMedPubMedCentral Totura AL, Whitmore A, Agnihothram S, Schafer A, Katze MG, Heise MT, et al. Toll-like receptor 3 signaling via TRIF contributes to a protective innate immune response to severe acute respiratory syndrome coronavirus infection. mBio. 2015;6:e00638-00615.CrossRefPubMedPubMedCentral
39.
go back to reference Frost FJ, Petersen H, Tollestrup K, Skipper B. Influenza and COPD mortality protection as pleiotropic, dose-dependent effects of statins. Chest. 2007;131:1006–12.CrossRefPubMed Frost FJ, Petersen H, Tollestrup K, Skipper B. Influenza and COPD mortality protection as pleiotropic, dose-dependent effects of statins. Chest. 2007;131:1006–12.CrossRefPubMed
40.
go back to reference McAuley DF, Laffey JG, O’Kane CM, Perkins GD, Mullan B, Trinder TJ, et al. Simvastatin in the acute respiratory distress syndrome. N Engl J Med. 2014;371:1695–703.CrossRefPubMed McAuley DF, Laffey JG, O’Kane CM, Perkins GD, Mullan B, Trinder TJ, et al. Simvastatin in the acute respiratory distress syndrome. N Engl J Med. 2014;371:1695–703.CrossRefPubMed
41.
go back to reference Vandermeer ML, Thomas AR, Kamimoto L, Reingold A, Gershman K, Meek J, et al. Association between use of statins and mortality among patients hospitalized with laboratory-confirmed influenza virus infections: a multistate study. J Infect Dis. 2012;205:13–9.CrossRefPubMed Vandermeer ML, Thomas AR, Kamimoto L, Reingold A, Gershman K, Meek J, et al. Association between use of statins and mortality among patients hospitalized with laboratory-confirmed influenza virus infections: a multistate study. J Infect Dis. 2012;205:13–9.CrossRefPubMed
42.
go back to reference Roccaforte V, Daves M, Lippi G, Spreafico M, Bonato C. Altered lipid profile in patients with COVID-19 infection. J Lab Precis Med. 2021;6:2–2.CrossRef Roccaforte V, Daves M, Lippi G, Spreafico M, Bonato C. Altered lipid profile in patients with COVID-19 infection. J Lab Precis Med. 2021;6:2–2.CrossRef
Metadata
Title
Efficacy of Statin Therapy in Patients with Hospital Admission for COVID-19
Authors
Daein Choi
Qinzhong Chen
Sascha N. Goonewardena
Hannah Pacheco
Priscilla Mejia
Robin L. Smith
Robert S. Rosenson
Publication date
15-09-2021
Publisher
Springer US
Published in
Cardiovascular Drugs and Therapy / Issue 6/2022
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-021-07263-2

Other articles of this Issue 6/2022

Cardiovascular Drugs and Therapy 6/2022 Go to the issue