Effects of common cardiovascular drugs on the risk of COVID-19 infection and poor prognosis

doi:10.3969/j.issn.1004-583X.2022.10.001

Abstract

Abstract:

Cardiovascular disease is the most-common complication of coronavirus disease 2019 (COVID-19). During the COVID-19 pandemic, the safety and efficacy of common cardiovascular drugs such as anti-hypertensive, lipid-lowering, antiplatelet, anticoagulant, hypoglycemic and antiarrhythmic drugs have remained controversial that required improved consensuses. With the increase of global cases of COVID-19 and the occurrence of the second wave of infection, it is urgent to reveal the effects of cardiovascular disease drugs on COVID-19 patients. This study aims to summarize the relationship between common cardiovascular drugs and the risk of COVID-19 infection and poor prognosis, thus providing references for medications in COVID-19 patients with cardiovascular diseases.

Key words: COVID-19, cardiovascular system, anticoagulant therapy, antiplatelet therapy, lipid-lowering therapy, anti-hypertensive therapy, hypoglycemic therapy, antiarrhythmic therapy, meta-analysis

CLC Number:

R563.12

Zhou Zihan, Cui Wei. Effects of common cardiovascular drugs on the risk of COVID-19 infection and poor prognosis[J]. Clinical Focus, 2022, 37(10): 869-888.

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URL: https://huicui.hebmu.edu.cn/EN/10.3969/j.issn.1004-583X.2022.10.001

https://huicui.hebmu.edu.cn/EN/Y2022/V37/I10/869

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References 144

[1]	World Health Organization (WHO). WHO Coronavirus (COVID-19) Dashboard[EB/OL]. 2021. Available at: https://covid19.who.int. Accessed Octobers 28, 2022.
[2]	Ferrario CM, Jessup J, Chappell MC, et al. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2[J]. Circulation, 2005, 111(20): 2605-2610. doi: 10.1161/CIRCULATIONAHA.104.510461 pmid: 15897343
[3]	Ishiyama Y, Gallagher PE, Averill DB, et al. Upregulation of angiotensin-converting enzyme 2 after myocardial infarction by blockade of angiotensin II receptors. Hypertension[J]. 2004, 43(5): 970-976.
[4]	Koshy AN, Murphy AC, Farouque O, et al. Renin-angiotensin system inhibition and risk of infection and mortality in COVID-19: A systematic review and meta-analysis[J]. Intern Med J, 2020, 50(12): 1468-1474. doi: 10.1111/imj.15002 pmid: 33191600
[5]	Chu C, Zeng S, Hasan AA, et al. Comparison of infection risks and clinical outcomes in patients with and without SARS-CoV-2 lung infection under renin-angiotensin-aldosterone system blockade: Systematic review and meta-analysis[J]. Br J Clin Pharmacol, 2021, 87(6): 2475-2492. doi: 10.1111/bcp.14660 pmid: 33217033
[6]	Tleyjeh IM, Bin Abdulhak AA, Tlayjeh H, et al. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers and the risk of SARS-CoV-2 infection or hospitalization with COVID-19 disease: A systematic review and meta-analysis[J]. Am J Ther, 2020, 29(1): e74-e84. doi: 10.1097/MJT.0000000000001319 URL
[7]	Xu J, Teng Y, Shang L, et al. The effect of prior angiotensin-converting enzyme inhibitor and angiotensin receptor blocker treatment on coronavirus disease 2019 (COVID-19) susceptibility and outcome: A systematic review and meta-analysis[J]. Clin Infect Dis, 2021, 72(11): e901-e913. doi: 10.1093/cid/ciaa1592 pmid: 33079200
[8]	Zhang X, Yu J, Pan LY, Jiang HY. ACEI/ARB use and risk of infection or severity or mortality of COVID-19: A systematic review and meta-analysis[J]. Pharmacol Res, 2020, 158: 104927. doi: 10.1016/j.phrs.2020.104927 URL
[9]	Asiimwe IG, Pushpakom S, Turner RM, et al. Cardiovascular drugs and COVID-19 clinical outcomes: A living systematic review and meta-analysis[J]. Br J Clin Pharmacol, 2021, 87(12): 4534-4545. doi: 10.1111/bcp.14927 pmid: 34101232
[10]	Liu X, Long C, Xiong Q, et al. Association of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with risk of COVID-19, inflammation level, severity, and death in patients with COVID-19: A rapid systematic review and meta-analysis[J]. Clin Cardiol, 2020, 10.1002/clc.23421.
[11]	Caldeira D, Alves M, Gouveia E Melo R, et al. Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers and the risk of COVID-19 infection or severe disease: Systematic review and meta-analysis[J]. Int J Cardiol Heart Vasc, 2020, 31: 100627.
[12]	Ren L, Yu S, Xu W, et al. Lack of association of antihypertensive drugs with the risk and severity of COVID-19: A meta-analysis[J]. J Cardiol, 2021, 77(5): 482-491. doi: 10.1016/j.jjcc.2020.10.015 URL
[13]	Yokoyama Y, Aikawa T, Takagi H, et al. Association of renin-angiotensin-aldosterone system inhibitors with mortality and testing positive of COVID-19: Meta-analysis[J]. J Med Virol, 2021, 93(4): 2084-2089. doi: 10.1002/jmv.26588 pmid: 33038021
[14]	Lee M, Docherty KF, Sattar N, et al. Renin-angiotensin system blockers, risk of SARS-CoV-2 infection and outcomes from CoViD-19: Systematic review and meta-analysis[J]. Eur Heart J Cardiovasc Pharmacother, 2022, 8(2): 165-178. doi: 10.1093/ehjcvp/pvaa138 URL
[15]	Ma Z, Wang MP, Liu L, et al. Does taking an angiotensin inhibitor increase the risk for COVID-19? - a systematic review and meta-analysis[J]. Aging (Albany NY), 2021, 13(8): 10853-10865.
[16]	Asiimwe IG, Pushpakom SP, Turner RM, et al. Cardiovascular drugs and COVID-19 clinical outcomes: A systematic review and meta-analysis of randomized controlled trials[J]. Br J Clin Pharmacol, 2022, 88(8): 3577-3599. doi: 10.1111/bcp.15331 pmid: 35322889
[17]	Hariyanto TI, Hananto JE, Intan D, et al. Pre-admission beta-blocker therapy and outcomes of coronavirus disease 2019 (COVID-19): A systematic review, meta-analysis, and meta-regression[J]. Cardiovasc Hematol Disord Drug Targets, 2022, 22(2):104-117. doi: 10.2174/1871529X22666220420112735 URL
[18]	Grover A, Oberoi M. A systematic review and meta-analysis to evaluate the clinical outcomes in COVID-19 patients on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers[J]. Eur Heart J Cardiovasc Pharmacother, 2021, 7(2): 148-157. doi: 10.1093/ehjcvp/pvaa064 URL
[19]	Hasan SS, Kow CS, Hadi MA, et al. Mortality and disease severity among COVID-19 patients receiving renin-angiotensin system inhibitors: A systematic review and meta-analysis[J]. Am J Cardiovasc Drugs, 2020, 20(6): 571-590. doi: 10.1007/s40256-020-00439-5 URL
[20]	Greco A, Buccheri S, D'Arrigo P, et al. Outcomes of renin-angiotensin-aldosterone system blockers in patients with COVID-19: A systematic review and meta-analysis[J]. Eur Heart J Cardiovasc Pharmacother, 2020, 6(5): 335-337. doi: 10.1093/ehjcvp/pvaa074 URL
[21]	Lo KB, Bhargav R, Salacup G, et al. Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers and outcomes in patients with COVID-19: A systematic review and meta-analysis[J]. Expert Rev Cardiovasc Ther, 2020, 18(12): 919-930. doi: 10.1080/14779072.2020.1826308 URL
[22]	Alamer AA, Almulhim AS, Alrashed AA, et al. Mortality, severity, and hospital admission among COVID-19 patients with ACEI/ARB use: A meta-analysis stratifying countries based on response to the first wave of the pandemic[J]. Healthcare (Basel), 2021, 9(2):127.
[23]	Lee HW, Yoon CH, Jang EJ, et al. Renin-angiotensin system blocker and outcomes of COVID-19: A systematic review and meta-analysis[J]. Thorax, 2021, 76(5): 479-486. doi: 10.1136/thoraxjnl-2020-215322 pmid: 33504565
[24]	Hassib M, Hamilton S, Elkhouly A, et al. Renin-angiotensin-aldosterone system inhibitors and COVID-19: A meta-analysis and systematic review[J]. Cureus, 2021, 13(2): e13124.
[25]	Bavishi C, Whelton PK, Mancia G, et al. Renin-angiotensin-system inhibitors and all-cause mortality in patients with COVID-19: A systematic review and meta-analysis of observational studies[J]. J Hypertens, 2021, 39(4): 784-794. doi: 10.1097/HJH.0000000000002784 pmid: 33560054
[26]	Xie Q, Tang S, Li Y. The divergent protective effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on clinical outcomes of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis[J]. Ann Palliat Med, 2022, 11(4): 1253-1263. doi: 10.21037/apm-21-972 URL
[27]	Sattar Y, Mukuntharaj P, Zghouzi M, et al. Safety and efficacy of renin-angiotensin-aldosterone system inhibitors in COVID-19 population[J]. High Blood Press Cardiovasc Prev, 2021, 28(4): 405-416. doi: 10.1007/s40292-021-00462-w URL
[28]	Fernando ME, Drovandi A, Golledge J. Meta-analysis of the association between angiotensin pathway inhibitors and COVID-19 severity and mortality[J]. Syst Rev, 2021, 10(1): 243. doi: 10.1186/s13643-021-01802-6 pmid: 34488897
[29]	Baral R, White M, Vassiliou VS. Effect of renin-angiotensin-aldosterone system inhibitors in patients with COVID-19: A systematic review and meta-analysis of 28, 872 patients[J]. Curr Atheroscler Rep, 2020, 22(10): 61. doi: 10.1007/s11883-020-00880-6 pmid: 32830286
[30]	COVID-19 RISk and Treatments (CORIST) Collaboration. RAAS inhibitors are not associated with mortality in COVID-19 patients: Findings from an observational multicenter study in Italy and a meta-analysis of 19 studies[J]. Vascul Pharmacol, 2020, 135: 106805. doi: 10.1016/j.vph.2020.106805 URL
[31]	Guo X, Zhu Y, Hong Y. Decreased mortality of COVID-19 with renin-angiotensin-aldosterone system inhibitors therapy in patients with hypertension: A meta-analysis[J]. Hypertension, 2020, 76(2): e13-e14.
[32]	Pranata R, Permana H, Huang I, et al. The use of renin angiotensin system inhibitor on mortality in patients with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis[J]. Diabetes Metab Syndr, 2020, 14(5): 983-990. doi: S1871-4021(20)30216-2 pmid: 32615377
[33]	Barochiner J, Martínez R. Use of inhibitors of the renin-angiotensin system in hypertensive patients and COVID-19 severity: A systematic review and meta-analysis[J]. J Clin Pharm Ther, 2020, 45(6): 1244-1252. doi: 10.1111/jcpt.13246 URL
[34]	Wang Y, Chen B, Li Y, et al. The use of renin-angiotensin-aldosterone system (RAAS) inhibitors is associated with a lower risk of mortality in hypertensive COVID-19 patients: A systematic review and meta-analysis[J]. J Med Virol, 2021, 93(3): 1370-1377. doi: 10.1002/jmv.26625 pmid: 33095513
[35]	Dai XC, An ZY, Wang ZY, et al. Associations between the use of renin-angiotensin system inhibitors and the risks of severe COVID-19 and mortality in COVID-19 patients with hypertension: A meta-analysis of observational studies[J]. Front Cardiovasc Med, 2021, 8: 609857. doi: 10.3389/fcvm.2021.609857 URL
[36]	Alsagaff MY, Mulia E, Maghfirah I, et al. Association of calcium channel blocker use with clinical outcome of COVID-19: A meta-analysis[J]. Diabetes Metab Syndr, 2021, 15(5): 102210. doi: 10.1016/j.dsx.2021.102210 URL
[37]	Kow CS, Ramachandram DS, Hasan SS. Clinical outcomes of hypertensive patients with COVID-19 receiving calcium channel blockers: A systematic review and meta-analysis[J]. Hypertens Res, 2022, 45(2): 360-363. doi: 10.1038/s41440-021-00786-z URL
[38]	Kow CS, Ramachandram DS, Hasan SS. Use of Calcium channel blockers and the risk of all-cause mortality and severe illness in patients with COVID-19: A systematic review and meta-analysis[J]. J Cardiovasc Pharmacol, 2022, 79(2): 199-205. doi: 10.1097/FJC.0000000000001144 pmid: 35485583
[39]	Yin J, Wang C, Song X, et al. Effects of renin-angiotensin system inhibitors on mortality and disease severity of COVID-19 patients: A meta-analysis of randomized controlled trials[J]. Am J Hypertens, 2022, 35(5): 462-469. doi: 10.1093/ajh/hpac001 pmid: 35512430
[40]	Singh R, Rathore SS, Khan H, et al. Mortality and severity in COVID-19 patients on ACEIs and ARBs-A systematic review, meta-analysis, and meta-regression analysis[J]. Front Med (Lausanne), 2021, 8: 703661.
[41]	Gnanenthiran SR, Borghi C, Burger D, et al. Renin-angiotensin system inhibitors in patients with COVID-19: A meta-analysis of randomized controlled trials led by the international society of hypertension[J]. J Am Heart Assoc, 2022, 11(17): e026143. doi: 10.1161/JAHA.122.026143 URL
[42]	Baral R, Tsampasian V, Debski M, et al. Association between renin-angiotensin-aldosterone system inhibitors and clinical outcomes in patients with COVID-19: A systematic review and meta-analysis[J]. JAMA Netw Open, 2021, 4(3): e213594. doi: 10.1001/jamanetworkopen.2021.3594 URL
[43]	Aparisi Á, Catalá P, Amat-Santos IJ, et al. Chronic use of renin-angiotensin-aldosterone inhibitors in hypertensive COVID-19 patients: Results from a Spanish registry and meta-analysis[J]. Med Clin (Barc), 2022, 158(7): 315-323. doi: 10.1016/j.medcli.2021.04.005 URL
[44]	Loader J, Taylor FC, Lampa E, et al. Renin-angiotensin aldosterone system inhibitors and COVID-19: A systematic review and meta-analysis revealing critical bias across a body of observational research[J]. J Am Heart Assoc, 2022, 11(11): e025289. doi: 10.1161/JAHA.122.025289 URL
[45]	Qiu R, Li J, Xiao Y, et al. The therapeutic effect and safety of the drugs for COVID-19: A systematic review and meta-analysis[J]. Medicine (Baltimore), 2021, 100(16): e25532. doi: 10.1097/MD.0000000000025532 URL
[46]	Lee T, Cau A, Cheng MP, et al. Angiotensin receptor blockers and angiotensin-converting enzyme inhibitors in COVID-19: Meta-analysis/meta-regression adjusted for confounding factors[J]. CJC Open, 2021, 3(7): 965-975. doi: 10.1016/j.cjco.2021.03.001 URL
[47]	Azad GN, Kumar A. ACEi/ ARB and deaths of COVID-19 patients[J]. Curr Hypertens Rev, 2022.
[48]	Kow CS, Ramachandram DS, Hasan SS. Effects of angiotensin ii receptor blockers on the risk of mortality in patients with COVID-19: An updated systematic review and meta-analysis of randomized trials[J]. Am J Hypertens, 2022, 35(8): 763-764. doi: 10.1093/ajh/hpac070 URL
[49]	Sharma R, Kumar A, Majeed J, et al. Drugs acting on the renin-angiotensin-aldosterone system (RAAS) and deaths of COVID-19 patients: A systematic review and meta-analysis of observational studies[J]. Egypt Heart J, 2022, 74(1): 64. doi: 10.1186/s43044-022-00303-8 pmid: 36068392
[50]	Ssentongo AE, Ssentongo P, Heilbrunn ES, et al. Renin-angiotensin-aldosterone system inhibitors and the risk of mortality in patients with hypertension hospitalised for COVID-19: Systematic review and meta-analysis[J]. Open Heart, 2020, 7(2) :e001353. doi: 10.1136/openhrt-2020-001353 URL
[51]	Laurentius A, Mendel B, Prakoso R. Clinical outcome of renin-angiotensin-aldosterone system blockers in treatment of hypertensive patients with COVID-19: A systematic review and meta-analysis[J]. Egypt Heart J, 2021, 73(1): 13. doi: 10.1186/s43044-021-00135-y pmid: 33544293
[52]	Gilstrap LG, Fonarow GC, Desai AS, et al. Initiation, continuation, or withdrawal of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and outcomes in patients hospitalized with heart failure with reduced ejection fraction[J]. J Am Heart Assoc, 2017, 6(2):e004675. doi: 10.1161/JAHA.116.004675 URL
[53]	.Joint Committee for Guideline Revision. 2018 Chinese guidelines for prevention and treatment of hypertension-a report of the revision committee of chinese guidelines for prevention and treatment of hypertension[J]. J Geriatr Cardiol, 2019, 16(3): 182-241.
[54]	Minz MM, Bansal M, Kasliwal RR. Statins and SARS-CoV-2 disease: Current concepts and possible benefits[J]. Diabetes Metab Syndr, 2020, 14(6): 2063-2067. doi: 10.1016/j.dsx.2020.10.021 pmid: 33120281
[55]	Castiglione V, Chiriacò M, Emdin M, et al. Statin therapy in COVID-19 infection[J]. Eur Heart J Cardiovasc Pharmacother, 2020, 6(4): 258-259. doi: 10.1093/ehjcvp/pvaa042 URL
[56]	Hariyanto TI, Kurniawan A. Statin and outcomes of coronavirus disease 2019 (COVID-19): A systematic review, meta-analysis, and meta-regression[J]. Nutr Metab Cardiovasc Dis, 2021, 31(6): 1662-1670. doi: 10.1016/j.numecd.2021.02.020 URL
[57]	Hariyanto TI, Kurniawan A. Statin therapy did not improve the in-hospital outcome of coronavirus disease 2019 (COVID-19) infection[J]. Diabetes Metab Syndr, 2020, 14(6): 1613-1615. doi: S1871-4021(20)30326-X pmid: 32882643
[58]	Kow CS, Hasan SS. Meta-analysis of effect of statins in patients with COVID-19[J]. Am J Cardiol, 2020, 134: 153-155. doi: 10.1016/j.amjcard.2020.08.004 pmid: 32891399
[59]	Scheen AJ. Statins and clinical outcomes with COVID-19: Meta-analyses of observational studies[J]. Diabetes Metab, 2021, 47(6): 101220. doi: 10.1016/j.diabet.2020.101220 URL
[60]	Onorato D, Pucci M, Carpene G, et al. Protective effects of statins administration in european and north american patients infected with COVID-19: A meta-analysis. semin thromb hemost[J]. 2021, 47(4): 392-399.
[61]	Wu KS, Lin PC, Chen YS, et al. The use of statins was associated with reduced COVID-19 mortality: a systematic review and meta-analysis[J]. Ann Med, 2021, 53(1): 874-884. doi: 10.1080/07853890.2021.1933165 URL
[62]	Chow R, Im J, Chiu N, et al. The protective association between statins use and adverse outcomes among COVID-19 patients: A systematic review and meta-analysis[J]. PLoS One, 2021, 16(6): e0253576. doi: 10.1371/journal.pone.0253576 URL
[63]	Kow CS, Hasan SS. The association between the use of statins and clinical outcomes in patients with COVID-19: A systematic review and meta-analysis[J]. Am J Cardiovasc Drugs, 2022, 22(2): 167-181. doi: 10.1007/s40256-021-00490-w URL
[64]	Vahedian-Azimi A, Mohammadi SM, Banach M, et al. Improved COVID-19 outcomes following statin therapy: An updated systematic review and meta-analysis[J]. Biomed Res Int, 2021, 2021: 1901772.
[65]	Pal R, Banerjee M, Yadav U, et al. Statin use and clinical outcomes in patients with COVID-19: An updated systematic review and meta-analysis[J]. Postgrad Med J, 2022, 98(1159): 354-359. doi: 10.1136/postgradmedj-2020-139172 URL
[66]	Permana H, Huang I, Purwiga A, et al. In-hospital use of statins is associated with a reduced risk of mortality in coronavirus-2019 (COVID-19): Systematic review and meta-analysis[J]. Pharmacol Rep, 2021, 73(3): 769-780. doi: 10.1007/s43440-021-00233-3 pmid: 33608850
[67]	Kollias A, Kyriakoulis KG, Kyriakoulis IG, et al. Statin use and mortality in COVID-19 patients: Updated systematic review and meta-analysis[J]. Atherosclerosis, 2021, 330: 114-121. doi: 10.1016/j.atherosclerosis.2021.06.911 pmid: 34243953
[68]	Zein A, Sulistiyana CS, Khasanah U, et al. Statin and mortality in COVID-19: A systematic review and meta-analysis of pooled adjusted effect estimates from propensity-matched cohorts[J]. Postgrad Med J, 2022, 98(1161): 503-508. doi: 10.1136/postgradmedj-2021-140409 URL
[69]	Diaz-Arocutipa C, Melgar-Talavera B, Alvarado-Yarasca Á, et al. Statins reduce mortality in patients with COVID-19: an updated meta-analysis of 147 824 patients[J]. Int J Infect Dis, 2021, 110: 374-381. doi: 10.1016/j.ijid.2021.08.004 pmid: 34375760
[70]	Wang L, Li H, Gu X, Wang Z, et al. Effect of antiplatelet therapy on acute respiratory distress syndrome and mortality in critically ill patients: A meta-analysis[J]. PLoS One, 2016, 11(5): e0154754. doi: 10.1371/journal.pone.0154754 URL
[71]	Signorelli SS, Platania I, Tomasello SD, et al. Insights from experiences on antiplatelet drugs in stroke prevention: A review[J]. Int J Environ Res Public Health, 2020, 17(16):5840. doi: 10.3390/ijerph17165840 URL
[72]	Du F, Jiang P, He S, et al. Antiplatelet therapy for critically ill patients: A pairwise and bayesian network meta-analysis[J]. Shock, 2018, 49(6): 616-624. doi: 10.1097/SHK.0000000000001057 pmid: 29176404
[73]	Giollo A, Adami G, Gatti D, et al. Coronavirus disease 19 (Covid-19) and non-steroidal anti-inflammatory drugs (NSAID)[J]. Ann Rheum Dis, 2021, 80(2): e12. doi: 10.1136/annrheumdis-2020-217598 pmid: 32321720
[74]	Micallef J, Soeiro T, Jonville-Béra AP. Non-steroidal anti-inflammatory drugs, pharmacology, and COVID-19 infection[J]. Therapie, 2020, 75(4): 355-362. doi: S0040-5957(20)30092-5 pmid: 32418728
[75]	Mohamed-Hussein A, Aly K, Ibrahim M. Should aspirin be used for prophylaxis of COVID-19-induced coagulopathy[J]. Med Hypotheses, 2020, 144: 109975. doi: 10.1016/j.mehy.2020.109975 URL
[76]	Wang Y, Ao G, Nasr B, et al. Effect of antiplatelet treatments on patients with COVID-19 infection: A systematic review and meta-analysis[J]. Am J Emerg Med, 2021, 43: 27-30. doi: 10.1016/j.ajem.2021.01.016 pmid: 33485124
[77]	Patoulias D, Papadopoulos C, Doumas M. Meta-analysis addressing the efficacy and safety of antiplatelet agents in patients with COVID-19[J]. Am J Cardiol, 2022, 175: 185-187. doi: 10.1016/j.amjcard.2022.04.038 pmid: 35644695
[78]	Ma S, Su W, Sun C, et al. Does aspirin have an effect on risk of death in patients with COVID-19? A meta-analysis[J]. Eur J Clin Pharmacol, 2022, 78(9): 1403-1420. doi: 10.1007/s00228-022-03356-5 URL
[79]	Salah HM, Mehta JL. Meta-analysis of the effect of aspirin on mortality in COVID-19[J]. Am J Cardiol, 2021, 142: 158-159. doi: 10.1016/j.amjcard.2020.12.073 pmid: 33417877
[80]	Kow CS, Hasan SS. Use of antiplatelet drugs and the risk of mortality in patients with COVID-19: A meta-analysis[J]. J Thromb Thrombolysis, 2021, 52(1): 124-129. doi: 10.1007/s11239-021-02436-0 URL
[81]	Martha JW, Pranata R, Lim MA, et al. Active prescription of low-dose aspirin during or prior to hospitalization and mortality in COVID-19: A systematic review and meta-analysis of adjusted effect estimates[J]. Int J Infect Dis, 2021, 108: 6-12. doi: 10.1016/j.ijid.2021.05.016 URL
[82]	Wijaya I, Andhika R, Huang I, et al. The effects of aspirin on the outcome of COVID-19: A systematic review and meta-analysis[J]. Clin Epidemiol Glob Health, 2021, 12: 100883.
[83]	Srivastava R, Kumar A. Use of aspirin in reduction of mortality of COVID-19 patients: A meta-analysis[J]. Int J Clin Pract, 2021, 75(11): e14515.
[84]	Srinivasan A, Brown J, Krishnamani PP, et al. Aspirin use is associated with decreased inpatient mortality in patients with COVID-19: A meta-analysis[J]. Am Heart J Plus, 2022, 20: 100191.
[85]	Dolhnikoff M, Duarte-Neto AN, de Almeida Monteiro RA, et al. Pathological evidence of pulmonary thrombotic phenomena in severe COVID-19[J]. J Thromb Haemost, 2020, 18(6): 1517-1519. doi: 10.1111/jth.14844 pmid: 32294295
[86]	Bianconi V, Violi F, Fallarino F, et al. Is acetylsalicylic acid a safe and potentially useful choice for adult patients with COVID-19[J]. Drugs, 2020, 80(14): 1383-1396. doi: 10.1007/s40265-020-01365-1 pmid: 32705604
[87]	Jose RJ, Manuel A. COVID-19 cytokine storm: The interplay between inflammation and coagulation[J]. Lancet Respir Med, 2020, 8(6): e46-e47. doi: 10.1016/S2213-2600(20)30216-2 pmid: 32353251
[88]	Tang N, Li D, Wang X, et al. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia[J]. J Thromb Haemost, 2020, 18(4): 844-847. doi: 10.1111/jth.14768 pmid: 32073213
[89]	Mycroft-West CJ, Su D, Pagani I, et al. Heparin inhibits cellular invasion by SARS-CoV-2: Structural dependence of the interaction of the spike s1 receptor-binding domain with heparin[J]. Thromb Haemost, 2020, 120(12): 1700-1715. doi: 10.1055/s-0040-1721319 URL
[90]	Parisi R, Costanzo S, Di Castelnuovo A, et al. Different anticoagulant regimens, mortality, and bleeding in hospitalized patients with COVID-19: A systematic review and an updated meta-analysis[J]. Semin Thromb Hemost, 2021, 47(4): 372-391. doi: 10.1055/s-0041-1726034 URL
[91]	Ge J, Ma Y, Wu Z, et al. Anticoagulation treatment for patients with coronavirus disease 2019 (COVID-19) and its clinical effectiveness in 2020: A meta-analysis study[J]. Medicine (Baltimore), 2021, 100(47): e27861. doi: 10.1097/MD.0000000000027861 URL
[92]	Yasuda H, Mayumi T, Okano H. Efficacy of different anticoagulant doses for patients with COVID-19: A systematic review and network meta-analysis[J]. Infection, 2022 : 1-11.
[93]	Ortega-Paz L, Galli M, Capodanno D, et al. Safety and efficacy of different prophylactic anticoagulation dosing regimens in critically and non-critically ill patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials[J]. Eur Heart J Cardiovasc Pharmacother, 2021, 8(7):677-686. doi: 10.1093/ehjcvp/pvab070 URL
[94]	Zhang S, Li Y, Liu G, Su B. Intermediate-to-therapeutic versus prophylactic anticoagulation for coagulopathy in hospitalized COVID-19 patients: A systemic review and meta-analysis[J]. Thromb J, 2021, 19(1): 91. doi: 10.1186/s12959-021-00343-1 pmid: 34819094
[95]	Kow CS, Ramachandram DS, Hasan SS. The effect of higher-intensity dosing of anticoagulation on the clinical outcomes in hospitalized patients with COVID-19: A meta-analysis of randomized controlled trials[J]. J Infect Chemother, 2022, 28(2): 257-265. doi: 10.1016/j.jiac.2021.11.008 URL
[96]	Kollias A, Kyriakoulis KG, Trontzas IP, et al. High versus standard intensity of thromboprophylaxis in hospitalized patients with COVID-19: A systematic review and meta-analysis[J]. J Clin Med, 2021, 10(23): 5549.
[97]	Jorda A, Siller-Matula JM, Zeitlinger M, et al. Anticoagulant treatment regimens in patients with covid-19: A meta-analysis[J]. Clin Pharmacol Ther, 2022, 111(3): 614-623. doi: 10.1002/cpt.2504 URL
[98]	Reis S, Popp M, Schmid B, et al. Safety and efficacy of intermediate- and therapeutic-dose anticoagulation for hospitalised patients with COVID-19: A systematic review and meta-analysis[J]. J Clin Med, 2021, 11(1):57. doi: 10.3390/jcm11010057 URL
[99]	Wills NK, Nair N, Patel K, et al. Efficacy and safety of intensified versus standard prophylactic anticoagulation therapy in patients with Covid-19: A systematic review and meta-analysis[J]. medRxiv, 2022, 2022.03.05.22271947.
[100]	Batista DR, Floriano I, Silvinato A, et al. Use of anticoagulants in patients with COVID-19: A living systematic review and meta-analysis[J]. J Bras Pneumol, 2022, 48(4): e20220041.
[101]	Ortega-Paz L, Galli M, Angiolillo DJ. Updated meta-analysis of randomized controlled trials on the safety and efficacy of different prophylactic anticoagulation dosing regimens in non-critically ill hospitalized patients with COVID-19[J]. Eur Heart J Cardiovasc Pharmacother, 2022, 8(3): E15-E17. doi: 10.1093/ehjcvp/pvac010 URL
[102]	Wills NK, Nair N, Patel K, et al. Efficacy and safety of intensified versus standard prophylactic anticoagulation therapy in patients with coronavirus disease 2019: A systematic review and meta-analysis[J]. Open Forum Infect Dis, 2022, 9(7): ofac285. doi: 10.1093/ofid/ofac285 URL
[103]	Valeriani E, Porfidia A, Ageno W, et al. High-dose versus low-dose venous thromboprophylaxis in hospitalized patients with COVID-19: A systematic review and meta-analysis[J]. Intern Emerg Med, 2022, 17(6): 1817-1825. doi: 10.1007/s11739-022-03004-x URL
[104]	Loffredo L, Di Castelnuovo A, Chiariello GA, et al. Full versus prophylactic-intermediate doses of anticoagulants in COVID-19: A meta-analysis[J]. Haematologica, 2022, 107(8): 1933-1939. doi: 10.3324/haematol.2022.280652 URL
[105]	Pilia E, Belletti A, Fresilli S, et al. Efficacy and safety of heparin full-dose anticoagulation in hospitalized non-critically ill COVID-19 patients: A meta-analysis of multicenter randomized controlled trials[J]. J Thromb Thrombolysis, 2022: 1-11.
[106]	Ena J, Valls V. Therapeutic-dose anticoagulation or thromboprophylaxis with low-molecular-weight heparin for moderate Covid-19: Meta-analysis of randomized controlled trials[J]. Clin Exp Med, 2022: 1-8.
[107]	Duo H, Li Y, Sun Y, et al. Effect of therapeutic versus prophylactic anticoagulation therapy on clinical outcomes in COVID-19 patients: A systematic review with an updated meta-analysis[J]. Thromb J, 2022, 20(1): 47. doi: 10.1186/s12959-022-00408-9 pmid: 35999599
[108]	Reis S, Popp M, Schießer S, et al. Anticoagulation in COVID-19 patients-An updated systematic review and meta-analysis[J]. Thromb Res, 2022, 219: 40-48. doi: 10.1016/j.thromres.2022.09.001 URL
[109]	Moonla C, Sosothikul D, Chiasakul T, et al. Anticoagulation and in-hospital mortality from coronavirus disease 2019: A systematic review and meta-analysis[J]. Clin Appl Thromb Hemost, 2021, 27: 10760296211008999.
[110]	Jiang L, Li Y, Du H, et al. Effect of anticoagulant administration on the mortality of hospitalized patients with COVID-19: An updated systematic review and meta-analysis[J]. Front Med (Lausanne), 2021, 8: 698935.
[111]	Giossi R, Menichelli D, Pani A, et al. A systematic review and a meta-analysis comparing prophylactic and therapeutic low molecular weight heparins for mortality reduction in 32, 688 COVID-19 patients[J]. Front Pharmacol, 2021, 12: 698008. doi: 10.3389/fphar.2021.698008 URL
[112]	Lu YF, Pan LY, Zhang WW, et al. A meta-analysis of the incidence of venous thromboembolic events and impact of anticoagulation on mortality in patients with COVID-19[J]. Int J Infect Dis, 2020, 100: 34-41. doi: 10.1016/j.ijid.2020.08.023 URL
[113]	Abdel-Maboud M, Menshawy A, Elgebaly A, et al. Should we consider heparin prophylaxis in COVID-19 patients? a systematic review and meta-analysis[J]. J Thromb Thrombolysis, 2021, 51(3): 830-832. doi: 10.1007/s11239-020-02253-x URL
[114]	McBane RD 2nd, Torres Roldan VD, Niven AS, et al. Anticoagulation in COVID-19: A systematic review, meta-analysis, and rapid guidance from mayo clinic[J]. Mayo Clin Proc, 2020, 95(11): 2467-2486. doi: 10.1016/j.mayocp.2020.08.030 pmid: 33153635
[115]	Kamel AM, Sobhy M, Magdy N, et al. Anticoagulation outcomes in hospitalized Covid-19 patients: A systematic review and meta-analysis of case-control and cohort studies[J]. Rev Med Virol, 2021, 31(3): e2180.
[116]	Tunjungputri RN, Tetrasiwi EN, Mulansari NA, et al. Parenteral and oral anticoagulant treatment for hospitalized and post-discharge COVID-19 patients: A systematic review and meta-analysis[J]. Acta Med Indones, 2022, 54(2): 190-209. pmid: 35818663
[117]	Aamir Waheed M, Rashid K, Rajab T, et al. Role of anticoagulation in lowering the mortality in hospitalized covid-19 patients: Meta-analysis of available literature[J]. Saudi Med J, 2022, 43(6): 541-550. doi: 10.15537/smj.2022.43.6.20220046 pmid: 35675936
[118]	Alsagaff MY, Mulia E, Maghfirah I, et al. Low molecular weight heparin is associated with better outcomes than unfractionated heparin for thromboprophylaxis in hospitalized COVID-19 patients: A meta-analysis[J]. Eur Heart J Qual Care Clin Outcomes, 2022: qcac046.
[119]	Zeng J, Liu F, Wang Y, et al. The effect of previous oral anticoagulant use on clinical outcomes in COVID-19: A systematic review and meta-analysis[J]. Am J Emerg Med, 2022, 54: 107-110. doi: 10.1016/j.ajem.2022.01.059 pmid: 35152118
[120]	Tacquard C, Mansour A, Godon A, et al. Anticoagulation in COVID-19: not strong for too long[J]. Anaesth Crit Care Pain Med, 2021, 40(2): 100857. doi: 10.1016/j.accpm.2021.100857 URL
[121]	Schulman S, Sholzberg M, Spyropoulos AC, et al. ISTH guidelines for antithrombotic treatment in COVID-19[J]. J Thromb Haemost, 2022, 20(10): 2214-2225. doi: 10.1111/jth.15808 URL
[122]	Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis[J]. Clin Chim Acta, 2020, 506: 145-148. doi: S0009-8981(20)30124-8 pmid: 32178975
[123]	Yang Y, Cai Z, Zhang J. Insulin treatment may increase adverse outcomes in patients with covid-19 and diabetes: A systematic review and meta-analysis[J]. Front Endocrinol (Lausanne), 2021, 12: 696087. doi: 10.3389/fendo.2021.696087 URL
[124]	Hariyanto TI, Lugito N, Yanto TA, et al. Insulin therapy and outcome from coronavirus disease 2019 (COVID-19): A systematic review, meta-analysis, and meta-regression[J]. Endocr Metab Immune Disord Drug Targets, 2022, 22(5):481-489. doi: 10.2174/1871530321666210709164925 URL
[125]	Wang W, Sun Y, Wang S, et al. The relationship between insulin use and increased mortality in patients with COVID-19 and diabetes: A meta-analysis[J]. Endocr Res, 2022, 47(1): 32-38. doi: 10.1080/07435800.2021.1967376 URL
[126]	Kan C, Zhang Y, Han F, et al. Mortality risk of antidiabetic agents for type 2 diabetes with COVID-19: A systematic review and meta-analysis[J]. Front Endocrinol (Lausanne), 2021, 12: 708494. doi: 10.3389/fendo.2021.708494 URL
[127]	Chen Y, Lv X, Lin S, et al. The association between antidiabetic agents and clinical outcomes of COVID-19 patients with diabetes: A bayesian network meta-analysis[J]. Front Endocrinol (Lausanne), 2022, 13: 895458. doi: 10.3389/fendo.2022.895458 URL
[128]	Nguyen NN, Ho DS, Nguyen HS, et al. Preadmission use of antidiabetic medications and mortality among patients with COVID-19 having type 2 diabetes: A meta-analysis[J]. Metabolism, 2022, 131: 155196. doi: 10.1016/j.metabol.2022.155196 URL
[129]	Kow CS, Hasan SS. Mortality risk with preadmission metformin use in patients with COVID-19 and diabetes: A meta-analysis[J]. J Med Virol, 2021, 93(2): 695-697. doi: 10.1002/jmv.26498 URL
[130]	Lukito AA, Pranata R, Henrina J, et al. The effect of metformin consumption on mortality in hospitalized COVID-19 patients: A systematic review and meta-analysis[J]. Diabetes Metab Syndr, 2020, 14(6): 2177-2183. doi: 10.1016/j.dsx.2020.11.006 pmid: 33395778
[131]	Yang W, Sun X, Zhang J, et al. The effect of metformin on mortality and severity in COVID-19 patients with diabetes mellitus[J]. Diabetes Res Clin Pract, 2021, 178: 108977. doi: 10.1016/j.diabres.2021.108977 URL
[132]	Ganesh A, Randall MD. Does metformin affect outcomes in COVID-19 patients with new or pre-existing diabetes mellitus? A systematic review and meta-analysis. Br J Clin Pharmacol, 2022, 88(6): 2642-2656. doi: 10.1111/bcp.15258 pmid: 35122284
[133]	Han T, Ma S, Sun C, et al. Association between anti-diabetic agents and clinical outcomes of COVID-19 in patients with diabetes: A systematic review and meta-analysis[J]. Arch Med Res, 2022, 53(2): 186-195. doi: 10.1016/j.arcmed.2021.08.002 URL
[134]	Kow CS, Hasan SS. A meta-analysis on the preadmission use of DPP-4 inhibitors and risk of a fatal or severe course of illness in patients with COVID-19[J]. Therapie, 2021, 76(4): 361-364. doi: 10.1016/j.therap.2020.12.015 URL
[135]	Bonora BM, Avogaro A, Fadini GP. Disentangling conflicting evidence on DPP-4 inhibitors and outcomes of COVID-19: Narrative review and meta-analysis[J]. J Endocrinol Invest, 2021, 44(7): 1379-1386. doi: 10.1007/s40618-021-01515-6 pmid: 33512688
[136]	Rakhmat II, Kusmala YY, Handayania DR, et al. Dipeptidyl peptidase-4 (DPP-4) inhibitor and mortality in coronavirus disease 2019 (COVID-19)-A systematic review, meta-analysis, and meta-regression[J]. Diabetes Metab Syndr, 2021, 15(3): 777-782.
[137]	Yang Y, Cai Z, Zhang J. DPP-4 inhibitors may improve the mortality of coronavirus disease 2019: A meta-analysis[J]. PLoS One, 2021, 16(5): e0251916. doi: 10.1371/journal.pone.0251916 URL
[138]	Patoulias D, Doumas M. Dipeptidyl peptidase-4 inhibitors and COVID-19-related deaths among patients with type 2 diabetes mellitus: A meta-analysis of observational studies[J]. Endocrinol Metab (Seoul), 2021, 36(4): 904-908. doi: 10.3803/EnM.2021.1048 URL
[139]	Zein A, Raffaello WM. Dipeptidyl peptidase-4 (DPP-IV) inhibitor was associated with mortality reduction in COVID-19 - A systematic review and meta-analysis[J]. Prim Care Diabetes, 2022, 16(1): 162-167. doi: 10.1016/j.pcd.2021.12.008 URL
[140]	Zhao LM, Chen XH, Qiu M. Commentary: Mortality risk of antidiabetic agents for type 2 diabetes with COVID-19: A systematic review and meta-analysis[J]. Front Endocrinol (Lausanne), 2021, 12: 825100. doi: 10.3389/fendo.2021.825100 URL
[141]	Hariyanto TI, Intan D, Hananto JE, et al. Pre-admission glucagon-like peptide-1 receptor agonist (GLP-1RA) and mortality from coronavirus disease 2019 (Covid-19): A systematic review, meta-analysis, and meta-regression[J]. Diabetes Res Clin Pract, 2021, 179: 109031. doi: 10.1016/j.diabres.2021.109031 URL
[142]	Azraai M, McMahon M, Dick R. Case report of amiodarone-associated allergic pneumonitis amidst the COVID-19 pandemic[J]. Rev Cardiovasc Med, 2021, 22(1): 181-184. doi: 10.31083/j.rcm.2021.01.267 URL
[143]	Clemente-Moragón A, Martínez-Milla J, Oliver E, et al. Metoprolol in critically ill patients with COVID-19[J]. J Am Coll Cardiol, 2021, 78(10): 1001-1011. doi: 10.1016/j.jacc.2021.07.003 pmid: 34474731
[144]	Caracciolo M, Correale P, Mangano C, et al. Efficacy and effect of inhaled adenosine treatment in hospitalized COVID-19 patients[J]. Front Immunol, 2021, 12: 613070. doi: 10.3389/fimmu.2021.613070 URL

作者	研究人群	分组		研究数量	研究人数	发病风险	进展为重型/ 危重型肺炎	入住ICU	机械通气/高级生命支持	死亡率
作者	研究人群	试验组	对照组	研究数量	研究人数	发病风险	进展为重型/ 危重型肺炎	入住ICU	机械通气/高级生命支持	死亡率
Koshy等^[4]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	6项研究(5项队列研究、1项病例对照研究)	73 122	无关	无关			无关
Chu等^[5]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	48项研究(41项队列研究、1项随机对照研究、6项病例对照研究)	237 169	降低		降低	降低	降低
Tleyjeh等^[6]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	10项研究(6项队列研究、4项病例对照研究)	277 264	无关
Xu等^[7]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	49项研究(24项队列研究、25项病例对照研究、1项随机对照研究)	1 242 953	未调整增加, 调整后无关	未调整增加, 调整后无关	未调整增加, 调整后无关	未调整增加, 调整后无关	未调整无关, 调整后无关
Zhang等^[8]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	12项研究(7项队列研究、5项病例对照研究)	19 000⁺	无关	无关			无关
	新冠肺炎合并高血压患者						无关			降低
Asiimwe等^[9]	普通人群及新冠肺炎患者	ACEIs/ARBs等	非ACEIs/ARBs 用药	390项研究(388项观察性研究、2项随机对照研究)	10 000 000⁺	未调整无关, 调整后无关	未调整增加, 调整后降低			未调整增加, 调整后降低
	新冠肺炎合并高血压患者					无关	无关			降低
Liu等^[10]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	11项研究(9项回顾性研究,2项病例对照研究)	33 483	无关	降低			降低
	新冠肺炎合并高血压患者					无关	无关			降低
Caldeira等^[11]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	27项研究(22项队列研究、4项病例对照研究、1项随机对照研究)	119 656	未调整无关, 调整后无关	未调整无关, 调整后无关			未调整无关, 调整后无关
	新冠肺炎合并高血压患者					无关	无关			降低
Ren等^[12]	普通人群及新冠肺炎患者	ACEIs/ARBs等	非ACEIs/ARBs 用药	53项研究(39项队列研究、14项病例对照研究)	2100 587	无关	无关	无关		无关
	新冠肺炎合并高血压患者	ACEIs/ARBs				无关	降低			降低
Yokoyama等^[13]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	17项研究(未注明研究类型)	77 021	无关				无关
	新冠肺炎合并高血压患者									降低
Lee等^[14]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	86项观察性研究	459 577	无关	无关	增加	增加	增加
	新冠肺炎合并高血压患者					无关	无关	无关	无关	无关
Ma等^[15]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	16项病例对照研究	116 111	未调整增加, 调整后无关	无关		无关	无关
	新冠肺炎合并高血压患者					无关
Asiimwe等^[16]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	10项随机对照研究	1 906	无关		无关	无关	无关
	新冠肺炎合并高血压患者							无关	无关	无关
Grover等^[18]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	16项研究(未注明研究类型)	123 576		降低			降低
Hasan等^[19]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	29研究(未注明研究类型)	48 856		无关			降低
Greco等^[20]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	14项研究(13项观察性研究、1项随机临床试验)	10 127		无关			无关
Lo等^[21]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	21项研究(19项队列研究、1项病例系列、1项病例对照研究)	24 191		无关			无关
Alamer等^[22]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	30项回顾性观察性研究	37 144		未调整无关, 调整后无关	未调整无关, 调整后无关	未调整无关, 调整后无关	未调整无关, 调整后无关
Lee等^[23]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	20项研究(未注明研究类型)	30 766		无关			降低
Hassib等^[24]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	8项研究(5项回顾性研究,2项队列研究,1项病例对照研究)	17 943		无关	无关	无关	无关
Bavishi等^[25]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	34项研究(31项队列研究,3项病例对照研究)	94 977		调整后无关	调整后无关	调整后无关	调整后无关
Xie等^[26]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	13项回顾性研究	10 434		降低			降低
Sattar等^[27]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	49项研究(41项回顾性研究、8项前瞻性研究)	83 269		无关	无关		无关
Fernando等^[28]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	26项队列研究	29 378		增加			无关
Baral等^[29]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	19项研究(12项队列研究、4项病例系列、3项病例对照研究)	28 872		降低			降低
	新冠肺炎合并高血压患者						降低			降低
Castelnuovo等^[30]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	19项回顾性观察性研究	29 057		无关	无关	无关	无关
	新冠肺炎合并高血压患者						无关	无关	无关	无关
Guo等^[31]	新冠肺炎合并高血压患者	ACEIs/ARBs	非ACEIs/ARBs 用药	9项研究(未标注研究类型)	3 936		无关			降低
Pranata等^[32]	新冠肺炎合并高血压患者	ACEIs/ARBs	非ACEIs/ARBs用药	15项回顾性研究	7 410		无关			无关
Barochiner等^[33]	新冠肺炎合并高血压患者	ACEIs/ARBs	非ACEIs/ARBs 用药	18项队列研究	17 311		降低	降低	降低	降低
Wang等^[34]	新冠肺炎合并高血压患者	ACEIs/ARBs	非ACEIs/ARBs 用药	26项队列研究	16 307		降低	降低	降低	降低
Dai等^[35]	新冠肺炎合并高血压患者	ACEIs/ARBs	非ACEIs/ARBs 用药	42项观察性研究	63 893		无关			无关
Yin等^[39]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	7项随机对照研究	1 321			无关	无关	无关
		ARBs						降低	降低	降低
Singh等^[40]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	68项研究(48项队列研究,20项病例对照研究)	133 402			无关	无关	无关
Gnanenthiran等^[41]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	14项随机对照研究	1 838			无关	无关	无关
Baral等^[42]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	52项研究(40项队列研究、6项病例系列、4项病例对照研究、1项随机临床试验、1项横断面研究)	101 949			调整后降低	调整后降低	调整后降低
	新冠肺炎合并高血压患者							降低	降低	降低
Aparisi等^[43]	新冠肺炎合并高血压患者	ACEIs/ARBs	非ACEIs/ARBs 用药	14项回顾性研究	5 213			无关	无关	降低
Loader等^[44]	新冠肺炎合并高血压患者	ACEIs/ARBs	非ACEIs/ARBs 用药	2项观察性研究	1 351 642				降低	降低
Qiu等^[45]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	9项研究(未注明研究类型)	7 789					无关
Lee等^[46]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	30项研究(未注明研究类型)	17 282					未调整无关, 调整后下降
Azad等^[47]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	6项研究(5项观察性性研究、1项病例系列)	1 566					无关
Kow等^[48]	新冠肺炎患者	ARBs	非ARBs用药	3项随机对照研究	443					无关
Sharma等^[49]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	68项研究(56项队列研究、12项病例对照研究)	128 078					无关
Ssentongo等^[50]	新冠肺炎合并高血压患者	ACEIs/ARBs	非ACEIs/ARBs 用药	14项队列研究	73 073					降低
Laurentius等^[51]	新冠肺炎合并高血压患者	ACEIs/ARBs	非ACEIs/ARBs 用药	10项回顾性观察性研究	19 073					无关
Lu等^[12]	新冠肺炎患者	CCBs	非CCBs用药	10项研究(3项队列研究、6项病例对照研究、1项回顾性研究)	427 749	无关	无关
Alsagaff等^[36]	新冠肺炎患者	CCBs	非CCBs用药	31项研究(27项回顾性研究、4项前瞻性观察研究)	119 298		无关	无关	无关	无关
	新冠肺炎合并高血压患者						无关	无关	无关	降低
Kow等^[37]	新冠肺炎合并高血压患者	CCBs	非CCBs用药	9项回顾性研究	18 835		降低	降低	降低	降低
Kow等^[38]	新冠肺炎患者	CCBs	非CCBs用药	23项研究(22项回顾性研究、1项前瞻性观察研究)	127 082		无关	无关	无关	无关
Lu等^[12]	新冠肺炎患者	β受体阻滞剂	非β受体阻滞剂用药	10项研究(5项队列研究、5项病例对照研究)	424 324	无关	无关
Hariyanto等^[17]	新冠肺炎患者	β受体阻滞剂	非β受体阻滞剂用药	43项研究(31项回顾性队列研究、7项前瞻性队列研究、5项研究病例对照研究)	11 388 556	增加	增加	增加	增加	增加
Lu等^[12]	新冠肺炎患者	利尿剂	非利尿剂用药	7项研究(4项队列研究、3项病例对照研究)	422 852	无关	无关

作者	研究人群	分组		研究数量	研究人数	发病风险	进展为重型/ 危重型肺炎	入住ICU	机械通气/高级生命支持	死亡率
作者	研究人群	试验组	对照组	研究数量	研究人数	发病风险	进展为重型/ 危重型肺炎	入住ICU	机械通气/高级生命支持	死亡率
Koshy等^[4]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	6项研究(5项队列研究、1项病例对照研究)	73 122	无关	无关			无关
Chu等^[5]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	48项研究(41项队列研究、1项随机对照研究、6项病例对照研究)	237 169	降低		降低	降低	降低
Tleyjeh等^[6]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	10项研究(6项队列研究、4项病例对照研究)	277 264	无关
Xu等^[7]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	49项研究(24项队列研究、25项病例对照研究、1项随机对照研究)	1 242 953	未调整增加, 调整后无关	未调整增加, 调整后无关	未调整增加, 调整后无关	未调整增加, 调整后无关	未调整无关, 调整后无关
Zhang等^[8]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	12项研究(7项队列研究、5项病例对照研究)	19 000⁺	无关	无关			无关
	新冠肺炎合并高血压患者						无关			降低
Asiimwe等^[9]	普通人群及新冠肺炎患者	ACEIs/ARBs等	非ACEIs/ARBs 用药	390项研究(388项观察性研究、2项随机对照研究)	10 000 000⁺	未调整无关, 调整后无关	未调整增加, 调整后降低			未调整增加, 调整后降低
	新冠肺炎合并高血压患者					无关	无关			降低
Liu等^[10]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	11项研究(9项回顾性研究,2项病例对照研究)	33 483	无关	降低			降低
	新冠肺炎合并高血压患者					无关	无关			降低
Caldeira等^[11]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	27项研究(22项队列研究、4项病例对照研究、1项随机对照研究)	119 656	未调整无关, 调整后无关	未调整无关, 调整后无关			未调整无关, 调整后无关
	新冠肺炎合并高血压患者					无关	无关			降低
Ren等^[12]	普通人群及新冠肺炎患者	ACEIs/ARBs等	非ACEIs/ARBs 用药	53项研究(39项队列研究、14项病例对照研究)	2100 587	无关	无关	无关		无关
	新冠肺炎合并高血压患者	ACEIs/ARBs				无关	降低			降低
Yokoyama等^[13]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	17项研究(未注明研究类型)	77 021	无关				无关
	新冠肺炎合并高血压患者									降低
Lee等^[14]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	86项观察性研究	459 577	无关	无关	增加	增加	增加
	新冠肺炎合并高血压患者					无关	无关	无关	无关	无关
Ma等^[15]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	16项病例对照研究	116 111	未调整增加, 调整后无关	无关		无关	无关
	新冠肺炎合并高血压患者					无关
Asiimwe等^[16]	普通人群及新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	10项随机对照研究	1 906	无关		无关	无关	无关
	新冠肺炎合并高血压患者							无关	无关	无关
Grover等^[18]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	16项研究(未注明研究类型)	123 576		降低			降低
Hasan等^[19]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	29研究(未注明研究类型)	48 856		无关			降低
Greco等^[20]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	14项研究(13项观察性研究、1项随机临床试验)	10 127		无关			无关
Lo等^[21]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	21项研究(19项队列研究、1项病例系列、1项病例对照研究)	24 191		无关			无关
Alamer等^[22]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	30项回顾性观察性研究	37 144		未调整无关, 调整后无关	未调整无关, 调整后无关	未调整无关, 调整后无关	未调整无关, 调整后无关
Lee等^[23]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	20项研究(未注明研究类型)	30 766		无关			降低
Hassib等^[24]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	8项研究(5项回顾性研究,2项队列研究,1项病例对照研究)	17 943		无关	无关	无关	无关
Bavishi等^[25]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	34项研究(31项队列研究,3项病例对照研究)	94 977		调整后无关	调整后无关	调整后无关	调整后无关
Xie等^[26]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	13项回顾性研究	10 434		降低			降低
Sattar等^[27]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	49项研究(41项回顾性研究、8项前瞻性研究)	83 269		无关	无关		无关
Fernando等^[28]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	26项队列研究	29 378		增加			无关
Baral等^[29]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	19项研究(12项队列研究、4项病例系列、3项病例对照研究)	28 872		降低			降低
	新冠肺炎合并高血压患者						降低			降低
Castelnuovo等^[30]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	19项回顾性观察性研究	29 057		无关	无关	无关	无关
	新冠肺炎合并高血压患者						无关	无关	无关	无关
Guo等^[31]	新冠肺炎合并高血压患者	ACEIs/ARBs	非ACEIs/ARBs 用药	9项研究(未标注研究类型)	3 936		无关			降低
Pranata等^[32]	新冠肺炎合并高血压患者	ACEIs/ARBs	非ACEIs/ARBs用药	15项回顾性研究	7 410		无关			无关
Barochiner等^[33]	新冠肺炎合并高血压患者	ACEIs/ARBs	非ACEIs/ARBs 用药	18项队列研究	17 311		降低	降低	降低	降低
Wang等^[34]	新冠肺炎合并高血压患者	ACEIs/ARBs	非ACEIs/ARBs 用药	26项队列研究	16 307		降低	降低	降低	降低
Dai等^[35]	新冠肺炎合并高血压患者	ACEIs/ARBs	非ACEIs/ARBs 用药	42项观察性研究	63 893		无关			无关
Yin等^[39]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	7项随机对照研究	1 321			无关	无关	无关
		ARBs						降低	降低	降低
Singh等^[40]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	68项研究(48项队列研究,20项病例对照研究)	133 402			无关	无关	无关
Gnanenthiran等^[41]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	14项随机对照研究	1 838			无关	无关	无关
Baral等^[42]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	52项研究(40项队列研究、6项病例系列、4项病例对照研究、1项随机临床试验、1项横断面研究)	101 949			调整后降低	调整后降低	调整后降低
	新冠肺炎合并高血压患者							降低	降低	降低
Aparisi等^[43]	新冠肺炎合并高血压患者	ACEIs/ARBs	非ACEIs/ARBs 用药	14项回顾性研究	5 213			无关	无关	降低
Loader等^[44]	新冠肺炎合并高血压患者	ACEIs/ARBs	非ACEIs/ARBs 用药	2项观察性研究	1 351 642				降低	降低
Qiu等^[45]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	9项研究(未注明研究类型)	7 789					无关
Lee等^[46]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	30项研究(未注明研究类型)	17 282					未调整无关, 调整后下降
Azad等^[47]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	6项研究(5项观察性性研究、1项病例系列)	1 566					无关
Kow等^[48]	新冠肺炎患者	ARBs	非ARBs用药	3项随机对照研究	443					无关
Sharma等^[49]	新冠肺炎患者	ACEIs/ARBs	非ACEIs/ARBs 用药	68项研究(56项队列研究、12项病例对照研究)	128 078					无关
Ssentongo等^[50]	新冠肺炎合并高血压患者	ACEIs/ARBs	非ACEIs/ARBs 用药	14项队列研究	73 073					降低
Laurentius等^[51]	新冠肺炎合并高血压患者	ACEIs/ARBs	非ACEIs/ARBs 用药	10项回顾性观察性研究	19 073					无关
Lu等^[12]	新冠肺炎患者	CCBs	非CCBs用药	10项研究(3项队列研究、6项病例对照研究、1项回顾性研究)	427 749	无关	无关
Alsagaff等^[36]	新冠肺炎患者	CCBs	非CCBs用药	31项研究(27项回顾性研究、4项前瞻性观察研究)	119 298		无关	无关	无关	无关
	新冠肺炎合并高血压患者						无关	无关	无关	降低
Kow等^[37]	新冠肺炎合并高血压患者	CCBs	非CCBs用药	9项回顾性研究	18 835		降低	降低	降低	降低
Kow等^[38]	新冠肺炎患者	CCBs	非CCBs用药	23项研究(22项回顾性研究、1项前瞻性观察研究)	127 082		无关	无关	无关	无关
Lu等^[12]	新冠肺炎患者	β受体阻滞剂	非β受体阻滞剂用药	10项研究(5项队列研究、5项病例对照研究)	424 324	无关	无关
Hariyanto等^[17]	新冠肺炎患者	β受体阻滞剂	非β受体阻滞剂用药	43项研究(31项回顾性队列研究、7项前瞻性队列研究、5项研究病例对照研究)	11 388 556	增加	增加	增加	增加	增加
Lu等^[12]	新冠肺炎患者	利尿剂	非利尿剂用药	7项研究(4项队列研究、3项病例对照研究)	422 852	无关	无关

作者	研究人群	分组		研究数量	研究人数	发病风险	进展为重型/危重型肺炎	入住ICU	机械通气/高级生命支持	死亡率
作者	研究人群	试验组	对照组	研究数量	研究人数	发病风险	进展为重型/危重型肺炎	入住ICU	机械通气/高级生命支持	死亡率
Hariyanto等^[56]	普通人群及	他汀类药物	非他汀类用药	35项(31项回顾性队列研究,2项前瞻性队列研究,2项病例对照研究)	1 930 583	无关	无关			无关
Hariyanto等^[56]	新冠肺炎患者	他汀类药物	非他汀类用药	35项(31项回顾性队列研究,2项前瞻性队列研究,2项病例对照研究)	1 930 583	无关	无关			无关
Hariyanto等^[57]	新冠肺炎患者	他汀类药物	非他汀类用药	9项(7项回顾性队列研究,1项病例对照研究, 1项病例系列研究)	3 449		无关			无关
Kow等^[58]	新冠肺炎患者	他汀类药物	非他汀类用药	4项回顾性研究	8 990		降低			降低
Scheen等^[59]	新冠肺炎患者	他汀类药物	非他汀类用药	18项回顾性观察性研究	44 795			无关	无关	无关
Onorato等^[60]	新冠肺炎患者	他汀类药物	非他汀类用药	7项回顾性研究	2 398			降低	降低	降低
Wu等^[61]	新冠肺炎患者	他汀类药物	非他汀类用药	22项观察性研究	63 537			无关	降低	降低
Chow等^[62]	新冠肺炎患者	他汀类药物	非他汀类用药	13项回顾性队列研究	110 087			无关	无关	非ICU患者降低,
Chow等^[62]	新冠肺炎患者	他汀类药物	非他汀类用药	13项回顾性队列研究	110 087			无关	无关	入院后接受他汀类药物治疗患者降低
Kow等^[63]	新冠肺炎患者	他汀类药物	非他汀类用药	35项回顾性观察性研究	139 024			调整后降低	调整后降低	调整后降低
Vahedian-Azimi等^[64]	新冠肺炎患者	他汀类药物	非他汀类用药	47项观察性研究	3 238 508			无关	降低	无关
Pal等^[65]	新冠肺炎患者	他汀类药物	非他汀类用药	14项(13项回顾性队列研究,1项病例对照研究)	19 988					调整后降低
Permana等^[66]	新冠肺炎患者	他汀类药物	非他汀类用药	13项(12项回顾性队列研究,1项前瞻性队列研究)	52 122					入院后接受他汀类药物治疗患者降低,
Permana等^[66]	新冠肺炎患者	他汀类药物	非他汀类用药	13项(12项回顾性队列研究,1项前瞻性队列研究)	52 122					入院前接受他汀类药物治疗患者无关
Kollias等^[67]	新冠肺炎患者	他汀类药物	非他汀类用药	22项回顾性观察性研究	114 688					调整后降低
Zein等^[68]	新冠肺炎患者	他汀类药物	非他汀类用药	8项倾向性评分匹配研究	14 446					调整后降低
Diaz-Arocutipa等^[69]	新冠肺炎患者	他汀类药物	非他汀类用药	25项队列研究	147 824					调整后降低

作者	研究人群	分组		研究数量	研究人数	发病风险	进展为重型/危重型肺炎	入住ICU	机械通气/高级生命支持	死亡率
作者	研究人群	试验组	对照组	研究数量	研究人数	发病风险	进展为重型/危重型肺炎	入住ICU	机械通气/高级生命支持	死亡率
Hariyanto等^[56]	普通人群及	他汀类药物	非他汀类用药	35项(31项回顾性队列研究,2项前瞻性队列研究,2项病例对照研究)	1 930 583	无关	无关			无关
Hariyanto等^[56]	新冠肺炎患者	他汀类药物	非他汀类用药	35项(31项回顾性队列研究,2项前瞻性队列研究,2项病例对照研究)	1 930 583	无关	无关			无关
Hariyanto等^[57]	新冠肺炎患者	他汀类药物	非他汀类用药	9项(7项回顾性队列研究,1项病例对照研究, 1项病例系列研究)	3 449		无关			无关
Kow等^[58]	新冠肺炎患者	他汀类药物	非他汀类用药	4项回顾性研究	8 990		降低			降低
Scheen等^[59]	新冠肺炎患者	他汀类药物	非他汀类用药	18项回顾性观察性研究	44 795			无关	无关	无关
Onorato等^[60]	新冠肺炎患者	他汀类药物	非他汀类用药	7项回顾性研究	2 398			降低	降低	降低
Wu等^[61]	新冠肺炎患者	他汀类药物	非他汀类用药	22项观察性研究	63 537			无关	降低	降低
Chow等^[62]	新冠肺炎患者	他汀类药物	非他汀类用药	13项回顾性队列研究	110 087			无关	无关	非ICU患者降低,
Chow等^[62]	新冠肺炎患者	他汀类药物	非他汀类用药	13项回顾性队列研究	110 087			无关	无关	入院后接受他汀类药物治疗患者降低
Kow等^[63]	新冠肺炎患者	他汀类药物	非他汀类用药	35项回顾性观察性研究	139 024			调整后降低	调整后降低	调整后降低
Vahedian-Azimi等^[64]	新冠肺炎患者	他汀类药物	非他汀类用药	47项观察性研究	3 238 508			无关	降低	无关
Pal等^[65]	新冠肺炎患者	他汀类药物	非他汀类用药	14项(13项回顾性队列研究,1项病例对照研究)	19 988					调整后降低
Permana等^[66]	新冠肺炎患者	他汀类药物	非他汀类用药	13项(12项回顾性队列研究,1项前瞻性队列研究)	52 122					入院后接受他汀类药物治疗患者降低,
Permana等^[66]	新冠肺炎患者	他汀类药物	非他汀类用药	13项(12项回顾性队列研究,1项前瞻性队列研究)	52 122					入院前接受他汀类药物治疗患者无关
Kollias等^[67]	新冠肺炎患者	他汀类药物	非他汀类用药	22项回顾性观察性研究	114 688					调整后降低
Zein等^[68]	新冠肺炎患者	他汀类药物	非他汀类用药	8项倾向性评分匹配研究	14 446					调整后降低
Diaz-Arocutipa等^[69]	新冠肺炎患者	他汀类药物	非他汀类用药	25项队列研究	147 824					调整后降低

作者	研究人群	分组		研究数量	研究人数	发病风险	进展为重型/危重型肺炎	入住ICU	机械通气/高级生命支持	血栓事件	出血事件	死亡率
作者	研究人群	试验组	对照组	研究数量	研究人数	发病风险	进展为重型/危重型肺炎	入住ICU	机械通气/高级生命支持	血栓事件	出血事件	死亡率
Wang等^[76]	新冠肺炎患者	阿司匹林等抗血小板药	非抗血小板治疗	9项(7项回顾性研究,2项前瞻性研究)	5 970		无关					未调整增加, 调整后降低
Patoulias等^[77]	新冠肺炎患者	阿司匹林等抗血小板药	非抗血小板治疗	3项随机对照试验	15 782					降低	增加	无关
Ma等^[78]	新冠肺炎患者	阿司匹林	非阿司匹林用药	18项(11项队列研究、3项病例对照研究、3项横断面研究、1项随机对照试验)	49 041	无关					无关	未调整无关, 调整后降低
		低剂量组 (80~100 mg/d)										降低
		中剂量组 (150 mg/d)										无关
Salah等^[79]	新冠肺炎患者	阿司匹林	非阿司匹林用药	3项回顾性研究	1 054							无关
Kow等^[80]	新冠肺炎患者	阿司匹林等抗血小板药	非抗血小板治疗	12项(11项回顾性研究,1项前瞻性研究)	57 227							无关
		阿司匹林	非阿司匹林抗血小板治疗									降低
Martha等^[81]	新冠肺炎患者	阿司匹林	非阿司匹林用药	6项回顾性研究	13 993							调整后降低
Wijaya等^[82]	新冠肺炎患者	阿司匹林	非阿司匹林用药	7项回顾性研究	34 415							降低
Srivastava等^[83]	新冠肺炎患者	阿司匹林	非阿司匹林用药	10项观察性性研究	56 696							降低
Srinivasan等^[84]	新冠肺炎患者	阿司匹林	非阿司匹林用药	14项(13项队列研究、1项随机对照试验)	164 539							降低