Skip to content
2000
Volume 32, Issue 7
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Background

Statins are primarily used to decrease elevated LDL-cholesterol and thus prevent atherosclerotic cardiovascular disease. Portal hypertension is one of the most important complications of chronic liver disease. Several studies indicated that statins might be beneficial for portal hypertension as well but there is still no clear answer whether this is true or not.

Methods

A literature search of the major databases was performed to find eligible randomized controlled trials (RCTs) analyzing the effect of statins on portal hypertension from inception to February 5th, 2021. Six RCTs with 442 patients who received statin or statin plus carvedilol were finally included. Meta-analysis was performed using the Comprehensive Meta-Analysis V2 software.

Results

Reduction of portal hypertension after statin treatment was not significant (WMD: -0.494, 95% CI: -1.239, 0.252, =0.194; I2:0%). The reduction of portal hypertension was robust in the leave-one-out sensitivity analysis.

Conclusion

Treatment with statins did not decrease significantly portal hypertension.

Loading

Article metrics loading...

/content/journals/cmc/10.2174/0929867331666230918114451
2023-09-26
2025-04-09
Loading full text...

Full text loading...

References

  1. ReinerŽ. Statins in the primary prevention of cardiovascular disease.Nat. Rev. Cardiol.201310845346410.1038/nrcardio.2013.80 23736519
    [Google Scholar]
  2. BanachM. ReinerZ. CiceroA.F.G. The year in cardiovascular disease - the year of upfront lipid lowering combination therapy.Arch. Med. Sci.20221861429143410.5114/aoms/156147
    [Google Scholar]
  3. JainM.K. RidkerP.M. Anti-inflammatory effects of statins: clinical evidence and basic mechanisms.Nat. Rev. Drug Discov.200541297798710.1038/nrd1901 16341063
    [Google Scholar]
  4. BahramiA. ParsamaneshN. AtkinS.L. BanachM. SahebkarA. Effect of statins on toll-like receptors: A new insight to pleiotropic effects.Pharmacol. Res.201813523023810.1016/j.phrs.2018.08.014 30120976
    [Google Scholar]
  5. Vahedian-AzimiA. MohammadiS.M. BanachM. Improved COVID-19 outcomes following statin therapy: An updated systematic review and meta-analysis.BioMed Res. Int.20212021190177210.1155/2021/1901772
    [Google Scholar]
  6. KandeloueiT. AbbasifardM. ImaniD. AslaniS. RaziB. FasihiM. Effect of statins on serum level of hs-CRP and CRP in patients with cardiovascular diseases: A systematic review and meta-analysis of randomized controlled trials.Inflammopharmacology202230236938310.1155/2022/8732360
    [Google Scholar]
  7. KhalifehM. PensonP. BanachM. SahebkarA. Statins as anti-pyroptotic agents.Arch. Med. Sci.20211751414141710.5114/aoms/141155 34522271
    [Google Scholar]
  8. KoushkiK. ShahbazS.K. MashayekhiK. SadeghiM. ZayeriZ.D. TabaM.Y. BanachM. Al-RasadiK. JohnstonT.P. SahebkarA. Anti-inflammatory action of statins in cardiovascular disease: The role of inflammasome and toll-like receptor pathways.Clin. Rev. Allergy Immunol.202160217519910.1007/s12016‑020‑08791‑9 32378144
    [Google Scholar]
  9. LiH. FörstermannU. Prevention of atherosclerosis by interference with the vascular nitric oxide system.Curr. Pharm. Des.200915273133314510.2174/138161209789058002 19754387
    [Google Scholar]
  10. GorabiA.M. KiaieN. PirroM. BianconiV. JamialahmadiT. SahebkarA. Effects of statins on the biological features of mesenchymal stem cells and therapeutic implications.Heart Fail. Rev.20212651259127210.1007/s10741‑020‑09929‑9
    [Google Scholar]
  11. BahramiA. BoS. JamialahmadiT. SahebkarA. Effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on ageing: Molecular mechanisms.Ageing Res. Rev.20205810102410.1016/j.arr.2020.101024 32006687
    [Google Scholar]
  12. Mahjoubin-TehranM. De VincentisA. MikhailidisD.P. AtkinS.L. MantzorosC.S. JamialahmadiT. SahebkarA. Non-alcoholic fatty liver disease and steatohepatitis: State of the art on effective therapeutics based on the gold standard method for diagnosis.Mol. Metab.20215010104910.1016/j.molmet.2020.101049 32673798
    [Google Scholar]
  13. ParizadehS.M.R. AzarpazhoohM.R. MoohebatiM. NematyM. Ghayour-MobarhanM. TavallaieS. RahseparA.A. AminiM. SahebkarA. MohammadiM. FernsG.A.A. Simvastatin therapy reduces prooxidant-antioxidant balance: results of a placebo-controlled cross-over trial.Lipids201146433334010.1007/s11745‑010‑3517‑x 21207250
    [Google Scholar]
  14. SahebkarA. ChewG.T. WattsG.F. Recent advances in pharmacotherapy for hypertriglyceridemia.Prog. Lipid Res.2014561476610.1016/j.plipres.2014.07.002 25083925
    [Google Scholar]
  15. SahebkarA. KotaniK. SerbanC. UrsoniuS. MikhailidisD.P. JonesS.R. RayK.K. BlahaM.J. RyszJ. TothP.P. MuntnerP. LipG.Y.H. BanachM. Statin therapy reduces plasma endothelin-1 concentrations: A meta-analysis of 15 randomized controlled trials.Atherosclerosis2015241243344210.1016/j.atherosclerosis.2015.05.022 26074317
    [Google Scholar]
  16. SahebkarA. SerbanC. MikhailidisD.P. UndasA. LipG.Y.H. MuntnerP. BittnerV. RayK.K. WattsG.F. HovinghG.K. RyszJ. KasteleinJ.J. BanachM. Association between statin use and plasma D-dimer levels. A systematic review and meta-analysis of randomised controlled trials.Thromb. Haemost.20151143546557 26017749
    [Google Scholar]
  17. SahebkarA. SerbanC. UrsoniuS. MikhailidisD.P. UndasA. LipG.Y.H. BittnerV. RayK.K. WattsG.F. HovinghG.K. RyszJ. KasteleinJ.J.P. BanachM. The impact of statin therapy on plasma levels of von Willebrand factor antigen.Thromb. Haemost.2016115352053210.1160/th15‑08‑0620 26632869
    [Google Scholar]
  18. SerbanC. SahebkarA. UrsoniuS. MikhailidisD.P. RizzoM. LipG.Y.H. Kees HovinghG. KasteleinJ.J.P. KalinowskiL. RyszJ. BanachM. A systematic review and meta-analysis of the effect of statins on plasma asymmetric dimethylarginine concentrations.Sci. Rep.201551990210.1038/srep09902 25970700
    [Google Scholar]
  19. SohrevardiS. NasabF. MirjaliliM. BagherniyaM. TaftiA. JarrahzadehM. AzarpazhoohM. SaeidmaneshM. BanachM. JamialahmadiT. SahebkarA. Effect of atorvastatin on delirium status of patients in the intensive care unit: A randomized controlled trial.Arch. Med. Sci.20191751423142810.5114/aoms.2019.89330 34522273
    [Google Scholar]
  20. BlandA.R. PayneF.M. AshtonJ.C. JamialahmadiT. SahebkarA. The cardioprotective actions of statins in targeting mitochondrial dysfunction associated with myocardial ischaemia-reperfusion injury.Pharmacol. Res.202217510598610.1016/j.phrs.2021.105986 34800627
    [Google Scholar]
  21. Vahedian-AzimiA. MannarinoM. ShojaieS. RahimibasharF. Esmaeili Gouvarchin GalehH. BanachM. BianconiV. PirroM. SahebkarA. The effect of statins on the prevalence and mortality of influenza virus infection: A systematic review and meta-analysis.Arch. Med. Sci.202218614410.5114/aoms/149633 36457966
    [Google Scholar]
  22. Rodríguez-MiguelA. Fernández-AntónE. Barreira-HernándezD. García-RodríguezL.A. GilM. García-LledóA. De AbajoF.J. Statins and colorectal cancer risk: A population-based case-control study and synthesis of the epidemiological evidence.J. Clin. Med.2022116152810.3390/jcm11061528 35329853
    [Google Scholar]
  23. AminF. FathiF. ReinerŽ. BanachM. SahebkarA. The role of statins in lung cancer.Arch. Med. Sci.202118114115210.5114/aoms/123225
    [Google Scholar]
  24. BytyçiI. PensonP.E. MikhailidisD.P. Prevalence of statin intolerance: a meta-analysis.Eur. Heart J.202243343213322310.1093/eurheartj/ehac015
    [Google Scholar]
  25. IwakiriY. TrebickaJ. Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy.JHEP Reports20213410031610.1016/j.jhepr.2021.100316 34337369
    [Google Scholar]
  26. AyadaI. van KleefL.A. ZhangH. LiuK. LiP. AbozaidY.J. LavrijsenM. JanssenH.L.A. van der LaanL.J.W. GhanbariM. PeppelenboschM.P. ZhengM.H. de KnegtR.J. PanQ. Dissecting the multifaceted impact of statin use on fatty liver disease: A multidimensional study.EBioMedicine20238710439210.1016/j.ebiom.2022.104392 36502575
    [Google Scholar]
  27. El-SeragH.B. JohnsonM.L. HachemC. MorganaR.O. Statins are associated with a reduced risk of hepatocellular carcinoma in a large cohort of patients with diabetes.Gastroenterology200913651601160810.1053/j.gastro.2009.01.053 19208359
    [Google Scholar]
  28. KaplanD.E. SerperM.A. MehtaR. FoxR. JohnB. AytamanA. Effects of hypercholesterolemia and statin exposure on survival in a large national cohort of patients with cirrhosis.Gastroenterology201915661693170610.1053/j.gastro.2019.01.026
    [Google Scholar]
  29. Motzkus-FeagansC. PakyzA.L. RatliffS.M. BajajJ.S. LapaneK.L. Statin use and infections in veterans with cirrhosis.Aliment. Pharmacol. Ther.201338661161810.1111/apt.12430 23889738
    [Google Scholar]
  30. MohantyA. TateJ.P. Garcia-TsaoG. Statins are associated with a decreased risk of decompensation and death in veterans with hepatitis C–related compensated cirrhosis.Gastroenterology20161502430440
    [Google Scholar]
  31. AbraldesJ.G. VillanuevaC. AracilC. TurnesJ. Hernandez-GuerraM. GenescaJ. Addition of simvastatin to standard therapy for the prevention of variceal rebleeding does not reduce rebleeding but increases survival in patients with cirrhosis.Gastroenterology201615051160117010.1053/j.gastro.2016.01.004
    [Google Scholar]
  32. KumarS. GraceN.D. QamarA.A. Statin use in patients with cirrhosis: A retrospective cohort study.Dig. Dis. Sci.20145981958196510.1007/s10620‑014‑3179‑2 24838495
    [Google Scholar]
  33. ChangF.M. WangY.P. LangH.C. TsaiC.F. HouM.C. LeeF.Y. LuC.L. Statins decrease the risk of decompensation in hepatitis B virus– and hepatitis C virus–related cirrhosis: A population‐based study.Hepatology201766389690710.1002/hep.29172 28318053
    [Google Scholar]
  34. StokkelandK. LagebornC.T. EkbomA. HöijerJ. BottaiM. StålP. Söderberg-LöfdalK. Statins and angiotensin‐converting enzyme inhibitors are associated with reduced mortality and morbidity in chronic liver disease.Basic Clin. Pharmacol. Toxicol.2018122110411010.1111/bcpt.12844 28691216
    [Google Scholar]
  35. IwakiriY. Pathophysiology of portal hypertension.Clin. Liver Dis.201418228129110.1016/j.cld.2013.12.001 24679494
    [Google Scholar]
  36. ZafraC. AbraldesJ.G. TurnesJ. BerzigottiA. FernándezM. García-PagánJ.C. RodésJ. BoschJ. Simvastatin enhances hepatic nitric oxide production and decreases the hepatic vascular tone in patients with cirrhosis.Gastroenterology2004126374975510.1053/j.gastro.2003.12.007 14988829
    [Google Scholar]
  37. KreiselW. LazaroA. TrebickaJ. Grosse PerdekampM. Schmitt-GraeffA. DeibertP. Cyclic GMP in liver cirrhosis—role in pathophysiology of portal hypertension and therapeutic implications.Int. J. Mol. Sci.202122191037210.3390/ijms221910372 34638713
    [Google Scholar]
  38. RockeyD.C. ChungJ.J. Reduced nitric oxide production by endothelial cells in cirrhotic rat liver: Endothelial dysfunction in portal hypertension.Gastroenterology1998114234435110.1016/S0016‑5085(98)70487‑1 9453496
    [Google Scholar]
  39. TripathiD.M. VilasecaM. LafozE. Garcia-CalderóH. Viegas HauteG. Fernández-IglesiasA. Rodrigues de OliveiraJ. García-PagánJ.C. BoschJ. Gracia-SanchoJ. Simvastatin prevents progression of acute on chronic liver failure in rats with cirrhosis and portal hypertension.Gastroenterology201815551564157710.1053/j.gastro.2018.07.022 30055171
    [Google Scholar]
  40. BoschJ. Gracia-SanchoJ. AbraldesJ.G. Cirrhosis as new indication for statins.Gut202069595396210.1136/gutjnl‑2019‑318237 32139553
    [Google Scholar]
  41. KaplanD.E. MehtaR. Garcia-TsaoG. AlbrechtJ. AytamanA. BaffyG. BajajJ. HernaezR. HuntK. IoannouG. JohnsonK. KanwalF. LeeT.H. MontoA. PandyaP. SchaubelD. TaddeiT.H. SACRED: Effect of simvastatin on hepatic decompensation and death in subjects with high-risk compensated cirrhosis: Statins and Cirrhosis: Reducing events of decompensation.Contemp. Clin. Trials202110410636710.1016/j.cct.2021.106367 33771685
    [Google Scholar]
  42. HigginsJ.P.T.G.S. Handbook for systematic reviews of interventions. version.LondonThe Cochrane Collaboration2009
    [Google Scholar]
  43. BorensteinM. HedgesL. HigginsJ. RothsteinH. Comprehensive meta-analysis, version 2 biostat.Englewood, NJ2005
    [Google Scholar]
  44. SuttonA.J. AbramsK.R. JonesD.R. JonesD.R. SheldonT.A. SongF. Methods for meta-analysis in medical research Wiley Chichester.2000
    [Google Scholar]
  45. HozoS.P. DjulbegovicB. HozoI. Estimating the mean and variance from the median, range, and the size of a sample.BMC Med. Res. Methodol.2005511310.1186/1471‑2288‑5‑13 15840177
    [Google Scholar]
  46. FerrettiG. BacchettiT. SahebkarA. Effect of statin therapy on paraoxonase-1 status: A systematic review and meta-analysis of 25 clinical trials.Prog. Lipid Res.201560507310.1016/j.plipres.2015.08.003
    [Google Scholar]
  47. BanachM. SerbanC. UrsoniuS. RyszJ. MuntnerP. TothP.P. JonesS.R. RizzoM. GlasserS.P. WattsG.F. BlumenthalR.S. LipG.Y.H. MikhailidisD.P. SahebkarA. Statin therapy and plasma coenzyme Q10 concentrations—A systematic review and meta-analysis of placebo-controlled trials.Pharmacol. Res.20159932933610.1016/j.phrs.2015.07.008 26192349
    [Google Scholar]
  48. AbraldesJ.G. AlbillosA. BañaresR. TurnesJ. GonzálezR. García-PagánJ.C. BoschJ. Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: A randomized controlled trial.Gastroenterology200913651651165810.1053/j.gastro.2009.01.043 19208350
    [Google Scholar]
  49. Pollo-FloresP. SoldanM. SantosU.C. KunzD.G. MattosD.E. da SilvaA.C. MarchioriR.C. RezendeG.F.M. Three months of simvastatin therapy vs. placebo for severe portal hypertension in cirrhosis: A randomized controlled trial.Dig. Liver Dis.2015471195796310.1016/j.dld.2015.07.156 26321186
    [Google Scholar]
  50. Addition of simvastatin to carvedilol does not improve hemodynamic response in cirrhotics with varices without prior bleed: Preliminary results of an open label RCT. In: ChoudharyR.V.A. JindalA. KumarG. SarinS.K. Eds.; Hepatology; Wiley-blackwell 111 river st: Hoboken 07030-5774, NJ USA.2016
    [Google Scholar]
  51. Alvarado-TapiasE. ArdevolA. PavelO. MontanesR. MurziM. Oblitas SusanibarE. Eds.; Hemodynamic effects of carvedilol plus simvastatin in cirrhosis with portal hypertension and no-response to beta-blockers: a doubleblind randomized trial; Alvarado-Tapias, E.; Ardevol, A.; Pavel, O.; Montanes, R.; Murzi, M.; Oblitas Susanibar, E., Eds.; Hepatology; Wiley-blackwell 111 river st: Hoboken 07030-5774, nj USA.,2016
    [Google Scholar]
  52. BishnuS. AhammedS.M. SarkarA. HembramJ. ChatterjeeS. DasK. DhaliG.K. ChowdhuryA. DasK. Effects of atorvastatin on portal hemodynamics and clinical outcomes in patients with cirrhosis with portal hypertension.Eur. J. Gastroenterol. Hepatol.2018301545910.1097/MEG.0000000000001006 29099421
    [Google Scholar]
  53. VijayaraghavanR. JindalA. AroraV. ChoudharyA. KumarG. SarinS.K. Hemodynamic effects of adding simvastatin to carvedilol for primary prophylaxis of variceal bleeding: A randomized controlled trial.Am. J. Gastroenterol.2020115572973710.14309/ajg.0000000000000551 32079861
    [Google Scholar]
  54. Moctezuma-VelázquezC. AbraldesJ.G. Montano-LozaA.J. The use of statins in patients with chronic liver disease and cirrhosis.Curr. Treat. Options Gastroenterol.201816222624010.1007/s11938‑018‑0180‑4 29572618
    [Google Scholar]
  55. ZachariasA.P. JeyarajR. HobolthL. BendtsenF. GluudL.L. MorganM.Y. Carvedilol versus traditional, non‐selective beta‐blockers for adults with cirrhosis and gastroesophageal varices.Cochrane Database Syst. Rev.2018101001151010.1002/14651858.CD011510.pub2
    [Google Scholar]
  56. PascalJ.P. CalesP. Propranolol in the prevention of first upper gastrointestinal tract hemorrhage in patients with cirrhosis of the liver and esophageal varices.N. Engl. J. Med.19873171485686110.1056/NEJM198710013171403 3306385
    [Google Scholar]
  57. WanS. HuangC. ZhuX. Systematic review with a meta-analysis: Clinical effects of statins on the reduction of portal hypertension and variceal haemorrhage in cirrhotic patients.BMJ Open201997e03003810.1136/bmjopen‑2019‑030038 31315875
    [Google Scholar]
  58. TrebickaJ. HennenbergM. LalemanW. ShelestN. BieckerE. SchepkeM. NevensF. SauerbruchT. HellerJ. Atorvastatin lowers portal pressure in cirrhotic rats by inhibition of RhoA/Rho-kinase and activation of endothelial nitric oxide synthase.Hepatology200746124225310.1002/hep.21673 17596891
    [Google Scholar]
  59. MarroneG. Maeso-DíazR. García-CardenaG. AbraldesJ.G. García-PagánJ.C. BoschJ. Gracia-SanchoJ. KLF2 exerts antifibrotic and vasoprotective effects in cirrhotic rat livers: Behind the molecular mechanisms of statins.Gut20156491434144310.1136/gutjnl‑2014‑308338 25500203
    [Google Scholar]
  60. TrebickaJ. SchierwagenR. Statins, Rho GTPases and KLF2: New mechanistic insight into liver fibrosis and portal hypertension.Gut20156491349135010.1136/gutjnl‑2014‑308800 25596180
    [Google Scholar]
  61. TrebickaJ. HennenbergM. OdenthalM. ShirK. KleinS. GranzowM. VogtA. DienesH.P. LammertF. ReichenJ. HellerJ. SauerbruchT. Atorvastatin attenuates hepatic fibrosis in rats after bile duct ligation via decreased turnover of hepatic stellate cells.J. Hepatol.201053470271210.1016/j.jhep.2010.04.025 20633948
    [Google Scholar]
  62. MarroneG. RussoL. RosadoE. HideD. García-CardeñaG. García-PagánJ.C. BoschJ. Gracia-SanchoJ. The transcription factor KLF2 mediates hepatic endothelial protection and paracrine endothelial–stellate cell deactivation induced by statins.J. Hepatol.20135819810310.1016/j.jhep.2012.08.026 22989565
    [Google Scholar]
/content/journals/cmc/10.2174/0929867331666230918114451
Loading
/content/journals/cmc/10.2174/0929867331666230918114451
Loading

Data & Media loading...

Supplements

PRISMA checklist is available as supplementary material on the publisher’s website along with the published article.

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test