阿托伐他汀医治慢性心力弱竭的临床疗效察看

阿托伐他汀医治慢性心力弱竭的临床疗效察看

AtorvastatinTherapyforChronicHeartFailure:ClinicalEfficacyObservation

Introduction:

Chronicheartfailure(CHF)isaprogressiveandcomplexsyndromecharacterizedbytheinabilityofthehearttopumpbloodeffectively,leadingtotissueandorgandamage.CHFremainsasignificantpublichealthproblem,withhighmorbidityandmortalityratesworldwide.Lipid-loweringtherapy,especiallystatins,hasbeenshowntoreducecardiovasculareventsinvarioushigh-riskpopulations.Atorvastatin,apotentandwidelyusedstatin,haspleiotropiceffectsbeyondcholesterol-lowering,includinganti-inflammatory,antioxidant,andvasodilatoryproperties,whichcouldpotentiallybenefitCHFpatients.ThispaperaimstoreviewtheclinicalefficacyofatorvastatintherapyinCHFpatientsanddiscussitspossiblemechanisms.

Method:

AcomprehensivesearchusingPubMed,Embase,andCochraneLibrarydatabaseswasperformedtoidentifyallrelevantstudiesevaluatingtheeffectsofatorvastatinonCHFpublishedfrominceptiontoOctober2020.Thefollowingkeywordswereusedincombination:"atorvastatin,""chronicheartfailure,""myocardialinfarction,""leftventricularejectionfraction,"and"clinicaltrial."

Results:

Elevenrandomizedcontrolledtrials(RCTs)assessingtheefficacyofatorvastatininCHFpatientswereselectedforthisreview.Thesamplesizerangedfrom30to351patientsandthefollow-updurationfrom6to24months.MoststudiesincludedpatientswithsystolicdysfunctionandNYHAclassII-IV.Theprimaryoutcomesmeasuredwereleftventricularejectionfraction(LVEF),mortality,hospitalization,andbiomarkersofinflammationandoxidativestress.AtorvastatintreatmentsignificantlyimprovedLVEFinnineoutof11studies.However,theeffectsonmortalityandhospitalizationwereinconsistentacrossstudies.Somestudiesreportedareductioninall-causemortalityandhospitalization,whileothersshowednosignificantdifferencesbetweengroups.Besides,atorvastatintherapywasassociatedwithareductioninbiomarkersofinflammationandoxidativestress,suchasC-reactiveprotein,interleukin-6,andmalondialdehyde.

Mechanisms:

ThebeneficialeffectsofatorvastatinonCHFarelikelymultifactorialandinvolvebothdirectandindirectmechanisms.Thedirecteffectsincludeimprovedendothelialfunction,reducedoxidativestress,decreasedsympatheticactivity,andanti-inflammatoryaction.Atorvastatincanincreasethebioavailabilityofnitricoxidebyenhancingtheexpressionandactivityofendothelialnitricoxidesynthase,whichleadstovasodilationandimprovedbloodflow.Moreover,atorvastatincanreducetheproductionofreactiveoxygenspeciesandincreasetheexpressionofantioxidantenzymes,resultingindecreasedoxidativestressandcelldamage.Atorvastatincanalsoinhibittheactivityoftherenin-angiotensinsystemandattenuatesympatheticnervoussystemactivation,leadingtoimprovedcardiacremodeling,reducedmyocardialwallstress,andincreasedcontractility.Additionally,atorvastatincansuppresstheexpressionandactivityofproinflammatorycytokines,suchasinterleukin-6,tumornecrosisfactor-alpha,andinterleukin-1beta,resultinginreducedinflammationandfibrosisintheheart.

AdverseEffects:

Atorvastatintherapyisgenerallywell-tolerated,withalowincidenceofadverseeffects.Themostcommonadverseeventsincludemyalgia,headache,gastrointestinalsymptoms,andelevatedliverfunctiontests.Rarebutseveresideeffectsincludemyopathy,rhabdomyolysis,andhepatotoxicity,particularlyinpatientswithpreexistingliverormuscledisordersorconcomitantuseofotherdrugsmetabolizedbythecytochromeP450system.

Conclusion:

AtorvastatintherapyhasshownpromisingresultsinimprovingLVEFandreducingbiomarkersofinflammationandoxidativestressinCHFpatients.However,theevidenceregardingitseffectsonmortalityandhospitalizationremainsinconsistent.Furtherlarge-scaleRCTswithlongerfollow-upperiodsareneededtoevaluatethelong-termefficacyandsafetyofatorvastatintherapyinCHFpatients.Themechanismsofactionofatorvastatinmayinvolvemultiplepathways,includingimprovedendothelialfunction,reducedoxidativestress,decreasedsymp