University of North DakotaUND Scholarly Commons

Nursing Capstones Department of Nursing

5-6-2016

Strategies to Continue Statin Use in Patients withMyalgiaCarrie Pfaff

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Recommended CitationPfaff, Carrie, "Strategies to Continue Statin Use in Patients with Myalgia" (2016). Nursing Capstones. 128.https://commons.und.edu/nurs-capstones/128

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Runninghead:STRATEGIESTOCONTINUESTATINUSE

StrategiestoContinueStatinUseinPatientswithMyalgia

CarriePfaff

UniversityofNorthDakotaCollegeofNursingandProfessionalDisciplines

STRATEGIESTOCONTINUESTATINUSE 2

Permission

Title StrategiestoContinueStatinUseinPatientswithMyalgia

Department Nursing

Degree MasterofScience

Inpresentingthisindependentstudyinpartialfulfillmentoftherequirementsfora

graduatedegreefromtheUniversityofNorthDakota,IagreethattheCollegeof

NursingofthisUniversityshallmakeitfreelyavailableforinspection.Ifurther

agreethatpermissionforextensivecopyingorelectronicaccessforscholarly

purposesmaybegrantedbytheprofessorwhosupervisedmyindependentstudy

workor,inherabsence,bythechairpersonofthedepartmentorthedeanofthe

GraduateSchool.Itisunderstoodthatanycopyingorpublicationorotheruseof

thisindependentstudyorpartthereofforfinancialgainshallnotbeallowed

withoutmywrittenpermission.Itisalsounderstoodthatduerecognitionshallbe

giventomeandtotheUniversityofNorthDakotainanyscholarlyusewhichmaybe

madeofanymaterialinmyindependentstudy.

05/05/2016

STRATEGIESTOCONTINUESTATINUSE 3

Abstract

Nothinghasproventobeaseffectiveinthetreatmentofcoronaryheartdiseaseas

hydroxymethylglutarylcoenzymeA(HMG-CoA)reductaseinhibitors,orstatins,and

sinceheartdiseasecontinuestobetheleadingcauseofdeathintheUnitedStates,it

isimperativeforpatientstobeabletotolerateandmaintainstatintherapy.Even

thoughstatinsareknowntohaveanimpressivesafetyprofileandaregenerallywell

tolerated,discontinuationoftherapydoesoccur,andismostoftenduetomyalgia

symptoms.Thepatientpresentedinthecasereportwasdiagnosedwithfamilial

hypercholesterolemia,andstatintherapyisavitalpieceofthetreatmentplan.The

goalofthisliteraturereviewistoevaluatebothalternativestatindosingand

vitaminDsupplementationtodetermineifusingeitherofthesestrategiesallows

patientstocontinuestatintherapy,thusreducingbothmorbidityandmortalityby

decreasingtheriskoffuturecardiovascularevents.

STRATEGIESTOCONTINUESTATINUSE 4

BackgroundandRationale

Heartdisease,accountingfor600,000deathsannually,continuestobethe

leadingcauseofdeathintheUnitedStates.Hypercholesterolemiaisoneofthe

majorriskfactorsfordevelopingheartdisease(CentersforDiseaseControland

Prevention,[CDC],2014).Additionally,accordingtotheCDC(2014),“Several

geneticdisordersareassociatedwithincreasedriskofprematureheartattacks.A

relativelycommondisorderisfamilialhypercholesterolemia,whichcauseshigh

levelsof‘bad’cholesterol(lowdensitylipoprotein,orLDLcholesterol)beginningat

birth”(para.2).Cholesterol,afat-like,waxysubstance,isacomponentofallbody

cells.ItplaysanecessaryroleintheproductionofhormonesandvitaminD,aswell

asaidinginfooddigestion.Ourbodiesarecapableofmakingallthecholesterolit

needstocarryoutthesefunctions.Therefore,theadditionalcholesterolfoundin

dietarysourcesneedstoberemovedviahigh-densitylipoproteins,orHDL,whichis

oftenreferredtoasthe“good”cholesterol.The“bad”cholesterol,orLDLas

mentionedpreviously,causesbuildupofplaqueleadingtoatherosclerosis,which

resultsinadecreaseofoxygen-richbloodflowthroughthearteriessupplyingthe

heartandthustherestofthebody(NationalHeart,Lung,andBloodInstitute,

[NHLBI],2014).Thisprocessleadstocoronaryarterydisease(CAD)alsocalled

coronaryheartdisease(CHD),themostcommonformofheartdisease(CDC,2015;

NHLBI,2014).Coronaryheartdiseasecanleadtoheartfailure,arrhythmias,heart

attack,andstroke(NHLBI,2015).

Sully,a24-year-oldmaleandthepatientpresentedinthiscasereport,was

diagnosedwithfamilialhypercholesterolemia.Thisinheritedconditionofelevated

STRATEGIESTOCONTINUESTATINUSE 5

cholesterolcancauseCADleadingtoheartattacksatanearlyage(NationalHuman

GenomeResearchInstitute,[NHGRI],2013).AccordingtotheNHGRI(2013),“Men

whohavefamilialhypercholesterolemiahaveheartattacksintheir40’sto50’s,and

85percentofmenwiththedisorderhaveaheartattackbyage60,”(Whatisfamilial

hypercholesterolemia,para.5).Theinheritedconditionisaresultofagene

mutationonchromosomenumber19,whichisresponsibleforremovingLDLfrom

thebloodstream.ThisalterationresultsinhighlevelsofLDLbeginningatbirth

(NHGRI,2013).Thefastinglipidpaneldrawnonthepatientinthiscasereport

revealedelevatedcholesterolandLDL;additionally,hisfatheralsohad

hypercholesterolemiaanddiedofaheartattackattheageof55.Thesefactorsled

tothefamilialhypercholesterolemiadiagnosis.

Thetreatmentoffamilialhypercholesterolemiahasseveralaspectsincluding

diet,exercise,weightmanagement,andmedication(NHLBI,2005).Statinsare

generallythemedicationofchoiceinhypercholesterolemiatreatment(Reinhart&

Woods,2012).Statinsinhibitcholesterolformationintheliveralongwith

increasinglivercellreceptorsthatareresponsibleforremovingLDLfromthe

bloodstream(Gotto,2002).StudieshaveshownstatinstodecreaseLDLby20to

40%,andinsomecasesbyevengreaterthan40%dependingonthedrugand

dosage(Weng,KaoYang,Lin,&Tai,2009).Eventhoughstatinsaregenerallywell

tolerated,studieshaverevealedthatasmanyas20%ofpatientsdiscontinueuse

duetoreportedmyalgias.Thisadversesideeffectofstatintherapyisnotwell

understood,anditcanbechallengingtodifferentiateitfromotherpossiblecauses.

Clinically,myalgiasareofconcernduetotheriskofrhabdomyolysis,whichissevere

STRATEGIESTOCONTINUESTATINUSE 6

muscledamagethatcanleadtokidneydamageandevendeath(Reinhart&Woods,

2012;Thompson,Clarkson,&Rosenson,2006).Theefficacyofalternativetherapies

hasnotproventoequalthatofstatins,specificallywhenspeaking“intermsof

mortalityriskreduction”(Reinhart&Woods,2012,p.292).AsstatedbyReinhart

andWoods(2012),“anystrategycapableofpreventingrepeatmyalgiainthese

patientswillhelpenabletheircontinueduseofstatinmedicationandhelplowerthe

morbidityandmortalityassociatedwithCHD”(p.292).Alternativedosingand

addingvitaminDsupplementationtoreducemyalgiasymptomsandmaintainstatin

therapyaretwostrategiesthathavebeenstudied.Therefore,thepurposeofthis

literaturereviewistodetermineifeitherstrategywilleffectivelyassistinthegoalof

continuingstatintherapyinpatientswithreportedmyalgia.

CaseReport

ChiefComplaint:requestingcholesterolcheckr/tfamilyhistoryHPI:This24-year-oldmalepresentstodayrequestingtohavehischolesterolchecked.Patientstateshismotherencouragedhimtocomeinbecausehisfather,whohadelevatedcholesterol,recentlydiedofaheartattack.Patientdenieschestpain,palpitations,hypertension,orshortnessofbreath.PastMedicalHistory:allergicrhinitisPastSurgicalHistory:tonsillectomyandadenoidectomyatage4FamilyHistory:Father–diedatage55fromaheartattack,Mother–aliveandwell,Brother–hypercholesterolemia,age27SocialHistory:PatientisanEMTanddoesshiftwork.Reportsexercisingfor30minutes4-5daysperweek.Patientdeniescaffeineintake,smoking,andrecreationaldruguse.Reportsfrequentfastfoodintakeanddrinks2beerseacheveningalongwithsocialdrinking1-2weekendspermonthwhereheconsumes5-6drinksonthoseoccasions.Medications:Zyrtecprn

STRATEGIESTOCONTINUESTATINUSE 7

Allergies:NKAROS:Constitutional:deniesfatigue,recentweightchange,fever,troublesleepingCardiovascular:denieschestpain,palpitations,hypertension,edemaRespiratory:deniesshortnessofbreathPsychological:deniesanxiety,depression,moodchangesPhysicalExam:Vitals:BP110/54,HR62,Temp37.1c,Ht6’1”,Wt200lbs.,BMI26.4General:alert,welldeveloped,noacutedistressSkin:colornormalCardiovascular:S1andS2,nomurmurs,regularrate,noJVDoredemanotedRespiratory:respirationrhythmanddepthnormal,cleartoauscultationPsychiatric:normalaffect,normalmoodLabs:Lipidpanel: BMP: LFT:Cholesterol–310 BUN–18 Albumin–4.0 Triglycerides–140 Sodium–139 AlkPhos-88HDL–60 Potassium–3.9 Totalbili–0.4LDL–209 Chloride–102 AST-20 CO2–27.3 ALT-22

Glucose–86 Totalprotein–7.4Creatinine–1.1Calcium–9.8Aniongap–9.7GFR->60Albumin–4.00AlkPhos–88TotalProtein–7.4

Impression/Plan:1.FamilialHypercholesterolemia–startLipitor20mgdaily,discussedimportanceofcomplianceandmedicationsideeffects,followalowcholesteroldietandreducesaturatedfatintake,continueexerciseregimen,maintainweight.Patientverbalizedunderstandingofaboveplanandisagreeable.Patientencouragedtocallwithanyquestionsorconcerns.Follow-upin3monthswithfastinglabs.Willrechecklipidpanel.Willconsiderdietaryconsultatthistime.

STRATEGIESTOCONTINUESTATINUSE 8

LiteratureSearchStrategy

AliteraturesearchwasconductedutilizingbothCINAHLandPubMed

databasesviatheUniversityofNorthDakotaHarleyE.FrenchLibraryoftheHealth

Scienceswebsite.AnadvancedsearchinPubMedwascompletedusingthemedical

subjectheading(MeSH)termsof“statins”AND“alternatedosing.”Thesearch

generated22articles.The“Englishlanguage”and“publishedwithinthelast10

years”filterswereadded,reducingthearticlesto17.Afterreviewingall17articles,

oneappearedtobemostrelatedtotheclinicalquestionbutwasnotincludedinthis

review;however,the“similararticles”featureattachedtothisparticulararticlewas

utilizedandanadditional136articlesweregenerated.Afterreviewingthearticles,

threeweredeterminedtoberelevant.Reviewofthereferencesectionsofthethree

articlesresultedintwoadditionalarticles,whichwereretrievedusingPubMed.An

additionalsearchinPubMedusingtheMeSHtermsof“statinintolerance”AND

“vitaminDsupplementation”andagainincludingthe“Englishlanguage”and

“publishedwithinthelast10years”filters,generatedeightarticlesforreview.Two

ofthesearticlesweredeterminedtobepertinenttotheresearchquestion.An

additionalarticlewasfoundandretrievedviaPubMedafterreviewofthereference

sections.TheCINAHLsearchwasconductedusingthesearchterms“statin”AND

“myalgia.”Thissearchresultedin67articles.The“Englishlanguage”and

“publishedwithinthelast10years”filterswereaddedreducingthearticlesto57.

Afterreview,onewasfoundtobepertinenttotheresearchquestion,andone

additionalarticlewasobtainedviaPubMedafterreviewofthereferencesection.

Thus,theliteraturesearchproducedatotalof10articles.

STRATEGIESTOCONTINUESTATINUSE 9

LiteratureReview

AlternativeDosing

Patientbenefitfromstatintherapyiswelldocumented,andresearchhas

proventhatitisessentialinthetreatmentofCHDespeciallyinreducingmorbidity

andmortality.Statinintoleranceduetomyalgiaoftenleadstodiscontinuationof

thislife-savingmedication.Alternativestatindosingisonestrategythathasbeen

studiedtodetermineifitleadstodecreasedintolerance,thusallowingpatientsto

continueontherapy(Reinhart&Woods,2012).Rosuvastatinandatorvastatinare

thetwomedicationsmostoftenstudiedastheirlonghalf-lifeprovidesthegreatest

chancetoachievetherapeuticlevelswithlessfrequentdosing(Gadarla,Kearns,&

Thompson,2008;Kennedy,Barnas,Schmidt,Glisczinski,&Paniagua,2011).Inthe

randomizedcontrolledtrial(RCT)presentedbyKennedyetal.(2011),17patients

wereevaluated.Thepatientsallhadadiagnosisofhypercholesterolemiaandwere

deemedstatinintolerantduetomyalgia.Thepatientswerenotcurrentlyonstatin

therapyandwerenotmeetingLDLgoalsaccordingtotheAdultTreatmentPanelIII

(ATPIII)NationalCholesterolEducationPanel(NCEP)Guidelines.Thestudyhad

twoeight-weekphasesandtheparticipantsswitchedtreatmentarmsafterthefirst

phase.Patientsweregivenonce-weeklyrosuvastatin5mgoraplaceboforfour

weeks,andiftheywerenotatLDLgoalafterthefirstfourweeks,thedosewas

increasedto10mg.Patientswererequiredtoremainconsistentwiththeirlifestyle

habitsthroughoutthestudy.A12.2%reductioninLDLwasnotedinthepatients

whoweregivenonce-weeklyrosuvastatinversus0.4%reductionintheplacebo

group,and20%attainedLDLgoalwhilezeropatientsmetgoalonplacebo.

STRATEGIESTOCONTINUESTATINUSE 10

Furthermore,11.8%ofpatientsreportedmyalgiawhileontheplacebotreatment,

and20%reportedmyalgiawhileonrosuvastatinleadingtotherapycessation

(Kennedyetal.,2011).Theauthorsconcluded,“Once-weeklylow-doserosuvastatin

isaneffectiveandwell-toleratedlipid-loweringtherapyoptionforpatientsnotat

LDLgoalandpreviouslyunabletotoleratestatinsbecauseofahistoryofmyalgias”

(Kennedyetal.,2011,p.308).

InanRCTconductedbyJafari,Ebrahimi,Ahmadi-Kashani,Balian,andBashir

(2003),54patientswereincludedinthestudyaftermeetingthecriteriaofanLDL

rangingfrom100to200mg/dLaswellasmeetingtheparametersconsidered

appropriatefortreatmentpertheNCEPguidelines.Therefore,patientswith

abnormalliverenzymesorcreatinekinase(CK),patientscurrentlytakinganother

cholesterol-reducingmedication,thosepregnantorbreastfeeding,orthosewho

experiencedpreviousintolerancetostatintherapywereexcluded.Thesix-week

trialincludedthreerandomizedgroupswhoreceivedeitheratorvastatin10mg

everyday,10mgeveryotherday,or20mgeveryotherday.Thegroupswere

relativelysimilarwhenconsideringage,gender,andweight.Outof54patients,46

finishedthestudy.Thosewhodidnotcompletethestudydidnotcometotheirsix-

weekfollow-upandwerethuslabeledasdropouts.Patientswereevaluatedwith

fastinglipids,liverfunction,andCKtests.Allthreegroupssawasignificant

reductioninLDLandtotalcholesterol,andthosewhotookatorvastatin20mgevery

otherdayalsoexperiencedasignificantincreaseinHDL.Allregimensevaluated

weredeemedwelltoleratedasnomyalgiawasreported,nosignificantincreasein

liverenzymesorCKwasnoted,andtherapycompliancewasachieved.Thesestudy

STRATEGIESTOCONTINUESTATINUSE 11

resultsindicatethatalternateatorvastatindosingiseffectiveandsafe(Jafarietal.,

2003).

ARCTevaluating35patientswasconductedbyMatalka,Ravnan,and

Deedwania(2002).Thestudyrequireddiagnosedhypercholesterolemia

participantstobeatleast18yearsofageandtomeetNCEPATPIItreatment

guidelines.Ifpatientswerecurrentlytakingacholesterol-loweringmedication,the

medicationwasdiscontinuedandthestudywasstartedsixweekslater.Patients

wereexcludedwithtriglyceridesover400mg/dL,uncontrolleddiabeteswithblood

glucosegreaterthan200mg/dL,orthree-monthhistoryofeithermyocardial

infarction,percutaneoustransluminalcoronaryangioplasty,orcoronaryartery

bypassgraft.Thestudyalsoexcludedpatientswithliverenzymesgreaterthan

threetimestheupperlimitofnormal,thosewhoconsumemorethan10alcoholic

beveragesperweek,alongwiththosetakingazoleantifungalmedications,warfarin,

oranyimmunosuppressants.Thepatientswereassignedrandomlytoreceive

eitheratorvastatin10mgeverydayoreveryotherdayforaperiodof12weeks.

Thedosewasdoubledatthesix-weekintervalifthepatientwasnotmeetingLDL

goal.Lipidlevelswereassessedatbaseline,sixweeks,andagainat12weeks.

Additionallabsweredrawninordertoevaluatesafety,whichincludedacomplete

bloodcount,chemistrypanel,CK,andliverfunctiontests.Atthesix-weekpoint,

patientsshowedanLDLreductionof27%inthealternate-daygroupand38%inthe

every-daygroup.Resultsatthe12-weekintervalincludeda35%LDLreductionin

thealternate-daygroupanda38%reductionintheevery-daygroup.Unfortunately,

therewasalsoadecreaseinHDLat12weeksinbothgroups.Thedosewasdoubled

STRATEGIESTOCONTINUESTATINUSE 12

in79%ofthosetakingatorvastatineveryotherdaycomparedto17%ofthe

patientstakingthemedicationdaily.GoalinLDLlevelswasachievedby43%of

thoseinthealternate-daygroupversus75%ofpatientsintheevery-daygroup.

Onlyonepatienthadtobewithdrawnfromthestudyduetomuscleweakness

(Matalka,Ravnan,&Deedwania,2002).AsstatedbyMatalka,Ravnan,and

Deedwania(2002),“Thestudyshowedthattheefficacyofalternate-day

administrationofatorvastatiniscomparabletothatofdailyadministrationin

reducingLDL-Cinpatientswithhypercholesterolemia”(p.676).

Aretrospectivechartreviewof40patientswhowereconsideredstatin

intolerantduetomyalgiaweregivenrosuvastatintwiceweeklyforatleastthree

weeks.Thirtypatientsweregiven5mgwhile10weregiven10mgeachweekon

MondaysandThursdays.Twenty-fourofthepatientswerealsotakingezetimibe,

fibrates,resins,andChineseredrice,eitheraloneorincombination.However,the

twice-weeklyrosuvastatindosingscheduledecreasedtotalcholesterolby19%and

reducedLDLby26%,aswellasresultingina14%reductionintriglycerides.No

significantchangewasnotedinHDLlevels.Eightpatientswereforcedto

discontinuetherapyduetomuscleaches,whichmeans80%ofthepatientsstudied

wereabletotoleratethetherapy.Theauthorsconcludedthatdosereduction

contributestodecreasedstatinintolerancepossiblybyallowingmusclerecovery

withintermittentdosing(Gadarlaetal.,2008).

AnotherretrospectivechartreviewconductedbyBackesetal.(2008)

included51patientswhoreceivedrosuvastatinonanalternatedosingscheduleof

everyotherdayforatleastonemonth.Allofthepatientshaddocumentedstatin

STRATEGIESTOCONTINUESTATINUSE 13

intoleranceandlipidlevelsdrawnpriortoandaftertreatment.Theresultsofthe

studyrevealedsignificantreductions(p<0.001)intriglycerides,LDL,andtotal

cholesterolwithoutsignificantchangesinHDL.Furthermore,64.9%ofthepatients

mettheNCEPATPIIILDL-Cgoal.Ofthe51patients,37wereabletotoleratethe

alternatedosing,whereas14hadreturnofmyalgiasymptomsandwereforcedto

discontinuetherapy.Theauthorstheorizedthatalternatedosingofrosuvastatin,

specificallyeveryotherday,canstillresultinadequateLDLreductionwhile

avoidingtherapyendingadverseeffectssuchasmyalgia.Thus,patientsarebetter

treatedwithalternatedosingthannotbeingtreatedatall(Backesetal.,2008).Also,

asstatedbyBackesetal.(2008),“Rosuvastatinappearstobearationalchoicefor

markedlyimprovinglipoproteinlevelsinstatin-intolerantpatientsbecauseofits

highpotency,longhalf-life,andlackofCYP3A4metabolism”(p.342).However,the

authorsdidrecognizesomestudylimitationsincludingthestudy’sretrospective

design,smallsamplesize,andthefactthatchangesmadeinlifestylemodifications

byindividualpatientswerenotevaluatedandwerenotdiscouraged(Backesetal.,

2008).

VitaminDSupplementation

AdeficiencyinvitaminDcanleadtomyalgia,whichisoftenthefirst

manifestationidentified(Sikkaetal.,2011).Sincestatinintoleranceismost

commonlycausedbymyalgia,thereisconsiderationthatinvestigatingvitaminD

levelsandthuscorrectinganydeficiencycanhelpcontinuestatinusebyresolving

myalgiasymptoms(Khayznikovetal.,2015).Intheprospectivecohortstudy

presentedbyKhayznikovetal.(2015),146patientswereassessed.Patients

STRATEGIESTOCONTINUESTATINUSE 14

includedwereconsideredstatinintolerantbyfailingtherapyoftwoormoreagents

alongwithlowserumvitaminDlevelslessthan32ng/mL.Patientswithpreviously

reportedrhabdomyolysis,thosetakingcorticosteroids,orthosewithany

comorbiditythatcouldleadtomuscleorbonepainwereexcluded.Thepatients

weregiveneither50,000or100,000unitsperweekofvitaminD2tocorrectthe

deficiency.VitaminDdoseswereadjustedtomaintainanormalrangeof50to80

ng/mL.Patientswerethengivenrosuvastatin10to20mgdailythreeweeksafter

thevitaminDinitiation.StatindosingwasalsoadjustedinanattempttoreduceLDL

tomeetATPIIIgoals.Patientscompletedfollow-upatsixmonths,12months,and

24months(Khayznikovetal.,2015).Ofthe146patients,88to95%wereableto

toleratestatintherapywithoutrecurrent“myalgia,myositis,myopathy,and/or

myonecrosis”withmedianvitaminDsupplementationof50,000unitsperweek

(Khayznikovetal.,2015,p.90).Theauthorsconcludedthatstatinintolerancedue

toadversemusculareffectsisassociatedwithvitaminDdeficiencyandcanbe

resolvedbysupplementation.Additionally,vitaminDhasproventobewell

toleratedanditssafetyisnotaconcern(Khayznikovetal.,2015).

Inanotherprospectivecohortdesignedstudy,thegoaloftheauthorswasto

determineiflowserumvitaminDlevelscorrelatetomyalgiainpatientsonstatin

therapy,andifthesymptomscanbereversedbyaddingsupplementation.Ofthe

621patientswhohadvitaminDlevelsdrawn,128complainedofmyalgia.The

vitaminDlevelswerelowin64%,or82,ofthepatientswithmyalgiasymptoms

comparedto43%ofthepatientswithoutsymptoms.Ofthe82patientswith

myalgia,38hadvitaminDlevelsbelow32ng/mLandwereinstructedtotake

STRATEGIESTOCONTINUESTATINUSE 15

50,000unitsperweekofvitaminDfor12weeks.Theywereallowedtocontinue

theircurrentstatinmedication,whichincludedrosuvastatin,atorvastatin,or

pravastatin(Ahmedetal.,2009).Attheendofthestudyperiod,Ahmedetal.

(2009)determined,“vitaminDsupplementationthatnormalizedserumvitaminD

levelswasconcurrentlyassociatedwithresolutionofmyalgiasin35of38(92%)

statin-treatedpatientswithmyalgiaandlowpretreatmentserumvitaminDlevels”

(p.15).Theauthorsdidrecognizesomestudylimitations,whichincluded

subjectivereportingofmyalgiasymptomsbypatients,lackofblinding,andnot

havingacontrolgroup(Ahmedetal.,2009).

Glueck,Abuchaibe,andWang(2011)alsopresentedaprospectivestudy

where68patientsdiagnosedwithhypercholesterolemia,unabletotolerateatleast

onestatinduetomyositis/myalgia,andwithlowserum25(OH)vitaminDlevels

lessthan32ng/mLwereevaluatedtoidentifyifvitaminDdeficiencycorrection

wouldresultintoleranceofstatintherapy.Patientsweregiven50,000unitsof

vitaminD2twiceweeklyforthreeweeksandthentheycontinuedonceweekly

dosing.StatintherapywasrestartedaftertheinitialthreeweeksofvitaminD

supplementation.Patientswereassessedatthreemonths,and91%ofthepatients

wereabletotoleratestatintherapywithvitaminDsupplementation(Glueck,

Abuchaibe,&Wang,2011).

Aretrospectivechartreviewof450patientstakingsimvastatin80mgwas

conductedandfoundthat11.1%ofpatientsreportedmyalgiaalongwithone

patient,or0.22%,whodevelopedrhabdomyolysis.Thestudyaimedtodetermine

whetherornotlowvitaminDlevelscontributetotheriskofdevelopingmyalgia

STRATEGIESTOCONTINUESTATINUSE 16

whileonstatintherapy.Manyvariableswereconsideredinthisanalysisincluding

baselinelaboratoryvalues,comorbidities,medications,anddemographics.The

resultsofthestudyrevealedavitaminDlevellessthan25ng/mLcorrelatestoa

25%incidenceinmyalgiacomparedto7.89%inthosewithlevelsgreaterthan25

ng/mL.Theauthorssuggestthatthisassociationindicatestheneedforserum

vitaminDmonitoringanddeficiencycorrectioninordertodecreasemyalgiain

patientsonstatintherapy,specificallyhigh-dosesimvastatin(Mergenhagenetal.,

2014).

Anotherretrospectivestudyassessed272patientsaged33to89yearsof

ageandaimedtoevaluatethepossibilityofarelationshipbetweenvitaminDlevels

andadversemuscleeffectsinpatientsonstatintherapy(Eisenetal.,2014).

Exclusioncriteriaincluded“conditionsknowntopredisposetomyalgia,CK

elevation,orvitaminDinsufficiencysuchashypothyroidism,renalfailure

(creatinine>1.2mg/dl),activeparticipationincompetitivesports,known

myopathy,vitaminDsupplementation,acutecoronarysyndrome,andelevated

baselineplasmaCKlevel”(Eisenetal.,2014,p.42-43).Theanalysiscompared

vitaminDlevelsandtheincidenceoflowvitaminDlevelstomyalgia,CKelevation,

oranyreportedmuscularadverseeffect.Variablesconsideredincludedage,gender,

hypertension,diabetes,smoking,CAD,andfamilyhistoryofprematureCAD.The

studydidnotfindastatisticallysignificantrelationshipbetweenvitaminDlevels

andreportsofmyalgia,CKelevation,oranymuscularadverseeffect.Therefore,the

authorsconcludedthatthereisnocorrelationbetweenvitaminDlevelsandadverse

musculareffectsinpatientsonstatintherapy.However,theauthorsdid

STRATEGIESTOCONTINUESTATINUSE 17

acknowledgethefactthatmyalgiaisasubjectivefindingandoftenhardtomeasure

(Eisenetal.,2014).

Summary

Inthealternativestatindosingstudiesincludedinthisliteraturereview,

recurrentmyalgiasymptomswerereportedin0to27%ofthepatients.

Atorvastatinfairedjustslightlybetterthanrosuvastatinwhenconsideringrecurrent

myalgiarates.AlternativedosingappearedtobeeffectiveandledtosignificantLDL

reduction.Somestudiesdemonstratedasignificantreductionintotalcholesterol

andtriglyceridesaswell.However,thestudiesreviewedsuggestedthatstatin

therapygiveninlowerdosesdoesnothaveaneffectonHDL.Regardless,

alternativedosingappearedtobeanacceptablestrategytocontinuestatinusein

patientswithmyalgia.Additionally,theimportanceofstatintherapyinpreventing

life-threateningcardiovasculareventsleadstothesuggestionthatpatientsare

bettertreatedatlowerdosesormoreinfrequentdosesthantonotbetreatedatall.

VitaminDsupplementationappearedtobeabitmorecontroversial.

However,moststudiesrevieweddidfindarelationshipbetweenlowvitaminD

levelsandstatin-inducedmyalgiawithonestudyreportingthecorrelationat25%.

ThreeofthestudiesreportedthatvitaminDsupplementationpreventedrecurrent

myalgiasymptomsatratesof91,92,and95%.Theresultsinthestudiesreviewed

atleastwarrantvitaminDlevelmonitoringandcorrectionofdeficiencyinan

attempttocontinuestatintherapyinpatientswithmyalgia.

TheresearchsuggestedthatalternativestatindosingandvitaminD

supplementationhavepotentialtoallowcontinuationoftherapyinpatientswith

STRATEGIESTOCONTINUESTATINUSE 18

myalgia.However,furtherinvestigationisneededtoverifytheseresultsasonly

threeofthestudiesreviewedwereRCTs,andmostofthestudieshadfairlysmall

samplesizes.Furthermore,guidelinedevelopmentwillneedtobecompletedin

orderforpractitionerstomosteffectivelytreatpatientsexperiencingmyalgiaon

statintherapy.

LearningPoints

§ StatintherapyisthemosteffectivetreatmentforCADprovenbyreductionin

morbidityandmortality.

§ Discontinuationoftherapyismostcommonlyaresultofmyalgiasymptoms.

§ Alternativestatindosing,(specificallywhenusingatorvastatinand

rosuvastatinduetotheirlongerhalf-life),atlowerdosesand/ordecreased

frequencyhasthepotentialtoallowpatientswhoexperiencetherapy

limitingmyalgiasonstandarddosingtocontinuetherapy.

§ VitaminDlevelsshouldbemonitored,supplementationshouldbeinitiated

tocorrectdeficiency,andstatintherapyshouldberechallengedwhenlevels

normalize.

§ Strategiestocontinuestatinuseinpatientswithmyalgiashouldbeexplored

bypractitionersandattemptsshouldbemadetocontinuetheiruse.

STRATEGIESTOCONTINUESTATINUSE 19

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