strategies to continue statin use in patients with myalgia
TRANSCRIPT
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University of North DakotaUND Scholarly Commons
Nursing Capstones Department of Nursing
5-6-2016
Strategies to Continue Statin Use in Patients withMyalgiaCarrie Pfaff
Follow this and additional works at: https://commons.und.edu/nurs-capstones
This Independent Study is brought to you for free and open access by the Department of Nursing at UND Scholarly Commons. It has been accepted forinclusion in Nursing Capstones by an authorized administrator of UND Scholarly Commons. For more information, please [email protected].
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
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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
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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.
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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
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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
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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
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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.
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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.
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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.
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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
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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
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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
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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
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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
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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
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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
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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
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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.
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STRATEGIESTOCONTINUESTATINUSE 19
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