Cost-Effectiveness of Intensive Atorvastatin Therapy in Secondary Cardivascular Prevention in UK, Spain

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Cost-Effectiveness of Intensive Atorvastatin Therapy in Secondary Cardiovascular Preventionin the United Kingdom, Spain, and Germany, Based on the Treating to New Targets StudyAuthor(s): Douglas C. A. Taylor, Ankur Pandya, David Thompson, Paula Chu, Jennifer Graff,James Shepherd, Nanette Wenger, Heiner Greten, Rafael Carmena, Michael Drummond andMilton C. WeinsteinSource: The European Journal of Health Economics, Vol. 10, No. 3 (Jul., 2009), pp. 255-265Published by: SpringerStable URL: http://www.jstor.org/stable/40283782.

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Eur J Health Econ (2009) 10:255-265DOI 10.1007/sl0198-008-0126-lORIGINALPAPER

Cost-effectivenessof intensive atorvastatin therapy in secondarycardiovascular prevention in the United Kingdom, Spain,and Germany, based on the Treating to New Targets studyDouglas C. A. Taylor Ankur Pandya David Thompson Paula Chu Jennifer Graff James Shepherd Nanette Wenger Heiner Greten Rafael Carmena *Michael Drummond *Milton C. Weinstein

Received: 6 March 2008 /Accepted: 13 August 2008 /Published online: 18 September 2008 Springer-Verlag 2008Abstract The Treatingto New Targets (TNT) clinicaltrial found that intensive 80 mg atorvastatin A80) treat-ment reduced cardiovascular events by 22% whencompared to 10 mg atorvastatin(A10) treatment. Weevaluatedthe cost-effectiveness of intensive A80 vs A 10treatment n the United Kingdom (UK), Spain, and Ger-many.A lifetime Markovmodel was developedto predictcardiovasculardisease-relatedevents, costs, survival,andquality-adjusted ife-years (QALYs). Treatment-specificevent probabilitieswere estimatedfrom the TNT clinicaltrial.Post-eventsurvival,health-relatedqualityof life, andcountry-specificmedical-carecosts were estimated using

publishedsources.Intensivetreatmentwith A80 increasedboth the per-patientQALYs and correspondingcosts ofcare, when comparedto the A 10 treatment, n all threecountries. The incremental cost per QALY gained was 9,500, 21,000, and 15,000 in the UK, Spain, andGermany, respectively. Intensive A80 treatmentis esti-mated to be cost-effective when comparedto A 10 treat-ment in secondarycardiovascularprevention.Keywords Cardiovascular isease Cholesterollowering Cost-effectivenessDecision analysis Markovmodel SecondarypreventionStatintherapyJEL Classification 111. C. A. Taylor (El) A. Pandya D. Thompson P. Chu M. Drummond M. C. Weinsteini3 Innovus, 10 Cabot Road, Suite 304,Medford, MA 02155, USAe-mail: [email protected]

J. GraffPfizer Inc., New York, NY, USAJ. ShepherdUniversity of Glasgow, Glasgow, UKN. WengerEmory University School of Medicine, Atlanta, GA, USAH. GretenHanseatisches HerzzentrumHamburg, Hamburg, GermanyR. CarmenaUniversidad de Valencia, Valencia, SpainM. DrummondUniversity of York, York, UKM. C. WeinsteinDepartmentof Health Policy and Management, HarvardSchoolof Public Health, Boston, MA, USA

IntroductionCardiovascular isease (CVD) is the leadingcauseof deathin theEuropeanUnion(EU), resulting n 1.9 million deathsand 105 billion in health-carecosts annually[1]. Regularuse of pharmacologie therapies, such as lipid-loweringstatins,has been shown to reducemorbidityand mortalityin primaryandsecondaryCVD prevention[2-5]. Previousstudies have also demonstrated hat reducing LDL cho-lesterol below the recommended evel of 100 mg/dL viamore intensive statin therapy provides an even greaterclinical benefitvs moderatestatintherapy n patientswithacute coronary syndromes[6].Recently, the Treating to New Targets (TNT) trialcomparedintensive lipid-loweringtreatmentwith atorva-statin80 mg to moderatestatintreatmentwith atorvastatin10 mg in patientswith stablecoronaryheartdisease(CHD)(previousmyocardial nfarction,previousor currentangina

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258 D. C. A. Tayloret al.Table 1 Firstand secondevent "I ~. '. IZ,,.,.. , . , , . Parameter Pointestimate SDprobabilities,.,.. usedin the model. CVD-relatedirstevents(1 year probabilityor atorvastatin 0 mg) (years1-10)aMyocardialnfarction 0.0123 0.0008Stroke 0.0055 0.0005

Congestiveheart ailure 0.0055 0.0005Revascularization 0.0350 0.0013Resuscitated ardiacarrest 0.0008 0.0002Peripheral rterydisease 0.0108 0.0007Transientschmie attack 0.0041 0.0004Documented ngina 0.0264 0.0011Hazard atiosassociatedwith atorvastatin 0 mg (years l-10)aMyocardialnfarction 0.7650 0.0713Stroke 0.7840 0.1096Congestiveheart ailure 0.6730 0.0928Revascularization 0.7250 0.0409Resuscitated ardiacarrest 1.0700 0.4225Peripheral rterydisease 0.9770 0.0921Transientschmieattack 0.8130 0.1312Documented ngina 0.8850 0.0543CVD-relatedirstevents(1 yearprobability)years ll+)bMyocardialnfarction 0.0102 0.0005Stroke 0.0049 0.0003Congestiveheart ailure 0.0046 0.0003Revascularization 0.0302 0.0009Resuscitated ardiacarrest 0.0009 0.0001Peripheral rterydisease 0.0107 0.0005Transientschmieattack 0.0037 0.0003Documented ngina 0.0249 0.0008

Secondmajorevents(1 yearprobability firstmajorevent)bMyocardialnfarction myocardialnfarction 0.0489 0.0104Stroke myocardialnfarction 0.0147 0.0059Congestiveheart ailureImyocardialnfarction 0.0440 0.0102Revascularizationmyocardialnfarction 0.3961 0.0244Myocardialnfarction stroke 0.0191 0.0096StrokeI stroke 0.0813 0.0189Congestiveheart ailureI stroke 0.0048 0.0046Revascularizationstroke 0.0335 0.0120Myocardialnfarction congestiveheart ailure 0.0452 0.0150StrokeIcongestiveheart ailure 0.0101 0.0072

CVDCardiovascularisease Congestiveheart ailureIcongestiveheart ailure 0.1759 0.0270a Source:TNTtrialdataand Revascularizationcongestiveheart ailure 0.0955 0.0210extrapolation Myocardialnfarction revascularization 0.0270 0.0044b Source:pooledTNTtrialdata StrokeIrevascularization 0.0105 0.0028andextrapolation;ssumption: Congestiveheart ailureIrevascularization 0.0135 0.0031equalrates or bothtreatment Revascularizationrevascularization 0.1349 0.0094groups

assigned an acute (immediate) cost; follow-up costs forcardiovascularevents were not incorporated,as CHDpatients were assumed to be already receiving routinefollow-up care related to their pre-existing cardiovascu-lar disease. The cost of revascularization was theweighted average cost of CABG and PTCA procedures.

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Cost-effectivenessf intensiveatorvastatinherapy 259Table 2 Mortality ndutility I " IT" Z I ^, / . , , Parameter Pointestimate SDparameterssedin the model, Mortalitymultiplierscomparedo generalpopulation)Myocardialnfarction18] 3.7 0.5100Stroke 11] 2.1 0.3260

Congestiveheart ailure[19] 2.3 0.4490Revascularization18] 2.0 0.3060Resuscitatedardiacarresta 3.7 0.5100StableCHD(non-CVDmortality nly) [18] 1.5 0.3060Utilities [23]StableCHD 0.78 0.0030Myocardialnfarction 0.65 0.0030Stroke 0.64 0.0030Congestiveheart ailure 0.63 0.0030Revascularization5 0.78 0.0030Resuscitated ardiacarrest 0.68 0.0030Inprobabilisticensitivity Myocardialnfarction nd stroke 0.61 0.0030

7 , ,.. Myocardialinfarction ndcongestiveheart ailure 0.60 0.0030were usedto drawmortality.. J 6multipliers, nd beta Myocardialnfarction nd revascularization 0.65 0.0030distributions ere usedto draw Strokeandcongestiveheart ailure 0.59 0.0030utilityparameters Strokeandrevascularization 0.64 0.0030CHDCoronary eartdisease Congestiveheart ailureand revascularization 0.63 0.0030a Assumption:esuscitated Minorevents decrements 0.0030cardiacarresthas samemortalitymultiplier s Peripheral rterydisease -0.10 0.0030myocardialnfarction Transientschmieattack -0.12 0.0030b Assumption: Documented ngina -0.12 0.0030revascularizationas same Death 0.00utilityvalueas stableCHD -

Table 3 Country-specific ^^r ^ ^ah^ Germanycparameters Atorvastatin rugcosts (2005) [25, 27, 29]Atorvastatin 0 mg 344 363 376Atorvastatin0 mg 539 726 661Eventcosts (2005) [24, 26, 28, 30]Myocardialnfarction 6,035 5,278 4,106Stroke 4,463 4,228 3,632

CABGCoronary ypassgraft Congestiveheart ailure 3,543 3,040 3,631surgery,PTCApercutaneous Coronary ypassgrafting urgery CABG) 16,893 14,935 11,492transluminaloronary Angioplasty PTCA) 5,724 4,054 3,894angioplasty,UKUnited Resuscitated ardiacarrest 3,796 4,525 2,582Kingdoma D . health-care. . Peripheralarterydisease 2,873 2,862 2,259Based. on health-care. . resource r Jgroup HRG) Transientschmieattack 1,313 2,362 2,943b Basedon diagnosis elated Documented ngina 863 2,343 1,617group grupos ealcionados or Revascularizationroportions28, 33, 34]el diagnostic, GRD) CABG(fraction f total) 0.45 0.14 0.32c Basedon German iagnosis pTCA(fraction f total) 0.55 0.86 0.68relatedgroup G-DRG) -

Revascularizationweights were estimated based on theportionof CABG and PTCA proceduresin each of thetargetcountries[29, 34, 35]. All costs used in the analysisare expressed in 2005 Euros. Table 3 displays the coun-try-specific costs and revascularizationweights used inthe analysis.

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260 D. C. A. Taylor et al.

AnalysesBase-case analysesThe primarycost-effectiveness outcome was incrementalcost per QALY gainedfor patientsreceiving 80 vs 10 mgatorvastatinor each of the targetcountries.Estimatesofincrementalcost per life-year saved were also calculated.SensitivityanalysesProbabilistic ensitivityanalyseswere performed o assessuncertaintyn the cost-effectivenessanalysis.Distributionsfor key model parameterswere derivedby non-parametricbootstrappingof the TNT patient population, focusingattention on event probabilitiesand hazard ratios [37].Parametershat were not based on the TNT trial, such ascosts and utilities, were assigned distributionsand variedbasedon the standarddeviationestimatesaround he meanvalues. All of the parametersin the model, with theexceptionof drugcosts, acute mortality,and overall mor-tality, were variedin the probabilisticsensitivityanalysis.Resultsof the probabilisticanalysiswere used to estimateconfidence ntervalsfor the cost-effectivenessratios andtogenerate cost-effectiveness acceptability curves showingthe probabilitythat treatmentwith 80 mg atorvastatin scost-effective at varyingcost per QALY thresholds.The impactof variability n individualmodelparameterson cost-effectiveness results was tested using one-waysensitivity analyses. Key model parameterswere variedthrough plausible ranges while examining the effects onthe cost-effectiveness ratio. Plausibleranges of parameterestimates were identified as the base-case value twostandarderrors when these data were available,or 25%for other model parameters.Finally, in the TNT trial, there was a non-significanttrendtowards an increase in non-cardiovascularmortalityat the 80 mg dose. An alternate mortality scenariothat incorporatedthis observation was included in thesensitivity analysis. In this scenario, treatment-specificpost-event and non-cardiovascularmortality rates wereestimatedusingKaplanMeiertime-to-eventanalysesof theTNT trial data (Table4). These treatment-specificrateswere extrapolatedto year 10 using parametricstatisticalmethods. After year 10, mortalityratesfrom the publishedliteraturewere used in common for both treatmentgroupsover the remainder of the study period. The rationalebehind switching to literature-basedmortality rates atyear 10 was twofold: (1) the mortalityrates observed inthe trial were very low, and would result in unreasonablyhigh life expectancies if used for the duration of themodel (approximately40% of patients would live past100 yearsof age); and (2) since it was assumedthat event

Table 4 Alternate mortality scenario parametersParameter Point estimateAcute and non-CVD mortality (1 year probability)3(for atorvastatin 10 mg)Post-myocardial infarction 0.073Post-stroke 0.098Post-congestive heart failure 0.102Post-revascularization 0.025Non-CVD mortality 0.006

Mortality hazard ratios associated with 80 mgaPost-myocardial infarction 1.332Post-stroke 0.936Post-congestive heart failure 1.532Post-revascularization 0.924Non-CVD mortality 1.177a Source: TNT trial data and extrapolationrates are equivalent between treatment groups afteryear 10, it is consistent to assume mortalityrates alsofollow this trend.

ResultsBase-case scenarioTreatmentwith 80 mg atorvastatin s estimated to yieldincreasedlife-years and QALYs vs atorvastatin10 mg ineach setting(Table5). Totaldiscountedcosts of secondarycardiovascularprevention are estimated to be 1,791, 3,880, and 2,896 higher per-patient or those receivingatorvastatin 80 mg in the UK, Spain, and Germany,respectively,reflectinghigherlifetimecosts of atorvastatin80 mg therapy 6,139 vs 3,851, 8,451 vs 4,153, and 7,533 vs 4,204). These therapycosts are offset in partby lower costs of treatingcardiovascularvents( 3,857 vs 4,353, 3,730 vs 4,148, and 3,518 vs 3,951). Theincrementalcost per QALY gainedfor atorvastatin 0 mgcomparedto 10 mg is estimatedto be 9,500, 21,000and 15,000 in the UK, Spain,and Germany.SensitivityanalysesResults of the probabilisticmodel analyses for the UK,Spain,andGermanyaredisplayed n the cost-effectivenessacceptabilitycurves (Fig. 2). These curves indicate thatatorvastatin80 mg is cost-effective in 99.8, 86.0, and96.9%of simulationsat thresholdsof 30,000 perQALY.The mean cost-effectiveness ratios and 95% confidenceintervalsbased on the probabilisticanalyseswere: 9,400(95% CI 5,900-20,600) per QALY gained for the UK; 20,700 (95%CI 13,400-44,100) perQALY gainedfor

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Cost-effectiveness f intensiveatorvastatinherapy 261Table 5 Cost-effectiveness f atorvastatin 0 mg vs atorvastatin 0 mg in the management f secondary ardiovascularreventionAtrovastatinherapy Total cost3 LYa QALYsa ICER costperLY) ICER costperQALY)UK base-caseanalysisAtorvastatin 0 mg 8,205 11.18 8.51Atorvastatin 0 mg 9,996 11.39 8.69 8,600 9,500Spanishbase-caseanalysisAtorvastatin 0 mg 8,301 11.44 8.70Atorvastatin0 mg 12,181 11.64 8.89 19,000 21,000German ase-caseanalysisAtorvastatin 0 mg 8,155 11.18 8.50Atorvastatin0 mg 11,051 11.39 8.70 13,000 15,000LYLife-years,QALY uality-adjustedife-years, CER ncremental ost effectiveness atioa Per-patient,iscounted t3.5% 36].Undiscounted Yfor80 mgvs 10 mgwere 15.51vs 15.17,15.97vs 15.63,and15.54vs 15.18 ntheUK,Spain,andGermany, espectively.UndiscountedQALY or 80 mgvs 10 mgwere 11.82 vs 11.52,12.17vs 11.87,and 11.85 vs 11.53 ntheUK,Spain,andGermany, espectively

Fig. 2 Probabilityhatintensiveatorvastatin0 mgtherapys cost-effectivewhencomparedo atorvastatin0 mgtherapyn the UnitedKingdom(UK),Spain,andGermanybasedon probabilisticsensitivityanalysis

Spain;and 14,700 (95%CI 9,500-30,300) per QALYgainedfor Germany.The results of the one-way sensitivity analyses for theUK aredisplayed n Fig. 3. These analysesindicatethatthemodel results are most sensitive to the daily costs ofatorvastatin 0 and 10 mg as well as the hazardratiofor MIfor patientsreceiving80 mg. The results areleast sensitiveto utilityvalues for any healthstateor event, minoreventcosts, and the hazardratios for minor events for patientsreceiving80 mg atorvastatin. imilarresultswereobservedfor Spain,and Germany analysesnot shown).Cost, outcome,and incrementalcost-effectivenessfind-ings for the alternatemortalityscenariosare presented nTable6. The incrementalcost-effectiveness of treatmentwith 80 mg atorvastatinompared o 10 mg is estimated o

be 15,800, 34,000 and 24,000 per QALY gained inthe UK, Spain,andGermany, espectively.Theseestimatesare higher than the base-case cost-effectiveness ratiosbecauseof higherhazardratios for patientsreceivingator-vastatin80 mg withrespect o severalmortalityparameters,including non-cardiovascularmortality and acute post-eventmortalities or MI andCHF.Inprobabilisticanalysesinvolving 1,000 bootstrapsets of estimates,the cost-effec-tiveness ratios with confidence intervals were 16,000(95% CI 6,300-dominated), 34,000 ( 13,000-domi-nated), and 24,000 ( 10,000-dominated) per QALYgained in each setting, where dominated indicates thatatorvastatin 0 mg was morecostly and less effective thanatorvastatin10 mg. The inclusion of trial-basedmortalityparameters,which were not significantlydifferentbetween

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262 D. C. A. Taylor et al.Fig. 3 One-way sensitivityanalyses for the UK base-casescenario comparingAtorvastatin 10 mg vsAtorvastatin80 mg for a subsetof model parameters.Numbersin parentheses reflect low andhigh values for each parameter

Table 6 Cost-effectiveness of atorvastatin 80 mg vs atorvastatin 10 mg in the managementof secondary cardiovascularpreventionfor alternate,trial-based, mortality scenariosAtrovastatinTherapy Total costa Life-yearsa (LY) QALYsa ICER ICER(QALY) (cost per LY) (cost per QALY)UK alternate mortality scenarioAtorvastatin 10 mg 8,993 12.46 9.44Atorvastatin 80 mg 10,951 12.56 9.56 18,500 15,800Spain alternate mortality scenarioAtorvastatin 10 mg 9,061 12.64 9.57Atorvastatin 80 mg 13,275 12.74 9.70 40,000 34,000Germany alternate mortality scenarioAtorvastatin 10 mg 8,984 12.49 9.47Atorvastatin 80 mg 12,159 12.61 9.60 28,000 24,000aa Per-patient,discounted at 3.5% [36]. Undiscounted LY for 80 mg vs 10 mg were 17.31 vs 17.10, 17.67 vj>17.46, and 17.41 vs 17.18 in the UK,Spain, and Germany, respectively. Undiscounted QALY for 80 mg vs 10 mg were 13.15 vs 12.94, 13.42 vs 13.20, and 13.23 vs 13.00 in the UK,Spain, and Germany, respectively

treatment roups n theTNT trial,led to the largervariationin cost-effectiveness results compared to the base-caseresults.DiscussionThe TNT trialdemonstrated ubstantialclinical benefit forstableCHD patientsreceiving both 80 and 10 mg atorva-statin compared to previous statin trials, with greaterreductions in cardiovascularevents in patients receivingthe 80 mg dose [7]. The results of ouranalysis suggest thatintensivelipid-loweringtreatmentwith atorvastatin80 mgrepresentsa cost-effective use of health-careresources inthe UK, Spain, and Germany. Under base-case assump-tions, the incrementalcost-effectiveness of treatmentwith80 mg atorvastatin s estimated to be 9,500, 21,000,and 15,000 per QALY, respectively.Cost-effectivenessor willingness to pay thresholdscan vary acrosscountries,therapeuticareas, and treatments.However, the results of

the probabilistic sensitivity analyses displayed in Fig. 2demonstrate hat f a payer n the UK is willingto payupto 20,000 perQALY gained( 29,400-2005 costs) for theA80 vs A 10 treatment hen thereis 99%likelihoodthat thetreatmentwould be cost-effective. Similarly,if a payerinSpainis willing to pay up to 30,000 perQALYgainedora payerin Germanywas willing to pay up to 50,000 perQALY gained for the A80 treatment,then there is 95%likelihood that A80 would be consideredcost-effectivevsA 10. Finally, in analysesof alternatescenariosthat incor-porated trial-based mortality, the cost-effectiveness oftreatmentwith atorvastatin80 mg vs atorvastatin10 mgwas less than 25,000 per QALY gained in the UK andGermany, and less than 35,000 per QALY gained inSpain.In the TNT trial, use of 80 mg atorvastatin oweredmean LDL cholesterol levels to 77 mg/dL, comparedto101 mg/dL observed in patientsreceiving 10 mg atorva-statin. The additional benefit demonstratedin patientsreceiving80 mg atorvastatins consistentwiththegrowing

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Cost-effectiveness of intensive atorvastatintherapy 263body of evidence thatsupports owering LDL cholesterolbelow the recommended evel of 100 mg/dL [5, 6]. Ourfindings suggest that these clinical benefits can also bejustifiedon cost-effectivenessgrounds.It is instructive to highlight distinct features of ouranalysis in relationto previous cost-effectiveness studiesfor statintherapies n similarpatientpopulations.The mostuniqueaspect of our study is the comparisonof intensivestatin therapyvs moderatestatin therapy.In the Tsevatet al. [38] cost-effectivenessstudy of the Cholesterol andRecurrentEvents(CARE)trial,as well as the Jnssonet al.[39] cost-effectivenessstudy of the ScandinavianSimva-statin Survival Study (4S), lifetime models were used toevaluatethe cost-effectivenessof statintherapiescomparedto placebo. The incrementalcost-effectiveness ratios forthe CAREand 4S studies were US $16,000 to $32,000 perQALY and 8,100 per life-year saved, respectively.Theincrementalcost-effectiveness ratios of our analysis findthe cost-effectivenessof intensive lipid-lowering therapyvs moderate herapyto be similarto moderatetherapyvsno treatment, s demonstratedn the CAREand 4S studies.Another mportantmthodologiedifferencebetween ourstudy and the CARE and 4S studies is the type of datacollectedin theclinicaltrials andhow thesedatawere usedto inform the cost-effectiveness models. Patient-levelhealth-care osts were collected in the CAREand 4S trials,while event costs were estimated from country-specificsourcesfor ouranalysis.We assumedthatonly acute eventcosts would be considered n the model, which is conser-vative with respect to the cost-effectiveness of treatmentwith 80 mg atorvastatin.This assumptiondoes not accountfor greaterlong-termpost-event rehabilitationcosts thatwould potentially be associated with patients receiving10 mg atorvastatin,and thus underestimatesthe cost-effectiveness of the 80-mg dosage. The 4S study alsoincorporatedhe costs of lost productivity,which were notincludedin the CARE analysisor our study.To estimate life expectancy,the CARE and 4S modelsused trial-basedmortalityestimates for the length of thetrial (6 and 5.5 years, respectively), and then switchedtoadjustedpopulation-based ife table sources to estimatemortality or the remainder f the models, which is similarto our alternatemortalityscenario. Trial-basedmortalitywas only included as a secondary analysis in our studybecause the TNT trial was not powered to detect differ-ences in mortality between treatment groups, and themortality results were not statistically significant. Thiseffect is demonstrated n the probabilisticresults of thealternate mortality scenarios, where 95% confidenceintervals or cost-effectivenessrangedfromvery favorableresultsfor treatmentwith atorvastatin 0 mg to the 80-mgdosage being dominatedby the 10-mg dosage in eachsetting.

Some important limitations of our study should benoted. One-way sensitivity analyses demonstrated hat themodel results are very sensitive to drug costs. We usedaverageprices as the source for drug costs in the model;alternativepricing schemes could substantiallyaffect theincremental cost effectiveness ratio (ICER). Also, asdemonstratedby the probabilisticresults of our alternatemortalityscenario,treatmentdifferences in mortalitymayhave a substantialmpacton the cost-effectivenessresults.The IncrementalDecrease in End points through Aggres-sive Lipid-lowering (IDEAL) study, which comparedatorvastatin 80 mg to 20-40 mg simvastatin, reportedsimilar, non-statistically significant,mortality findings tothe TNT trial [40]. However, neither trial had sufficientpower to assess whether patients receiving high dosagestatintherapyhave different non-cardiovascular nd post-event mortalityrisks compared o patients receiving mod-eratedosage treatment.Another limitation of our study involves the use ofutility weights derived from United States nationalsurveydata for patients in European settings [26]. While thisapproach ignores potential internationalheterogeneityinpatient preferences for cardiovascular health states, thecomprehensivenature of the catalog allowed for using aconsistent source for utility estimates. Additionally, weestimated cardiovascular event rates from pooled dataacross all sites included in the TNT trial, which includedpatientsin United States sites (53%) and sites elsewhere.Althoughthere may be variabilityin cardiovascular isksamong United States and other patient populations, wefound no evidence that the treatmenteffect of intensivestatintherapydifferedbetween these settings [10]. Finally,our studyalso used modelingtechniquesto extrapolate he5-yearTNT trial cardiovascular vent ratesout to 10 years.Althoughwe conservativelyassumed that these treatmentdifferencesdid not persistafteryear 10, long-termdata oncardiovascularevents in this population have not beenreportedandconsequently he accuracyof our model-basedprojections s unknown.Also, it is importantto note that countries may havedifferent criteria,other than cost per QALY, for deter-mining drug reimbursement limits. The Institute forQuality and Efficiency in Health-Care (IQWiG) inGermanyrecentlyrecommendednew guidelines for reim-bursementbased on an efficiency frontier analysis thatchooses drugs with the greatestbenefit for a given cost.Althoughthis type of analysis following IQWiGguidelinesdoes not necessarilybase a decisionon cost perQALY,thedecisionmaybe basedon metrics suchas thepreventionofmajorcardiovascular vents. Because our QALY measureis driven primarily by cardiovascularevents avoided, wewould expect to find similar results if using a costper-event-avoidedbenefit measure.

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264 D. C. A. Tayloret al.In conclusion, intensive lipid-loweringtreatmentwith80 mg atorvastatinappearsto be a cost-effective use ofhealth-care resources vs moderate statin treatment withatorvastatin10 mg in secondarycardiovascularpreventionin the UK, Spain,andGermany.Increases n the daily cost

of statin therapy associated with atorvastatin80 mg aresubstantiallyoffset by reduced costs of cardiovascularevents, and the remainingcost incrementyields gains inquality-adjusted urvival at a net cost that is lower thanacceptedthresholds or medical interventions.

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Cost-Effectiveness of Intensive Atorvastatin Therapy in Secondary Cardivascular Prevention in UK, Spain