cardiovascular risk management in hiv · hiv rna level (

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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health ProfessionalsACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals

ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals

CardiovascularRiskManagementinHIV

JudithA.Aberg,MDGeorgeBaehr ProfessorMedicine

IcahnSchoolofMedicineatMountSinaiHealthSystem

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LearningObjectivesUponcompletionofthispresentation,learnersshouldbebetterableto:

• AbilitytoeducateandcounselpersonswithHIVonrisk factormodificationtoreducetherisk ofcardiovascular disease.

• Abilitytodetectandmanagecardiovascularrisk factorsamongpersonswithHIVaccordingtoevidence-basedguidelines


FacultyandPlanningCommitteeDisclosuresPleaseconsultyourprogrambookortheConferenceApp.

Therewillbenooff-label/investigationalusesdiscussedinthispresentation.

Off-LabelDisclosure

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MultifactorialetiologyofCVDinHIV


Tobacco

Mdodo R et al. Ann Intern Med. 2015;162(5):335-344. doi:10.7326/M14-0954

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HIVandMultimorbidity 2000-2009

NAACORD Clin. Infect Dis 2017 Nov 15. doi: 10.1093/cid/cix998

28% 27% 30% 31% 32% 32% 33% 33% 32% 32%

7% 7% 9% 10% 11% 13% 14% 14% 15% 15%

2% 2% 2%

3% 3% 4%

4% 5% 6% 6%

0%

10%

20%

30%

40%

50%

60%

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009

6 conditions

5 conditions

4 conditions

3 conditions

2 conditions

1 condition

Perc

enta

ge o

f Ind

ivid

uals

in H

IV

Car

e w

ith A

ge-A

ssoc

iate

d C

ondi

tions

N= 4172 6325 8365 9121 9733 10861 11166 12277 9074 3705No of conditions

1 1162 1705 2512 2833 3137 3517 3687 4004 2892 11952 287 452 727 923 1108 1375 1601 1756 1363 5623 73 126 179 234 296 405 499 592 530 2144 2 8 16 30 39 69 96 111 120 525 0 1 1 1 1 1 8 10 8 36 0 0 0 0 0 0 0 0 1 0

HLDandHTNRemainMostCommon

NAACORD Clin. Infect Dis 2017 Nov 15. doi: 10.1093/cid/cix998

Hypercholesterolemia18.2%

Hypercholesterolemia19.8%3.6% 8.9% Hypertension 8.7%

0.8%0.8%1.0%

Diabetes 1.5% CKD1.3%

1.6%1.6%

1.3%

Hypertension 5.9%

2000N=4172

2009N=3705

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CardiovascularDiseaseMortalityAmongHIV-Infected

§ In HIV+ individuals, CVD deaths increased from 6% to 15% of all deaths (p<0.001)– Decreased in the general population: 47% →

39%

§ HIV associated with a 56% increased rate of CVD death

§ Both viremic and virologically suppressed HIV+ individuals had higher CVD mortality rates than uninfected individuals until age 65.

Hanna DB, et al. CID 2016;63:1122-9.

New York City HIV Surveillance Registry

Evaluation of age-adjusted mortality rates due to CVD inNew York City from 2001-2012; N=29,588 deaths

*Adjusted for sex, race/ethnicity, borough of residence, and calendar year

Adjusted relative rate* (95% CI) of CVD death for HIV-diagnosed New Yorkers, by age

0.27 (0.18-0.41)

0.65 (0.54-0.80)

1.10 (0.99-1.23)

1.31 (1.20-1.42)

1.75 (1.60-1.92)

2.66 (2.35-3.01)

3.02 (2.21-4.13)

2.81 (1.04-7.53)

85+

75-84

65-74

55-64

45-54

35-44

25-34

13-24

0.1 1 10

Age

CVD mortality was lower among HIV-diagnosed individuals with a suppressed HIV RNA level (<40 copies/mL) versus an unsuppressed level (age-standardized rate 3.9 vs. 7.7/1,000, p<0.001)


Treatment—PrimaryPrevention

• ThinkaboutASCVDriskandassessmentinHIVpatients*1st stepistoapplyGenpopguidelines

• Smokingcessationresources-Bupropion,varenicline andnon-pharmacologictherapies

• ARTforHIVVLSuppression• Manageco-morbidities:Glucose,HTN,Lipids,Obesity

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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health ProfessionalsAberg J, et al. Clin Infect Dis. 2014 Jan;58(1): 1-10 and e1-34http://www.eacsociety.org/guidelines/eacs-guidelines/eacs-guidelines.html


Question1:WhoisRecommendedtobeprescribedastatin?

• 1.PWHwithLDL>130mg/dL• 2.PWHwithLDL>190mg/dL• 3.PWHaged40-75withLDL160-190mg/dL andCACscorezero• 4.PWHaged40-75withACC/AHAriskscore5%

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TwoDifferentPreventionApproacheswithTwoDifferentPerspectives


SimilaritiesbetweentheACC/AHAandNLA• Lipidscreeningforprimarypreventionevery5years• Lifestyleadvocacyisrecommendedfirst• ASCVDriskreductionisprimarygoal• Moderate-HighStatinIntensityforprimarypharmacotherapy• Patient-providerdiscussionofrisk-to-benefitprecedesallprescribing• “Regular”lipidprofilestoassessadherence

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LipidManagement• 2013 AHA guidelines for general

population age >21 for ASCVD and aged 40-75 for other categories

– LDL-C >190, DM, ≥7.5%risk of atherosclerotic CV disease àstatins

– No lipid targets• Risk calculator controversy• How to apply to HIV+ pts

is uncertain

Stone NJ et al, Circulation, 2013


FourStatinBenefitGroups

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DefiningCVDriskamongPWH

• Riskscoresfluctuateasweage,changebehaviorsandtreatconditions• Atwhattimeistheriskscoreaccurate?• WhendoesHVIVcontributetorisk?


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HIVasRiskEnhancingFactor

• Inadults40to75yearsofagewithoutdiabetesmellitusand10-yearriskof7.5%to19.9% (intermediaterisk),risk-enhancingfactorsfavorinitiationofstatintherapy

• Risk-enhancingfactorsmay favorstatintherapyinpatientsat10-yearriskof5-7.5%(borderlinerisk).

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6. Inadults40to75yearsofageevaluatedforprimaryASCVDprevention,haveaclinician–patientriskdiscussionbeforestartingstatintherapy.

Riskdiscussionshouldincludeareviewofmajorriskfactors(e.g.,cigarettesmoking,elevatedbloodpressure,(LDL-C),hemoglobinA1C[ifindicated],andcalculated10-yearriskofASCVD);

•thepresenceofrisk-enhancingfactors(seeNo.8);•thepotentialbenefitsoflifestyleandstatintherapies;•thepotentialforadverseeffectsanddrug–druginteractions;•theconsiderationofcostsofstatintherapy;and•thepatientpreferences&valuesinshareddecision-making.

Top10TakeHomeMessages


Imaging• Inadults40to75yearsofagewithoutdiabetesmellitusandwithLDL-Clevels≥70mg/dl-89mg/dl(≥1.8-4.9mmol/L),ata10-yearASCVDriskof≥7.5%-19.9%,ifadecisionaboutstatintherapyisuncertain,considermeasuringCAC.– IftheCACscoreiszero,treatmentwithstatintherapymaybewithheldordelayed,exceptincigarettesmokers,thosewithdiabetesmellitus,andthosewithastrongfamilyhistoryofprematureASCVD.

– ACACscoreof1-99favorsstatintherapy,especiallyinthose>55yearsofage.

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Aberg J, et al. CID 2014

Cardiovascular Disease Prevention:Lipid Management• Screening: fasting lipids

– At HIV diagnosis– Start of ART– Change of ART– Every 6-12 months

• Lipid management– Beware of drug interactions

between statins and ART

Safe (Prava caution with DRV/r)

Statin Levelwith PI/cobi

Use

Pitavastatin --Pravastatin --Atorvastatin ↑Rosuvastatin ↑Simvastatin ↑↑↑Lovastatin ↑↑↑

Contraindicated

Use with caution/low dose


INTREPID:StatinsWorkinPWHwithDyslipidemia

. Aberg J et al. Lancet HIV 2017

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REPRIEVEStudy Design

REPRIEVEBaseline Demographics

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Characteris'cs Total (n=7530)

Sexat Birth

Age (years)

Male 5135 (68%)

Female 2395 (32%)

Median(Q1, Q3) 50 (45--55)

EverBeenona StatinNo 6927 (94%)

Yes 467 (6%)

10--yearASCVDRisk (%) Median(Q1,Q3) 4.3 (2.1--6.9)

Race

White 2349 (32%)

Black or African 3309 (44%)American

Asian 1136 (15%)

Ethnicity Hispanicor Latino 1890 (25%)

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BaselineCVDHistoryandRisk Factors

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Characteris'cs Total (n=7530)

Totalcholesterol (mg/dL) Median(Q1, Q3) 184 (162--208)

LDL calculated (mg/dL) Median(Q1,Q3) 108 (87--127)

HDL--C (mg/dL) Median(Q1,Q3) 48 (39--59)

SystolicBP(mmHg) Median(Q1,Q3) 122 (113--132)

BMI(kg/m2) Median(Q1,Q3) 25.8 (22.8--29.4)

Smoking Status

Current 1746 (24%)

Former 1811 (25%)

Never 3821 (52%)

FamilyHistoryof CVDNo 5812 (79%)

Yes 1333 (18%)


PCSK-9inhibitors??• LeuckerTM.JAmHeartAssoc2018

48PWHonART,noknownCADvs.15age/LDLmatchedHIVnegativePCSK-9levels65%higherPWHv.controlPWHwithmorecoronaryendothelialdysfunction(%changeincoronaryacrosssectionalareaduringisometrichandgriponMRI)

• ZanniMV.OpenForumInfectDis.2017149PWHv.69matchedHIVnegativePWHhigherPCSK-9;PCKS-9assoc.withsCD14andsCD163(monocyteactivation)LDL-candFraminghamscorebutnotsubclinicalcoronaryatheroscleroticplaque

• BoccaraF.AIDS2017103PWHbeforeandafterstartingPIbasedARTv.90HIVnegativePWHhigherPCSK-9,nochangepre/postPIbasedARTPCSK-9assoc.withdetectableVLandCD4<200

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Question2:WhoisRecommendedtobeprescribedaspirin?

• 1.PWHonstatins• 2.PWHwithknownASCVD• 3.PWHaged40-75asprimaryprevention• 4.PWHaged40-75withACC/AHAriskscore5%


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HypercoaguabilityinHIV

BibasMMediterrJHematolInfectDis2011


BackgroundASA• PWHonARThaveanincreasedriskofischemiccardiovascularevents• Activatedplateletshavebeenimplicatedinthromboticcardiovascularevents

becauseoftheirproinflammatoryandthrombogenic effects• PWHhaveincreasedcirculatingplatelet-monocytecomplexesandtheirplatelets

expresshighlevelsofP-selectin• Aspirinisalow-risk andlow-costplateletinhibitorthathasimmunomodulatory

properties• Aspirindecreasesriskofmortalityandcardiovasculareventsinindividualswith

knownCVDandmayplayanimportantroleincardiovascularandcancerpreventioninthoseatrisk

Refs:Triant etal.JID2012;205Suppl 3:5255-361.,Singhetal.2012;JVirol MethodsMay;181(2):170-6.,Mayneetal.JAIDS2012;59:340-346.,Berger,etal.AmJMed2012;12143-49.,Thunetal.NatRevClinOnc2012;9,259-267.,Hussainetal.Int Immunopharmacol 2012;12,10-20.

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AspirinBenefits• Aspirinhasprovenbenefitsinsecondaryprevention• QuestionabletonobenefitsasprimarypreventionexceptinDM

– ARRIVE:over12,000ptsRCTasa 100mgvsplb over5years(Lancet2018;392:1036-1046)• Nosignificantdifferencesintheratesofdeaths,heartattacks,orstrokes• SignificantincreaseinGIB

– ASCEND:over15,000ptswithDMRCTover7.4years(NEnglJMed2018;379:1529-1539)

• Seriousvascularevents658participants[8.5%]vs.743[9.6%];rateratio,0.88;95%confidenceinterval[CI],0.79to0.97;P=0.01)

• Majorbleedingeventsoccurredin314participants(4.1%)intheaspiringroup,ascomparedwith245(3.2%)intheplacebogroup(rateratio,1.29;95%CI,1.09to1.52;P=0.003)


TakeHomePoints• ExcessCVDriskinHIV+population(1.5x)• Individualsagingwith HIVvs.IndividualsnewlydiagnosedwithdifferentCVDrisk

• LargestmodifiableRFissmoking• Etiologymultifactorial:chronicinflammation,directviraleffect,ARVsetc.

• TreatHIVandmanageco-morbiditiesaggressively• NeedforimprovedCVDriskassessment• Anydiabeticw/LDL>70shouldbeonastatinandpossibleaspirin(oftenoverlookedpopulationinHIVclinicalpractice)

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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health ProfessionalsACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals

cardiovascular risk management in hiv · hiv rna level (

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