PolypillintheManagementofSecondaryPreven6oninLa6nAmerica:ALookattheFuture Alvaro Sosa Liprandi MD, MTSAC, FACC Head of Cardiology. Sanatorio Güemes, Buenos Aires. Argentina Director. Lezica Cardiovascular Institute, San Isidro. Argentina Director. Instituto Cardiovascular Austral, Ushuaia Director. Idea Médica, Research & Education Director. Post Graduated Medical School in Cardiology. Buenos Aires University

Yusuf et al, Lancet 2011

TOTAL

No drugs One drug Two drugs 3-4 drugs

100

75

50

25

0

PURE study, N= 153996; 17 countries; IHD= 5650

Low

Medium

High

Very Low

100

75

50

25

0

The care gap Secondary Prevention

TimetoMajorcardiacEventbyAdherenceLevels

BansilalSetal.JACC2016;68:789-801

Medica6onNon-Adherence…America’sanotherdrugproblem

13%ofthetotalUS

healthcareexpenditure!

45%ofUSpopula6on

Social and economic

Health care system

Condition related

Patient Related

Therapy related

FactorsReportedtoAffectAdherence

Socialandeconomic

Healthcaresystem

Condi6onrelated

§ Educa6onlevel§ SocialSupport§ Livingcondi6ons§ Insurance§ Medica6oncost§ Access

§ Cost§ Co-payments§ PoorAccess§ Longwait6mes§ Discon6nuityofcare

§ Chroniccondi6on§ Lackofsymptoms§ Depression§ Psychologicaldisorders

FactorsReportedtoAffectAdherence

Pa6entsrelated Therapyrelated

§ Physicalfactors(cogni6velevel)§ Phycologicalfactors§ Informa6on§ Mo6va6on§ Alcohol/Substancesabuse

§ Complexityofmedica6ons(N°andtechniques)§ Dura6on§ Changesinregimen§ Sideeffects§ Nopercep6onofbenefit

Improvingmedica6onadherence.Simplifica6onoftreatment:Polypill

Improvingmedica6onadherence.Simplifica6onoftreatment:Polypill

Wald NJ, Law MR BMJ 2003

Improvingmedica6onadherence.Simplifica6onoftreatment:Polypill

The Indian Polycap Study (TIPS) Lancet, 2009

Improvingmedica6onadherence.Simplifica6onoftreatment:Polypill

The Indian Polycap Study (TIPS) Lancet, 2009

Improvingmedica6onadherence.Simplifica6onoftreatment:Polypill

The Indian Polycap Study (TIPS) Lancet, 2009

RCTsUSINGAPOLYPILLTOSTUDYTHEEFFECTONADHERENCE

47

70

0

20

40

60

80

Control Polypill

KanyiniGAP

46

81

020406080100

Control Polypill

IMPACT

60

85

020406080

100

Control Polypill

UMPIRE

•  MedianFollowUp:15months

•  n=2004•  Primary+Secondary•  Selfreportedno.ofdays•  medica6onwastakenin

theprecedingweek

Selaketal.BMJ.2014(Published27May2014)

Pateletal.EuropeanJournalofPreven1veCardiology,2014

ThomS,etal.JAMA2013;310:918-929

•  MedianFollowUp:12months•  n=497•  Primary•  SelfReportednamesand

dosagesofallprescrip6onandOCDcurrentlybeingtaken.

•  MedianFollowUp:18months

•  n=623•  Primary+Secondary•  Selfreportedno.ofdays

medica6onwastakenintheprecedingweek

SpaceProgram:Results

PrimaryEndpoints–AdherenceaWer1Year

Kanyini-GAP(1)IMPACT(2)UMPIRE(3)Overall

96/249(38.6%)106/218(48.6%)602/925(65.1%)

196/249(78.7%)172/233(73.8%)827/935(88.4%)

1 1/4 4

2.04(1.72,2.42)<0.011.52(1.30,1.78)<0.011.36(1.29,1.43)<0.011.58(1.32,1.90)<0.01

Control Polypill

ControlBeber

PolypillBeber

RiskRa6o(95%CI) Pvalue

SPACEProgram:Results

UMPIRE:n=2002,India&EuropeKanyini-GAP:n=623AustraliaIMPACT:n=513enNewZealand

2.Selaketal.BMJ.2014(Published27May2014)

1.Pateletal.EuropeanJournalofPreven1veCardiology,2014

3.ThomS,etal.JAMA2013;310:918-929

Fixed-dOseCombina6onDrUgforSecondaryCardiovascularPreven6on.PhaseIIStudyStudySites

64 Clinical Sites in Spain, Italy, Argentina, Brazil and Paraguay (outpatients clinics and hospital-based clinic sites)

PROJECTOVERVIEWPhase1:Observa6onalü  Todeterminethepropor6onofpost-MI

pa6entsreceivingappropriatesecondarypreven6on

ü  Toes6matethelevelofpa6entadherence

ü  Toiden6fyfactorsthatcontributetopooradherence.

ü  MoriskyGreen:Assessmentofadherence

Phase2:Prospec6veRCTü  Tocompareadherencetotreatmentin

postMIpa6entsreceivingaFDCvs.thosewithconven6onaltreatment(3drugsprovidedseparately)

ü  PrimaryEndpoint:AdherencemeasuredbyMorisky-GreenandPillCountcombined

ü  ToevaluatetheeffectofTRINOMIAonBPandLDL-C

ü  SafetyandtolerabilityofTRINOMIA

Adherence-Visit+MG+PillCount

3drugsseparately

CNIC-FS*-FERRERTRINOMIAAspirin100

Ramipril2,5-5-10Simvasta6n40

2118

695

Phase1

Phase2

* Fuster-Sanz

R

9months

FOCUSPhase1–ResultsMORISKYGREEN:EVALUATIONOFADHERENCE(N=2118)

45,5

49,850,349,3

36,440

30,117,7

0 10 20 30 40 50 60

Global

EuropeItalySpain

AmericaArgenhna

BrazilParaguay

%adherent(OriginalMorisky-Green=20)

FOCUSPhase1Results

Pahentcharacterishcs

Sociodemographic:ü  Age**ü  Sexü  Socioeconomicstatusü  Illiteracy*ü  Educahonallevelü  Occupahonalhistoryü  Distancefrommedicalcentre**

Riskfactors:ü  Diabetesü  BMI*ü  Hypertensionü  Lipidlevelsü  Smoking**ü  Sedentary**ü  Familyhistory

Clinical:ü  AMIdate**ü  AMIlocahonü  HistoryofCHFü  Historyofanginaü  >10Pills*ü  Complexityoftreatment*

Psychosocialfactors:ü  Depression**(PHQ-9)ü  Socialsupport**

FACTORSTHATINFLUENCEADHERENCE

*p<0.05**p<0.001

FOCUSPhase2ResultsPOLYPILLVS.CONTROLAFTER9MONTHS

EFFECTONADHERENCE

59

68

545658606264666870

Control Polypill

p=0.049

MORISKYGREEN(20)

percen

tage

54,8 55,759

65,7

40

50

60

70

80

Visit1(1m) Visit3(9m)

MORISKY(20)+PILLCOUNT(80-110)

Control Polypill

Percen

tage

p=0.012

p=0.364

INTENTIONTOTREAT Control Polypill pvalue

SBP(mmHg) 0.88(-0.76;2.53) -0.32(-2.02;1.38) 0.32

DBP(mmHg) 0.38(-0.69;1.46) -0.11(-1.13;0.90) 0.51

LDL-chol(mg/dL) 2.17(-0.96;5.29) 5.27(-0.31;10.86) 0.34

PERPROTOCOL

SBP(mmHg) 0.63(-1.47;2.74) -0.97(-3.15;1.21) 0.30

DBP(mmHg) 0.49(-0.86;1.85) -0.58(-1.91;0.74) 0.27

LDL-chol(mg/dL) 2.90(-1.15;6.95) 5.13(-2.97;13.24) 0.64

TherewerenodifferencesbetweengroupsinBPorLDL-cholesterol

FOCUSPhase2Results

AdverseEffectsControl (n=345) n (%) Polypill (n=350) n (%)

AE 112 (32,5) 124 (35,4)SAE 23 (6,6) 21 (6,0)Patients interrupting Rx

13 (3,7) 14 (4,0)

Death* 1 (0,3) 1 (0,3)Re-infarction 2 (0,6) 2 (0,6)Hospitalization 23 (6,7) 21 (6,0)Hematological AE 6 (1,7) 5 (1,4)Other Cardiac AE# 4 (1,1) 10 (2,8)Musculoskeletal AE 10 (3,8) 5 (1,4)Cough 6 (1,7) 5 (1,4)Dizziness 2 (0,6) 2 (0,6)Hypotension 7 (0,2) 0 (0,0)

*Control (cancer); Polypill (traffic accident) # Other cardiac AE included for eg.- Non-specific angina

FOCUSPhase2Results

Q 3 / 2016 Q 2 / 2016

- Kick-off project,

Bibliographic review

2ª round Questionnaire

Fieldwork, Analysis

Q 4 / 2016

Results Presentations Publications

Q1 / 2017

1ª round Questionnaire

Fieldwork, Analysis

Timelines

Position paper: Pollypill as a strategy to improve adherence in primary and secondary prevention. A Latin American Perspective

Consensus expert panel – UCLA / DELPHI methods

Conclusions

Ø  Improvingadherencetotreatmentsshouldbeaprimarygoalinanabempttoreducecardiovascularmortality.

Ø  The loss of adherence to essenhal medicines is amulh-causal phenomenon, in which the complexityofthetreatmentisonlyonepartoftheproblem.

Ø  The simplificahon of the treatment through thepolypill has proven to be safe and effechve toimprovetheadherenceofourpahents.

Ø  The implementahon of this simple strategy will beparhcularly useful in terms of public health,especiallyinlow-andmoderate-incomecountries

Thank you

Álvaro Sosa Liprandi asosaliprandi@gmail.com