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Ventajas e Inconvenientes de la Triple Terapia en Prevención Secundaria
José R. González JuanateyServicio de Cardiología y UCC. Hospital Clínico Universitario de
Santiago de Compostela
Cumplimentación Terapéutica CV
Aspectos Metodológicos
Papel de la Prevención Secundaria
Cumplimentación y Pronóstico
“Polipíldoras” como Alternativa
Definition
Evidence-based health care is... ...the explicit, judicious and conscientious use of current best evidence from health care research in making decisions about the health care of individuals or populations.
E X KT2 = ROIEfficacy Knowledge
Translation (type 2)
Return on InvestmentReal Outcomes of Importance
E X KT2 = ROIWhere: E is typically ≤ 0.25KT2 is typically ≤ 0.25
Clinician adherence
~ 50%
Patient adherence
~50%
.25 X .25 = .06
So: ROI is typically...
E X KT2 = ROIWhere: E is typically ≤ 0.25KT2 is typically ≤ 0.25
Clinician adherence
50%
Patient adherence50% 75%
.25 X .25 = .06
So: ROI is typically...
.38 .09
E X KT2 = ROIWhere: E is typically ≤ 0.25KT2 is typically ≤ 0.25
Clinician adherence 50%
75%
Patient adherence
50% 75%
.25 X .25 = .06
So: ROI is typically...
.56 .14
Clinician adherence
50% 75%
For atrial fibrillation:
E Efficacy of warfarin for preventing stroke = 62%
KT2 Physician adherence = 50%Patient adherence = 41%
ROI = 12%
Compliance Challenge
Patient compliance
Physician compliance
Get with the
guidelines
Get with the pills
“Los fármacos no funcionan en los pacientes que no los toman”, …..
ni con los médicos que no los prescriben!!!!!
De las Guías a la Práctica Clínica
Morbilidad y mortalidad CV
Por qué no se alcanzan los Objetivos de lasGuías?
Falta de adherencia del paciente
Restricciones en la Accesibilidad al fármaco
No prescripción segúnlas Guías. Adherencia médico
Aumento de losCostes
Sanitarios
A pesar del amplio consenso sobre cuáles son los fármacos más efectivos para la prevención secundaria de la Cardiopatía Isquémica y otras
enfermedades arterioscleróticas vasculares, las recomendaciones no se aplican correctamente
Physician Complianace. Applying evidence in practice
Barrier Solutions
• poor access to current best evidence and guidelines
• development and testing of information systems that integrate evidence and guidelines with patient care
4
application
Systems
Summaries
Synopses
Syntheses
Studies
Examples
Computerized decision support
Evidence-based textbooks
Evidence-based journal abstracts
Systematic reviews
Original journal articles
OldeSchool EBHC
New School EBHC
The evolution of information resources for evidence-based decisions
All of these resources require that clinicians link the evidence with individual patient problems...
Systems are needed to link directly from patient problems to evidence
Free – Google “EvidenceUpdates”
Patient Compliance. Influencing individual patient decisions, actions and outcomes
Barrier Solutions• failure to engage patients
• encouraging adherence to recommended treatments
decisions
5
Key adherence question“During the past week, have you
missed any of your pills?”Typical response:“No…I might have missed one on
Saturday night when we were out...”
Interpretation…Adherence rate is less than 50%.Problem…Health professionals don’t know this!
Intervention Communities were randomised to receive CHAP (n=20) or no intervention (n=19). In CHAPcommunities, residents aged 65 or over were invited to
attend volunteer run cardiovascular risk assessment and education sessions held in community based pharmacies over a 10 week period; automated blood pressure readings and self reported risk factor data were collected and shared with participants and their family physicians and pharmacists.
Reduced admission rates for a composite of MI, CHF, stroke
Cardiovascular Health Awareness Project Kaczorowski et al, BMJ 2011
CIHR Trial of the Year 2012
Cumplimentación Terapéutica CV
Aspectos Metodológicos
Papel de la Prevención Secundaria
Cumplimentación y Pronóstico
“Polipíldoras” como Alternativa
Strategies to improve adherence to medicationsfor CV diseses in socioeconomically disadvantaged
populations. The Behaviour Change Whell
Laba TL et al. Inter J cardiol 2013;1676:2430–2440
Attributing falls in CHD deaths to changes in risk factors or to treatments (IMPACT analyses)
Ford et al. NEJM 2007
Contribución en el descenso de mortalidad por cardiopatía isquémica1988-2005 Tratamiento del infarto de
miocardio 47% Modificación de los factores
de riesgo 50%
Tratamientos fase aguda del IAM
47%
Control factores de riesgo cardiovascular50%
Flores-Mateo G. Rev Esp Cardiol. 2011
Mortalidad por Cardiopatía Isquémica. Modelo IMPACT en España (1988-2005)
8.530 menos muertes
0
-15000
-30000
-450001988 2005
Empeoramiento factores de riesgo +13%•Aumento de obesidad +6%•Aumento de diabetes +7%
Mejora de factores de riesgo -54%•Mejora en la PA -19%•Reducción del tabaco -16%•Mejora colesterol -27%•Actividad física -2%Tratamientos farmacológico -48%•Para IAM -10%•Prevención secundaria -10%•Insuficiencia cardiaca -10%•Revascularización -2%•Antihipertensivos -5%•Estatinas (p. primaria) -2%Inexplicables -2%
Explicación de la caída en muerte CV en España: 1988-2005
Estudio IMPACT -2014 (datos presentados en el congreso ESC 2014)
MONICA: change in coronary-event rates vs change in coronary risk factor score, lagged registration period
MONICA : change in CHD mortality rates against change in Treatment Score
Lim S.S. et al, Lancet 2007
0,6 0,8 1
• Aspirina• IECA• Estatinas• BB
- 34 %- 20 %- 29 %- 27 %
RRR
Estos cuatro medicamentos constituyen la base de la prevención CV secundaria post IM
Beneficio de las intervenciones farmacológicas
HR
Potential Cumulative Impact of 4 Simple Secondary Prevention Treatments
Risk Factors Control and Direct CV and Kidney ProtectionRRR Event rate
None 8%
ASA 25% 6%
-Blockers 25% 4.5%
Lipid lowering 30% 3.0%
ACE-inhibitors 25% 2.3%
CUMULATIVE BENEFITS ARE LIKELY TO BE IN EXCESS OF75% RRR, WHICH IS SUBSTANTIAL
Registro APTOR: Prevención secundaria óptima: uso de AAS y 3 más de las siguientes actuaciones alalta y al cabo de 1 año: estatinas, betabloqueantes, IECAs/ARA2, ejercicio o dieta.
38%41%
34%
25%
63%
28%
71%
46%
0%
10%
20%
30%
40%
50%
60%
70%
80%
Spai
n UK
Fran
ce
Czec
h Re
publ
ic
Germ
any
Gree
ce
Nord
ic
Austr
ia-H
unga
ry
Belg
ium
-Net
herla
nds
Patie
nts (
%)
• En España, únicamente el 38% de los pacientes recibían tratamiento óptimo
Registro APTOR
Guías de Práctica Clínica‐Evidencia
European Heart Journal 2006; 27,1298–1304
Seguimiento: 26,3 meses
Estudio CIBAR. Mortalidad y Morbilidad
Adherencia
ExitusIngresos
28,6
No adherencia
Exitus y/oingreso
29,5
4,9
0
10%
40%
p<0,01
36,538,1
p<0,01
p<0,005
20%
9,2
30%
GPC
1.095 pacientesSeguimiento : 26,3 meses
Seguimiento: 26,3 meses
Adherencia
Exitus CVIngresos CV
15,2
No adherencia
Exitus y/oingreso CV
15,7
2,3
0
10%
25%
p=0,0519,6
21,9
p<0,01
p<0,05
5,6
20%
GPC
1.095 pacientesSeguimiento : 26,3 meses
Estudio CIBAR. Mortalidad y Morbilidad CV
26,224120
1,0
0,8
0,6
0,4
0,2
0,0
99,8%
97,5%
97,8%
94,8%
Meses
Supe
rviven
cia cardiovascular
Cumplen recomendaciones GPCNo cumplen recomendaciones GPC
p<0,005
Estudio CIBAR. Supervivencia cardiovascular
26,224120
1,0
0,8
0,6
0,4
0,2
0
90,2%
84,9%
90,2%
83,3%
Meses
Supe
rviven
cia libre de
ingreso CV
Cumplen recomendaciones GPCNo cumplen recomendaciones GPC
p<0,01
Estudio CIBAR. Supervivencia libre de Hospitalización causa cardiovascular
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
GPC: Cumplimiento recomendaciones Guías de Práctica Clínica; DM: diabetes; ICC: insuficiencia cardíaca; IR: insuficiencia renal(TFG<60 ml/min); EF: ejercicio físico
1 100,1 3 5 70,70,3 0,5
GPC
ICC
DM
IR
EF
4,4 (2,4‐8,1) 0,001
1,9 (1,1‐3,5) 0,023
2,4 (1,3‐4,5) 0,005
0,43 (0,2‐0,8) 0,006
HR (IC‐95%) valor‐p
0,47 (0,2‐0,9) 0,031
Varia
bles
Estudio CIBAR.Determinantes Mortalidad CV
Resultados sobre la mortalidad al año
Zeymer U et al Curr Med Res Opin.2011 Aug;27(8):1563-70
3 fármacos
2 fármacos
0-1 fármacos
Global
RRR = - 36 % 3 vs 2
RRR = - 41 % 3 vs 0-1
Cumplimentación Terapéutica CV
Aspectos Metodológicos
Papel de la Prevención Secundaria
Cumplimentación y Pronóstico
“Polipíldoras” como Alternativa
Categoria de no adherencia
Desglose de causas
Sistema sanitario • Baja calidad de la relación entre el paciente y el proveedor• Falta de comunicación• Falta de continuidad en los cuidados.
Enfermedad • Asintomática (falta de recordatorios físicos)• Enfermedades mentales (p.Ej. Depresión)
Paciente • Impedimentos físicos• Alteraciones cognitivas• Problemas psicológicos o de comportamiento• Jóvenes• Raza no blanca.
Tratamiento • Complejidad de los tratamientos• Efectos adversos
Razones socioeconómicas
• Analfabetismo; bajo nivel cultural;• Coste alto de las medicaciones• Falta de apoyo social.
Razones para la no adherencia a los tratamientos
WHO 2003; Ho et al. Circulation 2009;119 (23):3028-3035
Datos de adherencia en España
Valencia (España) de 7053 pacientes con SCA seguidos durante 9 meses
(% pacientes que toman más de 75% de los días la medicación)
Sanfélix G. J Manag Care Pharm 2013;19:247-57.
Claxton. Clin Ther 2001; 23 (8): 1296-1310
Objetivo: Revisión de 76 estudios para evaluar la asociación entre las pautas terapéuticas y la adherencia (mediante monitorización electrónica) entre 1986-2000.Variables: Número de dosis ingeridas en relación a las prescritas.Tiempo de toma de la dosis en relación a lo prescrito.Resultados:Nº de DosisLa adherencia fue significativamente mayor:•En la toma de dosis única diaria
• en comparación con 3 veces al día (p = 0.008)
• en comparación a 4 veces al día (p < 0.001)
•En la toma de 2 dosis al día frente a 4 dosis al día (p = 0.001)
Frecuencia de las dosisUna pauta de dosificación más frecuente se asoció a menor adherencia.
79.0
69.0
65.0
51.0
0 10 20 30 40 50 60 70 80 90 100
Once daily dosing
Twice daily dosing
Three times daily dosing
Four times daily dosing
Mean adherence with dose taking (%, range)
Una al día
Dos al día
Tres al día
Cuatro al día
79,0
69,0
65,0
51,0
La falta de adherencia se relaciona con la polimedicación
Controlled BP (%)
Patients who are adherent are more likely to attain BP control
* <140/90 mmHg or <130/85 mmHg for patients with diabetesBramley et al. J Manag Care Pharm 2006;12:239–45
45% greater probability of control
Adherence(n = 165)(n = 46) (n = 629)
05
101520253035404550
Low (<50%) Medium (50-79%) High (>=80%)
Relative risk of a CV event
Adherence
Patients who are adherent are at lower CV risk
Mazzaglia et al. Circulation 2009;120:1598-1605
50% lower risk of a CV event
(n = 7,624)(n = 9,666) (n = 1,516)
0%10%20%30%40%50%60%70%80%90%
100%
Low (<40%) Medium (40-79%) High (>=80%)
Cumplimentación Terapéutica en Medicina CV
54%
19%
0% 20% 40% 60% 80%
Dos Dosis Diarias(n = 561)
p < 0,0001
Dosis Única Diaria(n = 8150)
Jackson y cols. Value Health Suppl 2006;9:A363
Persistencia (definida como los pacientes que tomaron el tratamiento de forma continuada durante 12 meses)
¿Que beneficios tiene ser adherente?
Revisión de estudios promovido por la ESCObjetivos: determinar cómo la falta de
adherencia influye en el riesgo relativo(RR) de ECV y de mortalidad por todaslas causas.
• Buena adherencia.
(≥80% de toma de medicación )
20% disminución del riesgo de ECV.38% disminución de mortalidad global
• 44 estudios incluidos, 1.978.919 participantes que padecieron 135.627 eventos cardiovasculares y 94.126 muertes por cualquier causa.
Chowdhury et al. Eur Heart J 2013
El 9,1% de todos los eventos son atribuibles a baja adherencia
Los beneficios de una buena adherencia
Chowdhury et al. Eur Heart J 2013
RR de ECV en función del grado de adherencia
RR de desarrollo de ECV en los pacientes con buena adherencia: 0.80 (0.77–0.84)
Los beneficios de una buena adherencia
Chowdhury et al. Eur Heart J 2013
RR de mortalidad total en función del grado de adherencia
RR de mortalidad por cualquier causa: 0.62 (0.57–0.67)
Effects of nonpersistence with medication on outcomes in high‐risk patients with CV disease. ONTARGET Trial
Bohm M et al. Am Heart J 2013;166:306–314
Effects of nonpersistence with medication on outcomes in high‐risk patients with CV disease. ONTARGET Trial
Bohm M et al. Am Heart J 2013;166:306–314
Discontinuation of Medication after a Non‐fatal event. ONTARGET
Bohm M et al. Am Heart J 2013;166:306–314
Relationship between medication adherence and post‐myocardial infarction outcomes: Medication adherence and
clinical outcomes
Choudhry NK et al. Am Heart J 2014;51:51–58
Highestbenefit
Relationship between medication adherence and post‐myocardial infarction outcomes: Medication adherence and
clinical outcomes
Choudhry NK et al. Am Heart J 2014;51:51–58
¿Protege la adherencia parcial?• Estudio MINERVA; relaciona incidencia de eventos con adherencia a estatinas e
IECAs:
- Muy adherentes 18.9% eventos CV
- Parcialmente adherentes 24.7% eventos CV
- No adherentes 26.3% eventos CV
Bansilal 2014
Sin diferencias (p=0.22)
•Los pacientes adherentes
sufren menos eventos
•La adherencia parcial no
revierte en el beneficio de una
disminución de eventos
Adherence to Secondary Prevention and Medications and Four‐yearOutcomes in Outpatients with Atherosclerosis. REACH Registry
Kumbhani DJ et al. Am J Med 2013;126:693–700Time Until CVD/MI/Stroke (months)
Less than 50% of patients are fully adherent with these
medications
Frecuency of dose categories after Acute MyocardialInfarction. Optimal Secondary Prevention Medication Dosing
Hospital Discharge Follow‐up
Arnold TL et al. J Am Coll Cardiol 2013;62:1791–1781
Frecuency of Follow‐up and medication dose after AcuteMyocardial Infarction. Optimal Secondary Prevention Medication Dosing
Arnold TL et al. J Am Coll Cardiol 2013;62:1791–1781
Cumplimentación Terapéutica CV
Aspectos Metodológicos
Papel de la Prevención Secundaria
Cumplimentación y Pronóstico
“Polipíldoras” como Alternativa
Reducción acumulada del riesgo de ECV modificando estilos de vida y Polipíldora*
*estimaciónWorking Group. Eur Hear J. 2013;doi:10.1093/eurheartj/eht407
Las combinaciones fijas de fármacos se asocian a mayor adherencia.
Las combinaciones fijas fármacos se asocian a mayor adherencia
Metaanálisis de estudios con polipíldoras demuestran que reducen PA y podrían reducir
eventos
Working Group. Eur Hear J. 2013;doi:10.1093/eurheartj/eht407
Half stand‐dose Polycap(TIPS‐1)
Standard‐dose Polycap(TIPS‐1 and TIPS‐2)
PILL collab group Wald 2012
LDL‐C and BP and AAS(e.g. Secondary prevention)
62% 48% 69% 57% 60% 56% 72% 64%
Combination pharmacotherapy to prevent CV disease: RCT
Cum RR of CVD with lifestyle modification + polypill in a smoker, with low fruits, vegs & exercise
InterventionCum risk reductions at different
adherence levels50% 75% 90%
Lifestyle + Polypill
Polypill + Combinedlifestyle modification
70.6% 82.0% 88.4%
Potential Cumulative Impact of 4 Simple Secondary Prevention Treatments
Risk Factors Control and Direct CV and Kidney Protection
RRR Event rate
None 8%
ASA 25% 6%
-Blockers* 25% 4.5%
Lipid lowering 30% 3.0%
ACE-inhibitors 25% 2.3%
-Blockers* benefit is time dependent and problems with SBP in ageing population
Compliance Challenge
Patient compliance
Physician compliance
Get with the
guidelines
Get with the pills Polypill
Strategies to Improve Adherence
Strategies to Improve Adherence
S — Simplify the regimenI — Impart knowledgeM—Modify patient beliefs and behaviorP — Provide communication and trustL — Leave the biasE — Evaluate adherence
http://www.acpm.org/?MedAdherTT_ClinRef
“A pill to prevent 80% of heart attacks” BMJ 2003
Polipíldora para prevención Cardiovascular:del Concepto a la Realidad
Reducción del numero de componentes para simplificar el tratamientoFavoreciendo la Adherencia
Estrategia Coste EfectivaFavoreciendo laasequibilidad
Favorece la accesibilidadglobal al tratamiento farmacológico
RCTS USING A POLYPILL TO STUDY THE EFFECT ON ADHERENCE
47
70
0102030405060708090100
Control Polypill
46
81
0102030405060708090
Control Polypill
60
85
0102030405060708090
Control PolypillSelak et al. BMJ . 2014
Patel et al. European Journal of Preventive Cardiology, 2014
Thom S, et al. JAMA . 2013;310:918‐929
KANYINI GAP IMPACT UMPIRERR=1,49 RR=1,75 RR=1,33
Castellano JM et al, J Am Coll Cardiol. 2014;64(6):613‐621
FOCUS project
Fixed‐dOse Combination DrUg for Secondary Cardiovascular PreventionA TWO PHASE STUDY
Castellano JM et al. A Polypill Strategy to Improve Adherence: Results From the FOCUS Project. J Am Coll Cardiol. 2014 Sep 1.pii: S0735-1097(14)05941-5. doi: 10.1016/j.jacc.2014.08.021 .
Phase 1: Observational • To determine the proportion of post‐MI patients
receiving appropriate secondary prevention• To estimate the level of patient adherence• To identify factors that contribute to poor adherence.
(Morisky Green: Assessment of adherence)• Availability of secondary prevention therapies
Phase 2: Prospective RCT• To compare adherence to treatment in post MI
patients receiving a FDC vs. those with conventional treatment (3 drugs provided separately)
• Primary Endpoint: Adherence measured by Morisky‐Green and Pill Count combined
• To evaluate the effect of TRINOMIA on BP and LDL‐C• Safety and tolerability of TRINOMIA
3 drugsseparately
CNIC‐FS*‐FERRERTRINOMIAAspirin 100
Ramipril 2,5‐5‐10Simvastatin 40
2118
695
Phase 1
Phase 2
Adherence‐MAQ + PillCount
* Fuster-Sanz
R
9 months 63 sites in 5 countries in Italy Spain, Brazil, Argentina and Paraguay
FOCUS Project
Castellano JM et al. A Polypill Strategy to Improve Adherence: Results From the FOCUS Project. J Am Coll Cardiol. 2014 Sep 1.pii: S0735-1097(14)05941-5. doi: 10.1016/j.jacc.2014.08.021 .
Attending Visit 3+ MAQ=20+Pill Count 80‐110 Attending all visits+MAQ=20+Pill Count 80‐110
p=0.019p=0.012
10% adherence increase with the CNIC-Ferrer polypill (Trinomia ASR) in patients with long-term evaluated CV disease
FOCUS Project: Phase 2, Results
Castellano JM et al. A Polypill Strategy to Improve Adherence: Results From the FOCUS Project. J Am Coll Cardiol. 2014 Sep 1.pii: S0735-1097(14)05941-5. doi: 10.1016/j.jacc.2014.08.021 .
INTENTION TO TREAT Control Polypill p value
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
PER PROTOCOL
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
There were no differences between groups on BP or LDL-cholesterol Possible differences in additional medication
FOCUS Project: Phase 2, Results
Castellano JM et al. A Polypill Strategy to Improve Adherence: Results From the FOCUS Project. J Am Coll Cardiol. 2014 Sep 1.pii: S0735-1097(14)05941-5. doi: 10.1016/j.jacc.2014.08.021 .
Control (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-Hypertension, Hypertriglicemia, High Cholesterol, Thoracic pain
No differences in the safety profile between groups
FOCUS Project: Phase 2, Results Safety
2002
SeguridadBioequivalencia
RCT Prevención Primaria
Wald & LawEstrategia vacunación6 componentes > 55añosReducción de ECV > 80 %
Tolerabilidad, PA, LDL‐CholTIPS‐1 (2009)PILL (2011)TIPS‐2 (2012)
AdherenciaUMPIREKANYINI‐GAPIMPACT
Evolución del concepto de la polipíldora
2014Eventos
HOPE‐3 (2016)TIPS‐3 (2019)
Variablesubrogada PROPS
Castellano JM, Sanz G, Fuster V. Can J Cardiol. 2014 May;30(5):520‐6.
2006
MINERVASECURE
La polipíldora: estrategia innovadora para laprevención cardiovascular
Concepto farmacológico: combinar variosfármacos que intervienen en los principalesprocesos causantes de la ECV, a dosis quemaximizan la eficacia y minimizan efectossecundarios.
Mejora AdherenciaPacientes/Médicos
Reducción de eventos Coste-efectivo
Conclusión
Cumplimentación Terapéutica CV
Aspectos Metodológicos
Papel de la Prevención Secundaria
Cumplimentación y Pronóstico
“Polipíldoras” como Alternativa
Evolución de la letalidad a 28 días. Primer IAM con onda Q.
Girona 1978-2006
-75-
4,2
8,1
6,5
18,4
12,8
9,5
12,7
0
5
10
15
20
1978-81 1982-85 1986-89 1990-93 1994-97 1998-01 2002-06
Exitus
%
P <0.001
51% fármacos
38% proc. invasivos
Sala C. Am Heart. J 2011; 62:444-50
Estimated reductions in CHD/Stroke of a Full dose Polycap in Those With Average Risk Factor Levels
% Relative Reduction
Reduction in Risk Factors
CHD Stroke
LDL‐C (mmol/L) Est (Simv 40) 1.1 35% 15%
DBP (mmHg) Est (3, full dose) 10.0 40% 50%
Platelet function Est (ASA 100 mg) Similar 32%* 16%
Combined Est ‐ 70 % 65 to 75%
*Without ASA, about a 50% RRR in CHD and stroke.
010203040506070
ASAonly
Statinonly
1 BPagent
2 BPagents
3 BPagents
Polycap(single)
Polycap(double)
Estim
ated
CVD
risk
redu
ctio
n, %
Effect of the 5 component Polycap on est RRR for CVD in hypertensives
66 62 197 108 127 150
P for trend <0.0001
70
Upsides and Downsides of the Polypill
Upsides: Lower costs, overcomes clin inertia, Could reduce CVD risk >65%, better adherence, more easily used by NPHW. Patient preferences.Downsides: Less flexibility in dosing and choice of the components of the combo, but in future 2 or 3 diff types of polypills available. Variable physician preference. Hard to commercialize (so, need new bus models).
Major Trials of the Polypill• HOPE 3: 12,700, factorial of comb BP lowering
+/-statin, intermediate risk.Results 2016. • TIPS 3: 5000 hi risk primary prevention (90%
Stage 1 hyp , 50% dysglycemics).Results 2018• Poly Iran: Mixture of
primary/secondary(n=7000).• HOPE 4: Strategy of global risk reduction in hi
risk primary/secondary using NPHW+ polypill + LS advice +trt supporter vs usual care. Pilot of 2000/full scale of 10,000
“The economics and politics of the project are fascinating. The ingredients are all off (or about to be off) patent, so the pill might be made very cheaply. This is good news, but large pharmaceutical companies are not keen. Not only will the profit margin be low but also many of their expensive drugs may be made redundant. A large generic company—perhaps one from India—might be best suited to manufacture the pill.”
Richard Smith, editor
“And what will happen to cardiologists and cardiac surgeons? Will they have to retrain as psychiatrists, hoping that nobody invents a “happy pill” to oblige further retraining.”
“. But do doctors need to be involved? We could do away with the screening. Maybe too we could buy the pills in supermarkets and pubs—perhaps even washing them down with a glass of red wine and preventing still more deaths.”
Richard Smith, editor
The phenomenal success in the battle against IHD … but how?
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But the Western model is not affordable in most countries…?
1. Western countries spend about 8%-18% of GDP (larger than LMIC) vs only 2-5% of GDP on health in LMIC; hi cost models not applicable globally.2. Shortage and maldistribution of doctors, nurses and pharmacists: Task shifting .3. Improve access to combo therapy(? Ess drug list) provided at no ( or v low) cost /universal health coverage for CVD prevention.4. Integrate CVD/NCD prevention with control of infectious diseases.
Malawi: a case studyBurden: 30% of adults have hypertension
6% of adults have diabetesFinances: 65% live off <$1.0/day
Human Resources: 2 doctors & 38 nurses/ 100,000 population Plan: -Integrating hypertension & DM control into TB & HIV control programmes
-Need NPHW and other non-health workers to control HTNBarriers: Human, drug stock-outs, access, distance, legal, patient attitudes about long term care
Brasil: Family Health Programmes as a platform for prevention & management of NCDs
• 2007: 72% of all deaths due to NCDs (i.e. half CVD/diabetes)• 50% decline in smoking between 1989 to 2009 • 2011: 32,000 family health care teams (1 MD, 1 Nurse, 1 Aux Nurse, 4‐
6 Community Health Workers), one per 1000 families (or 1/5000 people)
• Now covers half the population of Brasil ( 100 mill)• Priorities: a) Population groups: Preg women & children;
b) Conditions: TB, leprosy, HTN, diabetes• Impact: ‐increased use of primary health care
‐24% decline in NCD hosp‐Reduced mortality
How can hypertension be better controlled?
• 50% not detected: Opportunistic / efficient screening by NPHW.
• Clinical inertia and lack of control of other RF : Low(+full) dose combo BP therapy+ statins( +/-ASA).
• LS modification: advice+ reinforcement by NPHW.• Long term adherence: Pt supporter+ NPHW +
education(need for lifelong treatment even when BP is normal). Avoid “traditional” treatments.
• Enhance efficiency and decrease costs: NPHW + polypill + mgmt at home/community (greater access, less costs and time lost from work for patients).
Research to Action: HOPE-4.• Question: Can a community based strategy of
screening and treatment with a polypill by NPHW in hi & moderate risk individuals reduce CVD risk by 40% within 6 yrs?
• Setting: 190 communities( 10,000 people) in Columbia, Argentina, S Africa, Tanzania, Rwanda, India, Malaysia, Philippines & Canada.
• Intervention: Systematic screening for prevalent CVD, hypertension & diabetes .Communities randomized to active intervention ( NPHW based polycap+ LS advice ) or usual care.
• Outcomes: BP control, IH risk score, CVD & costs.
Interactions between societal determinants, risk factors and health systems on CVD and other NCDs
Societal Determinants
Behaviours & Risk Factors
Disease incidence & severity
Disease mortality
Risk factor control: -Health education-Treatments-Health SystemsHealth Systems:
Quality of health care—access, quality & affordability
Community structure, Architecture, Transport, Nature of Work, Food Policies§
Tobacco policies*
*Implemented §Potential
A Focussed Practical Strategy to Tackle CVD
1. Reduce tobacco use by 50% globally in 25 yrs (e.g. Brasil reduced smoking by 50% in 20 yrs!)
2. Family health teams to control hypertension (systematic screening, simple low dose combo of 2 BP lowering drugs + statins by NPHW; family supporters), diabetes and secondary prevention---integrate “horizontally” into other key programmes.
3. Universal (at no or very low cost) access to key drugs (ASA, diuretics, BB, CCB, statins) in combination (e.g. polypill) and metformin—and prescribed by NPHW
4. Basic universal coverage package to all for key prevention strategies and catastrophic illness.
Tob & HTN control, hi risk primary and secondary prevention
ACEI/ARB IN ACS PATIENTSDATA FROM CARDIOCHUS REGISTRY
Abu-Assi E, et al. Rev Esp Cardiol 2014 (submitted)
BETA-BLOCKERS IN ACS PATIENTSDATA FROM CARDIOCHUS REGISTRY
Curva de Kaplan Meiermostrando el beneficiopronóstico en términos demortalidad del tratamiento conbloqueadores beta tras el altapor un síndrome coronarioagudo después del propensityscore matching.
Abu-Assi E, et al. Rev Esp Cardiol 2014 (In press)
PACIENTES ADHERENCIA A LAS GPCSÍ NO p
Tº EVOLUCIÓN 6,8±5,6 8,5±6,2 <0,001
INFARTO 65% 46% <0,001
ANGIOPLASTIA 84% 66% <0,001
CIRUGÍA 20% 15% <0,05
HIPERTENSIÓN 62% 69% <0,05
DIABETES 28% 29% ns
DISLIPEMIA 74% 66% <0,005
INSUF CARDIACA 7% 14% <0,001
FIBRIL AURICULAR 5% 23% <0,001
ICTUS 6% 11% <0,005
ART PERIFÉRICA 13% 15% ns
EPOC 8% 23% <0,001
CIBAR. Barbanza Registry