Objetivos en el tratamiento de la dislipemia en pacientes con cardiopatía isquémica: “New kids on the block”

Dislipemia en
Pacientes con SCA.
“New kids in the block”
Novedades en Dislipemia. SEC 2015
José R González Juanatey
Servicio de Cardiología y UCC
Hospital Clínico Universitario
Santiago de Compostela

Disclosures:
Research Grants: AZ, Boehringer Ingelheim, Pfizer,
Novartis, Daichii-Sankyo, Sanofi-Aventis, Bayer, MSD,
Servier, Ferrer, Amgem, Rovi
Consultant/Honorarium. AZ, Boehringer-Ingelheim,
Bayer, Pfizer, BMS, MSD, Daichii-Sankyo, Servier,
Menarini; Sanofi-Aventis, Ferrer, Amgem, Rovi

J.R.G. JUANATEY
C.H.U.Santiago
•SCA y Dislipemia
•Situación en España
•Recomendaciones de Guías
•Alternativas Terapéuticas
•Futuro
Dislipemia en Pacientes con SCA

J.R.G. JUANATEY
C.H.U.Santiago
Picking Plaques
That Pop!
Narula & DeMaria
J Am Coll Cardiol
[Editorial] 2005
From Virmani, Narula, Leon, Willerson; The Vulnerable Atherosclerotic Plaques: 2007

J.R.G. JUANATEY
C.H.U.Santiago
IHD 2ªPrev. An Extraordinary Journey
Innovation Year Impact
B-Blockers 70´ Mortality
ASA 80´ Mortality
Life-style changes/Rehab 70-15´ Mortality
ACE Ih 80-90´ Morbi-mortality
Statins 90´ Mortality
Team Work 90´ Mortality
Revasc (subgroups) 00´ Morbi-mortality
Vorapaxar 13´ Morbi-mortality
Rivaroxaban 13´ Morbi-mortality
Ticagrelor 15´ Morbi-mortality
Ezetimibe 15´ Morbi-mortality
10
%/y
2
%/y

Riesgo CV de diferentes lípidos

Dislipidemia in CHD patients in Spain
Cordero A, Facila L. Rev Esp Cardiol 2015;15:2-7

Utilización de estatinas y control de cLDL en
pacientes con C. Isquémica en España
Todas p<0,01

¿Ha mejorado el grado de control de los
pacientes con cardiopatía isquémica crónica en
los últimos 5 años?
Resultados del Estudio CIBAR
Año 2007 (%) Año 2013 (%) Valor-p
Tensión arterial controlada 61,7 65,5 NS
LDL<70 8,4 20,8 <0,001
TG<200 88,9 88,4 NS
HDL>40♂/45♀ 63,2 61,8 NS
Ausencia Obesidad 60,0 59,7 NS
Ausencia Obesidad Central 45.7 44,6 NS
Presencia tabaquismo 10,7 7,3 NS
PRESCRIPCIÓN ESTATINAS 88.1 84.5
ATORVA 46.7
SIMVA 15.5
Grupo Barbanza. 2014

Utilización de estatinas y control de cLDL en
pacientes con C. Isquémica en España
Nº Global Ez. LDL<70
N: 279
LDL>70
N: 776
p
Ezetimibe
(n, %)
1055 145 (13.7)
Ez+Ator
80+27
mg/dL
51 (18.3)
84+33
mg/dL
94 (12.1) 0.01
LDL < 70 mg/dL
Ezetimibe 36.9%
No Ezetimibe 23.8% (p<0.01)

Guías para el tratamiento de la dislipemia
Objetivos de LDLc según LDLc y
categorías de riesgo cardiovascular
Intensidad de tratamiento con
estatinas según ECV, DM, LDLc y
riesgo estimado

Pacientes Objetivo c-LDL Clase Nivel
Pacientes con
riesgo “muy alto”
< 70 mg/dL (<1,8 mmol/l)
y/o reducción del c-LDL > 50%
cuando no pueda alcanzarse
el objetivo
I A1,2,3
Pacientes con
riesgo “alto”
< 100 mg/dL (<2,5 mmol/l) IIa A1,4,5
Pacientes de riesgo
“moderado”
< 115 mg/dL (< 3 mmol/l) IIa C
Objetivos terapéuticos c-LDL
1. Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL
cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet. 2010; 376:1670-81.
2. Pedersen TR, Faergeman O, Kastelein JJ, et al; Incremental Decrease in End Points Through Aggressive Lipid
Lowering (IDEAL) Study Group. High dose atorvastatin vs usual-dose simvastatin for secondary prevention after
myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005; 294:2437-45.
3. LaRosa JC, Grundy SM, Waters DD, et al; Treating to New Targets (TNT) Investigators. Intensive lipid lowering with
atorvastatin in patients with stable coronary disease. N Engl J Med. 2005; 352:1425-35.
4. Brugts JJ, Yetgin T, Hoeks SE, et al. The benefits of statins in people without established cardiovascular disease but
with cardiovascular risk factors: meta-analysis of randomised controlled trials. BMJ. 2009; 338:b2376.
5. Mills EJ, Rachlis B, Wu P, Devereaux PJ, Arora P, Perri D. Primary prevention of cardiovascular mortality and events
with statin treatments. A network metaanálisis involving more than 65,000 patients. J Am Coll Cardiol. 2008;
52:1769-81.

Very low levels of atherogenic liproteins and the
risk for CV events. A meta-analysis of statin trials
Boekholdt et al., JACC 2014
Riesgo
Mínimo!!!

Atorva 80 + Ezetimibe
LDL + 75%

Lipid treatment strategies in Patients with High CV Risk
Harold B, et al. J Clin Endocrinol Metab 2015; 100: 3140-3148.

Lipid treatment strategies in Patients with High CV Risk
LDL Goal
Harold B, et al. J Clin Endocrinol Metab 2015; 100: 3140-3148.

Grupo terapéutico
Antecedentes
de ECV
c-LDL > 190
mg/dl (1ª)
Diabetes (1 y 2)
40-75 años
Estatina de gran
potencia
( c-LDL > 50%)
Estatina de potencia
moderada
( c-LDL de 30 a 50%)
40-75 a. y riesgo
(10 a) > 7,5%
Atorva 80 (40)
Rosu 20
Atorva 10 (20)
Rosu 10 (5)
Simva 20-40
Prava, Lova 40
Fluva 80 (40x2)
Pita 4 (2)
< 75 a
> 75 a
Riesgo
< 7,5%
Riesgo
> 7,5%
c-LDL < 40 mg/dl x 2
AHA/ACC Guidelines, 2013
Tratamiento
Tratamiento Dislipemia. Influencia Edad

Patients stabilized post ACS ≤ 10 days:
LDL-C 50–125*mg/dL (or 50–100**mg/dL if prior lipid-lowering Rx)
Standard Medical & Interventional Therapy
Ezetimibe / Simvastatin
10 / 40 mg
Simvastatin
40 mg
Follow-up Visit Day 30, every 4 months
Duration: Minimum 2 ½-year follow-up (at least 5250 events)
Primary Endpoint: CV death, MI, hospital admission for UA,
coronary revascularization (≥ 30 days after randomization), or stroke
N=18,144
Uptitrated to
Simva 80 mg
if LDL-C > 79
(adapted per
FDA label 2011)
Study Design
*3.2mM
**2.6mM
Cannon CP AHJ 2008;156:826-32; Califf RM NEJM 2009;361:712-7; Blazing MA AHJ 2014;168:205-12
90% power to detect
~9% difference

LDL-C and Lipid Changes
1 Yr Mean LDL-C TC TG HDL hsCRP
Simva 69.9 145.1 137.1 48.1 3.8
EZ/Simva 53.2 125.8 120.4 48.7 3.3
Δ in mg/dL -16.7 -19.3 -16.7 +0.6 -0.5
Median Time avg
69.5 vs. 53.7 mg/dL

Simva* EZ/Simva* p-value
Primary 34.7 32.7 0.016
CVD/MI/UA/Cor Revasc/CVA
Secondary #1 40.3 38.7 0.034
All D/MI/UA/Cor Revasc/CVA
Secondary #2 18.9 17.5 0.016
CHD/MI/Urgent Cor Revasc
Secondary #3 36.2 34.5 0.035
CVD/MI/UA/All Revasc/CVA
0.936
Ezetimibe/Simva
Better
Simva
Better
UA, documented unstable angina requiring rehospitalization; Cor Revasc, coronary revascularization
(≥30 days after randomization); All D, all-cause death; CHD, coronary heart disease death;
All Revasc, coronary and non-coronary revascularization (≥30 days)
*7-year
event rates (%)
Primary and 3 Prespecified
Secondary Endpoints — ITT
0.8 1.0 1.1
0.948
0.912
0.945

The benefits in
Ezetimibe+statin arm are
consistent with that seen in
previous statin trials and as
predicted by CTT data

Various mechanisms how statins and ezetimibe
modify plaque characteristics and growth

J.R.G. JUANATEY
C.H.U.Santiago
SCA/CI/ECV/Diabetes/Score>10
STA prv
STA EZE
“naive”
STA EZE
>75 años
STA EZE

Sociedad de Cirugía Torácica y Cardiovascular
S E C T C V
Quality markers in cardiology
Main markers to measure quality of results (Outcomes) and
Quality measures related with better results in clinical practice
(performance metrics). A consensus position paper

Quality controls
% of patients
admitted toa
Rehabilitation
program
> 50% after AMI? ACS (Ideally all patients should
be offered some kind of rehabilitation program)
1 2 2 350, 359, 369,
371
Control of major risk
factorsand
adherenceto
guideline
recommendationsfor
lifestyle
Smoking: sustained smoking abstinence >50% in
CVD 1 3 3
358 - 360, 366,
367, 369, 371,
372
Hypertension optimal control (< 140/90) > 50%? 1 3 3 350, 360, 367,
371
LDL < 70, recommended target > 70% (1,8
mmml/L) or highest tolerated dose of statins > 50%
of patients
1 3 3
350, 359, 368,
371, 337
Adherencetoguideline
recommendationsof
lifestyle
Exercise, Diet, smoking counselling: Recommended
in 100% 1 2 2
350, 361, 364,
371, 372
AdherencetoESC /
AHA-ACCC
guideline
recommendation for
2nd
prevention
treatment
Antiplatelet, Statins, Beta-blockers, ACE-I,
aldosterone blockers unless contraindicated.
Recommended >90 % unless contraindicated
1 2 2
112 - 115, 350,
371, 371b
LDL<70 mg/dL, recommended target >70% Patients

J.R.G. JUANATEY
C.H.U.Santiago

Objetivos en el tratamiento de la dislipemia en pacientes con cardiopatía isquémica: “New kids on the block”

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Objetivos en el tratamiento de la dislipemia en pacientes con cardiopatía isquémica: “New kids on the block”