La aterosclerosis como enfermedad sistémica una visión integral de la enfermedad cardiovascular
Miércoles, 22/06/16 18:00h-20:00h Casa del Corazón, Madrid
http://cvvt.secardiologia.es
#CVVT
La enfermedad aterosclerótica en cardiología: particularidades y novedades
Dr. Leopoldo Pérez de Isla. Hospital Universitario Clínico San Carlos, Madrid
La enfermedad aterosclerótica en cardiología: particularidades y novedades
1. Excelencia en el manejo de la cardiopatía isquémica
La enfermedad aterosclerótica
en cardiología
particularidades y novedades
Dr. Leopoldo Pérez de Isla
Hospital Clínico San Carlos
Madrid
11. Caso clínico
Varón de 67 años
Asintomático salvo dolor ciático
Al realizar CRM para valorar posible hernia discal se
descubre neoplasia renal…
ES UNA PERSONA SANA
NO DEBO TRATARLE
12. Caso clínico
Varón de 45 años
Asintomático
En análisis rutinario es diagnosticado de infección por
VIH…
ES UNA PERSONA SANA
NO DEBO TRATARLE
16. Esperar signos y síntomas claros de enfermedad
coronaria antes del tratamiento no está
justificado
De alguna manera, la aparición de síntomas de enfermedad
puede ser visto como un fallo médico más que como el
punto de inicio de un tratamiento
William B. Kannel
19. Afectación multiterritorio
Pacientes con aterosclerosis no coronaria
Mismo riesgo de enfermedad coronaria clínica que pacientes con
enfermedad coronaria
21. Fernández-Friera L et al. The PESA study. Circulation. 2015 Jun 16;131(24):2104-13.
Progression of Early Subclinical Atherosclerosis Study
22. Fernández-Friera L et al. The PESA study. Circulation. 2015 Jun 16;131(24):2104-13.
Progression of Early Subclinical Atherosclerosis Study
• Presence of iliofemoral disease was more
strongly correlated with aortic disease and
CAC than with carotid disease
• Having disease in the iliofemorals
corresponds to a 70% probability of finding
disease in any other territory
• The absence of plaque in the iliofemorals
confers a 67% probability of being disease
free in the other vascular territories
23. Influence of Diabetes on the
Incidence of CV Death, MI or Stroke
REACH1: Patients with diabetes are at
heightened risk of CV death, MI or stroke
APOLLO2: ~1 in 4 patients with diabetes,
event-free for 1 year post-MI, suffered MI,
stroke or CV death within 3 years*
23
*Adjusted for age, sex, diabetes, >1 MI and renal disease
1. Cavender MA et al. Circulation 2015 2015;132:923–931
2. Janzon, M. et al. JACC 2015 [Poster]
16,9
26,0
0
5
10
15
20
25
30
Patients without diabetes
(n=32,477)
Patients with diabetes
(n=12,516)
Cumulative3-yearincidenceofCV
death,MIorstroke(%)
Diabetes (known atherothrombosis, prior ischaemic event)
Diabetes (known atherothrombosis subpopulation)
Diabetes (overall registry population)
Diabetes (known atherothrombosis,
no prior ischaemic event)
No diabetes (overall registry population)
Diabetes (risk factors only subpopulation)
10 20 30 40 500
0
5
10
15
20
25
AdjustedcumulativeincidenceofCV
death,MIorstroke(%)
Months
24.
25. Shah AD et al. Lancet Diabetes Endocrinol. 2015 Feb;3(2):105-113.
27. HL se asocia a enfermedad cerebrovascular
Hutter CM, et al. Am J Epidemiol 2004;160:430–435
Mabuchi H, et al. Atherosclerosis 1986;61:1–6.
Kroon AA, et al. J Intern Med. 1995 Nov;238(5):451-9.
28. Coronary Heart Disease,
Peripheral Arterial Disease
and Stroke in Familial
Hypercholesterolaemia:
Insights from the
SAFEHEART Registry
Pérez de Isla et al. Ongoing evaluation
35. Ticagrelor en pacientes con diferentes manifestaciones de enfermedad CV
5 ensayos clínicos:
Controlados
Con resultados clínicos cardiovasculares
Representando manifestaciones de afectación de diferentes territories
arteriales
THE PARTHENON PROGRAM
43. PEGASUS-TIMI 54: Ticagrelor in
Patients with Prior MI and PAD
Efficacy and safety of ticagrelor as long-term secondary
prevention in patients with prior myocardial infarction and
peripheral artery disease
44. PEGASUS-TIMI 54: Primary Endpoint
(CV Death, MI or Stroke) in the Placebo Arm,
by Baseline PAD Diagnosis
Bonaca MP et al. J Am Coll Cardiol 2016;DOI: 10.1016/j.jacc.2016.03.524
CVdeath,MIorstroke(%)
0
5
10
15
20
25
Days from randomization
0 180 360 540 720 900 108090 270 450 630 810 990
Patients with PAD
N=404
19.3%
Patients without PAD
N=6663
8.4%
PAD vs no PAD
Unadjusted HR 2.46 (95% CI 1.92–3.15) P<0.001
Adjusted HR 1.60 (95% CI 1.20–2.13) P=0.0013
No. at risk
Patients with PAD
Patients without PAD
404
6663
384
6508
367
6394
344
6159
309
5567
223
4120
104
1924
45. PEGASUS-TIMI 54: Efficacy Endpoints
at 3 Years in the Placebo Arm,
by Baseline PAD Diagnosis
Bonaca MP et al. J Am Coll Cardiol 2016;DOI: 10.1016/j.jacc.2016.03.524
KMrateat3years(%)
0
4
8
12
14
16
2
6
10
CVD Myocardial
infarction
Stroke All-cause mortality
HR
(95% CI)
P value
3.32
(2.30–4.79)
P<0.001
1.93
(1.35–2.75)
P<0.001
2.80
(1.68–4.67)
P<0.001
3.16
(2.35–4.27)
P<0.001
No PAD (N=6663)
PAD (N=404)
3.0%
9.6%
5.0%
9.5%
1.8%
4.0%
4.6%
14.0%
46. PEGASUS-TIMI 54: Bleeding Endpoints
at 3 Years in the Placebo Arm,
by Baseline PAD Diagnosis
Bonaca MP et al. J Am Coll Cardiol 2016;DOI: 10.1016/j.jacc.2016.03.524
KMrateat3years(%)
0
4
8
12
14
16
2
6
10
TIMI major bleeding TIMI major/minor bleeding ICH or fatal bleeding
HR
(95% CI)
P value
1.47
(0.53–4.07)
P=0.46
1.67
(0.72–3.85)
P=0.23
2.05
(0.62–6.76)
P=0.24
No PAD (N=6663)
PAD (N=404)
1.0%
1.6% 1.4%
2.2%
0.6%
1.3%
47. PEGASUS-TIMI 54 PAD Analysis:
Primary Endpoint (CV Death, MI or Stroke)
CVdeath,MIorstroke(%)
0
5
10
15
20
25
Days from randomization
0 180 360 540 720 900 108090 270 450 630 810 990
No PAD
ARR 1.0%
NNT 100
19.3%
15.2%
8.4%
7.4%
PAD
ARR 4.1%
NNT 25
P-interaction 0.41
PAD
No PAD
HR 0.75
95% CI 0.55–1.01
HR 0.86
95% CI 0.77–0.96
Benefit of ticagrelor (pooled)
by PAD at baseline
Ticagrelor pooled doses
Placebo
ARR, absolute risk reduction; NNT, number needed to treat
Bonaca MP et al. J Am Coll Cardiol 2016;DOI: 10.1016/j.jacc.2016.03.524
48. PEGASUS-TIMI 54 PAD Analysis:
Conclusions
• Pacientes post IAM + PAD tienen alto riesgo a largo plazo de
sufrir eventos aterotrombóticos
• Ticagrelor (60 mg bid) + AAS reduce los eventos
aterotrombóticos comparado con AAS solo
• Análisis post-hoc muestran:
– Reducción muerte CV
– Reducción mortalidad cualquier causa
1. Bonaca MP et al. J Am Coll Cardiol 2016;DOI: 10.1016/j.jacc.2016.03.524
2. Patel MR et al. European Journal of Preventive Cardiology 2015; 22: 734–742
49. EUCLID study design
Primary endpoint: Cardiovascular death, myocardial infarction
or ischaemic stroke
Key inclusion criteria:
Established PAD
defined as:
• Prior lower extremity
revascularization
>30 days
OR
• No prior lower
extremity
revascularization
but symptomatic
PAD with ABI ≤0.80
at enrolment
Key exclusion
criteria:
• Poor metabolizer
for CYP2C19
• Need for DAPT
• Revascularization
or amputation
planned in next
3 months
Patients (>50 years) with symptomatic PAD
Ticagrelor
90 mg bid
Clopidogrel
75 mg od
N ~ 13,500
Follow-up visits at 2, 6, 12 months;
every 6 months after first year
Telephone visits at 3-month intervals between regular visits
1:1
Double-blind
Double-dummy
Berger JS et al. Am Heart J 2016;175:86–93
50. PEGASUS-TIMI 54: Ticagrelor in
Patients with Prior MI and Diabetes
Efficacy and safety of ticagrelor as long-term secondary
prevention in patients with prior myocardial infarction
and diabetes mellitus
51. PEGASUS-TIMI 54: Atherothrombotic Event
Rates in the Placebo Arm Stratified by
Diabetes Status
• Pacientes con DM-2 tienen una tasa más alta de eventos
aterotrombóticos que pacientes sin DM-2
*Indicates nominal P value
Bhatt DL et al. J Am Coll Cardiol 2016; DOI: 10.1016/j.jacc.2016.03.529
Diabetes No diabetes HRadj (95% CI) P value
CV death, MI or stroke (%) 11.60% 7.83% 1.45 (1.22–1.73) <0.001*
CV death (%) 4.97% 2.64%
MI (%) 6.51% 4.66%
Stroke (%) 2.46% 1.70%
52. CVdeath,MIorstroke(%)
0
5
10
15
Time in days
0 180 360 540 720 900 1080
2257 2190 2129 2042 1862 1375 644
4549 4426 4320 4172 3794 2824 1302
4810 4702 4632 4461 4014 2968 1384
9545 9375 9232 8931 8030 6001 2791
Number at risk:
Diabetes placebo
Diabetes ticagrelor pooled
No diabetes placebo
No diabetes ticagrelor pooled
Diabetes placebo
Diabetes ticagrelor pooled
No diabetes placebo
No diabetes ticagrelor pooled
ITT population
11.6%
10.1%
7.8%
6.7%
PEGASUS-TIMI 54 Diabetes Analysis:
Primary Endpoint (CV Death, MI or Stroke)
Bhatt DL et al. J Am Coll Cardiol 2016; DOI: 10.1016/j.jacc.2016.03.529
53. PEGASUS-TIMI 54 Diabetes Analysis: Summary (1)
• Pacientes post IAM + DM-2 tienen alto riesgo a largo
plazo de sufrir eventos aterotrombóticos
• Ticagrelor + AAS reduce los eventos aterotrombóticos
comparado con AAS con/sin DM-2
• Ticagrelor + AAS aumenta sangrado comparado con
AAS con/sin DM-2 (pero muy baja incidencia de HIC y
Hemorragia mortal)
• Resultados similares pero a 12 meses en PLATO
*Indicates nominal P value. ARR, absolute risk reduction; NNT, number needed to treat
Bhatt DL et al. J Am Coll Cardiol 2016; DOI: 10.1016/j.jacc.2016.03.529
54. THEMIS
Nuevas evidencias de ticagrelor a largo plazo en
pacientes DM-2 y alto riesgo de eventos CV
https://clinicaltrials.gov/ct2/show/NCT01991795