INNOVATIONS IN CARDIOVASCULAR RISK IN THE LAST YEAR.
A EUROPEAN PERSPECTIVE
Vicente Bertomeu MartínezHead of Cardiology. Hospital Universitario San Juan de Alicante (Spain)Prof. of Cardiology UCAM. Director International Institute of CardiologyPresident Spanish Society of Cardiology
The FL Chapter ACC Annual MeetingOrlando, August 17, 2013
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Decrease in deaths from coronary heart disease attributed to treatments versus prevention
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Cardiovascular age
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HYPERTENSION
Guías 2003Guías 2003
Guías 2007Guías 2007
Revisión ESH 2009Revisión ESH 2009
Guías 2013Guías 2013
Historical perspeciveHistorical perspecive
ESH/ESC 2013 Hypertension guidelinesESH/ESC 2013 Hypertension guidelines
J Hypertens 2013;31:1281-1357J Hypertens 2013;31:1281-1357Eur Heart J 2013Eur Heart J 2013Blood Pressure 2013Blood Pressure 2013VBM 2013
JNC 2004
Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease)
Initial Drug ChoicesInitial Drug Choices
Drug(s) for the compelling Drug(s) for the compelling indications indications
Other antihypertensive drugs Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as (diuretics, ACEI, ARB, BB, CCB) as
needed. needed.
With Compelling With Compelling IndicationsIndications
Lifestyle ModificationsLifestyle Modifications
Stage 2 HypertensionStage 2 Hypertension (SBP (SBP >>160 or DBP 160 or DBP >>100 m100 mmHg) mHg)
2-drug combination for most (usually 2-drug combination for most (usually thiazide-type diuretic and thiazide-type diuretic and
ACEI, or ARB, or BB, or CCB)ACEI, or ARB, or BB, or CCB)
Stage 1 HypertensionStage 1 Hypertension(SBP 140(SBP 140–159 or DBP 90–99 mmHg)–159 or DBP 90–99 mmHg)
Thiazide-type diuretics for most. Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, May consider ACEI, ARB, BB, CCB,
or combination.or combination.
Without Compelling Without Compelling IndicationsIndications
Not at Goal Not at Goal Blood PressureBlood Pressure
Optimize dosages or add additional drugs Optimize dosages or add additional drugs until goal blood pressure is achieved.until goal blood pressure is achieved.
Consider consultation with hypertension specialist.Consider consultation with hypertension specialist.
JNC VII: Algorithm for Treatment of HypertensionJNC VII: Algorithm for Treatment of Hypertension
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Stratification of total CV risk in categories of Stratification of total CV risk in categories of low, moderate, high and very high risklow, moderate, high and very high risk
Stratification of total CV risk in categories of Stratification of total CV risk in categories of low, moderate, high and very high risklow, moderate, high and very high risk
ESH/ESC 2013 Hypertension guidelinesESH/ESC 2013 Hypertension guidelines
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Blood Pressure MeasurementsBlood Pressure MeasurementsBlood Pressure MeasurementsBlood Pressure Measurements
ESH/ESC 2013 Hypertension guidelinesESH/ESC 2013 Hypertension guidelines
• Office or clinic Blood PressureOffice or clinic Blood Pressure• Office or clinic Blood PressureOffice or clinic Blood Pressure
• Ambulatory Blood Pressure Monitoring (ABPM)Ambulatory Blood Pressure Monitoring (ABPM)
• Out-of-office Blood Monitoring PressureOut-of-office Blood Monitoring Pressure• Out-of-office Blood Monitoring PressureOut-of-office Blood Monitoring Pressure
• Home Blood Pressure Monitoring (HBPM)Home Blood Pressure Monitoring (HBPM)
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Blood Pressure treatment tarjetsBlood Pressure treatment tarjetsBlood Pressure treatment tarjetsBlood Pressure treatment tarjets
SBP < 140 mmHg, independently of the risk
- Low-to-moderate risk hypertensive patients(IB)
- Diabetes (IA)
- CKD (IIaB)
- Previous cardiovascular events (IIaB)
PAD < 90 mmHg
ESH/ESC 2013 Hypertension guidelinesESH/ESC 2013 Hypertension guidelines
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•14
Objetivos del Tratamiento. Guías ESC-ESH 2007
Objetivos del Tratamiento. Guías ESC-ESH 2007
140/90 mmHg o 140/90 mmHg o cifras inferiores si son cifras inferiores si son toleradastoleradas, en todos los hipertensos., en todos los hipertensos.
< 130/80 mmHg en < 130/80 mmHg en diabéticos y diabéticos y pacientes de alto ó muy alto riesgo:pacientes de alto ó muy alto riesgo: IctusIctus Enf. CoronariaEnf. Coronaria Enfermedad Renal CrónicaEnfermedad Renal Crónica ProteinuriaProteinuria
J Hypertens 2007; 25: 1.105-1.187VBM 2013
Adjusted risk of outcome events by achieved SBP divided into deciles. ONTARJET
0
5
10
15
20
25
30
112 121 126 130 133 136 140 144 149 161
0
0.5
1
1.5
2
2.5
3
0
5
10
15
20
25
30
112 121 126 130 133 136 140 143 149 1600
0.5
1
1.5
2
2.5
3
0
5
10
15
20
25
30
112 121 126 130 133 136 140 144 149 1610
0.5
1
1.5
2
2.5
3
0
5
10
15
20
25
30
112 121 126 130 133 136 140 144 149 1600
2
4
6
8
10
Ad
just
ed 4
.5-r
isk
of
even
tsH
azard R
atio, 95
% C
on
fiden
ce Interv
als Primary Study Outcome
Cardiovascular Mortality
Myocardial Infarction Stroke
In-treatment Systolic Blood Pressure, Deciles (mmHg)
0
5
10
15
20
25
30
112 121 126 130 133 136 140 144 149 161
0
0.5
1
1.5
2
2.5
3
0
5
10
15
20
25
30
112 121 126 130 133 136 140 143 149 1600
0.5
1
1.5
2
2.5
3
0
5
10
15
20
25
30
112 121 126 130 133 136 140 144 149 1610
0.5
1
1.5
2
2.5
3
0
5
10
15
20
25
30
112 121 126 130 133 136 140 144 149 1600
2
4
6
8
10
0
5
10
15
20
25
30
112 121 126 130 133 136 140 144 149 161
0
0.5
1
1.5
2
2.5
3
0
5
10
15
20
25
30
112 121 126 130 133 136 140 143 149 1600
0.5
1
1.5
2
2.5
3
0
5
10
15
20
25
30
112 121 126 130 133 136 140 144 149 1610
0.5
1
1.5
2
2.5
3
0
5
10
15
20
25
30
112 121 126 130 133 136 140 144 149 1600
2
4
6
8
10
0
5
10
15
20
25
30
112 121 126 130 133 136 140 144 149 1600
2
4
6
8
10
Ad
just
ed 4
.5-r
isk
of
even
tsH
azard R
atio, 95
% C
on
fiden
ce Interv
als Primary Study Outcome
Cardiovascular Mortality
Myocardial Infarction Stroke
In-treatment Systolic Blood Pressure, Deciles (mmHg)
Sleight, et al . J. Hypertens 2009;27:1360-69VBM 2013
Adjusted relationship between tertiles of changes in SBP within each quartile of baseline SBP on the primary outcome
Sleight, et al . J. Hypertens 2009;27:1360-69
11.04 (0.89 - 1.22) 0.5991.19 (1.01 - 1.40) 0.042
10.81 (0.69 - 0.95) 0.0100.94 (0.80 - 1.10) 0.415
10.76 (0.65 - 0.88) 0.00030.74 (0.63 - 0.87) 0.0002
10.80 (0.69 - 0.92) 0.0020.73 (0.63 - 0.86) <0.001
Reduced Risk
IncreasedRisk
HR (96% CI) p value
0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6
P fortrend
0.050
0.364
0.0001
0.0001
Quartile 1 : Baseline SBP <130 mmHgTertile 1: Increase by 10 mmHg
Tertile 2: Increase by 0 - 10 mmHgTertile 3: Decrease in BP
Tertile 1: No change or increase in BPTertile 2: Decrease by 1 9 mmHg
Tertile 3: Decrease > 9 mmHg
Tertile 1: Decrease ? 6 mmHg
Tertile 2: Decrease 6Tertile 3: Decrease > 15 mmHg
Tertile 1: Decrease Tertile 2: Decrease 13
Tertile 3: Decrease > 24 mmHg
Quartile 2 : Baseline SBP 131 -
Quartile 3 : Baseline SBP 143 -154 mmHg
: Baseline SBP > 154 mmHg
11.04 (0.89 - 1.22) 0.5991.19 (1.01 - 1.40) 0.042
10.81 (0.69 - 0.95) 0.0100.94 (0.80 - 1.10) 0.415
10.76 (0.65 - 0.88) 0.00030.74 (0.63 - 0.87) 0.0002
10.80 (0.69 - 0.92) 0.0020.73 (0.63 - 0.86) <0.001
Reduced Risk
IncreasedRisk
HR (96% CI) p value
0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6
P fortrend
0.050
0.364
0.0001
0.0001
Quartile 1 : Baseline SBP Tertile 1: Increase by 10 mmHg
Tertile 2: Increase by 0 - 10 mmHgTertile 3: Decrease in BP
Tertile 1: No change or increase in BPTertile 2: Decrease by 1
Tertile 3: Decrease > 9 mmHg
Tertile 1: Decrease ? 6 mmHgTertile 2: Decrease 6Tertile 3: Decrease > 15 mmHg
Tertile 1: Decrease Tertile 2: Decrease 13
Tertile 3: Decrease > 24 mmHg
Quartile 2 : Baseline SBP 131 -142 mmHg
Quartile 3 : Baseline SBP 143 - 154 mmHg
: Baseline SBP > 154 mmHg
Quartile 1 : Baseline SBP Tertile 1: Increase by 10 mmHg
Tertile 2: Increase by 0 - 10 mmHgTertile 3: Decrease in BP
Tertile 1: No change or increase in BPTertile 2: Decrease by 1 -
Tertile 3: Decrease > 9 mmHg
Tertile 1: Decrease ? 6 mmHgTertile 2: Decrease 6 - 15 mmHgTertile 3: Decrease > 15 mmHg
Tertile 1: Decrease <13 mmHgTertile 2: Decrease 13 -24 mmHg
Tertile 3: Decrease > 24 mmHg
Quartile 2 : Baseline SBP 131 -
Quartile 3 : Baseline SBP 143 - 154 mmHg
Quartile 4 : Baseline SBP > 154 mmHg
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Elderly HypertensivesElderly HypertensivesElderly HypertensivesElderly Hypertensives
ESH/ESC 2013 Hypertension guidelinesESH/ESC 2013 Hypertension guidelines
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Choice of antihypertensive drugChoice of antihypertensive drugChoice of antihypertensive drugChoice of antihypertensive drug
The main benefits of antihypertensive treatment are due to lowering of BP “per se”.
Reconfirm that: - Diurétics- Beta blockers- Calcium Antagonist- Angiotensin-converting enzyme (ACE) inhibitors- Angiotensin receptor blockers (ARAII)Are all suitable for the initiation and maintenance,
either as monotherapy or in some combinations
Guía de hipertensión ESH/ESC 2013Guía de hipertensión ESH/ESC 2013
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Possible CombinationsPossible CombinationsPossible CombinationsPossible Combinations
ESH/ESC 2013 Hypertension guidelinesESH/ESC 2013 Hypertension guidelines
Green continuous line: Preferred Green dashed line: Usseful (with limitations)Black dashed line: Posible but less testedRed continuous line: Not recomended
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Strategies in Resistant HypertensiónStrategies in Resistant HypertensiónStrategies in Resistant HypertensiónStrategies in Resistant Hypertensión
ESH/ESC 2013 Hypertension guidelinesESH/ESC 2013 Hypertension guidelines
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DISLIPEMIA
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DISLIPEMIA
• Parameters to be measured: CT, LDL, TG y HDL. • Main objective: LDL.
• Very high-risk patients: <70 mg/dl (level of evidence in IA) .• High-risk patients: <100 mg/dl (IIaA).• Moderate-risk patients: <115 mg/dl (IIaC). Reduction of at
least 50% of basal levels
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• Statins are the most
effective drugs for the
lowering of total
cholesterol and LDL.
•For every ↓ of 40 mg/dl
of LDL the morbidity and
mortality levels are
reduced by 22%.
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N Engl J Med. 2011 Nov 15.VBM 2013
The addition of the combination of nicotinic acid of modified release and laropiprant to the treatment of statins produced no additional significant reduction in the risk of combined deaths from coronary heart disease, non-fatal heart failures, ictus or revascularizations when compared to statin therapy. There was also a statistically significant increase in the incidence of some types of non-fatal serious adverse events in the group that received nicotinic acid of modified release and laropiprant.
MSD recommends that doctors stop prescribing TREDAPTIVE. MSD also recommends that, in due course, doctors review the treatment plans of patients that are taking TREDAPTIVE stopping treatment with TREDAPTIVE
About the HPS2-THRIVE trial
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Kastelein J et al. N Engl J Med 2008;358:1431-1443 Taylor A et al. N Engl J Med 2009;361:2113-2122
Intima-Media Thickness of the Carotid Artery during 24 and 14 Months of Therapy
ENHANCE-Trial
ARBITER-6 HALTS
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The results of the IMPROVIT trial which will be available in 2015, should finally put an end to this problem.
Adapted from Rosensen RS. Exp Opin Emerg Drugs 2004;9(2):269-279
LaRosa JC et al. N Engl J Med 2005;352:1425-1435
LDL-C mg/dL (mmol/L)
WOSCOPS – Placebo
AFCAPS - Placebo
ASCOT - PlaceboAFCAPS - Rx WOSCOPS - Rx
ASCOT - Rx
4S - Rx
HPS - Placebo
LIPID - Rx
4S - Placebo
CARE - Rx
LIPID - Placebo
CARE - Placebo
HPS - Rx
0
5
10
15
20
25
30
40(1.0)
60(1.6)
80(2.1)
100(2.6)
120(3.1)
140(3.6)
160(4.1)
180(4.7)
Rate
of
even
ts (
%)
6
Secondary prevention
Primary prevention
200(5.2)
PROVE-IT - PRA
PROVE-IT – ATV
TNT – ATV10
TNT – ATV80
Level of LDL-C and CV events
Lower is Better ???
CORONA - RxCORONA - Placebo
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Adapted from Rosensen RS. Exp Opin Emerg Drugs 2004;9(2):269-279
LaRosa JC et al. N Engl J Med 2005;352:1425-1435
LDL-C mg/dL (mmol/L)
WOSCOPS – Placebo
AFCAPS - Placebo
ASCOT - PlaceboAFCAPS - Rx WOSCOPS - Rx
ASCOT - Rx
4S - Rx
HPS - Placebo
LIPID - Rx
4S - Placebo
CARE - Rx
LIPID - Placebo
CARE - Placebo
HPS - Rx
0
5
10
15
20
25
30
40(1.0)
60(1.6)
80(2.1)
100(2.6)
120(3.1)
140(3.6)
160(4.1)
180(4.7)
Rate
of
even
ts (
%)
6
Secondary prevention
Primary prevention
200(5.2)
PROVE-IT - PRA
PROVE-IT – ATV
TNT – ATV10
TNT – ATV80
Level of LDL-C and CV events
CORONA - RxCORONA - Placebo
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HK Lee et al. Benefit of early statin therapy in patients with acute myocardial infarction who have extremely low
low-density lipoprotein cholesterol. J Am Coll Cardiol 2011;58:1664-1671.
•Patients post-STEMI
with LDL <70 mg/dl.
Patients receiving statins, despite having a low LDL level, had
lower rates of major cardiac events
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Most probably the benefits lies in the use of statinand not in the level of LDL
Cordero A, Bertomeu V, et al. Rev Esp Cardiol 2013
Benefits of statin therapy in patients with acute coronary syndrome
cLDL >70 mg/dl cLDL <70 mg/dl
•HR: 0,09 (IC 95% 0,05-0,17); p<0,01 •HR: 0,19 (IC 95% 0,08-0,44); p<0,01
Statin
Non-Statin
Mortality from any cause
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Cum
ulati
ve s
urvi
val r
ate
Cordero A, Bertomeu V, et al. Rev Esp Cardiol;
2012:65:319-25
Determinantes bioquímicos de SCA vs. DT no isquémico
Variables OR IC 95% p
Sexo femenino 0,36 0,23 - 0,57 <0,01
Fibrilación auricular 0,27 0,14 - 0,52 <0,01
Edad 1,05 1,03 - 1,06 <0,01
Tabaquismo activo 1,73 1,00 - 2,99 0,05
Diabetes 1,75 1,10 - 2,80 0,02
Glucemia >100 mg/dl 1,89 1,22 - 2,94 <0,01
HDL < 40 mg/dl 2,99 1,95 - 4,59 <0,01
HDL: principal determinante del SCA
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2. HDL-c: Inhibición de CETP
CETP
DalcetrapidAnacetrapidEvacetrapid
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2. HDL-c: Inhibición de CETP
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LDL-c: Inhib. Degradación LDL-R
Abifadel M, et al. Nature Genet 2003; 34:154-156
• Más LDL-Receptor• LDL-C sérico bajo • Más LDL-Receptor• LDL-C sérico bajo
Ausencia de PCSK9
• Menos LDL-Receptor• LDL-C sérico alto
• Menos LDL-Receptor• LDL-C sérico alto
Presencia de PCSK9
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Stein EA, et al. NEJM 2012;366:1108-18
LDL-c: Inhib. Degradación LDL-R
Cambio en LDL-c en 12 semanas
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But they must prove that there is also a reduction in the morbidity and mortality rates
A. Cordero
TOBACCO
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A. Cordero
Tobacco and STEMI
No Smokers
423 (51,2%) 401 (49,8%)17 exfumadores <1año (4,2%)
Cordero A, Bertomeu V, et al. Med Clin (Barc) 2012; 138:422-28 VBM 2013
A. Cordero
Differences between groups
Total Never smoker
Exsmoker Smoker p
Age 61,4 (12,5) 68,2 (12,1) 66,0 (11,2) 56,1 (10,6) <0,01
IMC 28,3 (4,8) 29,3 (4,8) 28,2 (3,9) 27,9 (5,1) <0,01
P. abdominal 100,0 (11,3) 99,7 (12,3) 101,4 (10,3) 99,5 (11,1) 0,20
Males 79,6% 51,3% 93,3% 86,3% 0,01
Diabetes tipo 1 1,6% 1,0% 2,6% 1,4% 0,35
Diabetes tipo 2 27,1% 35,9% 31,4% 21,0% 0,01
Dislipemia 57,8% 58,5% 57,2% 57,7% 0,57
HTA 56,8% 72,3% 61,9% 47,3% 0,01
Cordero A, Bertomeu V, et al. Med Clin (Barc) 2012; 138:422-28 VBM 20123
A. Cordero
Risk Profile
Non Smokers Exsmokers Smokers
130
140
150
160
170
GR
AC
E s
core
]
]
]
150,3 (30,6)
146,2 (30,9)
132,1 (30,1)
p<0,01
Cordero A, Bertomeu v, et al. Med Clin (Barc) 2012; 138:422-28 VBM 2013
A. Cordero
Risk Profile
]
]
]
80,00
85,00
90,00
Non smokers Exsmokers Smokerss
86,1 (24,0)85,2 (24,0)
87,1 (25,0)
p=0,3
GR
AC
E s
core
Wit
ho
ut
age
Cordero A, Bertomeu V, et al. Med Clin (Barc) 2012; 138:422-28 VBM 2013
The risk in smokers is the same as that ofnon smokers who are 10 years older
Trends in Mortality From Myocardial Infarction. A Comparative Study Between Spain and the United States: 1990-2006
Domingo Orozco-Beltrana, Richard S. Cooperb, Vicente Gil-Guillena, Vicente Bertomeu-
Martinezc, Salvador Pita-Fernandezd, Ramón Durazo-Arvizub, Concepción Carratala-Munueraa, Luis Cea-Calvoa, Vicente Bertomeu-Gonzalezc,, Teresa Seoane-Pilladoc, Luis E.
Rosadoe
Rev Esp Cardiol. 2012;65:1079-85VBM 2013
USA shows better results. Probably better implementations of Therapeutic Procedures and to having an effective and preventive policy against risk factors