innovations in cardiovascular risk in the last year. a european perspective

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


Revisión ESH 2009Revisión ESH 2009


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


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Blood Pressure MeasurementsBlood Pressure MeasurementsBlood Pressure MeasurementsBlood Pressure Measurements


• 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


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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


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 1: No change or increase in BPTertile 2: Decrease by 1


Tertile 1: Decrease ? 6 mmHgTertile 2: Decrease 6Tertile 3: Decrease > 15 mmHg

Tertile 1: Decrease Tertile 2: Decrease 13


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 1: No change or increase in BPTertile 2: Decrease by 1 -


Tertile 1: Decrease ? 6 mmHgTertile 2: Decrease 6 - 15 mmHgTertile 3: Decrease > 15 mmHg

Tertile 1: Decrease <13 mmHgTertile 2: Decrease 13 -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


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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


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


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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


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


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

innovations in cardiovascular risk in the last year. a european perspective

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