traitements associés chez l’hypertendu: statines, aspirine · chen z, et al. bmj ....

Traitements associés chez l’hypertendu:

Statines, Aspirine

Pr Jean-Jacques Mourad

CHU Avicenne, Université Paris 13, Bobigny

DU HTA, Mars 2012

[email protected]

Global Mortality 2000: Impact of Blood Pressure and Cholesterol

Ezzati M, et al. Lancet. 2002;360:1347-1360.

Attributable Mortality (in thousands; total 55,861 ,000)0 80007000600050004000300020001000

What Is Normal Cholesterol?

Chen Z, et al. BMJ. 1991;303:276-282.

0.25

0.50

1.00

2.00R

elat

ive

Ris

k of

CH

D

Mor

talit

y

139 147 155 162 170 178 186Mean Usual Cholesterol (mmol/L, mg/dL)

Relative risk of death ( ±±±± SD) from CHD by quartiles ofbaseline total cholesterol in 9021 Chinese people w ith 8-13 years’ follow-up.

18

129

4

3.6 3.8 4.0 4.2 4.4 4.6 4.8

Usual SBP (mmHg)

Flo

atin

g A

bsol

ute

Ris

k &

95%

CI

110 120 130 140 150 160

0.5

1.0

2.0

4.0

8.0

16.0

32.0

Coronary disease by usual SBP

-10mmHg70 + years RRR= 13%

60-69 years RRR= 22%

< 60 years RRR= 43%

Burden of Disease

HTN = hypertension; MI = myocardial infarction; PS = psychosocial.Reproduced with permission from Yusuf S, et al. Lancet. 2004;364:937-952.

Increased Number of CV Events (MI) in Patients With Hypertension Plus Other CV Risk Factors

Odd

s R

atio

(99

% C

I)512

256

128

64

32

16

8

4

2

1

2.9(2.6-3.2)

2.4(2.1-2.7)

1.9(1.7-2.1)

3.3(2.8-3.8)

13.0(10.7-15.8)

42.3(33.2-54.0)

68.5(53.0-88.6)

182.9(132.6-252.2)

333.7(230.2-483.9)

Smoking(1)

Diabetes(2)

HTN(3)

Lipids(4)

1+2+3 All 4 + Obes + PS All RFsRisk Factors

Risk Ratio

>20-Fold Increase OR (1.9 to 42.3)

Smoking

Diabetes

BloodPressure

Lipids

4 Risk Factors

3 Risk Factors

NON (OR HARDLY) MODIFIABLE RISK

FACTORS

MODIFIABLE RISK FACTORS

AGE

GENDER

SOCIO-ECONOMIC STATUS

FAMILIAL HISTORY

PERSONAL HISTORY

DIABETES MELLITUS

SMOKING

OVERWEIGHT

SEDENTARITY

BLOOD PRESSURE

LIPID PROFILE

INDIVIDUAL GLOBAL CV RISK

STATINES

ASCOT Study design

atenolol ±bendroflumethiazide

amlodipine ± perindopril

19,257 hypertensive

patients

PROBE design

ASCOT-BPLA

Investigator-lead, multinational randomised controlled trial

placeboatorvastatin 10 mg Double-blind

ASCOT-LLA10,305 patients

TC ≤ 6.5 mmol/L (250 mg/dL)

611

1314

2422

28

3162

7684

100

0 10 20 30 40 50 60 70 80 90 100

Peripheral vascular disease

Previous cerebrovascular events

LVH

Certain ECG abnorm alities

Plasm a TC:HDL-C ≥ 6

Type 2 diabe tes

Fam ily his tory of ear ly coronary disease

Sm oker

M icroalbum in/prote inuria

M ale

Age ≥ 55 years

Hypertens ion

ASCOT LLA: Patient Population Risk Factor Profile

All patients in ASCOT have hypertension plus ≥3 risk factors for CHD

Patients With Risk Factor (%)

Sever PS, et al. J Hypertens. 2001;19:1139-1147.

Basically primary prevention and no previous known CHD

0

1

2

3

4

0,0 0,5 1,0 1,5 2,0 2,5 3,0 3,5

Years

Cum

ulat

ive

inci

denc

e (%

)

36% reduction

ASCOT-LLA: Primary End Point: Nonfatal MI and Fatal CHD

HR = 0.64 (0.50-0.83)

Atorvastatin 10 mg Number of events 100

Placebo Number of events 154

P = 0.0005

Sever PS, Dahlöf B, Poulter N, Wedel H, et al, for the ASCOT Investigators . Lancet. 2003;361:1149-58.

0

1

2

3

0,0 0,5 1,0 1,5 2,0 2,5 3,0 3,5

Years

Cum

ulat

ive

Inci

denc

e (%

)

ASCOT-LLA: Secondary End Point: Fatal and Nonfatal Stroke

27% reduction

HR = 0.73 (0.56-0.96) P = 0.0236

Atorvastatin 10 mg Number of events 89

Placebo Number of events 121

Sever PS, Dahlöf B, Poulter N, Wedel H, et al, for the ASCOT Investigators. Lancet. 2003;361:1149-58.

European Heart Journal (2011) 32, 2525–2532

J Hypertens 2011; 29:592–599

NEJM 2008;359:2195

N Engl J Med 2008;359:2195-207

We randomly assigned 17,802 apparently healthy men and women with low-densitylipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol perliter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher torosuvastatin, 20 mg daily, or placebo

N Engl J Med 2008;359:2195-207

Hypertension. 2007;49:792-798

Arch Intern Med. 2012;172(2):144-152

Lancet 2010; 375: 735–42

JAMA. 2011;305(24):2556-2564

The benefit of combining a statin with antihypertensive treatment in hypertensive patients was well establishedby the ASCOT-LLA study, as summarized in the 2007 ESH/ESC guidelines.

The negative results obtained with another statin in the ALLHAT study can be attributed to insufficient lowering of total cholesterol (11% in ALLHAT as compared with 20% in ASCOT).

The beneficial effect of statin administration to patients without previous cardiovascular events has beenstrengthened by the findings of the JUPITER study, showing that lowering LDL-cholesterol by 50% in patients with baseline values less than 130 mg/dl (3.4 mmol/l), but elevated C-reactive protein (CRP), reduced cardiovascular events by 44%.

In conclusion, the recommendation given in the 2007 guidelines to consider statin therapy in hypertensive patients who have an estimated 10-year risk of cardiovascular events more than 20% can be reconfirmed, but the JUPITER study suggests that statin benefits can be observed also in patients with elevated CRP and at moderate cardiovascular risk (about 15% cardiovascular events in 10 years).

ESH 2009

ASPIRINE

Problème nosologique: Qu’appelle-on prévention primaire??

Lancet 2009;373:1849

J Hypertens 2002; 20:2301–2307

J Am Coll Cardiol 2010;56:956–65

BMJ 2008;337:a1840

BMJ 2009;339:B4531

NEJM 2005

39876 femmes; âge moyen 55ans;

HTA 26%; Tabagisme 13%; Obésité : 18.2%; Diabète 2.6%; Risque framingham <5% à 10 ans : 85%

NEJM 2005

In conclusion, the prudent recommendations of the 2007 ESH/ESC guidelines can be reconfirmed: antiplatelet therapy, in particular low-dose aspirin, should be prescribed to hypertensive patients with previous cardiovascular events;

It can also be considered in hypertensive patients without a history of cardiovascular disease with reduced renal function or with a high cardiovascular risk.

In patients receiving aspirin, careful attention should always be given to the increased possibility of bleeding,particularly gastrointestinal.

ESH 2009

traitements associés chez l’hypertendu: statines, aspirine · chen z, et al. bmj ....

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