Casablanca, le 30 Avril 2011

MEDITERANEAN GROUP FOR STUDY DIABETES

Prospective Studies Collaboration, Lancet 2002

Stroke IHD

IHD and Stroke related death regarding to age and systolic blood pressure level a

metaanalysis

BLOOD PRESSURE GOAL FOR DIABETIC PATIENTS

Guidelines

Guidelines Year BP Goal

JNC7 2003 <130 / 80mmHg

WHO / ISH 2003 <130 / 80mmHg

BHS 2004 <130 / 80mmHg

HAS 2005 <130 / 80mmHg

ESH 2007 <130 / 80mmHg

AHA 2007 <130 / 80mmHg

ADA 2008 <130 / 80mmHg

Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA. 2003;289:2560–2572.World Health Organization, International Society of Hypertension Writing Group. 2003 World Health Organization (WHO⁄ International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens. 2003;21:1983–1992.Williams B, Poulter NR, Brown MJ, et al. British Hypertension Society guidelines for hypertension management 2004 (BHS-IV): summary. BMJ. 2004;328:634–640. Mancia G, De Backer G, Dominiczak A, et al. 2007 Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007;25:1105–1187.Rosendorff C, Black HR, Cannon CP, et al. Treatment of hypertension in the prevention and management of ischemic heart disease. A scientific statement from the American Heart Association Council for High Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention. Circulation. 2007;115:2761–2788.American Diabetes Association. Standards of medical care in diabetes – 2008. Diabetes Care. 2008;31(suppl 1):S12–S54.

Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA. 2003;289:2560–2572.World Health Organization, International Society of Hypertension Writing Group. 2003 World Health Organization (WHO⁄ International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens. 2003;21:1983–1992.Williams B, Poulter NR, Brown MJ, et al. British Hypertension Society guidelines for hypertension management 2004 (BHS-IV): summary. BMJ. 2004;328:634–640. Mancia G, De Backer G, Dominiczak A, et al. 2007 Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007;25:1105–1187.Rosendorff C, Black HR, Cannon CP, et al. Treatment of hypertension in the prevention and management of ischemic heart disease. A scientific statement from the American Heart Association Council for High Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention. Circulation. 2007;115:2761–2788.American Diabetes Association. Standards of medical care in diabetes – 2008. Diabetes Care. 2008;31(suppl 1):S12–S54.

CLevel of evidence

CLevel of evidence

Zanchetti et al. Journal of Hypertension 2009,

Achieved systolic blood pressure (SBP) in diabetic patients included intrials comparing placebo (or less intense) with more intense

antihypertensive treatment (ordinates at left), and reductions in majorcardiovascular (CV) events (ordinates at right).

ABCD RW Schrier et al. Kidney Int 2002;61:1086-97.)

137±0.7/81±0.3 mm Hg

128±0.8/75±0.3 mm Hg

CV outcomes according to intervention: Intensive vs moderate

ABCD RW Schrier et al. Kidney Int 2002;61:1086-97

INVESTCooper-DeHoff RM et al. JAMA 2010;304:61-8

>140mmHg<130mmHg130-140mmHg

INVESTCooper-DeHoff RM et al. JAMA 2010;304:61-8

N Engl J Med 2010;362:1575-85.

N Engl J Med 362;17 nejm.org april 29, 2010

Average : 133.5 Standard vs. 119.3 Intensive, Delta = 14.2

Mean # Meds Intensive: 3.2 3.4 3.5 3.4 Standard: 1.9 2.1 2.2 2.3

OutcomesIntensive Therapy

(n=2363)Standard Therapy

(n=2371) Hazard Ratio(95% Cl)

p value

no. of events rate/ yr (%) no. of events rate/ yr (%)

Primary outcome 208 1.9 237 2.10.88

(0.73–1.06) 0.20

Prespecified secondary outcomes

Nonfatal MI 126 1.1 146 1.3 0.87 (0.68–1.10) 0.25

Stroke

Any 36 0.3 62 0.5 0.59(0.39–0.89) 0.01

Nonfatal 34 0.3 55 0.5 0.63 (0.41–0.96) 0.03

Death

From any cause 150 1.3 144 1.2 1.07 (0.85–1.35) 0.55

From CVD 60 0.5 58 0.50.86

(0.66-1.12) 0.74

Expanded primary outcome* 521 5.1 551 5.3

0.95 (0.84–1.07) 0.40

Major coronary disease event† 253 2.3 270 2.4

0.94 (0.79–1.12) 0.50

Fatal or nonfatal CHF 83 0.7 90 0.8 0.94 (0.70–1.26) 0.67

ACCORD BPNo difference between groups in the rate of the primary and secondary outcomes except stroke

* primary outcome plus revascularization or nonfatal heart failure† A major coronary disease event was defined as a fatal coronary event, nonfatal MI, unstable angina.

ACCORD Study Group. N Engl J Med March 14, 2010. Epub.

AC14

ACCORD BPSignificantly greater incidence of serious adverse events in the intensive therapy arm

Intensive Therapy(n = 2362)

N (%)

Standard Therapy(n = 2371)

N (%)P

Serious AE 77 (3.3) 30 (1.3) <0.0001

Hypotension 17 (0.7) 1 (0.04) <0.0001

Syncope 12 (0.5) 5 (0.2) 0.10

Bradycardia or Arrhythmia 12 (0.5) 3 (0.1) 0.02

Hyperkalemia 9 (0.4) 1 (0.04) 0.01

Renal Failure 5 (0.2) 1 (0.04) 0.12

eGFR* ever <30 mL/min/1.73m2 99 (4.2) 52 (2.2) <0.001

Any Dialysis or ESRD** 59 (2.5) 58 (2.4) 0.93

Dizziness on Standing† 217 (44) 188 (40) 0.36

† Symptom experienced over past 30 days from HRQL sample of N=969 participants assessed at 12, 36, and 48 months post-randomization.

* eGFR: estimated Glomerular Filtration Rate**ESRD: End Stage Renal Disease

ACCORD Study Group. N Engl J Med March 14, 2010. Epub.

AC15

Characteristic Mean or %

Blood Pressure mmHg 139/76

On Antihypertensive % 87

Creatinine (mg/dL) 0.9

eGFR (mL/min/1.73m2) 92

DM Duration (yrs)* 10

A1C (%) 8.3

BMI (kg/m2) 32* Median value

Characteristic Mean or %

Age (yrs) 62

Women % 48

2° prevention % 34

Race / Ethnicity

White % 61

Black % 24

Hispanic % 7

• Stable Type 2 Diabetes >3 months

• HbA1c 7.5% to 11% (or <9% if on more meds)• High CVD risk = clinical or subclinical disease or >2 risk factors

• Age (limited to <80 years after Vanguard)≥ 40 yrs with history of clinical CVD (secondary prevention)≥ 55 yrs otherwise

• Urine protein <1.0 gm/24 hours or equivalent

• Serum Creatinine <1.5 mg/dl

ACCORD BPS t u d y

Les patients inclus sont âgés et souvent non proteinuriques

Dogma Disputed:

Can Aggressively Lowering Blood Pressure in Hypertensive Patients

with Coronary Artery Disease Be Dangerous?

F Messerli et al. Ann Intern Med. 2006;144:884-893.

INVESTSecondary analysis of data from

F Messerli et al. Ann Intern Med. 2006;144:884-893.INVEST

CORONARY BLOOD FLOW ON DIASTOLE

Bakris GL et al. Am J Kidney Dis 2000; 36(3): 646-661

95 98 101 104 107 110 113 116 119

r = 0.69;P < 0.05

PAM1 (mmHg)

130/85

1 Préssion artérielle moyenne

2Débit de filtration glomérulaire

140/90

HTA non traitée

0

-2

-4

-6

-8

-10

-12

-14

Mo d

if ic a

ti on

du D

FG2

(ml /m

i n/a

n)

META ANALYSE DES CORRLATION ENTRE FONCTION RENALE & PRESSION ARTERIELLE

META ANALYSE DES CORRLATION ENTRE FONCTION RENALE & PRESSION ARTERIELLE

Independent and Additive Impact of

BP Control and ARB on Renal

Outcomes in the Irbesartan Diabetic

Nephropathy Trial:

Clinical Implications and Limitations

M A Pohl et al. J Am Soc Nephrol 2005.

trialIDNT

Adler et al., Kidney Int, 2003

0

20

25

15

(%)

10

5

ESRD

*

Estimate from the °UKPDS and the *RENAAL studies

Mortality

° Renal failure in type 2 diabetes

“a medical catastrophe of world-

wide dimension”

Ritz, AJKD (1999) Ritz, AJKD (1999) 3434: 795: 795

ANNUAL ESRD AND MORTALITY IN TYPE 2 DIABETICS WITH OVERT

NEPHROPATHY

A Zanchetti, Guido Grassi, G Mancia:

Wisdom should not be taken for evidence

When should antihypertensive drug treatment be initiated and to what levels should systolic blood pressure be lowered? A critical reappraisalWhen should antihypertensive drug treatment be initiated and to what levels should systolic blood pressure be lowered? A critical reappraisal

Journal of Hypertension 2009, 27:923–934Journal of Hypertension 2009, 27:923–934

BP GOAL IN HYPERTENSIVE TREATYED PATIENT:

The lower, NOT the better Reappraisal ESH 2009

BP GOAL IN HYPERTENSIVE TREATYED PATIENT:

The lower, NOT the better Reappraisal ESH 2009

G Mancia et al ESH 2007 & Reappraisal 2009Journal of hyprttrsion

CV MortalityCV Mortality

BPBP

Reappraisal ESH 2009

ESH 2007

CurveThe

Central SBP: difference 4,3 mm Hg (p < 0,0001)

Peripheral SBP: difference 0,7 mm Hg (p < 0,2)

2073 patients

amlodipine + Perindopril

atenolol + thiazide

Sfax, 13th century monument