HT and StrokeA treatment strategy

in neurology perspective

Surat Tanprawate, MD, FRCP(T), MSc(London)Division of Neurology, Chiang Mai University

Outline of my talk

Introduction to stroke risk factors

HT and stroke

BP target

Medication choice

Role of RAS inhibitor

Combination therapy

Apoplexy; Struck down with violenceStroke of God hand

Global burden of strokestroke is cause...disability (no. 1), dementia (no. 2), death (no. 3)

Johnston et al Lancet Neurol 2009

Thai stroke data...

•Public health statistic A.D. 2005

• Third cause of death

•Prevalence Thai stroke: 1,850/100,000

Classification of Ischemic stroke

original ‘TOAST classification; 1993’

Large artery atherosclerosis

Lacunar stroke(<1.5 cm)

Cardioembolism

Others

Albers et al. Chest 2004;126(3 Suppl):438S-512S

20%

25%

20%

Since 1948

Probability of stroke: a risk profile from the Framingham Study

Stroke. 1991;22:312-318Framingham risk score

Systolic Diastolic

Hypertension: Pathophysiology, Diagnosis, and Management.1995:127–144.

Stroke death rate by categories of systolic blood pressure and diastolic blood pressure.

Stroke death rate by categories of systolic blood pressure and diastolic

blood pressure.

Hypertension: Pathophysiology, Diagnosis, and Management.1995:127–144.

Stroke death rate by categories of systolic blood pressure and diastolic blood pressure.

Hypertension: Pathophysiology, Diagnosis, and Management.1995:127–144.

Treatment of Blood pressure

• Increase BP increase risk of stroke

• 5 mm Hg(DBP): ) 33% increase in stroke

• BP reduction of 5-6 mm Hg reduction

DBP(10-12 mm Hg SBP) reduce the risk of

stroke by 35-40%The RISC Group. Lancet.1990;335: 827-830

Neal B. MacMahon S. J Hypertens.1995; 13:1869-1873

Systematic review of 7 randomized trials of pharmacological blood-pressure-lowering treatment in patients with a prior stroke or TIA

Rashid P, Leonardi-Bee J. Stroke2003; 34(11):2741–8.

2 Large RCTPROGRESS studyPATS study

Blood pressure management in stroke

Guideline

Primary prevention

Secondary prevention

BP target

Drug choice

Stroke 2011;42;517-584

Primary Prevention of Stroke

Antihypertensive for primary stroke prevention

• In a meta-analysis of 23 randomized trials with stroke outcomes, antihypertensive drug treatment reduced risk of stroke by 32% (95% CI, 24% to 39%; P0.004) in comparison with no drug treatment

• No definitive evidence that any class of antihypertensive agents offers special protection against stroke

Stroke 2011;42;517-584

Stroke 2011;42;227-276

Secondary Prevention of Stroke

ASA/AHA guideline• An absolute target BP level and reduction are uncertain

and should be individualized, but benefit has been associated with an average reduction of approximately

10/5 mm Hg, and normal BP levels have been defined as 120/80 mm Hg by JNC 7 (Class IIa; Level B)

• The choice of specific drugs and targets should be individualized on the basis of pharmacological properties, mechanism of action, and consideration of specific patient characteristics for which specific agents are probably indicated (eg, extracranial cerebrovascular occlusive disease, renal impairment, cardiac disease, and diabetes) (Class IIa; Level B). (New recommendation)

Stroke 2011;42;227-276

RAS and role of ACEI, ARB

J Mol Med (2008) 86:715–722

ACEI

ARB

HOPE Study

-32%

Ramipril vs

Placebo

ARBs reduce risk of first stroke

►9,193 hypertensives for mean 4.8 years

►Blood pressure reduction (SBP/DBP mmHg) was 30/17 and 29/17 in the Losartan and Atenolol arms, respectively

Favoursatenolol

Favourslosartan

Primarycompositeendpoint

Cardiovascularmortality

Stroke Myocardialinfarction

Dahlöf et al. Lancet 2002;359:995–1003

LIFE study: Losartan vs AtenololA

dju

sted h

aza

rd r

ati

o

(95%

CI)

0.6

0.8

1.0

1.2

1.4

25% decrease stroke

Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE)

PROGRESS Study

Clinical evidence in secondary stroke prevention with RAS block

Progress study

• Perindopril vs Placebo

ProFess study

• Telmisartan vs Placebo

MOSES study

• Candesartan vs Nitrendipine

ONTARGET study

• Telmisartan vs Ramipril

In Reality

RAS blockade has clearly benefit beyond BP reduction for preventing stroke

ARB needs more clinical trial for proving clinical effectiveness over ACEI

ARB is less side effect than ACEI

Real situation

J Manag Care Pharm. 2007;13(8)(suppl S-b):S2-S8

What is the problem?

Therapeutic Inertia

Patient compliance

Combination BP lowering agent

Health Effects of Diuretics

• 3,081 Japanese patients with hypertension, CHD and/or HF

• Valsartan added to conventional non-ARB therapy versus supplementary conventional non-ARB treatment

ARB vs Non-ARB based therapy in Japanese patients

Thank You For Your Kind Attention

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