HT and Stroke

A 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 violence Stroke of God hand

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

Thai stroke data...

•Public health statistic A.D. 2005 • Third cause of death •Prevalence Thai stroke: 1,850/100,000
Johnston et al Lancet Neurol 2009

Classification of Ischemic stroke
original ‘TOAST classification; 1993’
Large artery atherosclerosis Lacunar stroke(<1.5 cm) Cardioembolism
20% 25% 20%

Others

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

Since 1948

Framingham risk score

Probability of stroke: a risk profile from the Framingham Study

Stroke. 1991;22:312-318

Systolic

Diastolic

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.

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

•5

Increase BP increase risk of stroke
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: 827830 Neal B. MacMahon S. J Hypertens.1995; 13:18691873

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

2 Large RCT PROGRESS study PATS study
Rashid P, Leonardi-Bee J. Stroke2003; 34(11):2741–8.

Blood pressure management in stroke
Guideline

Primary prevention Secondary prevention

BP target
Drug choice

Primary Prevention of Stroke
Stroke 2011;42;517-584

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

Secondary Prevention of Stroke
Stroke 2011;42;227-276

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

ACEI

ARB

J Mol Med (2008) 86:715–722

HOPE Study

-32%

Ramipril vs Placebo

Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE)
LIFE study: Losartan vs Atenolol ►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
1.4
Adjusted hazard ratio (95% CI) 1.2 1.0 0.8 0.6

ARBs reduce risk of first stroke
25% decrease stroke

Favours atenolol

Favours losartan Primary composite endpoint Cardiovascular mortality Stroke Myocardial infarction
Dahlöf et al. Lancet 2002;359:995–1003

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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