2/28/2011

Curriculum Vitae
Nama : Prof DR Dr Hasan Sjahrir SpS(K),
Jabatan/Pangkat : Guru besar Neurologi FK USU Medan/IV E Tempat lahir: Kediri, 30-9-1947 Menikah, 2 anak Jabatan/Posisi saat ini
1. 2. Anggota Dewan Penasehat Pengurus Pusat Asosiasi Profesor Indonesia Ketua II Pengurus Pusat Perdossi & Koordinator Nasional Kelompok Studi 3. Ketua Komisi Subspesialis Kolegium Neurologi Indonesia 4. Penasehat Kelompok Studi Nyeri Kepala Perdossi 5. Anggota International Headache Society 6. Ketua AAzI Wilayah Sumut 7. Ketua Pokdi Neurotraumatologi Perdossi Cabang Medan 8. Anggota Honorary Editorial Advisory Board Asia MIMS Indonesia 9. Anggota Editorial Board Medical Progress Journal Asia 10. Anggota Medical Advisory Board PT ASKES
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1 1

Key word: hypertension, ARB, stroke therapy

Hasan Sjahrir Department of Neurology Sumatera Utara University Medan

The Role of ARBs in The Management of Hypertensive Stroke Patients: Recent Updates

http://neurologi.usu.ac.id
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HYPERTENSION

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Hypertension (HT)
HT affects over 60 million Americans and 1 billion people worldwide predicted to rise 60% by 2025 to 1.56 billion, with only 50% of patients being adequately controlled. each increment in systolic BP of 20 mmHg or diastolic BP of 10 mmHg doubles the risk of stroke There were significant reductions (P<0.0001) in the rate of hospitalization and death from stroke associated with the increases in antihypertensive prescriptions
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Poulter N. Br J Cardiol 2010 Robinson JD. The Annals of Pharmacotherapy. 2009 Campbell NR. Hypertension. 2009 4

The INTERSTROKE study : 2010

O'Donnell MJ, Xavier D, Liu L, et al. Lancet 2010

Case control study : 3000 pts acute stroke from 22 countries

studies have failed to show a consistent relationship between total cholesterol and stroke risk
10 modifiable risk factors explain 90% of stroke risk

1. hypertension, current smoking, abdominal obesity, diet, and physical activity (80% of the risk of ischemic stroke and 90% of the risk of hemorrhagic strokes)
2. diabetes mellitus, alcohol intake, psychosocial factors, the ratio of apolipoprotein B to A1, and cardiac causes (atrial fibrillation or flutter, previous MI, and valve disease)
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The INTERSTROKE study : 2010

O'Donnell MJ, Xavier D, Liu L, et al. Lancet 2010

1. history of hypertension or blood pressure >160/90 (51.8%) 2. low regular physical activity (28.5%) 3. elevated waist-to-hip ratio (26.5%) 4. blood lipid level (ratio of ApoB to ApoA) (24.9%) 5. current smoking (18.9%) 6. poor diet (18.8%)
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7. cardiac causes (arrhythmia, MI or valvular disease) 6.7% 8. depression (5.2%) 9. diabetes mellitus (5.0%) 10. psychosocial stress (4.6%) 11. alcohol intake >30 drinks per month (3.8%)

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Metabolic Syndrome criteria

AHA/ASA CRITERIA 2010

At least when 3 following features are present

1. increased waist circumference (102 cm in men; 88 cm in women), 2. elevated triglyceride levels (150 mg/dL), 3. reduced high-density lipoprotein cholesterol (<40 mg/dL in women; <50 mg/dL in men), 4. elevated blood pressure (systolic 130 mm Hg, or diastolic 85 mm Hg), and 5. elevated fasting glucose (100 mg/dL).
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JNC 7
Classification Normal Prehypertension SBP, mm Hg < 120 120139 or DBP, mm Hg < 80 8089 No Compelling Indication No antihypertensive drug No antihypertensive drug With Compelling Indication* No anti HT drug Drugs for compelling indication

Stage 1 hypertension

140159 9099 or

Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination

Drugs for compelling indication. Other drugs (diuretics, ACEI, ARB, BB, CCB) as needed Drugs for compelling indication. Other drugs (diuretics, ACEI, ARB, BB, CCB) as needed
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Stage 2 hypertension

160 or

> 100

Two-drug combination for most(usually thiazide-type diuretic and ACEI or ARB or BB or CCB)

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Compelling indications are (1) CHF (2) MI (3) DM (4) Chronic Renal Failure (5) prior stroke

Poulter N. Br J Cardiol 2010

HYPERTENSION (HT)
British Hypertension Society (BHS) and National Institute for Health and Clinical Excellence (NICE) 2006 Pts aged 55 years and over, or black patients of any age, the initial therapy should be either CCB or a diuretic (thiazide or thiazide-type diuretic e.g. indapamide, chlorthalidone) Pts younger than 55 years, first-choice therapy should be ACEi or an ARBs if an ACEi is not tolerated
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JNC7 2004 uncomplicated HT: Thiazide-tdiuretics : alone or combined high-risk conditionsthe initial use of other anti-HT drug (ACEi, ARBs, -blockers, CCB). Pts HT will require 2 anti HT to achieve goal BP<140/90 mmHg, or <130/80 mmHg for pts with DM or chr kidney dis. If BP >20/10 mmHg above goal BP initiating therapy with 2 agents, one of which usually should be a thiazide-diuretic.
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Beta blockers
beta blockers have negative effects on both glucose/ impaired glycemic control and lipid metabolism/ cause dyslipidemia favor weight gain -blockers may have a reduced ability to protect against stroke (particularly atenelol was unable to prevent stroke in HT patients) although beta blockers reduce brachial blood pressure effectively, they do not lower central systolic blood pressure as much as ACEi, diuretics, or calcium antagonists,
2/28/2011

Lindholm LH, et al. a new meta-analysis Lancet 2005 Sierra A. Current Drug Therapy, 2006, 1, 9-16 Venkatesh Aiyagari and Philip B. Gorelick. Stroke 2009

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CCB & ACEi controversy

rates of fatal coronary heart disease (CHD) or nonfatal myocardial infarction (MI) in older hypertensive patients were similar in CCB- and ACE-inhibitortreated patients CCBs significantly increased the risk of heart failure ACE inhibitors increased the risk of stroke, angina, peripheral artery disease (PAD), gastrointestinal (GI) bleeding, and angioedema. (p>0.0001)(Six-year event rate per 100 persons) CCBs are safer and better tolerated.
2/28/2011

Leenen F. Hypertension 2006.

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Beta blockers & Stroke

Beta blockers are not as effective as other antihypertensive drugs in reducing stroke Beta Blockers showed

Lindholm LH, et al. a new meta-analysis Lancet 2005

The metaanalysis of 13 such trials, a total of 105,951 pts.

Outcome (comparing RR with beta 95% CI blockers with other anti HT) Stroke MI Outcome
Stroke MI

1.16

1.04-1.30

a 16% increased risk in stroke

compared with other antihypertensive drugs and a 3%

All-cause mortality 1.03

1.09 1.00

1.02 RR with beta blockers 0.93-1.12 95% CI (+diuretic) 0.99-1.08

0.98-1.21 0.81-1.22 0.89-1.05
95% CI 0.71-0.93 0.83-1.05
12 0.86-1.04

All-cause 0.97 mortality Outcome (comparing RR with beta

with placebo) Stroke MI All-cause mortality blockers 0.81 0.93 0.95

increase in allcause mortality.

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Beta blockers
beta blockers have negative effects on both glucose/ impaired glycemic control and lipid metabolism/ cause dyslipidemia favor weight gain -blockers may have a reduced ability to protect against stroke (particularly atenelol was unable to prevent stroke in HT patients) although beta blockers reduce brachial blood pressure effectively, they do not lower central systolic blood pressure as much as ACEi, diuretics, or calcium antagonists,
2/28/2011

Lindholm LH, et al. a new meta-analysis Lancet 2005 Sierra A. Current Drug Therapy, 2006, 1, 9-16 Venkatesh Aiyagari and Philip B. Gorelick. Stroke 2009

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CCB & ACEi controversy

rates of fatal coronary heart disease (CHD) or nonfatal myocardial infarction (MI) in older hypertensive patients were similar in CCB- and ACE-inhibitortreated patients CCBs significantly increased the risk of heart failure ACE inhibitors increased the risk of stroke, angina, peripheral artery disease (PAD), gastrointestinal (GI) bleeding, and angioedema. (p>0.0001)(Six-year event rate per 100 persons) CCBs are safer and better tolerated.
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Leenen F. Hypertension 2006.

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ANGIOTENSIN RECEPTOR BLOCKERs (ARBs)

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LIVER KIDNEY

PULMO & KIDNEY

AT2 activation upregulation of the AT2 receptors blood pressurelowering, cardiovascular remodelling ,stroke prevention recruiting cerebral collateral vessels enhancing neuronal resistance to anoxia, attenuating prothrombosis, inflammation, endothelial dysfunction that mediate atherosclerosis .

Arteriole, sympathic Adrenal, pituitary

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List of ARBs in US
Trade Name
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. Cozaar (Merck) Hyzaar (Merck) Avapro (Bristol-Myers Squibb) Avalide (Bristol-Myers Squibb) Diovan (Novartis) Diovan HCT (Novartis) Atacand (AstraZeneca) Atacand HCT (AstraZeneca) Teveten (Solvay Pharma Inc) Teveten HCT (Solvay Pharma In Micardis (Boehringer Ingelheim) Micardis HCT (Boehringer Ingelh Benicar (Sankyo Pharma, Inc)

Chemical Name
losartan losartan/hydrochlorothiazide irbesartan irbesartan/hydrochlorothiazide valsartan valsartan/hydrochlorothiazide candesartan cilexetil candesartancilexetil/hydrochlorothiazide Eprosartan eprosartan/hydrochlorothiazide Telmisartan telmisartan/hydrochlorothiazide olmesartan
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Positive effect of ARB

1. blood glucose control by increasing insulin sensitivityreduced new onset diabetes 2. platelet anti-aggregating effects, 3. hypouricemic effects, 4. atrial antifibrillatory effects. 5. reduces the development of oxidative stress, 6. diminishing activation of inflammatory cells, including monocyte migration and adhesion to endothelial cells 2/28/2011

Fitchett d.Vascular Health and Risk Management 2007 Townsend RR.Clin J Am Soc Nephrol 2008 Hankey GJ Stroke 2009

8. may have protective effects for stroke that are independent of blood pressure reduction, 9. antiproliferative, 10. contribute to protect atherosclerosis and atherothrombosis 11. both ACEi and ARBs have been shown to alter factors that promote fibrinolysis and reduce thrombosis 12. encourage plaque rupture by enhancing MMP-1 activity
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Role & safety of ARB

patients with HTN with comorbidities, such as HF, MI, DM, chronic kidney disease, and stroke, ACEi and ARBs appear to provide added benefit beyond solely lowering blood pressure.

ACEi and ARBs may be beneficial in the prevention of DM, AF, and recurrent stroke. A combination of an ARB and an ACE inhibitor may be more effective than either agent alone.
A meta-analysis of the combination of ACE inhibitors and ARBs vs ACE inhibitors alone found that combination reduced ambulatory blood pressure by 4.7/3.0 mm Hg overall compared with 3.8/2.9 mm Hg for ACE inhibitor monotherapy.
2/28/2011 19 (Miller AE et al. Formulary. 2006;41:274284.)

ARBs and Cerebrovascular Protection

STUDY LIFE 2002 SCOPE 2002 MOSES 2005 PRoFESS 2007 Ontarget 2004 VALUE 2004 ACCESS 2003 N 9193 4964 1405 20.332 25.620 15 245 500 TIME/ DRUG YRS 4.8 3.7 2.5 2.5 5 4.2 1 losartan/atenolol Candesartan/placebo eprosartan/nitrendipine Telmisartan/placebo Telmisartan/ramipril Valsartan/amlodipine Candesartan/placebo STROKE REDUCTION % 26 28 25 5 32 -15 52

Losartan Intervention For Endpoint reduction in hypertension (LIFE) study SCOPE:Study on Cognition and Prognosis in the Elderly The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) study Acute Candesartan Cilexetil Therapy in Stroke Survivors (ACCESS) Blood Pressure Lowering Treatment Trialists (BPLTC) Ongoing Telmisartan Alone and inCombination with Ramipril Global Endpoint Trial (ONTARGET) Morbidity and mortality after stroke, eprosartan compared with nitrendipine for secondary prevention(MOSES) 2/28/2011 20

The Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC)

A meta- analysis of 26 trials

ACE inh reduction in the risk for stroke by 19% , for each 5-mm Hg reduction in BPARBs was 26%.
There were no significant differences between ARB- and ACE inhibitor- based regimens for blood pressure-dependent effects on stroke.

there were no significant differences in the effects of ARBs or ACE I on stroke.

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Lancet 2003; 362: 15271535. 21

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Angiotensin Receptor Blocker

CANDESARTAN
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Stroke prevention with the angiotensin II type 1receptor blocker candesartan in elderly patients with isolated systolic hypertension. 4964 pts : age 70 to 89 years.
1158 patients : systolic BP > 160 mm Hg and diastolic BP was no less than 90 mm Hg. The drug was given to 754 patients and the remainder served as controls.

The results of the study are interesting. Despite the fact that there was no significant change in blood pressure in the treated group, there was a 42% reduction in stroke.
2/28/2011

Papademetriou V, et al. J Am Coll Cardiol. 2004;44:1175-1180.

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The ACCESS Study

Evaluation of Acute Candesartan Cilexetil Therapy in Stroke Survivors
Joachim Schrader, MD et al (Stroke. 2003;34:1699-1703.)

Background and Purpose-to

assess the safety of modest blood pressure reduction by candesartan cilexetil in the early treatment of stroke.
MethodsFive hundred patients were recruited in a prospective, double-blind, placebocontrolled, randomized, multicenter phase II study.

Conclusionsthat early neurohumoral inhibition has similar

beneficial effects in cerebral and in myocardial ischemia. The fact that no cardiovascular or cerebrovascular event occurred as a result of hypotension. candesartan cilexetil is a safe for early therapeutic option. 2/28/2011 24

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The Candesartan Atenolol Carotid Haemodynamics Endpoint Trial (CACHET)

Ariff et al Stroke 2006

candesartan (8 to 16 mg per day) and atenolol (50 to 100 mg per day) reduced intima-media thickness (IMT) and intima-media area (IMA) and increased distensibility to similar extents after 52 weeks of treat.

despite similar reductions in BP, treatment with atenolol resulted in a lesser reduction in left ventricular mass index, a decrease in lumen diameter and a reduction in carotid blood flow compared with candesartan. candesartan demonstrated BP-independent effects on ventricular and carotid arterial structure.
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Candesartan Augments Ischemia-Induced Proangiogenic State and Results in Sustained Improvement After Stroke
Anna Kozak, MS et al. (Stroke. 2009; 40:1870-1876.)

Background - acute treatment with candesartan in an experimental

model of stroke resulted in vascular protection and improved outcomes at 24 hours poststroke, (the mechanisms are unknown. )

ConclusionCandesartan after reperfusion augments ischemiainduced angiogenic state and provides long-term benefits. The beneficial effects may involve vascular protection and enhancement of early angiogenic remodeling. (Matrix metalloproteinase-2 activity and vascular endothelial growth factor expression were higher and cerebrospinal fluid was significantly more proangiogenic)
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SCAST TRIAL
The Scandinavian Candersartan Acute Stroke
Sandset EC et al. International Journal of Stroke Oct 2010 International randomised, placebo controlled, double blind trial 2500 pts within 30 hours of stroke SBP > 140 mmHg Randomly assigned to candesartan or placebo for 7 days (doses increasing from 4 to 16 mg once daily) Follow up period is 6 months Study outcomes: Functional : mRS Vascular death ( MI or stroke) Barthel Index EuroQol MMSE 2/28/2011 Health economy cost Sandset EC, Bath PMW, Boysen G, et al. Lancet Februari 2011

trial found no benefit and a hint of possible harm associated with antihypertensive treatment with candesartan in the acute phase of stroke the results of 10 previous trials of BP lowering in acute stroke, increase the reliability of the evidence and suggest that pharmacologically lowering blood pressure does not have a beneficial effect.
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STROKE
Management of Hypertensive Stroke Patients: Recent Updates
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Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack
A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association Karen L. Furie, MD, MPH, FAHA, Chair et al (Stroke. 2011;42:00-00.)

1. DEFINITION:TIA (old): a sudden neurological deficit of presumed vascular origin lasting less than 24 hours 2. TIA(new): a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, 2/28/2011 without acute infarction

Stroke Ischemic have been defined as

1. large-artery atherosclerotic infarction, (extra/intracranial ) 2. embolism from a cardiac source; 3. small-vessel disease; 4. other determined cause such as dissection, hypercoagulable states, or sickle cell disease; 5. Infarcts of undetermined 30 cause.

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Relationship Between Therapeutic Changes in Blood Pressure and Outcomes in Acute Stroke: A Metaregression
Chamila M. Geeganage, Philip M.W. Bath (Hypertension. 2009;54:775-781.)

37 trials involving 9008 pts

Large fall and increase blood pressures during the acute phase of stroke are associated with a poor outcome
outcomes were not significantly reduced at any level of change in BP Both acute ischemic stroke and primary intracerebral hemorrhage are associated with high blood pressure (BP) in 75% of patients Additional BP lowering treatment might be more efficiently started very soon after the stroke (eg, within 6 to 12 hours of onset). Unfortunately there were insufficient data to analyze treatment effects in the hyperacute phase (6 hours). 2/28/2011 31

blood pressure changes in acute ischemic stroke

Spence JD. Hypertension 2009

High blood pressure during acute stroke Autoregulation is lost in the ischemic regionaggravates cerebral edema progressive reduction in perfusion pressure, strangulation of the salvageable penumbra, and progressive infarction
SBP >180 mm Hg doubled the risk of poor outcomes SBP < 136 mm Hg increased the risk of poor outcomes by 30%. In patients over age > 80 years, a BP reduction > 28 mm Hg gave a 21.7-fold increase in the risk of poor outcomes 2/28/2011 32

CLASS I

AHA/ASA Guidelines 2011 for Treatable Vascular Risk Factors : Hypertension PRIMARY PREVENTION( Goldstein LB) SECONDARY PREVENTION(Furie KL)

1. BP reduction is recomm for 1. the JNC 7 report, including both prevention of recurrent both lifestyle modification and stroke and other vascular pharmacological therapy, are events in persons who are recommended (Class I; Level A) beyond the first 24 hours 2. SBP should be a goal of <140 (Class I; Level A) mm Hg and diastolic BP to <90 2. The optimal drugs are mm Hg are associated with a recommended is uncertain. lower risk of stroke and The available data that cardiovascular events (Class I; diuretics or the combination Level A). DM or renal disease, of diuretics and an ACEI are the BP goal is <130/80 mm Hg useful (Class I; Level A) 33 (Class I; Level A).

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CLASS I

PRIMARY PREVENTION (Goldstein LB 2011)

AHA/ASA Guidelines 2011 for Treatable Vascular Risk Factors : Hypertension & Diabetes
SECONDARY PREVENTION (Furie KL 2010)

Treatment of hypertension Use of existing guidelines in adults with diabetes with for glycemic control and an ACEI or an ARB is useful BP targets in patients with (Class I; Level of Evidence diabetes is recommended A). for patients who have had a stroke or TIA (Class I; Level of Evidence B).
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CLASS II

Guidelines for Treatable Vascular Risk Factors : Hypertension SECONDARY STROKE PREVENTION RECOMMENDATION AHA/ASA 2011 1. Because this benefit extends to persons with and without a documented history of Hypertension, this recommendation is reasonable for all patients with ischemic stroke or TIA who are considered appropriate for BP reduction (Class IIa; Level B) An absolute target BP level and reduction are uncertain and should be individualized, but benefit has been associated with an average reduction of

2.

approximately 10/5 mm Hg, and normal BP levels have been defined as 120/80 mm Hg by JNC 7 (Class IIa; Level B) 3. Several lifestyle modifications have been associated with BP reduction and are a reasonable part of a comprehensive antihypertensive
therapy These modifications include salt restriction; weight loss; consumption of a diet rich in fruits, vegetables, and low-fat dairy products; regular aerobic physical activity; and limited alcohol consumption.(Class IIa; Level of Evidence C)
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Furie KL et al. AHA/ASA Guidelines for the Prevention of Stroke /TIA .Stroke 2011

A meta-analysis of RCTs showed that antihypertensive medications BP lowering is associated with a 30% to 40% reduction in risk of stroke, recurrent stroke or TIA. There are excellent clinical outcome trial data proving that lowering BP with several classes of drugs, will reduce the complications of HT angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers (BBs), Calcium channel blockers (CCBs), thiazide-type diuretics,

The choice of specific drugs and targets should be individualized and consideration of specific patient characteristics for which specific agents are probably indicated (Class IIa; Level of Evidence B). 2/28/2011

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THE BEST CHOICE OF RECOMMENDATION 1 HT ALONE ACEi, ARB,BBs,CCBs, Thiazide 2 HT + STROKE 3 HT+ DIABETES MELLITUS 4 HT+ RENAL DISEASE 5 HT+ AF 6 HEART FAILURE 7 HT+STABLE ANGINA PECTORIS 8 HT+ ACUTE CORONARY SYNDR (UNSTABLE ANGINA, MI) 9 HT+ POST MYOCARD INFARC ACEIs + thiazide diuretic Thiazide diuretics, BBs, ACEIs, ARBs, and CCBs ACEIs and ARBs ACEI, ARB ACEIs, BBs, ARBs and aldosterone blockers BB, alternative long-acting CCBs BBs and ACEIs ACEIs, BBs, and aldosterone antagonists
JNC7 Suresh,Lip YH. Expert Rev Cardiovasc Ther. 2008 37

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Management of Blood Pressure for Acute and Recurrent Stroke (Venkatesh Aiyagari and Philip B. Gorelick. Stroke 2009;40;2251-2256) IV thrombolytic tx: BP should be lowered if > 185 mm Hg systolic or >110 mm Hg diastolic. After thrombolytic tx, SBP should be kept <180 mm Hg and DBP < 105 mm Hg. Anti HT agents should be give : the DBP is > 120 mm Hg or the SBP is > 220 mm Hg and limiting the drop in BP during the first 24 hours by approximately 15%. BP-lowering therapy as soon as 24 hours after acute ischemic stroke all major classes of BP-lowering agents may diminish recurrent stroke risk. Although some studies have suggested ACEi and ARBs may be more effective in recurrent stroke prevention than other anti HT drug 2/28/2011 38

ARBs Should Be Regarded as First-Line Drugs for Stroke Prevention in Both Primary and Secondary Prevention Settings : No
Martin H. Strauss and Alistair Hall Stroke 2009;40;3161-3162

In a meta-analysis of ARB versus any active comparator or placebo by these authors (n=53 318, 11 trials), ARB did not reduce stroke (OR, 0.92; 95% CI, 0.79 to 1.08) 2 large metaregression analyses (n=45 212, 9 trials; n=39 487, 8 trials), found no blood pressure-independent effects of ARB on stroke. In 2 major trials this year, ARB compared with placebo had absolutely failed to reduce stroke. ARB is not the choice of first-line therapy for prevention of stroke
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ARBs Should Be Regarded as First-Line Drugs for Stroke Prevention in Both Primary and Secondary Prevention Settings : No
Martin H. Strauss and Alistair Hall Stroke 2009;40;3161-3162

It has been suggested that antihypertensive agents that increase Ang II levels (eg, ARB, dihydropyridine calcium channel blocker, diuretics) are more effective at preventing stroke than those that reduce Ang II levels (eg, angiotensin converting enzyme inhibitor and blockers) Extensive clinical trials confirm that ARBs have no unique role in the prevention of stroke. If one considers the unique cardiovascular protective benefits of ACEIs, however, the choice of first-line therapy for prevention of stroke is perhaps not a choice at all!
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Hypertension: in Over-50s
Just Focus on Systolic Pressure systolic pressure rises with age, diastolic pressure increases until around age 50 and falls thereafter In persons older than 50 years, systolic blood pressure greater than 140 mmHg is a much more important cardiovascular disease (CVD) risk factor than diastolic blood pressure international guidelines advocate a target for systolic pressure treatment of below 140 mm Hg, and below 130 mm Hg for patients with diabetes
JNC 7 41 Williams B et al. Lancet 2008;

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High dietary salt intake seen to worsen risk of ischemic strokes

Northern Manhattan Study, "people who consumed more than 4000 mg per day of sodium had more than double the risk of stroke compared with those who consumed less than 1500 mg(AHA) hazard ratio 2.29 (95% CI 1.07-4.92). 2657 people from the cohort study (9.7 years)
US dietary guidelines allow for a greater intake but still recommend that it fall below 2300 mg/day, or about a teaspoon of salt per day.
Gardener H, Rundek T, Wright C, et al. Dietary sodium intake is a risk factor for incident ischemic stroke: The Northern Manhattan Study (NOMAS). International Stroke Conference 2011; February 9, 2011
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Government Salt-Reduction Policy

small reductions (10%) in sodium intake would result in decreases in blood pressure with two approach scenario models
1. the government working with food manufacturers to voluntarily cut sodium in processed foods. 2. scenario would be to create a "sodium tax" on food reducing the number of heart attacks and strokes would save $32 billion in medical costs

Smith-Spangler CM et al. Annals of Internal Medicine 2010 Frieden TR and Briss PA. Annals of Internal Medicine 2010
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(Stroke. 2010;41:2108-2129.)

Guidelines for the Management of Spontaneous Intracerebral Hemorrhage

A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. The American Association of Neurological Surgeons and the Congress of Neurological Surgeons have reviewed this document and affirm its educational content. Lewis B. Morgenstern, MD, FAHA, FAAN, Chair et al
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AHA/ASA Guidelines for the Management of Spontaneous ICH in Adults

Stroke. 2007;38:2001-2023 HT may increase the risk of ongoing bleeding from ruptured small arteries and arterioles during the 1st hours. High BP is correlated with increased ICP and volume of hemorrhage overaggressive treatment of BP may decrease cerebral perfusion pressure (CPP) and theoretically worsen brain injury
2/28/2011

Stroke. 2010;41:2108-2129 HT could contribute to hydrostatic expansion of the hematoma, peri-hematoma edema, and rebleeding. High BP during acute stroke aggravates cerebral edema. a systolic BP of 150 to 220 mm Hg, acute lowering of systolic BP to 140 mm Hg is probably safe
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AHA/ASA Guidelines for Treating BP in Spontaneous ICH (class C)-2010 SBP and MAP mmHg SBP > 200 mm Hg or MAP >150 mm Hg, TREATMENT 2007/2010

consider agressive reduction of BP with continuous IV infusion with frequent BP monitor every 5 min IV Anti HT :labetalol, hydralazine, SBP > 180 mm Hg or Consider monitoring enalapril, esmolol, nicardipine, ICP and reducing BP MAP >130 mm Hg using intermittent or continuous (nitroglycerin, and nitroprusside) IV there is the possibility of lowering of BPisby no CPP >60-8020% in medications keep more that mmHg elevated ICP the first 24 hours SBP > 180 mm Hg or Consider a modest reduction of BP (eq MAP is 130 mm Hg MAP of 110 mmHg or target BP of 160/90 there is not evidence of mmHg) using intermittent or continuous IV elevated ICP medications to control BP, and clinically reexamine the patient every 15 min
2/28/2011 46

AHA/ASA Guidelines for the Management of Spontaneous ICH in Adults

Stroke. 2007 The recommendation was to maintain a systolic BP 180 mm Hg and/or mean arterial pressure 130 mm Hg. Isolated systolic BP 210 mmHg is not clearly related to hemorrhagic expansion or to neurological worsening. Reduction in mean arterial pressure by 15% (mean 142 to 119 mm Hg) does not result in CBF reduction in humans
2/28/2011

Stroke 2010

systolic BP above 140 to 150 mm Hg within 12 hours of ICH is associated with more than double the risk of subsequent death or dependency the goal target of less than 140/90 or less than 130/80 mm Hg for diabetes or kidney disease is "reasonable. the BP pressure target, duration of therapy, and whether such treatment improves clinical outcomes remain unclear. 47

Control of elevated blood pressure in acute intracerebral hemorrhage

The EuropeanStroke Initiative Guidelines recommend a target mean arterial pressure (MAP) of 125 mmHg in patients with a history of hypertension and 110 mmHg in those without a history of hypertension The Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT) : early intensive blood pressure reduction is clinically feasible, well tolerated, and may reduce hematoma expansion in ICH, The relative risk of hematoma expansion was 36% lower (95% confidence interval 0-59%, P = 0.05)
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Adeoye O. Medicine Reports 2010

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Smoking, Hypertension Have Synergistic Effect on Hemorrhagic Stroke Risk for every 10-mm Hg rise in SBP, smokers had an additional 15% increase in risk of haemorrhagic stroke. Nonoptimal blood pressure levels and smoking are the 2 most common causes of death in the world

2/28/2011

Nakamura K. Stroke 2008

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Hematoma expansion in ICH

14-38% of ICHs expand within 24 hrs Hypertension may predispose to ICH enlargement
SBP(mmHg) hematome enlargment %

>200
176-200 150-175 <150
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21.5
14.3 13.6 8.4
Fuyii et al, Stroke 1998, Venkatesh Aiyagari and Philip B. Gorelick. Stroke 2009
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Hematoma enlargment

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AHA/ASA Guidelines for Spontaneous ICH-2010

In terms of clot removal, that for most patients with ICH, the

usefulness of surgery is "uncertain."

Pts with cerebellar hemorrhage who are deteriorating neurologically or brainstem compression and/or hydrocephalus surgical removal of the hemorrhage as soon as possible.(CLASS 1) Initial th/ of pts with ventricular drainage alone rather than surgical removal is not recommended (CLASS III) For patients presenting with lobar clots of more than 30 mL and within 1 cm of the surface, evacuation of supratentorial ICH by standard craniotomy might be considered (CLASS IIb)
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Morgenstern LB et al.Stroke 2010;

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Stroke haemorrhage

3 dec 07 21 dec 07 16 jan 08

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Brain stem Bleeding

2/28/201111

Juli 2008

12 agustus 2008
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THE END
Hasan Sjahrir Department of Neurology Sumatera Utara University Medan

http://neurologi.usu.ac.id

2/28/2011

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