1 Prevention and Management Prevention and Management of hypertensive stroke of hypertensive stroke Dr. LO, Man Dr. LO, Man- wai wai MBChB (CUHK) MBChB (CUHK) MRCP (UK) MRCP (UK) MPH (CUHK) MPH (CUHK) FHKCP FHKCP FHKAM (Medicine) FHKAM (Medicine) Specialist in Neurology Specialist in Neurology Dept. of Medicine Dept. of Medicine Queen Elizabeth Hospital Queen Elizabeth Hospital 4 Dec 2006 4 Dec 2006 Content Content How does HT cause stroke? How does HT cause stroke? What are the clinical and radiological What are the clinical and radiological manifestations for HT manifestations for HT- related stroke? related stroke? How should we lower BP in acute stroke? How should we lower BP in acute stroke? What is the current concepts in anti What is the current concepts in anti- hypertensive therapy for prevention of hypertensive therapy for prevention of first and recurrent stroke? first and recurrent stroke?
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Prevention and Management Prevention and Management
of hypertensive strokeof hypertensive stroke
Dr. LO, ManDr. LO, Man--waiwai
MBChB (CUHK)MBChB (CUHK)
MRCP (UK)MRCP (UK)
MPH (CUHK)MPH (CUHK)
FHKCPFHKCP
FHKAM (Medicine)FHKAM (Medicine)
Specialist in NeurologySpecialist in Neurology
Dept. of MedicineDept. of Medicine
Queen Elizabeth HospitalQueen Elizabeth Hospital
4 Dec 20064 Dec 2006
ContentContent
�� How does HT cause stroke?How does HT cause stroke?
�� What are the clinical and radiological What are the clinical and radiological manifestations for HTmanifestations for HT--related stroke?related stroke?
�� How should we lower BP in acute stroke?How should we lower BP in acute stroke?
�� What is the current concepts in antiWhat is the current concepts in anti--hypertensive therapy for prevention of hypertensive therapy for prevention of first and recurrent stroke?first and recurrent stroke?
22
How does HT cause stroke?How does HT cause stroke?
� small benefit in reducing the death and recurrent stroke rate
� net decrease of 9deaths or occurrences of further stroke per 1000 patients (level Ia)
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IV IV thrombolysisthrombolysis
FDA approval 1996FDA approval 1996iv tPA iv tPA <3 hr<3 hr improved outcome at 3 monthsimproved outcome at 3 months
NINDSNINDS
TPATPA--treated group treated group were at least were at least 30%30%more likely to have more likely to have minimal or no minimal or no disability at 3 disability at 3 monthsmonths
Benefit were Benefit were consistent consistent regardless of age, regardless of age, stroke subtype or stroke subtype or prior use of aspirinprior use of aspirin �
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6.4% tPA vs. 0.6% in placebo (within 36hrs)
Mortality rate in both treatment group was similar at 3mo & at 1 year
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IntraIntra--arterial arterial
thrombolysisthrombolysis
MERCI balloon guide MERCI balloon guide
cathetercatheterFDA August 11, 2004 FDA August 11, 2004
1st medical 1st medical device device specifically specifically
indicated to indicated to --
retrieve blood clots from the retrieve blood clots from the
brain in ischemic stroke for brain in ischemic stroke for --
patients who fail or are patients who fail or are
ineligible for iv tPAineligible for iv tPA
1717
BP lowering BP lowering in acute phasein acute phase
IschaemicIschaemic penumbrapenumbra
1818
IschaemicIschaemic penumbrapenumbra
Cerebral Cerebral autoregulationautoregulation
1919
Cerebral Cerebral autoregulationautoregulation
Normotensive patient
Hypertensive patient
CBF
Mean arterial BP
BP management in acute BP management in acute
ischaemicischaemic strokestroke
�� CBF is pressure dependent in CBF is pressure dependent in ischaemicischaemic
brain regionsbrain regions
�� Further reduction Further reduction
�� irreversibly injure theirreversibly injure the ischaemicischaemic
penumbra penumbra
�� increase stroke volumeincrease stroke volume
2020
BP management in BP management in
acute acute ischaemicischaemic strokestroke
�� Transient HT Transient HT –– common after acute common after acute ischaemicischaemic strokestroke
�� Causes: Causes: �� anxietyanxiety
�� painpain
�� neuroendocrineneuroendocrine factorsfactors
�� stroke locationstroke location
�� compensatory response to brain hypoxia or compensatory response to brain hypoxia or increased ICPincreased ICP
BP management in acute BP management in acute
ischaemicischaemic strokestroke
�� Manage stress responses, pain, nausea and Manage stress responses, pain, nausea and vomiting, bladder distension or other sources of vomiting, bladder distension or other sources of anxietyanxiety
�� Early BP elevations often decline spontaneously Early BP elevations often decline spontaneously during the first minutes to hours during the first minutes to hours
�� May not require pharmacologic RxMay not require pharmacologic Rx
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Blood pressure decreaseBlood pressure decrease during the during the acute acute
phasephase of ischemic stroke is associated with of ischemic stroke is associated with
brain injury and poor stroke outcomebrain injury and poor stroke outcome
Castillo J, Castillo J, LeiraLeira R, Garcia MM, Serena J, Blanco M, R, Garcia MM, Serena J, Blanco M, DavalosDavalos A.A.
Stroke. 2004 Feb;35(2):520Stroke. 2004 Feb;35(2):520--6. 6. EpubEpub 2004 Jan 15. 2004 Jan 15.
Power Grade 3/5
Power Grade 1/5
Anti-HT Drugfor BP 180/90
2222
““Stroke in evolutionStroke in evolution””??
NonNon--specificspecific
�� Failure of collateral circulationFailure of collateral circulation
�� Systemic hypotensionSystemic hypotension
�� Cardiac Cardiac arrthymiaarrthymia
�� EmbolizationEmbolization or propagation of thrombusor propagation of thrombus
�� Progressive occlusion of vessel lumenProgressive occlusion of vessel lumen
Blood Pressure and Stroke: An Overview of Published ReviewsBlood Pressure and Stroke: An Overview of Published ReviewsCarlene M.M. Carlene M.M. LawesLawes, Derrick A. Bennett, , Derrick A. Bennett, ValeryValery L. L. FeiginFeigin, and Anthony Rodgers, and Anthony Rodgers
Stroke 2004 35: 776 Stroke 2004 35: 776 -- 785785
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BP level & risk of vascular BP level & risk of vascular
diseasedisease
�� JNC VIIJNC VII
�� Risk begins at 115/75 Risk begins at 115/75 mmHgmmHg
�� No limits below this No limits below this pointpoint
�� No JNo J--curve responsecurve response
Stage 2 HT
Stage 1 HT
Prehypertension
Normal
120120
140140
160160
8080 1001009090
SBPSBP
DBPDBP
Classification of BP by JNC 7Classification of BP by JNC 7
3030
Which drug should we use?Which drug should we use?
Any class effect?Any class effect?
Blood Pressure Lowering Treatment Trialists' Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomized trials.
Lancet. 2003;362:1527-1535.
Comparison with placeboComparison with placebo
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Blood Pressure Lowering Treatment Trialists' Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomized trials.
Lancet. 2003;362:1527-1535.
Direct comparison between Direct comparison between antianti--HT regimenHT regimen
Size does matterSize does matter
Size (intensity)Size (intensity)
of BP of BP ��
Type of Type of
antianti--HT RxHT Rx
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Compelling reasons & Compelling reasons &
recommendationsrecommendations
����������������Recurrent Recurrent CVACVA
����������������CRFCRF
����������������������������������������DMDM
��������������������������������High CHD High CHD riskrisk
Risk factors for Risk factors for thiazidethiazide--induced induced hyponatraemiahyponatraemia..
K.M. Chow, C.C. K.M. Chow, C.C. SzetoSzeto, T.Y., T.Y.--H. Wong, C.B. Leung P.K.H. Wong, C.B. Leung P.K.--T. Li T. Li
Q J Med 2003; 96: 911Q J Med 2003; 96: 911--917917
Stroke prevention in DiabeticsStroke prevention in Diabetics
�� 40 40 –– 60% adult with type 2 DM have HT60% adult with type 2 DM have HT
�� Any difference in BP management for Any difference in BP management for this special group of patients to prevent this special group of patients to prevent stroke?stroke?
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UKPDS UKPDS Event Rates for Select Event Rates for Select Endpoints With Endpoints With
Tight Tight vsvs Less Tight Blood Pressure ControlLess Tight Blood Pressure Control
0
10
20
30
40
50
60
70
80
Any DM-related endpoint
DM-
related deathStroke Microvascular
complications
Events per 1000 patient yrs P=0.005
P=0.02 P=0.01 P=0.009
Less tight (n=390) mean achieved BP 154/87 mmHg
Tight (n=758) mean achieved BP 144/82 mmHg
UKPDS Group. BMJ. 1998;317:703–713.
-33
-25
-21
-16
-12
-50
-40
-30
-20
-10
0
Microalbuminuria at 12 yrs Microvascular complications
Retinopathy Myocardial Infarction
Any DM endpoint
% relative risk reduction
P=0.03
P<0.01
P<0.01
P=0.05
P=0.02
UKPDS Group. Lancet. 1998;352:837-853.
UKPDS Relative Risk Reduction for UKPDS Relative Risk Reduction for Intensive Intensive vsvs Less Intensive Less Intensive Glucose ControlGlucose Control
Over 10 years, HbA1c was 7.0% (6.2-8.2) in the intensive group (n=2,729) compared with 7.9% (6.9-8.8) in the conventional group (n=1,138).
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UKPDS Findings:UKPDS Findings:Tight BP Control vs. Intensive Glucose ControlTight BP Control vs. Intensive Glucose Control
�� Tight vs. Less tightTight vs. Less tight BP control BP control reduces risk ofreduces risk of
�� Any diabetesAny diabetes--related endpoint related endpoint 24% 24% P=0.005P=0.005
�� HOPE HOPE substudysubstudy (Ambulatory BP)(Ambulatory BP)�� 10/4 mmHg reduction over 24hr10/4 mmHg reduction over 24hr�� 17/8 mmHg reduction during nighttime17/8 mmHg reduction during nighttime�� �� BP lowering effect leading to stroke risk reduction?BP lowering effect leading to stroke risk reduction?
Comparative Effects of Ramipril on Ambulatory and Office Blood PressuresPer Svensson; Ulf de Faire; Peter Sleight; Salim Yusuf; Jan Östergren
Hypertension. 2001;38:e28
PROGRESS PROGRESS ((perindoprilperindopril))�� N = 6105N = 6105�� HxHx of stroke or TIAof stroke or TIA�� ACEI, ACEI + ACEI, ACEI + indapamideindapamide
�� Recurrent major CVS events:Recurrent major CVS events:�� 40% RRR (95% CI 29 40% RRR (95% CI 29 –– 49)49)
�� No benefit when ACEI was given aloneNo benefit when ACEI was given alone�� Benefit also shown in Benefit also shown in normotensivenormotensive patientspatients
PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack.
Lancet. 2001;358:1033- 1041.
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AHA/ ASA Guideline 2006AHA/ ASA Guideline 2006Secondary Prevention of StrokeSecondary Prevention of Stroke
�� How much?How much?�� Benefit seen in reduction of ~10/5 mmHgBenefit seen in reduction of ~10/5 mmHg�� Normal BP < 120/80 mmHg by JNCNormal BP < 120/80 mmHg by JNC--77
All patients with All patients with ischaemicischaemic strokestroke
or TIAor TIAAntiAnti--HT RxHT Rx
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AHA/ ASA Guideline 2006AHA/ ASA Guideline 2006Secondary Prevention of StrokeSecondary Prevention of Stroke