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MANAGEMENT OF HYPERTENSION WITH COMPELLING INDICATIONS TO
PREVENT SECONDARY STROKE
Alwi Shahab
Department of Neurology University of SriwijayaPalembang
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STROKE IS A LEADING CAUSE OF DEATH AND DISABILITYBURDEN FOR
FAMILYEMERGENCY CASES DEMANDS RAPID DIAGNOSIS AND MANAGEMENT OF
ATTENDING PHYSICIANSPROMPT EFFORT TO PREVENT SECONDARY STROKE
(RECURRENCY)
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EPIDEMIOLOGY15 million people has stroke worldwide each year
(WHO, 2008)High blood pressure contributes to more than 12.7
million of themIn US alone, approximately 795,000 people has stroke
yearly. About 600,000 of these are first attacks and 185,000 are
reccurent attacksHigh blood pressure is the most important risk
factor for stroke
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EPIDEMIOLOGYAccording to Riskesdas Depkes RI (2007), the most
important cause of mortality for all ages is stroke
(15,4%)Incidence of stroke from the database of hospitals gathered
is 63,52 per 100,000.
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HYPERTENSION AS RISK FACTORHypertensionHemorrhagic
StrokeIschemic StrokeVessel wall abnormalityDefects in
hemostasisSmokingLipid disorderDiabetes
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STROKE RISK FACTOR IN INDONESIAHypertension 73.9%Smoking 20.45
%Previous stroke 19.9 %Ischemic heart disease 19.9%Diabetes
Mellitus 17.3%Dyslipidemia 16.4 %Atrial fibrillation 5.8 %Valvular
heart disease 3.4 %Policythemia 1.7 %Contraceptive pills 1.5
%Alcohol 1.4 %Jusuf Misbach;Penelitian multisenter RS di
Indonesia;1996
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HYPERTENSION AS RISK FACTOR OF STROKE INMOH.HOESIN GENERAL
HOSPITAL PALEMBANG
YEAR%200276,08200385,1200485,5200578,09200686,73200792,88
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PATHOGENESISHypertensionSpasm + atheromaBrittle wallDegeneration
and thickening of wallDilated aneurysm (Charcot-Bouchard)Prone to
ruptureNarrow lumenProne to thrombosisHemorrhageIschemic
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Systolic and diastolic hypertension equally increase risk of
strokeHigher blood pressure = higher risk of strokeNo particular
level of hypertension associated with incidents of strokeFremingham
study: most stroke cases occur at systolic of 140-159 mmHg
(60%)
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DISTRIBUTION OF STROKE CASES BY CLASSIFICATION OF AETIOLOGY AND
INITIAL BLOOD PRESSURE
Chart1
2521
3120
4524
13989
14295
141286
Cc
Christine, Shahab, RSMH. 2003-2006
Iskemik
Hemoragik
Sheet1
OptimalNormalBorderlineHT stg 1HT stg 2HT stg 3
Iskemik253145139142141
Hemoragik2120248995286
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DISTRIBUTION OF STROKE CASES BY CLASSIFICATION OF AETIOLOGY AND
TYPES OF HYPERTENSIONChristine, Shahab, RSMH, 2003-2006
Chart1
1928
12470
283360
Iskemik
Hemoragik
2,1%
14,2%
32%
3,1%
7,9%
40,7%
Sheet1
Isolated Systolic HypertensionIsolated Diastolic
HypertensionCombined Hypertension
Iskemik19124283
Hemoragik2870360
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EFFECT OF INTIIAL BLOOD PRESSURE ON EARLY NEUROLOGICAL
DETERIORATIONSYSTOLIC BP ON ADMISSION (mmHg)EARLY NEUROLOGICAL
DETERIORATIONS %Castillo, et al., Stroke 2004 35:520 -
Chart1
60
50
20
10
15
35
Column1
Sheet1
Column1
n = 18 12060
n = 29 121-14050
n = 39 141-16020
n = 78 161-18010
n = 49 181-20015
n = 87 >20035
To resize chart data range, drag lower right corner of
range.
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RECURRENT STROKE1 in4 (25%-35%) of the 795,000 stroke in US have
recurrent stroke. Within 5 years ofa firststroke,risk 40%. Within5
years of a stroke, 24 percent of women and 42 percent of men will
experience recurrent stroke.Recurrent strokes have higher rate of
death and disability.
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CONTROVERSY OF LOWERING BP DURING ACUTE STROKELowering BP
prevents :Development of cerebral edemaRisk of hemorrhagic
eventsImpairment of vessel wallsStroke recurrency
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Aggresive lowering of BP :
Perfusion decline in penumbra
Deterioration of neurological function
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JNC 7
BP CLASSIFICATIONSBP (mmHg)DBP (mmHg)Normal
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ALGORITHM FOR TREATMENT OF HYPERTENSIONJNC 7 , Jama May
21,2003
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THERAPEUTIC STRATEGIES OF HYPERTENSIONESH-ESC GUIDELINES 2003Add
a third drugat low doseChoose betweenSingle agent at low dose2 drug
combination at low dose Previous agentat full doseSwitch to
differentAgent at low dosePrevious combinationat full dose2-3 drug
combination3 drug combinationat effective doseIf goal BP not
achievedIf goal BP not achievedJ.hypertension 2003 ,21, 1011 -
1053
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Antihypertensive drugs shouldLower blood pressure
effectivelyHave a favourable safety profileReduce cardiovascular
morbidity and mortalityFive drug
categoriesDiureticsBeta-blockersACE inhibitorsCalcium channel
blockersAngiotensin-receptor blockersANTIHYPERTENSIVE DRUGS
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WHEN TO START?
BEYOND THE FIRST 24 HOURS IS RECOMMENDED FOR BOTH PREVENTION OF
RECURRENT STROKE IN PERSONS WITH ISCHEMIA STROKE OR TIA(American
Stroke Association Recommendation 2011)
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A systematic review found that chronic reduction of blood
pressure in patients with prior ischemic or hemorrhagic stroke or
transient ischemic attack reduced secondary stroke by 24%, nonfatal
stroke by 21%, myocardial infarction by 21%, and total vascular
events by 21% over a period of 2-5 years.Rashid, Leonardi-Bee,
Bath, University of Nottingham 2003
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RAAS INHIBITORS TRIALSHOPE (Heart Outcomes Prevention
Evaluation) 2000.9,297 patientsRamipril 10mg/day vs Placebo 32%
risk of stroke 61% risk of fatal stroke
LIFE (Losartan Intervention For Endpoint reduction in
hypertension) 20029,193 patients Losartan 50-100mg + HCT 12,5-25mg
VS Atenolol 50-100mg + HCT 12,5-25mgLosartan + HCT 28% risk of
stroke
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RAAS INHIBITORS TRIALSONTARGET (Ongoing Telmisartan Alone and in
combination with Ramirpil Global Endpoint Trial) 200817,118
patients Telmisartan 80mg/day vs Telmisartan 80mg/day + Ramipril
10mg/dayTelmisartan non-inferior to Ramipril. Combination results
in no benefit.
VALUE (Valsartan Antihypertensive Long-term Use Evaluation )
200315,245 patientsValsartan + HCT vs Amlodipine + HCTEqually
effective in preventing stroke
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RAAS INHIBITORS TRIALSPROGRESS ( Preventing Strokes by Lowering
Blood Pressure in Patients with Cerebral Ischemia) 20016,105
patientsPerindopril 4mg + Indapamide 2,5mg vs Placebo 43% risk of
stroke
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CCB TRIALSMOSES (Morbidity and Mortality Affter Stroke,
Eprosartan compared with Nitrendipine for Secondary Prevention)
20051,405 patientsEprosartan 600mg/day vs Nitrendipine
10mg/dayEprosartan 25% risk of stroke
FACET (Fosinopril Versus Amlodipine Cardiovascular Events
Randomized Trial) 1998380 patientsAmlodipin 10mg/day vs Fosinopril
20mg/dayEqually effective BP. Lower risk of stroke in Fosinopril
group
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CCB TRIALSASCOT (Anglo-Scandinavian Cardiac Outcomes TrialBlood
Pressure Lowering Arm) 200319,257 patientsAmlodipin 5-10mg/day +
Perindopril 4-8mg/day vs Atenolol 50-100mg/day +
bendroflumethiazide 1.25 2.5 mgAmlodipin + Perindopril 23% risk of
stroke
ACCOMPLISH ( ACE-i + Amlodipine vs ACE-i + HCT in High Risk
Hypertensives) 200811,506 patientsBenazepril 20-40mg + Amlodipine
5-10mg vs Benazepril 20-40mg + HCT 12,5-25mg Benazepril +
Amlodipine 17% risk of non fatal and fatal stroke
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BETA BLOCKER TRIALS Cochrane reviewed 2 RCTs involving 2193
participants. Both studies randomised participants to either
beta-blocker (atenolol 5 mg) or placebo. No statistical differences
were noted among the groups in risks of fatal and non-fatal stroke
(risk ratio 0,94, 95% confidence interval 0.75 to 1.17). No
significant differences for all other outcomes analysed (death from
all causes, cardiac death, non fatal-myocardial infarction, major
vascular events)
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DIURETIC TRIALSPAST (Post stroke Antihypertensive Treatment
Study) 19955,682 patientsIndapamide 2,5mg/day vs Placebo 29% risk
non-fatal and fatal stroke
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ASA/AHA RECOMMENDATION Recommended combination of
antihypertensive drugs
ACE-i / ARB + DiureticsACE-i / ARB + CCB
ASA/AHA p.42-43, 2011
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POSSIBLE COMBINATIONS OF ANTIHYPERTENSIVE AGENTSGuidelines
Committee. J Hypertens 2003; 21: 1011-53.
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ESC (2011) & ASH (2010) RECOMMENDATIONPreferred
CombinationRAAS inhibitors + CCBRAAS inhibitors + diuretics
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ESC (2011) & ASH (2010) RECOMMENDATIONAcceptable
CombinationsBeta-blockers + DiureticsCCB + DiureticsCCB + Beta
BlockersDual CCB
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ESC (2011) & ASH (2010) RECOMMENDATIONUnacceptable
CombinationsDual RAAS inhibitorRAAS inhibitor +
Beta-blockersBeta-blockers + Antiadrenergic drugs
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DRUGS OF CHOICE IN SPESIFIC CONDITIONS In association with
Nondiabetic Chronic Kidney DiseaseTarget BP < 140/90 mmHgInitial
therapy is ACE inhibitor or ARB if intoleranceThiazide diuretics
are recommended as additive In most cases, combination therapy is
neededACE inhibitor + ARB is not recommended
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DRUGS OF CHOICE IN SPESIFIC CONDITIONS In association with
Diabetes MellitusTarget BP < 130/80 mmHgInitial therapy is ACE
inhibitor or ARBCombination therapy is recommended if SBP is 20
mmHg above target or DBP is 10 mmHg above targetDihydropyridine CCB
is preferred to Thiazide for combination therapy
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DRUGS OF CHOICE IN SPESIFIC CONDITIONS In association with
Coronary Artery DiseaseACE-i is recommended For stable angina, beta
blockers are preferred. CCB may also be used (except short acting
Nifedipine)ACE-i + ARB is not recommended
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DRUGS OF CHOICE IN SPESIFIC CONDITIONS In association with
recent STEMI or NSTEMIBoth ACE-i + beta blockers as initial
therapyARB if ACE-i is intoleratedCCB if beta blockers is
intoleratedNon-dihidropyridine CCB must not be used if there is
heart failure
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DRUGS OF CHOICE IN SPESIFIC CONDITIONS In association with Heart
FailureACE-i is recommended. ARB if ACE-i is intoleratedHydralazine
+ ISDN if both ACE-i and ARB are intoleratedACE-i + ARB is
rationale but monitor for hyperkalemia and renal function.
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CONCLUSION Prevention of stroke must be started as soon as 24
hours beyond onset Lowering blood pressure significantly lower risk
of recurrent stroke Recommended antihypertensive drugs includes
ACE-i/ARB + Diuretics or ACE-i/ARB + CCB Selection or addition of
antihypertensive drugs should be adjusted towards spesific
conditions of patients
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THANK YOU
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