MANAGEMENT OF HYPERTENSION WITH COMPELLING INDICATIONS TO PREVENT SECONDARY STROKE

Alwi Shahab

Department of Neurology University of SriwijayaPalembang

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)

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

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.

HYPERTENSION AS RISK FACTORHypertensionHemorrhagic StrokeIschemic StrokeVessel wall abnormalityDefects in hemostasisSmokingLipid disorderDiabetes

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

HYPERTENSION AS RISK FACTOR OF STROKE INMOH.HOESIN GENERAL HOSPITAL PALEMBANG

YEAR%200276,08200385,1200485,5200578,09200686,73200792,88

PATHOGENESISHypertensionSpasm + atheromaBrittle wallDegeneration and thickening of wallDilated aneurysm (Charcot-Bouchard)Prone to ruptureNarrow lumenProne to thrombosisHemorrhageIschemic

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%)

DISTRIBUTION OF STROKE CASES BY CLASSIFICATION OF AETIOLOGY AND INITIAL BLOOD PRESSURE

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2521

3120

4524

13989

14295

141286

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Christine, Shahab, RSMH. 2003-2006

Iskemik

Hemoragik

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OptimalNormalBorderlineHT stg 1HT stg 2HT stg 3

Iskemik253145139142141

Hemoragik2120248995286

DISTRIBUTION OF STROKE CASES BY CLASSIFICATION OF AETIOLOGY AND TYPES OF HYPERTENSIONChristine, Shahab, RSMH, 2003-2006

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1928

12470

283360

Iskemik

Hemoragik

2,1%

14,2%

32%

3,1%

7,9%

40,7%

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Isolated Systolic HypertensionIsolated Diastolic HypertensionCombined Hypertension

Iskemik19124283

Hemoragik2870360

EFFECT OF INTIIAL BLOOD PRESSURE ON EARLY NEUROLOGICAL DETERIORATIONSYSTOLIC BP ON ADMISSION (mmHg)EARLY NEUROLOGICAL DETERIORATIONS %Castillo, et al., Stroke 2004 35:520 -

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60

50

20

10

15

35

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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.

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.

CONTROVERSY OF LOWERING BP DURING ACUTE STROKELowering BP prevents :Development of cerebral edemaRisk of hemorrhagic eventsImpairment of vessel wallsStroke recurrency

Aggresive lowering of BP :

Perfusion decline in penumbra

Deterioration of neurological function

JNC 7

BP CLASSIFICATIONSBP (mmHg)DBP (mmHg)Normal

ALGORITHM FOR TREATMENT OF HYPERTENSIONJNC 7 , Jama May 21,2003

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

Antihypertensive drugs shouldLower blood pressure effectivelyHave a favourable safety profileReduce cardiovascular morbidity and mortalityFive drug categoriesDiureticsBeta-blockersACE inhibitorsCalcium channel blockersAngiotensin-receptor blockersANTIHYPERTENSIVE DRUGS

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)

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

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

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

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

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

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

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)

DIURETIC TRIALSPAST (Post stroke Antihypertensive Treatment Study) 19955,682 patientsIndapamide 2,5mg/day vs Placebo 29% risk non-fatal and fatal stroke

ASA/AHA RECOMMENDATION Recommended combination of antihypertensive drugs

ACE-i / ARB + DiureticsACE-i / ARB + CCB

ASA/AHA p.42-43, 2011

POSSIBLE COMBINATIONS OF ANTIHYPERTENSIVE AGENTSGuidelines Committee. J Hypertens 2003; 21: 1011-53.

ESC (2011) & ASH (2010) RECOMMENDATIONPreferred CombinationRAAS inhibitors + CCBRAAS inhibitors + diuretics

ESC (2011) & ASH (2010) RECOMMENDATIONAcceptable CombinationsBeta-blockers + DiureticsCCB + DiureticsCCB + Beta BlockersDual CCB

ESC (2011) & ASH (2010) RECOMMENDATIONUnacceptable CombinationsDual RAAS inhibitorRAAS inhibitor + Beta-blockersBeta-blockers + Antiadrenergic drugs

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

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

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

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

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.

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

THANK YOU

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