Blood Pressure Management in Acute Stroke Bradley Molyneaux, M.D., Ph.D. Departments of Neurology & Critical Care Medicine University of Pittsburgh
80 yo M w/ R MCA syndrome NIHSS 14
A balancing act
Cerebral blood flow & ischemia Symptoms of stroke Dead brain Ischemic brain Alive, but nonfunctional Normal brain Functional ml/100g/min Courtesy Leslie-Mazwi, T.
Autoregulation of CBF CBF is dependent on adequate CPP CPP = MAP - CPP Chestnut RM, Ann NY Acad Sci, 2014
Brief periods of hypotension can severely exacerbate infarct Powers. Neurology. 1993. 43:461-7
Relationship of baseline systolic BP to outcome Jo Leonardi-Bee et al. Stroke. 2002;33:1315-1320
Vemmos KN, J Int Med, 2004
Non-recanalized patients Recanalized patients Ana Inês Martins et al. Stroke. 2016;47:1571-1576
Blood pressure drops faster if recanalization Heinrich P. Mattle et al. Stroke. 2005;36:264-268
Time Course of Hypertension in Acute Stroke CATIS Trial. JAMA. 2014;311(5):479-489
Hyperacute management Target blood pressure by clinical scenario BP < 220/120 if no tpa BP < 185/110 prior to tpa BP < 180/105 after tpa SBP < 140-160 after thrombectomy Consider trial of temporary augmentation If large vessel occlusion If any sedation
Antihypertensive Treatment Nicardipine Minimal cerebral vasodilatation Titratable, 5 to 15 mg/hr; q5-15mins Can result in shunt and hypoxia Clevidipine Similar to nicardipine More rapidly titratable, 2 32 mg/hr; q90 secs Caution lipid load Labetalol Bolus 10-20 mg Caution longer half life Enalaprilat; Esmolol
Antihypertensive Treatment: other options Hydralazine Variable effects causing over correction Difficult to titrate Sodium nitroprusside effect on ICP Sodum nitroprusside Generally avoid Some risk of increased ICP Transient antiplatelet effects Anile et al 1981, Acta Neurochirurgica
Trials of treating acute hypertenson: CATIS PRoFESS VENTURE CHHIPS RIGHT ENOS COSSACS SCAST VENUS
SCAST candesartan vs placebo 2029 patients SBP > 140 Randomized w/in 30 hrs Sandset et al. Lancet 2011 377, 741-750
SCAST no benefit, possible harm p =0.048 Sandset et al. Lancet 2011 377, 741-750
ENOS transdermal glyceryl trinitrate 4011 patients SBP > 140 Randomized w/in 48 hrs Twice the BP reduction of SCAST Lancet 2015 385, 617-628
ENOS possible benefit if given early Investigating in RIGHT-2 200/850 enrolled Lancet 2015 385, 617-628
CATIS antihypertensives vs none 4071 patients SBP 140-220 Randomized w/in 48 hrs CATIS Trial. JAMA. 2014;311(5):479-489
CATIS antihypertensives vs none Primary Outcome mrs 3 at hospital discharge No difference (33.6%); p = 0.98 4071 patients SBP 140-220 Randomized w/in 48 hrs CATIS Trial. JAMA. 2014;311(5):479-489
CATIS subgroup
Trials of treating acute hypertenson: Meng Lee et al. Stroke. 2015;46:1883-1889
Summary Hyperacute blood pressure by clinical scenario SBP < 220/120 if no tpa BP < 185/110 prior to tpa BP < 180/105 after tpa SBP < 140-160 after thrombectomy No evidence of benefit from early PO blood pressure regimen
Series of trials with mixed results CHHIPS; UK 179 pts SBP>160 within 36 hrs of stroke (mean 19 hrs). Randomize to labet or placebo. No differrence between groups. COSSACS Conclusion: the study found no benefits of early continuation of antihypertensive medication after acute stroke, but it also found no substantial harms. SCAST Conclusion: when associated with large declines in systolic BP, early use of candesartan may be harmful in AIS patients. CATIS FAST MAG ENOSS
Trials of anti-hypertensives in acute stroke Study Stoke type n ACCESS 20 I: 100% H: 0% Mean onset time to Inclusion BP and target randomization BP reduction (hours) 342 29.8 Mean SBP 6 24 hours after admission 200 mm Hg or DBP 110 mm Hg. Mean SBP 24 36 hours after admission 180 mm Hg or DBP 105 mm Hg. Target 10 15% BP reduction within 24 hours. Drug Candesarta n Mean BP reduction in treatment group No significant reduction Stroke classification NA Functional independence and Comments cerebrovascular events No difference in Treatment Barthel Index at 3 population had months. No higher BPs than difference in other studies cerebrovascular events at 12 months PRoFESS substudy 22 I: 100% H: 0% 1,360 58 Inclusion SBP 121 180 Telmisartan SBP Small-artery mm Hg and DBP 110 mm Hg reduction 6.1 occlusion: 52% mm Hg at 7 Cardioembolic: days and 5.8 1.8% mm Hg at 90 days No difference in mrs Post-hoc score at 30 days or analysis. stroke recurrence at Dysphasic 90 days patients excluded. SCAST 23 I: 85% H: 14% CHHIPS 12 I: 86% H: 14% 2,029 18 Inclusion SBP >140 mm Hg. Fixed dose-escalation schedule. No target specified. 179 Treatment: 19.8 hours Placebo: 17.4 hours Inclusion SBP >160 mm Hg. Target SBP of 145 155 mm Hg or 15 mm Hg decrease at 4 hours. Candesarta n SBP reduction 5 mm Hg and DBP reduction 2 mm Hg on day 7. Lacunar infarct: 27% for candesartan, 31% for placebo No difference in mrs Dose score or stroke adjustments if recurrence at 6 SBP <120 mm months Hg or if clinically indicated Oral SBP Lacunar infarct: No difference in Treatment labetalol (50 reduction 14 28% treatment and death or dependency discontin ued if mg), oral lisinopril (5 mg), or placebo 16% placebo rate at 2 weeks between treatment and placebo SBP <140 mm Hg within 8 hours of drug administration mm Hg and DBP reduction 7 mm Hg with lisinopril at 24 hours COSSACS 25 I: 59% H: 5% 763 23.6 hours after stroke onset and 16 hours after last dose of antihypertensiv e drug Inclusion SBP <200 mm Hg and DBP <120 mm Hg. No target reduction Continuatio n of home medications SBP reduction 13 mm Hg and DBP reduction 8 mm Hg at 2 weeks Lacunar infarct: 38% No difference in No BP death or dependency differences rate at 2 weeks. between control No difference in and treatment stroke recurrence at groups prior to 6 months 2 weeks. CATIS 26 I: 100% H: 0% 4,071 Treatment: 15.3 hours Control: 14.9 hours Inclusion SBP 140 200 Predefined mm Hg. algorithm Target SBP reduction involving 10 25% at 24 hours. ACE-I, Target BP <140/90 mm CCB, and Hg at 7 days. diuretics SBP reductions 8.1 and 9.3 mm Hg, and DBP reductions 3.8 and 4.0 mm Hg at 24 hours and 7 days Lacunar infarct: treatment 20.5%, control 18.9% No difference in IV thrombolytic death or disability use in <3% of rate at 14 days after participants. randomization. No difference in mrs score at 3 months ACE-I: angiotensin-converting enzyme inhibitors, BP: blood pressure, CCB: calcium-channel blockers, DBP: diastolic BP, I: ischemic, H: hemorrhagic, mrs: modified Rankin Scale, SBP: systolic BP. McManus & Liebeskind, J Clin Neurol. 2016 Apr;12(2):137-146.