BLOOD PRESSURE MANAGEMENT IN THE ACUTE PHASE

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1 BLOOD PRESSURE MANAGEMENT IN THE ACUTE PHASE Ελένη Κορομπόκη, MD, PhD, FESO Α Νευρολογική Κλινική, ΕΚΠΑ, Αιγινήτειο Νοσοκομείο Κλινική Ερευνήτρια, Department of Stroke Medicine, Imperial College London, UK

2 Disclosures χ No, nothing to disclose Yes, please specify: Company Name Honoraria/ Expenses Consulting / Advisory Board Funded Resear ch Royalties / Patent Stock Options Ownershi p/ Equity Position Employee Other (please specify) Amgen Bayer Pfizer x x EU-Horizon 2020 (member of PRESTIGE-AF consortium) x x x

3 Blood pressure management in acute stroke

4 Acute IS and SAP on admission The Athens Stroke Outcome Project >140mmHg: 75% >180mmHg: 21% N=2160 Up to 80% of acute ischemic stroke patients have elevated BP on admission

5 Spontaneous decrease of blood pressure in patients with acute stroke Wallace et al. JAMA 1981

6 Elevated BP at the acute phase of IS Pre-existing HTN Britton M et al. Stroke 1986 Activation of neuroendocrine systems Stress of hospitalization Stroke subtype Cushing s reflex Carlberg B et al. J Int Med 1990 Vemmos K et al. Blood Pres Monit 2004 Yatsu FM et al. Arch Neurol 1985 Olson T et al. Stroke 1992 Other factors: headache, pain, urine retention, infection

Spontaneous decline after 24-72h 2. Impaired autoregulation and risk of hypoperfusion 3.

7 BP lowering at the acute phase of IS Lowering BP 1. Risk of hemorrhagic transformation 2. Cerebral edema 3. Stroke recurrence 4. Hypertensive encephalopathy Not lowering BP 1. Spontaneous decline after 24-72h 2. Impaired autoregulation and risk of hypoperfusion 3. U shaped relationship between BP and outcomes 4. Presence of severe arterial stenoses (bilateral) Fisher and Mattle, Stroke 2017.

8 Impaired autoregulation of cerebral blood flow at the acute phase of IS

area) BP lowering would decrease penumbral perfusion When penumbra

9 BP at the acute phase of stroke and penumbral perfusion Ischaemic core (brain tissue destined to die) Penumbra (salvageable brain area) BP lowering would decrease penumbral perfusion When penumbra disappears elevated BP is no longer needed Fisher and Mattle, Stroke 2017.

10 Study n Drug Inclusion BP Outcome ACCESS (2003) 342 Candesartan Mean SBP 6 24h after admission 200 mmhg or DBP 110 mmhg. Mean SBP 24 36h after admission 180 mm Hg or DBP 105 mm Hg No difference in Barthel Index at 3 months. No difference in cerebrovascular events at 12 months PRoFESS substudy (2009) SCAST (2011) CHHIPS (2009) 1360 Telmisartan SBP mmhg and DBP 110 mmhg 2029 Candesartan SBP>140 mm Hg. Fixed dose-escalation schedule. 179 Oral labetalol or SBP >160 mmhg. lisinopril or placebo No difference in mrs at 30 days or stroke recurrence at 90 days No difference in mrs or stroke recurrence at 6 months No difference in death or dependency rate at 2 weeks COSSACS (2010) 763 Continuation of home medications SBP<200 mm Hg and DBP <120 mm Hg. No difference in death or dependency rate at 2 weeks. No difference in stroke recurrence at 6 months CATIS (2014) ENOS (2015) 4071 ACE-I, CCB,diuretics (pre-defined algorithm) 4011 Glyceryl trinitrate (transdermal) SBP of mm Hg SBP of mmhg No difference in death or disability rate at 14 days after randomization. No difference in mrs at 3 months Significant BP lowering, acceptable safety but not improvement in functional outcome

11 Krishman K et al. Stroke

12 Main causes of discrepant results Gazecki et al. J Hypertens 2018

13 Stroke is a heterogeneous and complex disease Large artery atherosclerosis Cardioembolic Lacunar One size fits all maybe not valid

14 High BP is associated with worse outcome in patients who receive thrombolysis SITS-ISTR ( patients) Ahmed N, et al. Stroke 2009

15 Management of HTN in acute IS Whelton et al., Hypertension 2017

Proposed antihypertensive agents for the management of arterial hypertension in acute stroke Intravenously Labetalol 10-20mg over 1-2 min, may repeat or double every 10 min (maximum 300mg)

18 Proposed antihypertensive agents for the management of arterial hypertension in acute stroke Intravenously Labetalol 10-20mg over 1-2 min, may repeat or double every 10 min (maximum 300mg) Nicardipine 5mg/h infusion as initial dose, titrate to desired effect by increasing 2.5mg/h every 5 min (maximum 15mg/h) Nitroprusside 0.5 μg/kg/min as initial dose with continuous BP monitoring Urapidil 10-50mg, followed by 4-8mg/h Nitroglycerin 5mg, followed by 1-4mg/h Esmolol 500μg/kg loading dose; maintenance use μg/kg/min Subcutaneously Clonidine mg Transdermally Glyceryl trinitrate 5mg Sublingually Lisinopril 5mg Orally Angiotensin converting inhibitors or Angiotensin II receptor blockers with or without diuretic (secondary stroke prevention)

19 Antihypertensive drug classes on additional mechanisms Bath et al. Stroke 2018

20 Completed and ongoing trials Bath et al. Stroke 2018

21 Conclusions Elevated BP is common at the acute phase of IS and often decreases spontaneously The management of post-stroke HTN remains controversial RCTs failed to demonstrate improved outcomes with BP lowering at the acute phase of IS In patients who are not candidates for thrombolysis it might be reasonable to lower BP if >220/120 mm Hg by 15% In patients who receive endovascular treatment BP should be lowered to <185/110 mmhg Future well designed studies are needed.

22 Thank you for your attention

Blood Pressure Management in Acute Stroke. Bradley Molyneaux, M.D., Ph.D. Departments of Neurology & Critical Care Medicine University of Pittsburgh

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