The impact of hyperacute blood pressure lowering on the early clinical outcome following intracerebral hemorrhage Ryo Itabashia, Kazunori Toyodaa,b, Masahiro Yasakaa,b, Takahiro Kuwashiroa, Hideaki Nakagakia, Fumio Miyashitaa, Yasushi Okadab, Hiroaki Naritomia and Kazuo Minematsua Journal of Hypertension 2008, 26:2016–2021 Cardiology R2 김양균

Introduction Intracerebral hemorrhage (ICH)  blood pressure (BP)↑ High BP  hematoma expansion  poor outcome Current guideline : IV antihypertensive therapy (eg. Nicardipine) By AHA (American Heart Association) By ISH (International Society of Hypertension) SBP > 180 mmHg DBP > 105 mmHg Mean blood pressure > 130 mmHg target BP < 180/105 mmHg BP > 220/120 mmHg  reduced by less than 20%

Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT) : target SBP < 140 mmHg  hematoma growth ↓ Several issues –which level the acute BP should be reduced –whether SBP or DBP is the optimal indicator –The absolute BP value or percentage reduction of BP ? An observational study using the prospective databases The purpose of this study which level of BP lowering whithin the initial 24h of hospitalization positive early clinical outcome in hyperacute ICH patients

Methods 688 Japanese patients with non-traumatic ICH from January 1999 through October 2003 SBP > 180mmHg, DBP > 105 mmHg or MBP > 130 mmHg  224 pts –IV antihypertensive therapy Exclusion criteria –Died within the initial 24h –Surgical hematoma evacuation –Disability prior to ICH –Secondary hemorrhage d/t trauma, tumor, dural arteriovenous fistula, arteriovenous malformation, aneurysm Early hematoma enlargement –ABC/2 by brain CT  40% ↑ (24 h CT – admission CT)

Prospective database –Age, gender, hypertension (BP > 140/90 mmHg, before stroke), DM, hypercholesterolemia, hypocholesterolemia, smoking habit, alcohol consumption, heart disease, liver disease, stroke history, antithrombic therapy In all patients, antihypertensive agents after CT detection of the hematoma Iv (nicardipine, nitroglycerine  diltiazem) 7days  oral change BP24h : BP within the initial 24 h Mean of the three BP values (at 6,12, 24h after admission) ∆BP : the reduction in BP24h compared with after admission 100 – 100 x BP24h/BPi (%)

Primary outcome –Completely independent activity of daily living (ADL) at 3 weeks Corresponding mRS score of 1 of less Secondary outcome –Hematoma enlargement withing the first 24h –Mortality at 3 weeks post-ICH

Results 27 %

5 %

14 %

Discussion Hyperacute BP lowering & early clinical outcome of ICH ICH pts with BPi > 180/105 mmHg lowering SBP < 138 mmHg during initial 24h of hospitalization independent ADL (mRS score ≤ 1) Hematoma growth : predictor of mortality & poor functional outcomes high admission BP → ongoing bleeding & rebleeding → mortality ↑ soon after ICH onset - both BP & the risk of hematoma growth ↑↑ growth of perihematomal edema affects functional outcome Appropriate control of hyperacute BP prevent growth of hematoma & edema improve outcome at 3 weeks after multivariate adjustment adjustment for time after onset X

On the contrary, lowering BP –reduce global cerebral blood flow (CBF) –exacerbates perihematomal ischemia rapid BP decline within 24h after ICH → mortality ↑ reduced MBP by 15% did not alter global or perihematonal CBF BP lowering to be more beneficial than harmful!!

Percentage reduction of the SBP ≠ good indicator for functional outcome –greatest SBP reduction included a very high admission SBP –poor outcome DBP not a good indicator of outcome Limitations –not a randomized controlled study –antihypertensive agent doses were chosen by each physician –BP after the initial 24h were not assessed –chronic outcome at 3months were not assessed –rate of hematoma enlargement & mortality : too low to assess

Conclusion Lowering the systolic blood pressure to less than 138 mmHg during the initial 24h appears to be predictive of favorable early outcome in ICH patients. Radnomized controlled trials to answer this question are needed.