Lisa Manning1, Yoichiro Hirakawa2, Hisatomi Arima2, Xia Wang2, John Chalmers3, Jiguang Wang4, Richard Lindley2, Emma Heeley2, Candice Delcourt3, Bruce Neal2, Pablo Lavados5, Stephen M Davis6, Christophe Tzourio7, Yining Huang8, Christian Stapf9, Mark Woodward2, Peter M Rothwell10, Thompson G Robinson1, Craig S Anderson11. 1. Department of Cardiovascular Sciences, University of Leicester, Leicester, UK; NIHR Biomedical Research Unit in Cardiovascular Disease, University of Leicester, Leicester, UK. 2. The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia. 3. The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia; Royal Prince Alfred Hospital, Sydney, NSW, Australia. 4. The Shanghai Institute of Hypertension, Rui Jin Hospital, Shanghai Jiaotong University, Shanghai, China. 5. Servicio de Neurología, Departamento de Medicina, Clínica Alemana, Universidad del Desarrollo, Santiago, Chile; Universidad de Chile, Santiago, Chile. 6. Melbourne Brain Centre, Royal Melbourne Hospital, Melbourne, VIC, Australia; University of Melbourne, Melbourne, VIC, Australia. 7. INSERM, U897, Bordeaux, France; University of Bordeaux, Bordeaux, France. 8. Department of Neurology, Peking University First Hospital, Beijing, China. 9. Department of Neurology, APHP - Hôpital Lariboisière, Paris, France; DHU NeuroVasc Paris - Sorbonne, Paris, France; Université Paris Diderot - Sorbonne Paris Cité, Paris, France. 10. Stroke Prevention Research Unit, University Department of Clinical Neurology, John Radcliffe Hospital, Oxford, UK. 11. The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia; Royal Prince Alfred Hospital, Sydney, NSW, Australia. Electronic address: canderson@georgeinstitute.org.au.
Abstract
BACKGROUND: High blood pressure is a prognostic factor for acute stroke, but blood pressure variability might also independently predict outcome. We assessed the prognostic value of blood pressure variability in participants of INTERACT2, an open-label randomised controlled trial (ClinicalTrials.gov number NCT00716079). METHODS: INTERACT2 enrolled 2839 adults with spontaneous intracerebral haemorrhage (ICH) and high systolic blood pressure (150-220 mm Hg) without a definite indication or contraindication to early intensive treatment to reduce blood pressure. Participants were randomly assigned to intensive treatment (target systolic blood pressure <140 mm Hg within 1 h using locally available intravenous drugs) or guideline-recommended treatment (target systolic blood pressure <180 mmHg) within 6 h of onset of ICH. The primary outcome was death or major disability at 90 days (modified Rankin Scale score ≥3) and the secondary outcome was an ordinal shift in modified Rankin Scale scores at 90 days, assessed by investigators masked to treatment allocation. Blood pressure variability was defined according to standard criteria: five measurements were taken in the first 24 h (hyperacute phase) and 12 over days 2-7 (acute phase). We estimated associations between blood pressure variability and outcomes with logistic and proportional odds regression models. The key parameter for blood pressure variability was standard deviation (SD) of systolic blood pressure, categorised into quintiles. FINDINGS: We studied 2645 (93·2%) participants in the hyperacute phase and 2347 (82·7%) in the acute phase. In both treatment cohorts combined, SD of systolic blood pressure had a significant linear association with the primary outcome for both the hyperacute phase (highest quintile adjusted OR 1·41, 95% CI 1·05-1·90; ptrend=0·0167) and the acute phase (highest quintile adjusted OR 1·57, 95% CI 1·14-2·17; ptrend=0·0124). The strongest predictors of outcome were maximum systolic blood pressure in the hyperacute phase and SD of systolic blood pressure in the acute phase. Associations were similar for the secondary outcome (for the hyperacute phase, highest quintile adjusted OR 1·43, 95% CI 1·14-1·80; ptrend=0·0014; for the acute phase OR 1·46, 95% CI 1·13-1·88; ptrend=0·0044). INTERPRETATION:Systolic blood pressure variability seems to predict a poor outcome in patients with acute intracerebral haemorrhage. The benefits of early treatment to reduce systolic blood pressure to 140 mm Hg might be enhanced by smooth and sustained control, and particularly by avoiding peaks in systolic blood pressure. FUNDING: National Health and Medical Research Council of Australia.
RCT Entities:
BACKGROUND: High blood pressure is a prognostic factor for acute stroke, but blood pressure variability might also independently predict outcome. We assessed the prognostic value of blood pressure variability in participants of INTERACT2, an open-label randomised controlled trial (ClinicalTrials.gov number NCT00716079). METHODS: INTERACT2 enrolled 2839 adults with spontaneous intracerebral haemorrhage (ICH) and high systolic blood pressure (150-220 mm Hg) without a definite indication or contraindication to early intensive treatment to reduce blood pressure. Participants were randomly assigned to intensive treatment (target systolic blood pressure <140 mm Hg within 1 h using locally available intravenous drugs) or guideline-recommended treatment (target systolic blood pressure <180 mm Hg) within 6 h of onset of ICH. The primary outcome was death or major disability at 90 days (modified Rankin Scale score ≥3) and the secondary outcome was an ordinal shift in modified Rankin Scale scores at 90 days, assessed by investigators masked to treatment allocation. Blood pressure variability was defined according to standard criteria: five measurements were taken in the first 24 h (hyperacute phase) and 12 over days 2-7 (acute phase). We estimated associations between blood pressure variability and outcomes with logistic and proportional odds regression models. The key parameter for blood pressure variability was standard deviation (SD) of systolic blood pressure, categorised into quintiles. FINDINGS: We studied 2645 (93·2%) participants in the hyperacute phase and 2347 (82·7%) in the acute phase. In both treatment cohorts combined, SD of systolic blood pressure had a significant linear association with the primary outcome for both the hyperacute phase (highest quintile adjusted OR 1·41, 95% CI 1·05-1·90; ptrend=0·0167) and the acute phase (highest quintile adjusted OR 1·57, 95% CI 1·14-2·17; ptrend=0·0124). The strongest predictors of outcome were maximum systolic blood pressure in the hyperacute phase and SD of systolic blood pressure in the acute phase. Associations were similar for the secondary outcome (for the hyperacute phase, highest quintile adjusted OR 1·43, 95% CI 1·14-1·80; ptrend=0·0014; for the acute phase OR 1·46, 95% CI 1·13-1·88; ptrend=0·0044). INTERPRETATION: Systolic blood pressure variability seems to predict a poor outcome in patients with acute intracerebral haemorrhage. The benefits of early treatment to reduce systolic blood pressure to 140 mm Hg might be enhanced by smooth and sustained control, and particularly by avoiding peaks in systolic blood pressure. FUNDING: National Health and Medical Research Council of Australia.
Authors: Adam de Havenon; Nora F Fino; Brian Johnson; Ka-Ho Wong; Jennifer J Majersik; David Tirschwell; Natalia Rost Journal: Stroke Date: 2019-09-20 Impact factor: 7.914
Authors: Jatinder S Minhas; William Rook; Ronney B Panerai; Ryan L Hoiland; Phil N Ainslie; Jonathan P Thompson; Amit K Mistri; Thompson G Robinson Journal: Br J Anaesth Date: 2019-12-06 Impact factor: 9.166
Authors: Adnan I Qureshi; Yuko Y Palesch; Lydia D Foster; William G Barsan; Joshua N Goldstein; Daniel F Hanley; Chung Y Hsu; Claudia S Moy; Mushtaq H Qureshi; Robert Silbergleit; Jose I Suarez; Kazunori Toyoda; Haruko Yamamoto Journal: Stroke Date: 2018-05-22 Impact factor: 7.914
Authors: Adam de Havenon; Jennifer J Majersik; Gregory Stoddard; Ka-Ho Wong; J Scott McNally; A Gordon Smith; Natalia S Rost; David L Tirschwell Journal: Stroke Date: 2018-08 Impact factor: 7.914