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Early blood pressure lowering in patients with intracerebral haemorrhage and prior use of antithrombotic agents: pooled analysis of the INTERACT studies
  1. Lili Song1,
  2. Else Charlotte Sandset2,3,
  3. Hisatomi Arima3,
  4. Emma Heeley3,
  5. Candice Delcourt3,
  6. Guofeng Chen4,
  7. Jie Yang5,
  8. Guojun Wu6,
  9. Xia Wang3,
  10. Pablo M Lavados7,
  11. Yining Huang8,
  12. Christian Stapf9,
  13. Jiguang Wang10,
  14. Thompson G Robinson11,
  15. John Chalmers3,
  16. Richard I Lindley3,
  17. Craig S Anderson3
  18. for the INTERACT2 Investigators
  1. 1Department of Neurology, Shanghai 85th Hospital of PLA, Shanghai, China
  2. 2Department of Neurology, Oslo University Hospital, Oslo, Norway
  3. 3The George Institute for Global Health, Royal Prince Alfred Hospital and University of Sydney, Sydney, New South Wales, Australia
  4. 4Department of Neurology, Xuzhou Central Hospital, Xuzhou, China
  5. 5Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
  6. 6Department of Neurology, Hebei Yutian Hospital, Yutian, China
  7. 7Servicio de Neurología, Departamento de Medicina, Clínica Alemana, Universidad del Desarrollo, and Universidad de Chile, Santiago, Chile
  8. 8Department of Neurology, Peking University First Hospital, Beijing, China
  9. 9Department of Neuroscience, CRCHUM, University of Montreal, Montreal, Quebec, Canada
  10. 10The Shanghai Institute of Hypertension, Rui Jin Hospital, Shanghai Jiaotong University, Shanghai, China
  11. 11Department of Cardiovascular Sciences and NIHR Biomedical Research Unit in Cardiovascular Disease, University of Leicester, Leicester, UK
  1. Correspondence to Professor Craig S Anderson, The George Institute for Global Health, Royal Prince Alfred Hospital and the University of Sydney, P.O. Box M201, Missenden Road, Sydney, NSW 2050, Australia; canderson{at}


Objective Antithrombotic agents increase risks of intracerebral haemorrhage (ICH) and associated adverse outcomes. We determined differential effects of early blood pressure (BP) lowering in patients with/without antithrombotic-associated ICH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (INTERACT1 and 2).

Design Post hoc pooled analyses of the INTERACT studies—international, multicentre, prospective, open, blinded end point trials of patients with ICH (<6 h) and elevated systolic BP (SBP 150–180 mm Hg) randomly assigned to intensive (target SBP <140 mm Hg) or guideline-based (SBP <180 mm Hg) BP management. Associations of antithrombotic use and (1) death or dependency (modified Rankin scale scores 3–6) were analysed using logistic regression, and (2) of increased haematoma+intraventricular haemorrhage volume (IVH) with/without intraventricular haemorrhage (IVH) over 24 h were estimated in analyses of covariance.

Results In all, 3184 patients were included in these analyses. Antithrombotic-associated ICH (364 patients, 11%) was not associated with a significantly increased risk of death or dependency (OR 1.38, 95% CI 0.93 to 2.04). There was no heterogeneity in the BP-lowering treatment effect on death or dependency. Among 1309 patients who underwent follow-up CT after 24 h, absolute increase in haematoma±IVH volume was larger (5.2/5.0 mL) in those with compared to those without prior antithrombotics (2.2/0.9 mL; p=0.022/0.031). Intensive BP lowering reduced haematoma±IVH growth by 4.7/7.1 mL in patients on antithrombotics versus 1.3/1.4 mL in those without, although these differences did not reach statistical significance (p homogeneity=0.104/0.059).

Conclusions In patients with ICH, prior antithrombotic therapy is associated with greater haematoma growth, which may be reduced by early intensive BP-lowering treatment.

Trial registration number NCT00226096, NCT00716079.

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  • Twitter Follow Else Sandset at @ECSandset

  • Contributors LS contributed to data interpretation and wrote the first draft of the report. ECS contributed to analyses and writing the report. HA supervised and conducted the analyses, and contributed to writing the report. TGR, JC, RIL and CSA obtained funding, and were responsible for planning of the study, supervision, data interpretation and writing of the report. EH, CD, XW, PML, YH, CS, RIL and TGR provided comments on data interpretation and the report.

  • Funding The INTERACT2 study was supported by Programme Grant (571281) and Project Grants (512402 and 1004170) from the National Health and Medical Research Council (NHMRC) of Australia. ECS holds a South-Eastern Norway Regional Health authority postdoctoral grant. HA held an Australian Research Council (ARC) Future Fellowship during much of these analyses. CSA holds a NHMRC Senior Principal Research Fellowship. All the authors had full access to the data.

  • Competing interests YH reports receiving reimbursement for travel expenses from Osaka Pharmaceuticals. CSA reports receiving reimbursement for travel expenses and honorarium from Takeda China, and is on Advisory Committees for Medtronic and Astra Zeneca.

  • Ethics approval Regional health authorities of all sites involved.

  • Provenance and peer review Not commissioned; externally peer reviewed.