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Publications

Journal Article Ahead of print

PubMed: 42556370 DOI: 10.1016/j.lanhl.2026.100889

Frailty, clinical outcomes, and treatment effects of a care bundle in acute intracerebral haemorrhage: a post-hoc analysis of the INTERACT3 trial.

Lancet Healthy Longev

Authors: Tao Liu, Linan Chen, Yang Liu, Zhihao Zhao, Leibo Liu, Lu Ma, Laurent Billot, Qiang Li, Alejandra Malavera, Paula Muñoz-Venturelli, Asita de Silva, Nguyen Huy Thang, Kolawole W Wahab, Jeyaraj D Pandian, Mohammad Wasay, Octavio M Pontes-Neto, Rongcai Jiang, Carlos Abanto, Antonio Arauz, Lili Song, Katie Harris, Richard I Lindley, Ruth Peters, David D Ward, Kenneth Rockwood, Xin Hu, Chao You, Craig S Anderson, Xiaoying Chen

Affiliations

  • The George Institute for Global Health, Faculty of Medicine, University of New South Wales Sydney, Randwick, NSW, Australia.
  • Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.
  • Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.
  • The George Institute for Global Health, Faculty of Medicine, University of New South Wales Sydney, Randwick, NSW, Australia; Clinical Research Center, Faculty of Medicine Clinica Alemana Universidad del Desarrollo, Santiago, Chile.
  • Clinical Trials Unit, Faculty of Medicine, University of Kelaniya, Colombo, Sri Lanka.
  • Stroke Unit, 115 People's Hospital, Ho Chi Minh City, Viet Nam.
  • Department of Medicine, University of Ilorin & University of Ilorin Teaching Hospital, Ilorin, Nigeria.
  • Neurology Department, Christian Medical College and Hospital, Ludhiana, India.
  • Department of Medicine, The Aga Khan University, Karachi, Pakistan.
  • Department of Neuroscience and Behavioral Sciences, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
  • Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
  • The Cerebrovascular Disease Research Center, National Institute of Neurological Sciences, Lima, Peru.
  • Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez, Mexico City, Mexico.
  • The George Institute for Global Health, Faculty of Medicine, University of New South Wales Sydney, Randwick, NSW, Australia; Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, China; Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, Shanghai, China.
  • Westmead Applied Research Centre, University of Sydney, Sydney, NSW, Australia.
  • Centre for Health Services Research, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Woolloongabba, QLD, Australia; Australian Frailty Network, The University of Queensland, Woolloongabba, QLD, Australia.
  • Divisions of Neurology & Geriatric Medicine, Department of Medicine, Dalhousie University, Halifax, NS, Canada; Nova Scotia Health Frailty and Elder Care Network, Halifax, NS, Canada.
  • Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.
  • Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.
  • The George Institute for Global Health, Faculty of Medicine, University of New South Wales Sydney, Randwick, NSW, Australia; Clinical Research Center, Faculty of Medicine Clinica Alemana Universidad del Desarrollo, Santiago, Chile; Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, China; Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, Shanghai, China; Department of Neurology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; The George Institute for Global Health China, Beijing, China.

Abstract

BACKGROUND

Frailty has been widely associated with poor outcomes in mixed stroke cohorts, but evidence specific to intracerebral haemorrhage, particularly from settings in low-income and middle-income countries and regarding treatment-effect modification, remains scarce. We aimed to evaluate the association between frailty and several clinical outcomes and to ascertain whether frailty modifies the treatment effect of a care bundle in individuals with acute intracerebral haemorrhage.

METHODS

We conducted a post-hoc analysis of the third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral haemorrhage (INTERACT3) international, stepped-wedge, cluster-randomised controlled trial (NCT03209258; Chinese Clinical Trial Registry ChiCTR-IOC-17011787), which enrolled individuals with acute spontaneous intracerebral haemorrhage at 121 hospitals in nine low-income and middle-income countries and one high-income country. Frailty was quantified using a 30-item cumulative-deficit frailty index; individuals were categorised as non-frail (frailty index ≤0·10), pre-frail (frailty index >0·10 to <0·21), or frail (frailty index ≥0·21). The primary outcome was 6-month all-cause mortality. Mixed-effects regression models, adjusted for key prognostic variables and clustering by hospital site, were used to estimate associations and treatment interactions across frailty strata.

FINDINGS

Of the 7036 individuals enrolled in INTERACT3, 7035 with available frailty data were included in this analysis (mean age 62·0 years; 2533 [36·0%] women and 4502 [64·0%] men). 3185 (45·3%) were non-frail, 3000 (42·6%) were pre-frail, and 850 (12·1%) were frail. Increasing frailty was associated with higher 6-month mortality and poorer functional outcomes. These associations were attenuated but persisted after multivariable adjustment (mortality: adjusted hazard ratio [HR] 1·48 [95% CI 1·20-1·83]; major disability among survivors: adjusted odds ratio 1·73 [1·40-2·14] for frail vs non-frail individuals). The care bundle was associated with lower mortality point estimates across frailty groups (non-frail adjusted HR 0·66 [95% CI 0·46-0·94], pre-frail adjusted HR 0·80 [0·61-1·05], and frail adjusted HR 0·65 [0·43-0·98]; p for interaction=0·30). Absolute mortality rate reductions were larger among individuals with frailty (116·9 events per 1000 person-years) than among individuals without frailty (44·1 events per 1000 person-years). No clear evidence of treatment-by-frailty interaction was observed for death or major disability at 6 months (p for interaction=0·27).

INTERPRETATION

Frailty showed a graded association with poor prognosis in acute intracerebral haemorrhage, and these associations were attenuated but generally persisted after adjustment for age, baseline neurological severity, and other prognostic factors. We found no clear evidence that frailty modified the effect of the INTERACT3 care bundle on mortality. Mortality estimates favoured the care bundle across frailty strata, with larger absolute mortality reductions observed among individuals with frailty. These findings support offering protocolised acute care to individuals with imaging-confirmed spontaneous intracerebral haemorrhage who present within 6 h of symptom onset, irrespective of frailty status, while also maintaining individualised clinical judgement regarding prognosis and functional recovery.

FUNDING

None.

MeSH

Mortality, Patient Care Bundles, Income, Therapeutics, Frailty, Prognosis