Sex differences in treatment, radiological features and outcome after intracerebral haemorrhage: Pooled analysis of Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage trials 1 and 2

Abstract

Introduction: Reports vary on how sex influences the management and outcome from acute intracerebral haemorrhage. We aimed to quantify sex disparities in clinical characteristics, management, including response to blood pressure lowering treatment, and outcomes in patients with acute intracerebral haemorrhage, through interrogation of two large clinical trial databases.

Patients and methods: Post-hoc pooled analysis of the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage trials 1 and 2, where patients with a hypertensive response (systolic, 150-220 mmHg) after spontaneous intracerebral haemorrhage (<6 h) were randomised to intensive (target <140 mmHg <1 h) or guideline-recommended (<180 mmHg) blood pressure lowering treatment. The interaction of sex on early haematoma growth (24 h), death or major disability (modified Rankin scale scores 3-6 at 90 days), and effect of randomised treatment were determined in multivariable logistic regression models adjusted for baseline confounding variables.

Results: In 3233 participants, 1191 (37%) were women who were significantly older, had higher baseline National Institutes of Health Stroke Scale scores and smaller haematoma volumes compared to men. Men had higher three-month mortality (odds ratio 1.48, 95% confidence interval 1.10-2.00); however, there was no difference between women and men in the combined endpoint of death or major disability. There were no significant sex differences on mean haematoma growth or effect of randomised blood pressure lowering treatment.

Discussion: Men included in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage trials had more comorbidities, larger baseline haematoma volumes and higher mortality after adjustment for age, as compared with women.

Conclusion: Men included in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage trials had a greater odds of dying after intracerebral haemorrhage than women, which could not be readily explained by differing casemix or patterns of blood pressure management.

Clinical trial registration: The Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage trials studies are registered with ClinicalTrials.gov (NCT00226096 and NCT00716079).

Keywords: Sex differences; blood pressure; haematoma growth; intracerebral haemorrhage; perihaematomal oedema.

Conflict of interest statement

Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: ECS has received speaker fees from Bayer and Novartis. JC has received research grants from Servier, administered through the University of Sydney, as principal investigator for the ADVANCE trial and ADVANCE-ON post-trial study, and also received honoraria from Servier for speaking about those studies at scientific meetings. CSA holds a Senior Investigator Fellowship and grants from the National Health and Medical Research Council (NHMRC), and reports grants and honorarium travel reimbursement from Takeda China.

© European Stroke Organisation 2020.

Figures

Figure 1.

BP in women and men over seven days.