Treatment for intracerebral hemorrhage: Dawn of a new era

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Treatment for intracerebral hemorrhage: Dawn of a new era

David J Seiffge david.seiffge@insel.ch and Craig S AndersonView all authors and affiliations

Volume 19, Issue 5

https://doi.org/10.1177/17474930241250259

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• • Abstract
  • Intracerebral hemorrhage—the deadly sibling of ischemic stroke
  • Treatment of ICH before 2023—widespread frustration and nihilism
  • Treatment targets in ICH
  • The year 2023—dawn of a new era
  • First: care bundle approaches for hyperacute treatment
  • Second: direct oral anticoagulants—new challenges for ICH treatment
  • Third: andexanet alfa—a specific reversal agent for factor Xa-inhibitor–associated ICH
  • Fourth: future challenges—factor XI inhibitors
  • Fifth: hematoma evacuation: one positive trial and unanswered questions
  • Summary and outlook
  • Declaration of conflicting interests
  • Funding
  • References
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Abstract

Intracerebral hemorrhage (ICH) is a devastating disease, causing high rates of death, disability, and suffering across the world. For decades, its treatment has been shrouded by the lack of reliable evidence, and consequently, the presumption that an effective treatment is unlikely to be found. Neutral results arising from several major randomized controlled trials had established a negative spirit within and outside the stroke community. Frustration among researchers and a sense of nihilism in clinicians has created the general perception that patients presenting with ICH have a poor prognosis irrespective of them receiving any form of active management. All this changed in 2023 with the positive results on the primary outcome in randomized controlled trials showing treatment benefits for a hyperacute care bundle approach (INTERACT3), early minimal invasive hematoma evacuation (ENRICH), and use of factor Xa-inhibitor anticoagulation reversal with andexanet alfa (ANNEXa-I). These advances have now been extended in 2024 by confirmation that intensive blood pressure lowering initiated within the first few hours of the onset of symptoms can substantially improve outcome in ICH (INTERACT4) and that decompressive hemicraniectomy is a viable treatment strategy in patients with large deep ICH (SWITCH). This evidence will spearhead a change in the perception of ICH, to revolutionize the care of these patients to ultimately improve their outcomes. We review these and other recent developments in the hyperacute management of ICH. We summarize the results of randomized controlled trials and discuss related original research papers published in this issue of the International Journal of Stroke. These exciting advances demonstrate how we are now at the dawn of a new, exciting, and brighter era of ICH management.

Intracerebral hemorrhage—the deadly sibling of ischemic stroke

Intracerebral hemorrhage (ICH) is caused by the rupture of cerebral vessels which results in bleeding within the brain parenchyma and/or ventricles.¹ Overall, ICH comprises approximately 10–15% of all strokes worldwide, but the rates are higher in low- and middle-income countries.² Compared to ischemic stroke, the incidence of ICH has increased in recent years and the prognosis remains poor.^3,4 Current estimates predict a significant increase in the incidence of ICH in Europe related to aging and greater use of anticoagulants, with major implications for health care systems and societies.⁵

Treatment of ICH before 2023—widespread frustration and nihilism

For decades, treatment of ICH has been overshadowed by limited evidence and a presumed lack of effective treatment options reflected by neutral and restrictive guideline recommendations.^6,7 Several randomized controlled trials of surgical treatment (i.e. different approaches to evacuation of parenchymal or intraventricular hematoma),^8–11 blood pressure (BP) control,^12,13 and hemostatic therapies,^14–16 resulted in either borderline significant or neutral results. The evidence was persuasive from INTERACT2,¹² and stronger when pooled with other trials as part of an individual patient data meta-analysis,¹⁷ for a beneficial effect of early intensive BP lowering. Although a study-level meta-analysis of hematoma evacuation also found a potential benefit,¹⁸ there is ongoing uncertainty over which patients have the most to gain from neurosurgery along with the optimal timing and technique of intervention. Collectively, these efforts have contributed to somewhat of a negative spirit within (and outside) the stroke community, and in turn degrees of frustration and nihilism regarding treatment approaches and the perception of a uniformly poor prognosis for patients with ICH.¹⁹

Treatment targets in ICH

Several promising treatment targets exist for ICH (Figure 1). In the hyperacute phase, the primary aim is to stop the bleeding which grows from the original site in “domino” or “avalanche” fashion through the secondary shearing of neighboring vessels.²⁰ Restricting the ongoing bleeding cascade—usually depicted as hematoma expansion on follow-up imaging—is paramount as it is consistently identified as a major predictor of poor outcome from ICH.^21–23 The other key predictors of outcome are an early time-window (i.e. <6 h of onset), high BP, baseline hematoma volume (medium to large), intraventricular extension, and prior use of oral anticoagulation therapy.^24,25 Even a small initial hematoma may evolve into a devastating large lesion (Figure 2).

Figure 1. Treatment targets in intracerebral hemorrhage.

 

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