Between 2020 and 2024, several major publications have highlighted the critical need and urgency of developing therapies to deal with the public health problem that cerebral haemorrhage will represent over the next few years. Here is a snapshot of the current knowledge and challenges.

1. Burden of Ischemic and Hemorrhagic Stroke Across the US From 1990 to 2019

Characteristics of the publication:

–       Journal: JAMA Neurology (Impact Factor=29, rank 3/212 in clinical neurology)

–       Main authors: Dr. Kevin N. Sheth (MD. – Yale Center for Brian & Mind Health).

– https://jamanetwork.com/journals/jamaneurology/article-abstract/2815830?resultClick=3

Key information

Using data published by the Global Burden of Disease group in 2020, Kevin Sheth and colleagues analysed the burden of ischaemic and haemorrhagic stroke in the United States between 1990 and 2019. The study highlights that “the increasing absolute burden of stroke, coupled with a notable rise in hemorrhagic stroke, suggests an evolving and substantial public health challenge in the US“. Between 1990 and 2019, the incidence, prevalence and burden associated with ICHs increased.

As a reminder, the direct and indirect cost of stroke in the United States was $56.5 billion (in 2022, (Tsao et al., 2023)). ICH accounts for >30% of stroke buden in the USA as reported by the GBD (Feigin et al., 2021). In terms of projections, the number of US adults 65 years or older is expected to double over the next 40 years with a substantial impact on stroke epidemiology! In 2035, total direct medical stroke-related costs are projected to double to $94.3 billion.

About K Sheth (from https://medicine.yale.edu/profile/kevin-sheth/)

Dr. Kevin Sheth is a founding Director of the Yale Center for Brain & Mind Health and the Vice Chair for Clinical and Translational Research for the departments of Neurology. and Neurosurgery. He leads prevention efforts in neurologically vulnerable populations and works towards advancing therapies for acute brain injury such as stroke and brain hemorrhage. In pioneering the development of new strategies to treat brain swelling, his work has changed the fundamental approach to brain injury in the ICU and spurred the creation of new technologies in drug delivery and neuroimaging. Highly collaborative, interdisciplinary efforts from the lab have culminated in the first phase III trial to prevent brain swelling in stroke, the first phase III NIH funded prevention trial in brain hemorrhage, and the deployment of the first portable bedside MRI for brain injury in the world. His team at Yale has served as a national model for academic critical care neurology units. In recent years his group has also turned their attention to public health prevention efforts, focusing on cardiometabolic risk factors that can prevent decline in brain health resulting from stroke, dementia, and depression.

He is currently a principal investigator for two NIH neuroscience networks, StrokeNet, and SIREN. He is a multi-PI for four additional RO1/UO1 awards from the NIH. Dr. Sheth has served as PI or co-PI for 8 multicenter clinical trials in stroke. He is a winner of the prestigious Robert Siekert Award from the American Heart Association (AHA), the Derek Denny Brown Award from the American Neurological Association and an elected member of the American Society for Clinical Investigation (ASCI). Most recently, he was the recipient of the Stroke Research Mentorship Award from the American Heart Association. Dr. Sheth is the author of over 300 publications. His work has been showcased in The Washington Post, Wall Street Journal, Scientific American, NPR, and CNN.

Finally, Dr. Sheth has formed exciting partnerships with entrepreneurs, pharmaceutical companies, and medical device start-ups to bring forward highly innovative solutions. These efforts have resulted in extensive knowledge of FDA pathways, development of phase I-III drug programs, and implementation of new technology into the clinical workspace. The principal theme of his efforts are towards collaboration and an improved understanding of neurological disease.

2. Burden of intracerebral haemorrhage in Europe: forecasting incidence and mortality between 2019 and 2050

Characteristics of the publication:

–       Journal: The Lancet Regional Health – Europe (Impact Factor=20.9, rank 1/168 in Health Care Sciences and Services / rank 5/400 in Public, Environmental and occupational Health)

– PRESTIGE-AF consortium

– https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(24)00008-5/fulltext

Key information

This research paper leverages the three primary stroke risk factors identified in the Global Burden of Diseases, Injuries, and Risk Factors study (Feigin et al., 2021) — specifically hypertension, diabetes, and obesity — to generate robust forecasts regarding the burden of intracerebral hemorrhage during the aforementioned period. Projections indicate an escalation in the European burden of intracerebral hemorrhage in absolute terms between 2019 and 2050. Here are some key projections regarding the incidence of ICH in EU5 (↗6.3%) and Benelux:

–       Germany …………. ↘5.2% (though the baseline was +50% vs France in 2019)

–       🔴 France ……………. ↗5.5%

–       🔴 Italy ……………….. ↗7.6%

–       Spain ……………… ↘3.8%

–       🔴 United Kingdom … ↗↗30.1%

–       🔴 BeNeLux………….. ↗↗23.8%

Dr. Wafa and collaborators assert, “The expected surges in new cases (and deaths) from intracerebral haemorrhage in Europe emphasises the persistent and upcoming challenge for healthcare systems.”

In 2018, the Stroke Alliance for Europe established a Stroke Action Plan for Europe (SAP-E), with a goal to reduce the incidence of all new strokes by 10% by 2030, but also to reduce burden (Norrving et al., 2018). The prospect of an increase in the number of cases of cerebral haemorrhage would be a failure to achieve this objective (at least for the haemorrhagic component of strokes) but would also generate a very significant cost, as the burden associated with ICH is greater than for AIS.

There is an unequivocal imperative to step up investment in prevention, research, and the development of new therapeutic solutions to mitigate the escalating costs associated with rising demand.

It is imperative to progress with novel treatments for ICH patients. @Op2Lysis

About SAP-E

The Stroke Action Plan for Europe (SAP-E) is a pan-European initiative that was outlined by the European Stroke Organisation (ESO) and the Stroke Alliance for Europe (SAFE). It is the largest stroke project ever undertaken in Europe and sets targets to improve stroke care across the continent run until 2030.

The SAP-E is a truly collaborative document resulting from more than a year of dedicated efforts from ESO, SAFE and countless stakeholders. The SAP-E addresses the entire chain of care from primary prevention through to life after stroke. The aim of the SAP-E is to set a roadmap and define goals for the treatment of stroke in Europe through 2030. The plan was formally launched in the EU Parliament on 23 May 2018.

The implementation of the SAP-E is guided by a dedicated Steering Committee and a coalition of over 90 National Coordinators.

About Prestige AF

The PRESTIGE-AF project, funded by the European Commission, brings together scientists and clinicians from across Europe to determine the best way to reduce the risk of further stroke in people with atrial fibrillation (AF), a common type of irregular heartbeat, who have recently had a bleed in their brain, called an intracerebral haemorrhage (ICH).

PRESTIGE-AF stands for: PREvention of STroke in Intracerebral haemorrhaGE survivors with Atrial Fibrillation.

At the core of the PRESTIGE-AF project is a clinical trial alongside three optional sub-studies that participants in the trial can take part in.

About GBD and IHME

An independent population health research organization based at the University of Washington School of Medicine, the Institute for Health Metrics and Evaluation (IHME) works with collaborators around the world to develop timely, relevant, and scientifically valid evidence that illuminates the state of health everywhere. In making our research available and approachable, we aim to inform health policy and practice in pursuit of our vision: all people living long lives in full health. IHME delivers to the world timely, relevant, and scientifically valid evidence to improve health policy and practice.

3. One-year healthcare costs of patients with spontaneous intracerebral hemorrhage treated in the intensive care unit

Characteristics of the publication:

–       Journal: European Stroke Journal (Impact Factor= 6.1, rank in the TOP 20% in Clinical Neurology and in Peripheral Vascular Disease)

–       Main authors: Rahul Raj (Neurosurgeon, Helsinki University Central Hospital | HUCH, MD, PhD)

– https://journals.sagepub.com/doi/10.1177/23969873221094705

Key information

Economic impact of intracerebral haemorrhage: an urgent need for therapeutic innovation to reduce the cost of ICH

A recent study published in the European Stroke Journal highlights the staggering costs associated with Intracerebral Haemorrhage (ICH) and the urgent need to find effective therapeutic solutions.

The research, based on a comprehensive analysis of healthcare and economic data from a database of 1,000 patients treated between 2003 and 2013 in Finland, reveals alarming figures for the financial burden of ICH. The mean 12-month direct cost was €49,754 per patient (regardless of clinical outcome), with >80% of costs associated with hospitalisation and rehabilitation. Not taken into account in this study is that ICH is also associated with mortality (45% at 12 months) and a high-rate heavy disability (51% of the survivors at 12 months) resulting in substantial economic expenditure due to lost productivity. In addition, although recovery is faster in the first few weeks, it can continue for many months after ICH. Therefore, assessing the long-term costs would provide a more complete estimate of the total economic burden of ICH on society.

The study highlights critical unmet medical needs in the management of ICH. Despite advances in medical care, treatment options remain limited, leaving patients and carers to grapple with the heavy physical, emotional and financial consequences of the disease.

⚠ The urgency of developing effective treatments cannot be overstated 🚑 💊.

Indeed, Marika Smeds and her colleagues have smartly pointed out that “total costs were substantially lower for those with a favourable outcome than for those who were permanently disabled at 12 months (€58,852 versus €81,553), highlighting the importance and effectiveness of investment in improving and maintaining functional capacity”.

Significant savings could be made by healthcare systems with innovative, high-performance drugs, which is what Op2Lysis is proposing to develop for intracerebral haemorrhage.