ICH Location May Guide Secondary Prevention Strategy 

April 10, 2023

Patients who have had a lobar intracerebral hemorrhage (ICH) are at greater risk of having a major adverse cardiovascular event, particularly recurrent ICH, than those who have had a non-lobar ICH, a new study suggests.

However, those who had had a non-lobar ICH appeared to have an increased risk of having an ischemic stroke or myocardial infarction (MI). 

"This study helps us to identify the highest-risk patients with regard to tailoring secondary prevention approaches," senior author David Gaist, PhD, Odense University Hospital, Odense, Denmark, commented to theheart.org | Medscape Cardiology.

The study was published online April 5 in JAMA Network Open.

The authors point out that ICH is associated with a high short-term case fatality rate, and survivors have an increased risk for recurrent stroke.

The location of an ICH can reflect its underlying pathophysiology, with a non-lobar location associated with hypertensive arteriolosclerosis compared with cerebral amyloid angiopathy, which almost exclusively involves lobar locations, they write.

Several studies have investigated the association between hematoma location and the risk for recurrent ICH, but only limited data are available on the overall risk of other major adverse cardiovascular events (MACEs). The current study therefore aimed to examine the risk for MACEs by hematoma location from an unselected, large cohort of patients with spontaneous ICH.

Using the Danish National Patient Registry and the Danish Stroke Registry, the researchers identified 2819 patients aged 50 years or older who had been hospitalized with a first-ever spontaneous ICH from January 2009 to November 2018 in southern Denmark. 

The location of the ICH in the brain was retrieved from medical records. Based on this information, intracerebral hemorrhage was categorized as lobar or non-lobar. The verified spontaneous ICH cohorts were linked to registry data until the end of 2018 to identify the occurrence of MACEs, and separately recurrent ICH, ischemic stroke and MI. Stroke outcome events were validated using medical records.

Results showed that after adjusting for potential confounders, compared with patients with non-lobar ICH, those with lobar ICH had higher rates of MACEs, with a rate per 100 person-years of 10.84 vs 7.91 (adjusted hazard ratio [aHR], 1.26).

This was driven by an increased rate of recurrent ICH (3.74 vs 1.24 per 100 person-years; aHR, 2.63).

However, rates of ischemic stroke and MI were numerically but not significantly higher in the non-lobar ICH group, with ischemic stroke rates per 100 person-years of 1.45 in those with lobar ICH vs 1.77 in those with non-lobar ICH (aHR, 0.81) and MI rates of 0.42 vs 0.64 (aHR, 0.64).

Gaist noted that these results are "remarkably similar" to those reported in a recent meta-analysis of previous studies.

The researchers also found that the increased risks were seen early. 

"We saw an increased risk of recurrent ICH in patients with a lobar index ICH within the first year and even within the first 30 days," Gaist commented. In contrast, patients with non-lobar ICH were at increased risk for ischemic events (ischemic stroke and MI) in the first 30 days after ICH.

"Together, these findings may have potential clinical implications because they identify a group of vulnerable patients who might benefit from more targeted prevention efforts," the authors suggest.

Gaist drew particular attention to the need for optimal blood pressure control in these patients. "That's a really important message," he said, adding that other modifiable risk factors such as smoking should urgently be addressed.

On the use of other medications such as antithrombotics, he said: "The whole conundrum of whether these patients should receive antithrombotic drugs is currently being addressed in clinical trials, and we will have to await the results of those studies."

"Novel Insight" Into Risk Stratification

In an accompanying commentary, Marialaura Simonetto, MD, and Santosh B. Murthy, MD, Weill Cornell Medicine, New York City, note that survivors of a nontraumatic ICH have a 2- to 3-fold increased risk for MACEs, and although it has been speculated that this may be because of antithrombotic drug interruption and poor long-term risk factor control, recent studies have shown that this increased risk is independent of vascular risk factors, including atrial fibrillation, occlusive vascular disease, and antithrombotic medication use.

They say that the current study "sheds light on the importance of hematoma characteristics, particularly hematoma location, on future cardiovascular risk after ICH."

The editorialists point out that even in the absence of vascular risk factors such as atrial fibrillation and occlusive vascular disease, the rates for MACEs were "strikingly high."

The observations from the study, they write, "not only imply that hematoma location may help guide secondary stroke prevention efforts targeted to ischemic or hemorrhagic stroke recurrence, but also highlight the timing of preventive strategies in that early implementation is perhaps warranted."

Noting that "current guidelines equivocate about the use of antithrombotic and statin medications after ICH because of the perceived risk of recurrent ICH," Simonetto and Murthy say the present study "provides novel insight into the risk stratification of major adverse cardiovascular events after ICH to help delineate the high-risk group that can then be targeted with optimal secondary stroke prevention strategies."

Although trials investigating the safety and efficacy of anticoagulation in ICH survivors with atrial fibrillation are ongoing, as are trials investigating statin therapies in patients with lobar ICH, "given the emerging association between ICH and future ischemic events even in the absence of atrial fibrillation, trials examining the net benefit of antiplatelet and lipid-lowering therapy after ICH, particularly deep hemorrhages, are warranted," they conclude.

The current study was funded by a grant from the Novo Nordisk Foundation. Gaist reports receiving speakers' honoraria from Pfizer and Bristol-Myers Squibb outside the submitted work. Co-author Magdy Selim, PhD, reported receiving grants from National Institute of Neurological Disorders and Stroke during the conduct of the study. Co-author Rustam Al-Shahi Salman, PhD, reported receiving grants from the British Heart Foundation paid to The University of Edinburgh during the conduct of the study and personal fees from Recursion Pharmaceuticals Consultancy paid to The University of Edinburgh and personal fees from Bioxodes Consultancy paid to The University of Edinburgh outside the submitted work.

Murthy reported receiving grants from the National Institutes of Health and receiving personal fees for medicolegal consulting in stroke outside the submitted work. Simonetto reports no relevant financial relationships.

JAMA Network Open. Published online April 5, 2023. Full text, Editorial 

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