Statin use does not increase the risk of intracerebral haemorrhage

Disease and treatment 24. jan 2023 3 min Professor and Consultant Neurologist David Gaist Written by Kristian Sjøgren

Several studies have indicated that statin use may increase the risk of intracerebral haemorrhage (ICH): bleeding into the brain tissue. A registry study in Denmark has challenged this by showing that statin use is actually associated with fewer first-ever ICHs.

The medications statins reduce the level of cholesterol in the blood and are associated with a lower risk of thrombosis (blood clots) in the brain and heart.

However, studies have differed in their findings on associations between statin use and ICH, with some studies finding that statin use may increase the risk.

A study in Denmark provides evidence that contradicts this hypothesis.

The researchers not only examined statin use and the risk of ICH but also investigated whether statin use could be associated with a higher risk of ICH in some locations of the brain and not in others.

The results clearly show that statins were not associated with a higher risk of ICH anywhere in the brain. In fact, statin use was associated with a lower risk of ICH.

“There has been concern about statins having a platelet-inhibiting effect in addition to the cholesterol-lowering effect and thereby increasing the risk of ICH. But we find the opposite, and in fact it seems that the longer people have been using statins, the lower their risk of ICH,” explains lead researcher, David Gaist, Professor and Consultant Neurologist, Department of Neurology, Odense University Hospital and the University of Southern Denmark, Odense.

The research has been published in Neurology.

Data on 1.2 million people

The researchers analysed data using linked nationwide registries, including the Danish Stroke Registry and the Danish National Patient Registry, to identify people older than 55 years within the Region of Southern Denmark with a first-ever case of ICH.

The researchers subsequently reviewed the medical records to ensure that the ICH was spontaneous, meaning that it was not caused by underlying trauma, a tumour or vascular malformations. They also identified the location of the ICH in the brain.

The researchers also obtained data from the Danish National Prescription Registry to identify who had used statins during the study period.

The researchers analysed data on 1.2 million people. They then compared statin use among people with a first-ever ICH during the study period with sex- and age-matched controls from the background population. They also considered comorbidities and the use of other relevant drugs.

“We found no association between statin use and a higher risk of first-ever ICH,” says David Gaist.

Compared ICH in different locations

The researchers also investigated whether statin use could affect the risk of ICH in different locations of the brain.

They focused on lobar and non-lobar ICHs. Lobar ICHs are located more superficially in the lobes of the brain. Conversely, non-lobar ICHs are primarily located deeper in the brain, such as the basal ganglia, thalamus and brainstem.

The researchers identified 989 people (52% women, mean age 76.3 years) with lobar ICH and 1,175 people with non-lobar ICH (46% women, mean age 75.1 years).

David Gaist says that ICHs in these two locations of the brain can have different pathophysiology.

Non-lobar ICH can occur as a result of arteriolosclerosis (atherosclerosis in small arteries). Lobar ICH can be caused by either arteriolosclerosis or cerebral amyloid angiopathy, a condition in which amyloid-beta peptide deposits in the walls of primarily small arteries.

The researchers compared statin use between people who had had a lobar or non-lobar ICH and matched 39,500 controls and 46,755 controls, respectively, from the background population who had never had ICH.

In a substudy with about 1,000 patients with ICH, the researchers assessed the CT brain scans from the time of diagnosis and used an internationally recognized anatomical template to determine the location of the ICH without knowing about statin use.

“The study is among the largest in the world regarding the association between the location of ICH and statin use,” explains David Gaist.

Long-term statin use associated with lower risk

The results confirmed the finding in the main study that statin use was associated with a lower risk of ICH.

In the main study, 31.4% of cases (people who had an ICH) and 30% of controls used statins during the study period.

After adjusting the analysis for age, sex, use of other medications and comorbidities, statin use was associated with a 17% lower risk of lobar ICH and 16% lower risk of non-lobar ICH.

In addition, the researchers again found that long-term statin use was associated with a lower risk of first-ever ICH.

Using statins for more than 5 years was associated with a 33% lower risk of lobar ICH and 38% lower risk of non-lobar ICH.

“Note that we investigated first-ever ICH. We did not include people who had a previous ICH in our study, and the results may differ for this group, but for first-ever ICH, statins seem to be associated with lower risk,” says David Gaist.

Good news for statin users

According to David Gaist, the results are encouraging, although he emphasises that the study was observational and not a randomised controlled trial.

But all other things being equal, the results still indicate that statin use is not associated with a higher risk of first-ever ICH in either the lobar or non-lobar locations of the brain.

“On the contrary, statins appear to be associated with a lower risk of first-ever ICH, which is good news for those who may have been concerned about taking statins,” concludes David Gaist.

The researchers from the University of Southern Denmark and Odense University Hospital are now investigating how statin use affects the risk of subsequent ICHs.

Association between statin use and intracerebral hemorrhage location: a nested case–control registry study” has been published in Neurology. In 2022, the Novo Nordisk Foundation awarded a grant to David Gaist for the project Lobar Intracerebral Haemorrhage: Risk Factors, Course and Association with Cerebral Amyloid Angiopathy.

The principal research area of the clinical group is the epidemiology of stroke and other cerebrovascular disorders, particularly associations of thes...

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