Statin Use in ICH Linked to Lower Risk for Subsequent Stroke

Use of statins in patients who have had an intracerebral hemorrhage (ICH) was not associated with any increase in their risk of having another ICH, and was tied to a lower risk for any stroke and ischemic stroke, in a new study.

The researchers conclude that the lower risk for any stroke was largely due to a lower risk for ischemic stroke, but caution that confirmation of these findings in a randomized trial is needed.

The study was published online August 30 in Neurology, the medical journal of the American Academy of Neurology.

“Our study is observational and therefore cannot prove cause and effect,” lead author, David Gaist, MD, PhD, professor of clinical neurology and head of cerebrovascular research, University of Southern Denmark, in Odense, told Medscape Medical News.

Dr David Gaist

“Having said that, we feel that our large study does provide reassuring news to patients with ICH regarding statin use. We found that statin use was associated with a lower risk of stroke, particularly ischemic stroke, and importantly, statins were not associated with a higher risk of recurrent ICH,” Gaist said.

Studies show that one of the main concerns of patients with a history of intracerebral hemorrhage is the fear of having another stroke, he added. “I hope our study can reduce this fear as far as the use of statins after an ICH is concerned, pending data from randomized trials focused on this population.”

Previous studies have raised concerns as to whether treating people with a history ICH could increase their risk of having another ICH.

Yet, withholding statins from survivors of ICH who have an indication for them could translate into poorer prevention of secondary cardiovascular events, and ultimately lead to an increased risk for ischemic stroke, heart attack, and other vascular events. Results of the previously reported Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial, for example, showed that statin treatment reduced overall and ischemic stroke, but there was a signal of increased hemorrhagic stroke.

To gain more insight into the role of statins in this scenario, the investigators used the Danish Stroke Registry to identify 15,151 individuals who had a first-ever ICH between January 2003 and December 2021. All were aged 50 years or older, and survived for more than 30 days.

Participants were followed from 30 days after their first ischemic stroke to the first occurrence of another stroke, death, or the end of follow-up, which was an average of 3.3 years, to determine whether use of statins after ICH was associated with the risk for any stroke, ischemic stroke, or recurrent ICH.

From their sample, the investigators identified 1959 cases of any subsequent stroke and compared them with 7400 cases who did not have another stroke and who were similar in age, sex, and other factors.

Of those who had another stroke, 757 (39%) took statins vs 3044 (41%) who did not have a second stroke. After adjusting for factors such as hypertension, diabetes, and alcohol use, statin use was associated with a 12% lower risk for another stroke (adjusted odds ratio [aOR], 0.88; 95% confidence interval [CI], 0.78 – 0.99).

Of the 1073 people with ischemic stroke, 427 (40%) took statins compared with 1687 (42%) who did not have another stroke. Again, after adjusting for confounding factors, statin use was associated with a 21% lower risk for an ischemic stroke after the initial bleeding stroke (aOR, 0.79; 95% CI, 0.67 – 0.92).

Of the 984 people with recurrent ICH, 385 (39%) took statins, compared with 1532 (41%) of the 3755 matched controls. After adjustments, no association between statin use and recurrent ICH was found (aOR, 1.05; 95% CI, 0.88 – 1.24).

An Important Topic

Commenting on this study for Medscape Medical News, Christopher Kellner, MD, assistant professor, neurosurgery, and director, Intracerebral Hemorrhage Program, Icahn School of Medicine at Mount Sinai, New York City, noted that the subject of continuing statin use is of critical importance.

“Physicians and patients need to know if taking statins after having an intracerebral hemorrhage helps them reduce their ischemic stroke risk without increasing their risk for a recurrent intracerebral bleed,” Kellner said.

“This study suggests that patients who had bleeding in the brain and then were put back on a statin had a decreased ischemic stroke risk and did not have an increased intracerebral hemorrhage risk. It’s an interesting finding because it argues against another finding that came around in the literature a while ago in the SPARCL trial, which found that statins reduced overall stroke risk but at a cost: an elevated risk of ICH,” he noted.

“That was a post-hoc finding, but it created a bit of an issue and has caused people to debate for years, does taking statins after stroke increase your risk of intracerebral hemorrhage or not?” he said.

The current study does not answer the question definitively, nor was it supposed to. But it does have strengths, including its extensive data base, a national stroke registry encompassing the entire Danish population of some 5.8 million people, and offers more evidence for the safety of continued statin use in a population that needs them, Kellner said.

“This paper is not the ultimate answer, but it is another argument in favor of taking statins after intracerebral hemorrhage,” Kellner said.

“Ultimately, that question needs to be answered by a randomized trial,” he noted. One such trial, funded by the National Institute of Neurological Disorders and Stroke, is called the StATins Use in intRacerebral hemorrhage patieNts (SATURN) trial. “One of the investigators on the current paper, Magdy Selim, MD, PhD, Harvard Medical School, Beth Israel Deaconess Hospital, Boston, is the Principal Investigator of that trial,” he noted.

Neurology. Published online August 30, 2023. Abstract

The study was funded by the Novo Nordisk Foundation. Gaist reports that he receives speaker honoraria outside of this work from Bristol Myers Squibb and Pfizer. Kellner reports no relevant financial relationships.

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