Recurrent stroke: Statins may reduce risk after bleeding stroke

• Statin use does not increase the risk of subsequent intracerebral hemorrhages for people who have already experienced one, says a new study.
• At the same time, statins can reduce the chances of having an ischemic stroke after an intracerebral hemorrhage.
• The study may put to rest concerns about statins and intracerebral hemorrhages, with the drugs being prescribed more frequently to address a variety of conditions, most notably high cholesterol.

People who have had an intracerebral hemorrhage, a type of bleeding stroke, should consider taking statins, according to a new study.

The findings indicate that while statins do not increase or decrease the risk of subsequent intracerebral hemorrhages, they do reduce the risk of ischemic stroke.

Ischemic strokes, which are caused by a blockage in an artery or blood vessel in the brain, are the most common type of stroke. They affect about 87% of those who have strokes.

Bleeding strokes strike about 13% of people who have strokes and include intracerebral hemorrhages and subarachnoid hemorrhages. Intracerebral hemorrhages are twice as common.

Intracerebral hemorrhages are among the most deadly forms of stroke, striking an estimated 10 to 25 per 100,000 people worldwide. The 30-day survival rate has not significantly improved for them over the last 20 years.

The study followed 15,151 people from Denmark who had had a first bleeding stroke and had survived for 30 days, continuing until they had another stroke, emigrated, died, or until the study ended. Prescription data on these individuals allowed the researchers to see who did or did not take statins after their stroke.

From this group, the researchers performed a nested analysis comparing:

• 1,959 patients who had had any kind of stroke with 7,400 control individuals similar in sex, age, and other factors
• 1,073 patients who had had an intracerebral hemorrhage, with 4,035 people in a control group
• 984 patients with recurring intracerebral hemorrhages, with 3,755 people in a control group.

After factoring in variables, the researchers concluded that using statins was associated with a 21% lower risk of an ischemic stroke after a first intracerebral hemorrhage without affecting the risk of a recurrence.

The study is published in Neurology.

Why this is good news for statin users

“Statins also have pleiotropic effects. So, they have effects of cholesterol lowering, but they also have a number of healthy anti-inflammatory effects at the cellular level and on multiple organ systems,” said Dr. Sandra Narayanan, vascular neurologist and neuro-interventional surgeon at Pacific Stroke & Neurovascular Center at the Pacific Neuroscience Institute, who was not involved in the study.

Dr. Narayanan noted that the number of people with high cholesterol that might be treated with statins is steadily rising, and new benefits of the drugs are becoming apparent.

“Randomized clinical trials have established high-intensity statin therapy as beneficial in patients with acute ischemic stroke,” said Dr. Gregg C. Fonarow, Eliot Corday professor of cardiovascular medicine and science at UCLA, who was also not involved in the study.

“Guidelines recommend the use of high intensity statin therapy in individuals after acute ischemic stroke as a routine standard of care,” he said.

“The potential benefits of statins are still being unlocked,” said Dr. Narayanan.

However, “There were a number of trials, including the SPARCL trial [alluded to in the study] that suggested patients who had taken statins in the setting of intracerebral hemorrhage may be at higher risk of recurrent hemorrhage, particularly if lipid levels were lowered significantly, and that is probably what would happen if you take statins,” said Dr. Narayanan.

Dr. Narayanan called this a dilemma “because many patients who are taking statins but also have an intracranial hemorrhage are taking statins for a comorbid condition that likely needs addressing.”

The lipid-lowering singled out in the SPARCL study has medical benefits for conditions such as major cardiovascular disease.

“That vascular risk factor can’t be managed because the patient can’t be on statins for concern of recurrent intracranial hemorrhage. It’s a real medical management dilemma. So I think this study is helpful,” said Dr. Narayanan.

She noted that this is “a different type of study.” It found no additional risk of recurrent intracerebral hemorrhage in a population who had already had one through nested sub-analyses of that population with a comforting one to four case-to-control ratio for each subgroup.

However, further randomized research is needed to confirm the findings.

Causes of intracerebral strokes

Dr. Narayanan pointed out that certain populations, such as Asian people, may be at a higher risk of experiencing intracerebral hemorrhage.

“Male gender, older patients, patients who have other diseases or vasculopathies of the intracranial arteries,” may also be at a higher risk, she added.

She noted that “moyamoya disease narrows the large arteries of the brain, and it can peak in two time periods, both pediatric and young adults, and that can cause both ischemic and hemorrhagic stroke.” She added that cerebral amyloid and angiopathy are more common causes as patients get older.

Risk factors for brain bleeds

Dr. Narayanan also listed some other risk factors for intracerebral hemorrhages, including acquired lifestyle factors that can affect macro and microvascular changes. She cited tobacco abuse, alcohol abuse, and abuse of certain substances that activate the sympathetic nervous system.

She also mentioned “what we call sympathomimetic drugs,” namely cocaine, amphetamines, cannabis, and heroin, as risk factors.

These are drugs “that are not as much known for their hyper-acute blood pressure and heart rate-elevating response.” She said a number of these have been linked to an increased risk of multiple types of intracranial hemorrhage.

High blood pressure heightens stroke risk

Ischemic strokes and intracerebral strokes share one prominent risk factor: hypertension.

High blood pressure can “cause variable mechanisms of injury to the extra and intracranial arteries, as well as other organ systems such as the kidneys, which participate in the regulation of blood pressure in a more systemic fashion. That has long-term effects on the elasticity as well as thinning and friability of the small vessels,” said Dr. Narayanan.

“One of the key strategies for reducing the risk of recurrent stroke after a primary intracerebral hemorrhagic stroke is blood pressure-lowering therapy. Excellent blood pressure control in these patients is essential to lowering the risk of recurrent events.”
— Dr. Gregg C. Fonarow

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