Statins Reduce Recurrence After Stroke of Unknown Cause

Pauline Anderson

August 02, 2011

August 2, 2011 — A new study has shown that young patients treated with a statin after a stroke of undetermined cause were 77% less likely to have a new vascular event, suggesting that statins should be considered in such patients.

"Despite its limitations, we think our study has an obvious impact on clinical practice by helping clinicians make this crucial decision of whether or not to initiate a life-long medication in a young patient who had suffered his/her first ischemic stroke," said lead study author Jukka Putaala, MD, PhD, from the Department of Neurology, Helsinki University Central Hospital, Finland, in an email to Medscape Medical News.

"In most ischemic stroke patients, statins should be considered, but there remains uncertainty of the benefit of statins in certain subgroups of young patients, such as those with carotid artery dissection," he said.

The study was published in the August 1 issue of Neurology.

Statin Users

For the study, researchers at the Helsinki University Central Hospital used a database of patients with a first ischemic stroke and gathered data on their statin use. The analysis included 215 patients aged 15 to 49 years (mean age, 39.1 years) with a stroke of undetermined cause; patients with known causes of stroke, such as carotid artery occlusion or dissection, were excluded.

The composite vascular endpoint of the study was any stroke, myocardial infarction, or other artrial occlusvie event, revascularizaiton, or vascular death. The patients were followed up for a mean of 9 years.

One-third (33%) of patients in the analysis received a statin some time after their stroke; most — 58% — took simvastatin. These patients were more likely to be older and have higher levels of total cholesterol, low-density lipoprotein (LDL), and triglycerides and had hypertension or coronary heart disease more frequently.

There were 29 events (20%) among patients never taking a statin, none among those taking a continuous statin, and 4 (11%) among those who had discontinued use of a statin.

Those who had discontinued or continued use of a statin were at reduced risk for compostite vascular endpoint events (hazard ratio, 0.23; 95% confidence interval, 0.08 – 0.66; P = .006). The association remained after adjusting for age, high blood pressure, and taking high blood pressure medication.

Higher LDL Levels

The association was significant despite the higher LDL levels in those taking a statin at baseline (2.6 mmol/L for those never taking a statin vs 3.4 mmol/L for those taking a statin at any time), which the researchers found "surprising," said Dr. Putaala.

"We conclude that statins should be considered irrespective of the current LDL level (or other lipoprotein levels or triglycerides) at the time of ischemic stroke," he said. "This is due to their multiple suggested pleiotropic effects (eg, improving endothelial function, modulation of inflammatory responses, maintaining plaque stability, and preventing thrombus formation) rather than lipid-lowering effects."

The study included only young patients with a stroke of unknown cause. According to Dr. Putaala, 20% to 30% of strokes are of an unknown cause in a younger population.

Because the analysis was restricted to this population, the results may not apply to other young stroke patients, he said. "We would not expect that the effect would be similar or this clear in young patients with known etiology, and since our analysis is restricted to patients with unknown cause, the results are not directly generalizable to known causes."

Although simvastatin was the most common statin used by subjects in the study, the numbers were too small to tease out any differences between statin type in terms of the outcome. However, said Dr. Putaala, "we believe that our findings represent a group effect of statins."

SPARCL Comparison

Asked to comment, Howard S. Kirshner, MD, professor and vice chair, Department of Neurology, Vanderbilt Medical Center, Nashville, Tennessee, and a member of the American Academy of Neurology, said the study is the only one he knows of that looks at statin therapy in young patients who had a stroke of undetermined cause.

The other study that supported statin use in stroke patients, the Stroke Prevention with Aggressive Reduction in Cholesterol Levels or SPARCL trial, showed that statin therapy was beneficial in preventing another stroke, but only in patients who had an LDL level of over 100 mg/dL, he pointed out.

"The current study did not require any specific lipid level, although untreated patients were more likely to have normal levels," said Dr. Kirshner in an email. "Perhaps the LDL limit of 100 or above should not apply, although there is still some concern that very low LDL levels may be associated with intracerebral hemorrhage (not mentioned in this study). The SPARCL study did find more hemorrhages in the group treated with statin therapy. The current study was not large enough (215 patients) to answer this question."

For his part, Dr. Putaala said that although some studies have found a slightly elevated risk for intracerebral hemorrhage in patients taking a statin, the beneficial effect of these agents on the prevention of future vascular events "clearly overcome this."

The take-home message, said Dr. Kirshner, is that statins should probably be prescribed to all ischemic stroke patients, including younger patients with no obvious evidence of an atherosclerotic cause of the stroke.

Dr. Putaala has received funding for travel from Boehringer Ingelheim and Genzyme Corporation, serves on the editorial board of Frontiers in Stroke, and receives research support from the Helsinki University Central Hospital, the Finnish Medical Foundation, and the Finnish Brain Foundation. For conflict information on other authors, see original paper.

Neurology. 2011;77:426-430.

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