High-Dose Statin Therapy Reduces Incidence, Severity of Recurrent Stroke

From the American Neurological Association

CHICAGO—High-dose statin therapy after an ischemic stroke in patients with or without heart disease can reduce the incidence or the severity of recurrent stroke, according to data from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial, which were presented at the American Neurological Association annual meeting.

When a statin was taken during the month preceding a second ischemic stroke, fewer fatal and severe strokes and fewer transient ischemic attacks (TIAs) occurred. Furthermore, the incidence of recurrent stroke was reduced in patients taking a statin, said Larry B. Goldstein, MD, of Duke University Medical Center, Durham, NC.

N Engl J Med

These data from the randomized, placebo-controlled SPARCL trial (. 2006; 355:549-559) are the best available evidence demonstrating that statins have biologic effects unrelated to their lipid-lowering effects, Dr Goldstein said. “If you are supposed to be taking a statin and are taking it, if you have another ischemic stroke, that stroke is going to be less severe.”

SPARCL included 4731 patients (mean age, 63 years) who had a stroke or TIA during the previous 6 months. None of the patients had a history of heart disease. At baseline, mean low-density lipoprotein cholesterol (LDL-C) level was 133 mg/dL. Patients were randomized to receive 80 mg atorvastatin (Lipitor) daily or placebo and were followed for a mean of 4.9 years. The primary end point was fatal or nonfatal stroke.

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During follow-up, the statin-treated patients had a 37% reduction in LDL-C, while the placebo-treated patients had no significant reduction in LDL-C. Second ischemic strokes occurred in 218 of the statin-treated patients and 274 of the placebo patients. The rate of recurrent fatal or nonfatal stroke was 11.2% in the treatment group and 13.1% in the placebo group ( = .03). SPARCL is the first trial to show that statin treatment offers statistically significant protection against recurrent stroke, Dr Goldstein said.

A significant reduction in other major cardiovascular events was also observed among atorvastatin-treated patients (P = .003). Although overall mortality was similar in both groups, there was a small increase in the number of hemorrhagic strokes among statin users.

A secondary analysis of the 492 second ischemic stroke patients was used to determine whether there was a connection between statin treatment and the severity of recurrent stroke. Results of previous studies have conflicted, but experimental data suggest that statins may have neuroprotective effects, said Dr Goldstein.

The severity of second stroke among the SPARCL participants was measured using the National Institutes of Health Stroke Scale and other standard indexes at baseline and at 90 days after the second stroke.

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Results showed a significant decrease in stroke severity among patients who took atorvastatin during the month before the second stroke compared with patients who had not taken a statin ( = .007).

“The distribution shifted down. The number of fatal and severe strokes was reduced by about half, and there was an increase in the number of mild strokes,” said Dr Goldstein.

However, patients who stopped taking atorvastatin more than 1 month before their second stroke had no reductions in stroke rate or severity.

Overall, of patients who had second strokes, 50.9% of the mild strokes occurred in patients who had taken atorvastatin during the previous month, and 42.8% occurred in the placebo group. The respective rates for moderate stroke were 36% and 32.4%; for severe stroke, they were 6.9% and 11.3%, and for fatal stroke, they were 6.3% and 13.5%.

Key points

• Patients who have had an ischemic stroke or TIA are at risk for recurrent stroke.

• The SPARCL trial provides the best available evidence demonstrating that statins have biologic effects unrelated to their lipid-lowering effects.

• It also showed that highdose statin therapy can significantly reduce the risk of recurrent stroke.

• Recurrent strokes were less severe in patients taking a high-dose statin in the previous month.