Atorvastatin demonstrates reduction of stroke incidence in patients experiencing recent stroke or TIA

Atorvastatin reduced the overall incidence of strokes and cardiovascular events in patients without known coronary disease who had recently experienced a stroke or a transient ischemic attack (TIA), according to a randomized, placebo-controlled, double-blind study of 4,731 patients. Results from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study, however, also demonstrated an increase in the incidence of hemorrhagic strokes among those receiving atorvastatin compared with placebo.

Patients enrolled in the study had low-density lipoprotein (LDL) cholesterol levels of 100 to 190 mg/dL and had experienced a stroke or TIA within 1 to 6 months prior to enrollment. Subjects were randomized to atorvastatin 80 mg/d (n=2,365) or placebo (n=2,366), with a median follow-up period of 4.9 years. Interim efficacy analyses performed during the course of the study resulted in P values of <.048 being required to indicate significant differences in data between groups. The primary end point was any nonfatal or fatal stroke, and secondary composite outcomes included stroke or TIA, major coronary event, major cardiovascular event, any coronary event, revascularization procedure, and any cardiovascular event.

Following randomization, patients were permitted to continue taking aspirin or other antiplatelet medications, angiotensin-converting enzyme (ACE) inhibitors, dihydropyridine derivatives, beta blockers, angiotensin-II receptor antagonists, vitamin K antagonists, or open-label statins. Aspirin and antiplatelet medications were the most frequently used among both the placebo and treatment groups (94.1% and 93.6%, respectively). At baseline, mean LDL cholesterol levels were similar in both groups.

The lower mean LDL cholesterol level observed in the atorvastatin group could indicate that the beneficial effects of statin therapy on the risk of recurrent stroke stem from a reduction in the risk of cerebral infarction, the authors said.

Atorvastatin treatment also reduced the risk of coronary events or noncoronary revascularization procedures, with 434 patients in the group (9.2%) experiencing the events or undergoing the procedures.

"Our results support the concept that from the standpoint of statin treatment, stroke or TIA should be considered a coronary heart disease risk equivalent," the authors stated.

Researchers observed differences between the 2 groups in the hazard ratios based on the type of stroke occurring. Patients in the atorvastatin group experienced fewer ischemic strokes than the placebo group (218 vs 274), translating into an adjusted HR of 0.78 (95% CI, 1.08–2.55). Of the 88 patients who experienced hemorrhagic strokes, patients in the atorvastatin group had a higher incidence of the event than the placebo group (55 vs 33, respectively) and a higher risk of hemorrhagic strokes (adjusted HR=1.66; 95% CI, 1.08–2.55).

"The small number of patients with brain hemorrhage at entry in our study precludes any meaningful conclusions regarding the relative risks and benefits of statin treatment in this population," the authors stated. "The potential risk of recurrent hemorrhage should be considered when deciding whether to administer a statin to patients who have had a hemorrhagic stroke."

Nineteen patients in the entire study population experienced strokes that did not have classified causes, with more patients in the placebo group (12) experiencing those types of strokes, translating into an adjusted HR for the atorvastatin group of 0.55 (95% CI, 0.51–1.40). Researchers observed no significant difference in the incidence of fatal hemorrhagic stroke between groups.

SOURCE Amarenco P, Bogouslavsky J, Callahan A III, et al; for the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355:549–559.