SPARCL Trial
The trial that investigated high-dose atorvastatin (80 mg daily) in patients with a history of stroke, including intracerebral hemorrhage, is the SPARCL trial (Stroke Prevention by Aggressive Reduction in Cholesterol Levels). 1
Trial Design and Population
SPARCL enrolled 4,731 adults who had experienced an ischemic or hemorrhagic stroke (or TIA presumably owing to atherosclerotic causes) in the prior 1 to 6 months with LDL-C levels of 100 to 190 mg/dL 1
Patients were randomized to atorvastatin 80 mg daily versus placebo and followed for a median of 4.9 years 1
The trial specifically included patients with hemorrhagic stroke at baseline (approximately 2% of participants), making it unique in evaluating statin effects in this high-risk population 2
Primary Findings
Atorvastatin reduced the primary endpoint of fatal or nonfatal stroke from 13.1% in the placebo group to 11.2% in the atorvastatin group (adjusted HR 0.84,95% CI 0.71-0.99) 1
The treatment reduced ischemic stroke by 22% and major cardiovascular events by 20% 3
Critical Safety Signal: Hemorrhagic Stroke Risk
SPARCL identified an increased risk of hemorrhagic stroke with atorvastatin 80 mg: 2.3% versus 1.4% with placebo (HR 1.68,95% CI 1.09-2.59; p=0.0168) 4
The incidence of fatal hemorrhagic stroke was similar between groups (17 atorvastatin vs 18 placebo), but non-fatal hemorrhagic strokes were significantly higher in the atorvastatin group (38 vs 16) 4
Patients who entered the trial with a hemorrhagic stroke appeared to be at particularly increased risk for recurrent hemorrhagic stroke (16% atorvastatin vs 4% placebo) 4
Clinical Implications from SPARCL
The trial established that high-dose atorvastatin is effective for secondary stroke prevention in patients with recent ischemic stroke or TIA 1
However, the risk-benefit ratio must be carefully considered in patients with recent hemorrhagic stroke, particularly those with lobar ICH location 1, 4
SPARCL findings led to FDA labeling warnings about increased hemorrhagic stroke risk with atorvastatin 80 mg in patients with recent hemorrhagic stroke 4