SPARCL Trial: Statins in Stroke
In patients with recent ischemic stroke or TIA and LDL 100 to 190 mg/dL without known coronary heart disease, does high-intensity atorvastatin (80 mg daily) reduce recurrent stroke compared with placebo?
Amarenco et al. (NEJM 2006) · 4,731 patients
Population
Included
- Age 18 years or older
- Ischemic stroke or TIA within 1 to 6 months of randomization
- LDL cholesterol 100 to 190 mg/dL (2.6 to 4.9 mmol/L)
- No known coronary heart disease at entry
Eligible patients
- Men and women over 18 years of age
- Had had an ischemic or hemorrhagic stroke or a TIA, diagnosed by a neurologist within 30 days after the event, 1 to 6 months before randomization
- Stroke was defined by focal clinical signs of central nervous system dysfunction of vascular origin that lasted for at least 24 hours; TIA was defined by the loss of cerebral or ocular function for less than 24 hours, presumably owing to atherosclerotic causes
- Patients with hemorrhagic stroke were included only if they were deemed by the investigator to be at risk for ischemic stroke or coronary heart disease
- Ambulatory, with a modified Rankin score of no more than 3
- An LDL cholesterol level of at least 100 mg per deciliter (2.6 mmol per liter) and no more than 190 mg per deciliter (4.9 mmol per liter)
Excluded
- Known coronary heart disease or prior coronary revascularization
- Prior statin use within 3 months (washout required)
- Cardioembolic stroke requiring anticoagulation as primary prevention
- Severe hepatic disease or creatine kinase elevation
Cardioembolic source / other defined cause
- Atrial fibrillation
- Other cardiac sources of embolism
- Subarachnoid hemorrhage
Source: SPARCL Investigators (Amarenco P et al.), N Engl J Med 2006· Retrieved 2026-06-09
Primary Outcome
Negligible absolute difference
Stroke-free at 5 Years
Study Arms
- Agent
- Atorvastatin
- Dose
- 80 mg
- Route
- Oral
- Frequency
- Once daily
- Duration
- Median follow-up 4.9 years
- Co-interventions
- All patients were counseled to follow the National Cholesterol Education Program Step 1 (or similar) diet throughout the study; patients taking lipid-altering drugs at screening stopped them 30 days before the screening visit
Double-blind. To preserve masking, if LDL cholesterol fell below 40 mg/dL (1.0 mmol/L) in an atorvastatin-treated patient, the investigator for a randomly chosen placebo patient was notified and LDL was remeasured in both
- Agent
- Matching placebo
- Dose
- Matching placebo
- Route
- Oral
- Frequency
- Once daily
- Duration
- Median follow-up 4.9 years
- Co-interventions
- Same National Cholesterol Education Program Step 1 (or similar) diet counseling as the atorvastatin group
Double-blind, placebo-controlled
Safety
Hemorrhagic stroke (atorvastatin vs placebo)
2.3%
1.4%
Atorvastatin significantly increased hemorrhagic stroke risk (HR 1.66, P=0.02). The absolute excess was 0.9 percentage points over 4.9 years. This risk is highest in patients with prior hemorrhagic stroke; atorvastatin is relatively contraindicated in that group. /* claimId: sparcl-hemorrhagic-stroke | source: Amarenco NEJM 2006 Table 3 */
Trial Design
Type
- Randomized double-blind placebo-controlled trial
- 1:1 allocation (Atorvastatin vs. Placebo)
Timeline
Enrolled 2001-2005
N
4,731
Enrollment
4,731 patients across 205 centers in 27 countries. Enrolled 2001 to 2005. Median follow-up 4.9 years.
ClinicalTrials.gov
NCT00147602Bedside Pearl
SPARCL established atorvastatin 80 mg as a standard in secondary stroke prevention, but the hemorrhagic stroke signal (HR 1.66) is real and matters. The net benefit is favorable in ischemic stroke patients, but in a patient with prior hemorrhagic stroke, you are adding a drug that independently increases hemorrhagic stroke by 66% without clear ischemic benefit in that subgroup. In hemorrhagic stroke, statin use post-discharge is a shared decision, not a reflex.
See also