SPARCLOVMC LANDMARK TRIALS SERIES

Amarenco P, et al. "High-dose atorvastatin after stroke or transient ischemic attack". The New England Journal

of Medicine. 2006. 355(6):549-559.

STROKE PREVENTION by Aggressive Reduction in Cholesterol Levels (SPARCL)

BACKGROUND

CARE, LIPID, and 4S trials showed that the role of statins in primary prevention of stroke and TIA in patients with high risk CVA

However, prior to SPARCL, there were not clear guidelines for secondary prevention of stroke and TIA

Primary Prevention•Well population•Address risk factors•Education and prevention•Eg: Immunizations, exercise programs

Secondary Prevention•People at risk of health problem•Screening at risk groups• Intervention and medication to control risk factors and early intervention

Tertiary Prevention•People with a health problem•Rehab, preventing complications and improving quality of life

CLINICAL QUESTION

For patients prior stroke or TIA, does HIGH-DOSE ATORVASTATIN

reduce the risk of recurrent stroke?

DESIGN

Analysis: Intention-to-treat Multicenter, double blind, parallel-group, randomized, placebo-controlled trial N=4,731 patients with prior stroke/TIA

Atorvastatin (n=2,365) Placebo (n=2,366)

Setting: 205 centers Enrollment: 1998-2001 Mean follow-up: 4.9 years Primary outcome: fatal or non-fatal stroke

POPULATION

Inclusion Criteria Age ≥18 years Ischemic stroke, hemorrhagic stroke, or TIA

in the 1-6 months before randomization TIAs diagnosed by a neurologist within 30 days of

the primary event Those with hemorrhagic stroke thought to be at

risk for ischemic stroke or CAD by the investigator Modified Rankin score ≤3 LDL 100-190 mg/dL (2.59-4.92 mmol/L)

Exclusion Criteria Non-ambulatory Atrial fibrillation Cardiac sources of embolism Subarachnoid hemorrhage While not a strict exclusion criterion,

patients with LDL >160 mg/dL (4.14 mmol/L) were excluded in 15 of 205 centers

INTERVENTIONS

Cessation of any lipid-lowering medications 30 days before screening Randomization to atorvastatin 80mg PO daily or placebo Counseling on the National Cholesterol Education Program Step 1 or similar diets

throughout the study Visits on months 1, 3, and 6 months and every 6 months subsequently Labs and EKGs at screening, at regular intervals during study, and at completion of the

study

CRITICISMS

Power of SPARCL study not sufficient to assess mortality SPARCL did not have a run-in period (period when placebo is given); for that reason, it

is harder to assess tolerability of high-dose atorvastatin in SPARCL

BOTTOM LINE

In patients with prior stroke/TIA,Atorvastatin reduces risk of recurrent ischemic stroke BUT may increase risk of

hemorrhagic stroke

DISCUSSION QUESTIONS

For a patient with history of ischemic stroke, would you give Atorvastatin? When would you re-consider giving Atrovastatin?

What is a run-in period?

DISCUSSION QUESTIONS

For a patient with history of ischemic stroke, would you give Atorvastatin? ANSWER: Yes, give High-dose Atorvastatin 40mg or 80mg

When would you re-consider giving Atorvastatin? ANSWER: For patients with ischemic stroke

What is a run-in period? Period before trial begins when no treatment is given

Screen & Consent

RUN-IN Period

(Placebo given)

Randomization!

Group A

Group B

Placebo responders, non-compliant participants, participants intolerant of medications, etc

Satisfactory

DROPPED!

BOARD-LIKE QUESTION

77yo F, hx HTN, HLD presented to ED with left facial droop and left sided weakness. Emergent CT scan showed no bleed. MRI showed evidence of right MCA CVA.The following day, PE showed HR 91, BP 138/62, RR 14 bpm, sating 100% on RA. Nuchal rigidity is present. Patient responds to loud voice.Finger stick glucose over 24 hours shows 140-179 mg/dL.

Which treatment would help reduce risk of recurrent stroke?A. IV dopamineB. IV insulin C. Oral AtorvastatinD. Oral Nimodipine

BOARD-LIKE QUESTION

Educational Objective: Statin use in ischemic stroke and TIAKey Point:- Statins are used in ischemic stroke or TIA from

atherosclerotic subtype as it reduces risk of recurrent stroke

- Efficacy of statins for secondary stroke prevention or neuroprotective agent in subarachoid hemorrhage has not been established

- Nimodipine (L-type calcium channel blocker) helps prevent neurologic complications after subarachoid hemorrhage by reducing vasospam in clinical trials

ANSWERWhich treatment would help reduce risk of recurrent stroke?A. IV dopamineB. IV insulin C. Oral AtorvastatinD. Oral Nimodipine