Statin Treatment and Stroke Outcome in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Trial

Abstract

on behalf of the SPARCL InvestigatorsBackground and Purpose-Laboratory experiments suggest statins reduce stroke severity and improve outcomes. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial was a placebo-controlled, randomized trial designed to determine whether treatment with atorvastatin reduces strokes in subjects with recent stroke or transient ischemic attack (nϭ4731). We analyzed SPARCL trial data to determine whether treatment favorably shifts the distribution of severities of ischemic cerebrovascular outcomes. Methods-Severity was assessed with the National Institutes of Health Stroke Scale, Barthel Index, and modified Rankin Scale score at enrollment (1 to 6 months after the index event) and 90 days poststroke in subjects having a stroke during the trial. Results-Over 4.9 years, strokes occurred in 576 subjects. There were reductions in fatal, severe (modified Rankin Scale score 5 or 4), moderate (modified Rankin Scale score 3 or 2), and mild (modified Rankin Scale score 1 or 0) outcome ischemic strokes and transient ischemic attacks and an increase in the proportion of event-free subjects randomized to atorvastatin (PϽ0.001 unadjusted and adjusted). Results were similar for all outcome events (ischemic and hemorrhagic, PϽ0.001 unadjusted and adjusted) with no effect on outcome hemorrhagic stroke severity (Pϭ0.174 unadjusted, Pϭ0.218 adjusted). If the analysis is restricted to those having an outcome ischemic stroke (ie, excluding those having a transient ischemic attack or no event), there was only a trend toward lesser severity with treatment based on the modified Rankin Scale score (Pϭ0.0647) with no difference based on the National Institutes of Health Stroke Scale or Barthel Index. Conclusion-The

Randomized Controlled Trial of Early Versus Delayed Statin Therapy in Patients With Acute Ischemic Stroke

“…25 A retrospective observational study reported that 1-year survival rates among patients with ischemic stroke who were administered statins before or during admission were higher than the counterparts. 6 About disability outcomes, the subanalysis of SPARCL Trial also showed that statin administration at nonacute phase was associated with reduced disability measured by mRS. 26 Another non-RCT found that statin withdrawal for 3 days after ischemic stroke onset in patients previously on statins was associated with significantly worse disability status after 90 days compared with patients receiving statins immediately after onset. 4 Thus, statin withdrawal at acute phase or nonadministration at nonacute phase should be associated with worse outcomes in patients with acute ischemic stroke, but the clinical significance of early administration to naive patients should be evaluated.…”

The THRombolysis and STatins (THRaST) study

“…[7][8][9] The Stroke Prevention with Aggressive Reductions in Cholesterol Levels (SPARCL) trial showed a trend toward less severity for outcome 90 days after stroke with atorvastatin administration (80 mg), compared with placebo, in patients having a stroke during the trial. 10 So far, few studies have assessed the efficacy and safety of statin treatment in ischemic stroke patients treated with IV thrombolysis. Two recent meta-analyses showed that prior statin use may increase the risk of symptomatic intracerebral hemorrhage (sICH) within 36 hours after IV recombinant tissue plasminogen activator (rtPA), though without influencing 3-month functional outcome.…”

Statins for Neuroprotection After Acute Ischemic Stroke

“…7 Although this analysis was post hoc, and not clearly supported by benefit measured by the National Institutes of Health Stroke Scale and Barthel Index, these data are the largest to date in a randomized trial of treatment with a standardized high-dose statin in the acute phase at stroke onset. This intriguing signal from SPARCL, when combined with supportive experimental and epidemiological data, suggests that more randomized trials of acute statin therapy are needed.…”