Effects of acute treatment with pravastatin on cerebral vasospasm, autoregulation, and delayed ischemic deficits after aneurysmal subarachnoid hemorrhage: a phase II randomized placebo-controlled trial.
OBJECTIVE
Statins may improve cerebral vasomotor reactivity through cholesterol-dependent and -independent mechanisms. A phase II randomized controlled trial was conducted to examine the hypothesis that acute pravastatin treatment could improve cerebrovascular autoregulation and reduce vasospasm-related complications after aneurysmal subarachnoid hemorrhage (SAH).


METHODS
A total of 80 aneurysmal SAH (aSAH) patients (18 to 84 years of age) within 72 hours from the ictus were randomized equally to receive either oral pravastatin (40 mg) or placebo daily for up to 14 days. Primary end points were the incidence, duration, and severity of cerebral vasospasm, and duration of impaired autoregulation estimated from transcranial Doppler ultrasonography. Secondary end points were the incidence of vasospasm-related delayed ischemic deficits (DIDs) and disability at discharge.


RESULTS
Prerandomization characteristics were balanced between the 2 groups. No treatment-related complication was observed. The incidences of vasospasm and severe vasospasm were reduced by 32% (P=0.006) and 42% (P=0.044), respectively, and the duration of severe vasospasm was shortened by 0.8 days (P=0.068) in the pravastatin group. These measurements were maximal on the ipsilateral side of ruptured aneurysms. The duration of impaired autoregulation was shortened bilaterally (P< or =0.01), and the incidence of vasospasm-related DIDs and mortality were decreased by 83% (P<0.001) and 75% (P=0.037), respectively, in the pravastatin group.


CONCLUSIONS
Acute treatment with pravastatin after aSAH is safe and ameliorates cerebral vasospasm, improves cerebral autoregulation, and reduces vasospasm-related DID. Unfavorable outcome at discharge was reduced primarily because of a reduction in overall mortality. This is the first demonstration of clinical benefits with immediate statin therapy for an acute cerebrovascular disorder.
Tseng
Ming-Yuan
MY
Department of Neurosurgery, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 2QQ, United Kingdom.
Czosnyka
Marek
M
Richards
Hugh
H
Pickard
John D
JD
Kirkpatrick
Peter J
PJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006706:Homeostasis; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D002532:Intracranial Aneurysm / Q000628:therapy; D007511:Ischemia; D002546:Ischemic Attack, Transient; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010919:Placebos; D017035:Pravastatin / Q000627:therapeutic use*; D012044:Regression Analysis; D013345:Subarachnoid Hemorrhage / Q000628:therapy*; D013997:Time Factors; D017585:Ultrasonography, Doppler, Transcranial; D020301:Vasospasm, Intracranial / Q000628:therapy*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010919:Placebos; D017035:Pravastatin