Biological effects of acute pravastatin treatment in patients after aneurysmal subarachnoid hemorrhage: a double-blind, placebo-controlled trial.
OBJECTIVE
The authors previously demonstrated that acute pravastatin therapy in patients after aneurysmal subarachnoid hemorrhage (SAH) ameliorates vasospasm-related delayed ischemic neurological deficits. The object of this study was to continue to examine potential mechanisms of these beneficial effects.


METHODS
Eighty patients with aneurysmal SAH (age range 18-84 years; time to onset 1.8 +/- 1.3 days) were enrolled in a double-blind study and randomized to receive 40 mg of oral pravastatin or placebo daily for as long as 14 days. Daily transcranial Doppler ultrasonography and blood tests every 3 days (including full blood cell counts, coagulation profiles, fasting glucose and lipid profiles, and serum biochemistry) were performed during the trial period.


RESULTS
No significant differences were found in baseline laboratory data between the trial groups. Subsequent measurements during the 14-day trial showed reduced low-density lipoprotein (LDL) cholesterol levels and total/high-density lipoprotein cholesterol ratios between Days 3 and 15 (p < 0.05), and increased D-dimer levels (p < 0.05) on Day 6, in the pravastatin group. Patients who received pravastatin but developed vasospasm had significantly lower baseline LDL cholesterol levels or a less extensive reduction in LDL cholesterol levels (p < 0.05), and greater increases in plasma fibrinogen (p = 0.009) and serum C-reactive protein on Day 3 (p = 0.007), compared with those patients without vasospasm. The reduction in LDL cholesterol levels on Day 3 in the placebo group correlated with the duration of normal cerebral autoregulation on the ipsilateral side of the ruptured aneurysm (p = 0.002).


CONCLUSIONS
In addition to functioning through a cholesterol-independent pathway, cerebrovascular protection from acute statin therapy following aneurysmal SAH may also function through cholesterol-dependent mechanisms.
Tseng
Ming-Yuan
MY
Department of Neurosurgery, Addenbrooke's Hospital, University of Cambridge, United Kingdom.
Hutchinson
Peter J
PJ
Turner
Carole L
CL
Czosnyka
Marek
M
Richards
Hugh
H
Pickard
John D
JD
Kirkpatrick
Peter J
PJ
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000209:etiology / Q000517:prevention & control; D002097:C-Reactive Protein / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D002532:Intracranial Aneurysm / Q000150:complications*; D007958:Leukocyte Count; D008055:Lipids / Q000097:blood; D016015:Logistic Models; D008875:Middle Aged; D010976:Platelet Count; D017035:Pravastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D012307:Risk Factors; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000209:etiology*; D020301:Vasospasm, Intracranial / Q000150:complications / Q000209:etiology
D008078:Cholesterol, LDL; D005338:Fibrin Fibrinogen Degradation Products; D006454:Hemoglobins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; C036309:fibrin fragment D; D005340:Fibrinogen; D002097:C-Reactive Protein; D017035:Pravastatin