pitavastatin and Intracranial-Aneurysm

Statins have pleiotropic effects that are considered beneficial in preventing cerebral vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (aSAH). Many studies using statins have been performed but failed to show remarkable effects. We hypothesized that a long-acting statin would be more effective, due to a longer half-life and stronger pleiotropic effects. Patients with aSAH were randomly assigned to a pitavastatin group (4 mg daily; n = 54) and a placebo group ( n = 54) after repair of a ruptured aneurysm. The primary efficacy end point was vasospasm-related delayed ischemic neurological deficits (DIND), and the secondary end points were cerebral vasospasm evaluated by digital subtraction angiography (DSA), vasospasm-related new cerebral infarctions, and outcome at three months. Severe cerebral vasospasms on DSA were statistically fewer in the pitavastatin group than in the placebo group (14.8% vs. 33.3%; odds ratio, 0.32; 95% confidence interval, 0.11-0.87, p = 0.042); however, the occurrence of DIND and new infarctions and outcome showed no statistically significant differences between the groups. The present study is the first to prove the definite, statin-induced amelioration of cerebral vasospasm on DSA. However, administration of any type of statin at the acute phase of aSAH is not recommended.

Topics: Adult; Aged; Aneurysm, Ruptured; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intracranial Aneurysm; Male; Middle Aged; Quinolines; Subarachnoid Hemorrhage; Vasospasm, Intracranial

Recent investigations strongly suggest that the pathophysiology of cerebral aneurysms (CA) is closely associated with chronic inflammation in vascular walls. Nuclear factor kappaB (NF-kappaB) has a key role in the formation and progression of CAs. Because statins exert anti-inflammatory effects in various vascular diseases, we investigated the effect of pitavastatin on NF-kappaB activation and CA formation in experimentally induced CAs in rats.. CAs were induced in Sprague-Dawley rats with or without administration of pitavastatin (4 mg/kg/d orally). Size, change of internal elastic lamina, and media thickness of induced CAs were measured in both groups after aneurysm induction. The effects of pitavastatin on NF-kappaB activation in aneurysmal walls were examined by immunohistochemistry and gel shift assay. Expression of downstream genes was analyzed by quantitative polymerase chain reaction and immunohistochemistry. To examine whether pitavastatin has a suppressive effect on preexisting CAs, pitavastatin administration started 1 month after aneurysm induction.. Pitavastatin treatment significantly prevented CA progression (P < 0.01) and NF-kappaB activation in aneurysmal walls. Expression of monocyte chemotactic protein-1, vascular cell adhesion molecule-1, interleukin-1beta, inducible nitric oxide synthase, and matrix metalloproteinase-9 in aneurysmal walls was also inhibited by pitavastatin. Pitavastatin treatment led to media thickening in preexisting CAs.. Pitavastatin has a suppressive effect on CA progression through the inhibition of NF-kappaB activation in aneurysmal walls. Moreover, pitavastatin treatment can cause the regression of degenerative changes in preexisting CA walls. Pitavastatin is a promising candidate for a novel preventive agent against subarachnoid hemorrhage.

Topics: Animals; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intracranial Aneurysm; Male; NF-kappa B; Quinolines; Rats; Rats, Sprague-Dawley; Signal Transduction; Treatment Outcome