pitavastatin and Cerebral-Infarction

The JAPAN-ACS study demonstrated that statins significantly reduced coronary plaque volume in patients with acute coronary syndrome (ACS). The clinical implications of plaque regression for clinical outcomes in ACS patients has not been established. The Extended JAPAN-ACS study was conducted to evaluate the relationship between coronary plaque regression and long-term clinical outcome, and to explore the factors associated with cardiovascular events.. Patients with intravascular ultrasound (IVUS) data at both enrollment and follow-up in the JAPAN-ACS study were enrolled and observed for at least 3 years. Patients were divided into lesser and greater coronary plaque regression groups. The primary endpoint was defined as a composite of the following events: cardiovascular death, nonfatal myocardial infarction, nonfatal cerebral infarction, and unstable angina. The median value of the percent change in plaque volume, 18.0%, was used as a cutoff point. There were 4 primary events (3.4%) in the lesser regression group, and 2 events (1.7%) in the greater regression group (P=0.4). Cumulative secondary cardiovascular events did not differ between the 2 groups. Multivariate analysis identified the high-density lipoprotein cholesterol (HDL-C) at baseline and the % change of the external elastic membrane volume as independent risk factors of cardiovascular events.. Coronary plaque regression induced by an intensive statin regimen did not predict future cardiovascular events in ACS patients. Rather, the baseline HDL-C level and reverse vessel remodeling might serve as predictors for cardiovascular events.

Topics: Acute Coronary Syndrome; Aged; Angina, Unstable; Atorvastatin; Biomarkers; Cerebral Infarction; Cholesterol, HDL; Coronary Artery Disease; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Plaque, Atherosclerotic; Predictive Value of Tests; Proportional Hazards Models; Pyrroles; Quinolines; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Hypercholesterolemia has been identified as an important risk factor for stroke. It has been reported that statins might reduce the risk for new or recurrent cardiovascular events and strokes.. This paper reports on the effects of pitavastatin on cerebral blood flow in 2 elderly patients.. Two patients, a 72-year-old right-handed Japanese man and a 77-year-old right-handed Japanese woman, both with a history of cerebral infarction, received 6-month treatment with pitavastatin 2 mg/d for complicated hypercholesterolemia. To assess regional cerebral blood flow (rCBF), single-photon emission computed tomography (SPECT) studies with technetium-99m-ethyl cysteinate dimer were carried out before and after pitavastatin administration. Tomography was evaluated using the Easy z Score Imaging System. None of the patients' other treatments, with the exception of pitavastatin initiation, were modified during the treatment period. In both patients, serum total cholesterol concentrations were improved within 3 months of initiation of pitavastatin treatment, with no marked changes in clinical symptoms. In both patients, improvement was found in rCBF on SPECT. The z score of the left parietal lobe in 1 patient was improved, from 2.20 to 1.69. That of the other patient was also improved, from 2.42 to 1.94.. In both patients, clinically significant improvement in rCBF was found after 6-month treatment with pitavastatin 2 mg/d.

Topics: Aged; Cerebral Infarction; Cerebrovascular Circulation; Cholesterol; Cysteine; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Organotechnetium Compounds; Quinolines; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

Pitavastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, is a potent cholesterol-lowering drug that reduces the risk of myocardial infarction and stoke. In this study, we examined its neuroprotective effects against hippocampal CA1 neuronal damage following transient cerebral ischemia in gerbils. Forebrain ischemia was induced by occlusion of bilateral common carotid arteries for 5 min. Pitavastatin, at a dose of 3, 10 or 30 mg/kg, was administered orally twice a day for 5 consecutive days and transient cerebral ischemia was induced in mice 1 h after the last treatment with pitavastatin. Histopathological observations showed that neuronal damage to the hippocampal CA1 neurons, which was observed 5 days after ischemia in animals, was prevented by pitavastatin treatment. Immunohistochemical staining for copper/zinc superoxide dismutase (SOD) and manganese SOD decreased in the hippocampal CA1 sector of gerbils 2 days after ischemia when histological neuronal destruction was not yet found, but was clearly observed in pitavastatin-treated animals. These results indicate that pitavastatin can protect dose-dependently against ischemia-induced neuronal damage and that the mechanism of the neuroprotection may be related to the preservation of SODs, especially copper/zinc-SOD. This in part explains how pitavastatin therapy, which targets free radicals, has beneficial effects against disorders including ischemic stroke.

Topics: Animals; Cerebral Infarction; Disease Models, Animal; Dose-Response Relationship, Drug; Free Radical Scavengers; Free Radicals; Gerbillinae; Hippocampus; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunohistochemistry; Ischemic Attack, Transient; Male; Nerve Degeneration; Neuroprotective Agents; Oxidative Stress; Quinolines; Superoxide Dismutase