Fluvastatin significantly improved endothelium-dependent vasodilation compared with placebo (change of 108% vs -26%; P≤0.05), an effect mediated by increased nitric oxide bioavailability.
RCT (n=29)
double-blind
randomized
Does fluvastatin improve endothelium-dependent vasodilation in patients with hypercholesterolemia?
Fluvastatin improves endothelial function in hypercholesterolemic patients by increasing the bioavailability of nitric oxide.
Absolute Event Rate: 108% vs -26%
p-value: p=≤0.05
BACKGROUND: Impaired endothelium-dependent vasodilation is an early sign of atherosclerosis in hypercholesterolemic patients. We hypothesized that lipid-lowering therapy can improve endothelial function and that this effect is mainly mediated by increased bioavailability of nitric oxide (NO). METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled trial, we studied 29 patients (age, 50+/-12 years) with hypercholesterolemia (LDL cholesterol > or = 160 mg/dL) randomly assigned to receive either fluvastatin (40 mg twice daily; 17 patients) or placebo (12 patients). Forearm blood flow was measured by plethysmography before and after 24 weeks of treatment. Endothelium-dependent vasodilation was assessed by intra-arterial infusion of acetylcholine (ACh; 3, 12, 24, and 48 microg/min) and basal NO synthesis rate by intra-arterial infusion of NG-monomethyl-L-arginine (L-NMMA; 1, 2, and 4 micromol/min). Simultaneous intra-arterial infusion of L-NMMA (4 micromol/min) and ACh (12, 24, and 48 microg/min) was used to test whether any increase in endothelium-dependent vasodilation after lipid-lowering therapy could be blocked by this NO synthase inhibitor. Endothelium-dependent vasodilation improved significantly after 24 weeks of lipid-lowering therapy compared with before therapy (ACh 24 microg/min: 240+/-34% before versus 347+/-50% after therapy; P< or =0.01) and placebo (changes between after and before therapy with ACh 24 microg/min: 108+/-39% for fluvastatin versus -26+/-32% for placebo; P< or =0.05). This improvement in endothelium-dependent vasodilation could be blocked by simultaneous administration of L-NMMA (ACh 24 microg/min plus L-NMMA 4 micromol/min: 170+/-69% before versus 219+/-47% after treatment; P=NS). CONCLUSIONS: Lipid-lowering therapy with fluvastatin can improve disturbed endothelial function in hypercholesterolemic patients compared with placebo. This improvement is mediated by increased bioavailability of NO.
John et al. (Tue,) conducted a rct in Hypercholesterolemia (n=29). Fluvastatin vs. Placebo was evaluated on Change in endothelium-dependent vasodilation (ACh 24 microg/min) (p=≤0.05). Fluvastatin significantly improved endothelium-dependent vasodilation compared with placebo (change of 108% vs -26%; P≤0.05), an effect mediated by increased nitric oxide bioavailability.