(3S-5S-6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3-5-dihydroxyhept-6-enoic-acid and Coronary-Restenosis

Recent experimental and clinical data suggest that lowering serum lipid levels with statins may prevent or delay the process of restenosis. The purpose of this trial is to determine whether lipid levels relate to restenosis and/or whether statin therapy can prevent or delay the process of restenosis after intracoronary stenting.. One hundred thirty-six patients who underwent single coronary artery stenting from June 1995 to June 1997 in our institution were included in the study. All these patients were followed for at least 9 months (mean 392+/-148 days) for major adverse cardiac events (MACE). We defined as MACE the occurrence of death, myocardial infarction, or need for target lesion revascularization. From this cohort, 103 patients had at least one lipid parameter from the lipid profile evaluated within 2 months from the date of the procedure. Patients who had the stent because of an acute myocardial infarction were included in the study only if their lipid profile was evaluated before or at least 6 weeks after the event. Patients with triglyceride levels above 500 had both triglyceride and low-density lipoprotein cholesterol levels excluded from the statistical analysis. Patients were divided into two groups based on lipid levels: normal (Group I; n=31) and elevated (Group II; n=72). Patient outcomes were also analyzed by statin therapy use.. There was no significant difference in MACE rates between the two groups when outcomes were analyzed by lipid levels (22.6% versus 20.8% P=0.8). Furthermore, outcomes were analyzed by use of statin therapy (Group III, n=53, on statin versus Group IV, n=50, on no statin). There was also no difference in MACE rates between the two groups (20.8% versus 22%; P=0.8).. The process of restenosis has unique features that differentiate it from atherosclerosis. Although lipid-lowering therapy is crucial in delaying the process of atherosclerosis, its role in the prevention of restenosis is yet to be proven.

Topics: Aged; Anticholesteremic Agents; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Restenosis; Coronary Vessels; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypolipidemic Agents; Indoles; Lipids; Male; Middle Aged; Stents; Triglycerides

Elevated Lipoprotein (a) [Lp (a)] has been reported frequently, but not consistently, to be associated with restenosis following percutaneous transluminal coronary angioplasty (PTCA). The purpose of this study was to examine the association between Lp (a) and restenosis and clinical events in the context of a multi-centre randomised restenosis [Fluvastatin Angioplasty Restenosis (FLARE)] study of patients undergoing elective PTCA with full angiographic follow up. In the FLARE trial 40 mg fluvastatin twice daily did not influence restenosis, compared with placebo, after successful balloon angioplasty, measured as late loss in 834 patients, but did reduce the risk of death or myocardial infarction. Lp (a) was not effected by fluvastatin. Lp (a) and other biochemical details were established prior to planned PTCA. Among those undergoing successful PTCA, follow up angiography was performed at 26+/-2 weeks. Clinical follow up was complete to week 40. Included in this analysis are the 823 patients who underwent successful angioplasty and had a baseline Lp (a) performed yielding 891 lesions for quantitative coronary angiography (QCA). No association was observed between Lp (a) and either quantitative markers of restenosis or binary restenosis rates. Late loss was 0.27 (SD 0.51) in the lowest quintile (Lp (a) 0-4 g/dl) compared with 0.23 (SD 0.49) (P>0.05). Elevated Lp (a) was not associated with an increased risk of individual or combined major coronary events over 40 weeks. A major adverse cardiac event (MACE) occurred in 41 (24%) of the lowest quintile and 42 (26%) of the highest (P>0.05). In conclusion, elevated Lp (a) was not associated with restenosis or clinical events following elective coronary balloon angioplasty in this randomised clinical trial and should not be considered a risk factor for post angioplasty restenosis.

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Death, Sudden, Cardiac; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Lipoprotein(a); Male; Middle Aged; Myocardial Infarction; Risk Factors

Thrombospondin-1 (TSP-1) and transforming growth factor-beta1 (TGF-beta1) are both implicated in the pathogenesis of in-stent restenosis. This study evaluated the hypothesis that the HMG-CoA reductase inhibitor fluvastatin inhibits TGF-beta1 induced TSP-1 expression via inhibition of p38 mitogen activated protein kinase (MAPK) phosphorylation in human coronary artery smooth muscle cells (HCASMC) and may therefore have anti-restenosis potential. Fluvastatin significantly reduced TSP-1 mRNA and protein expression in HCASMC in a concentration-dependent manner with a significant reduction in expression observed after treatment with 0.25 microM fluvastatin. TGF-beta1 (5 ng/ml) induced phosphorylation of p38 MAPK and induced TSP-1 mRNA and protein expression in HCASMC. Fluvastatin abolished TGF-beta1-induced phosphorylation of p38 MAPK and TGF-beta1-induced TSP-1 expression. Blockade of the p38 MAPK pathway with the upstream inhibitor SB-203580 also abolished TGF-beta1-induced TSP-1 expression. We conclude that fluvastatin decreases expression of TSP-1 and abolishes the ability of TGF-beta1 to induce TSP-1 expression in HCASMC; this may be achieved by preventing signalling through the p38 MAPK pathway. Targeted delivery of fluvastatin may therefore be a useful therapeutic objective for prevention of the intimal hyperplasia associated with in-stent restenosis.

Topics: Adult; Cells, Cultured; Coronary Restenosis; Coronary Vessels; Dose-Response Relationship, Drug; Enzyme Inhibitors; Fatty Acids, Monounsaturated; Fluvastatin; Gene Expression Regulation; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Imidazoles; Indoles; Male; MAP Kinase Signaling System; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Pyridines; RNA, Messenger; Thrombospondin 1; Transforming Growth Factor beta; Transforming Growth Factor beta1

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Lipoproteins; Myocardial Ischemia