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

Statins have been proved to be effective in reduction of mortality and morbidity when started in the early secondary prevention in stabilized patients after acute coronary syndrome (ACS). The safety and efficacy of statin administration directly in the first-line therapy in unstable ACS patients is not clear. The aim of our study was, therefore, to assess the effect of statin treatment initiated immediately at hospital admission of patients with ACS.. The trial was stopped prematurely after enrollment of one hundred and fifty-six patients with ACS that were randomized at admission to fluvastatin 80 mg (N = 78) or placebo (N = 78). Study medication was administered immediately after randomization and then once daily for 30 days; all patients were then encouraged to continue in open-label statin therapy and at the end of one-year follow-up 75% in the fluvastatin group and 78% in the placebo group were on statin therapy.. We did not demonstrate any difference between groups in the level of C-reactive protein, interleukin 6, and pregnancy-associated plasma protein A on Day 2 and Day 30 (primary endpoint). Fluvastatin-therapy, however, significantly reduced one-year occurrence of major adverse cardiovascular events (11.5% vs. 24.4%, odds ratio (OR) 0.40, 95% CI 0.17-0.95, P = 0.038). This difference was caused mainly by reduction of recurrent symptomatic ischemia (7.7% vs. 20.5%, OR 0.32, 95% CI 0.12-0.88, P = 0.037).. This study failed to prove the effect of fluvastatin given as first-line therapy of ACS on serum markers of inflammation and plaque instability. Fluvastatin therapy was, however, safe and it may reduce cardiovascular event rate that supports immediate use of a statin in patients admitted for ACS.. NCT00171275.

Topics: Acute Coronary Syndrome; Aged; C-Reactive Protein; Chi-Square Distribution; Czech Republic; Double-Blind Method; Drug Administration Schedule; Early Termination of Clinical Trials; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Inflammation Mediators; Interleukin-6; Kaplan-Meier Estimate; Male; Middle Aged; Odds Ratio; Patient Admission; Patient Selection; Placebo Effect; Pregnancy-Associated Plasma Protein-A; Prospective Studies; Risk Assessment; Sample Size; Secondary Prevention; Time Factors; Treatment Outcome

Experimental data demonstrate that inflammation plays an important role in the initiation, progression, and complications of atherosclerosis. Statins were shown to downregulate inflammatory cytokines.We conducted this study to investigate the effects of fluvastatin therapy on plasma interleukin-18 (IL-18) and interleukin-10 (IL-10) concentration in patients with acute coronary syndrome.. Serum IL-18 and IL-10 levels were measured in 90 patients with acute coronary syndrome, 47 patients with stable angina pectoris, and 55 normal control subjects. Patients in the acute coronary syndrome group were randomly assigned to a fluvastatin group and a routine group.The fluvastatin group was given fluvastatin 40 mg/day and the routine group a placebo.After one month of follow-up, serum IL-18, IL-10 levels, and serum lipid concentration were measured again. Serum IL-18 levels were significantly higher in the acute coronary syndrome group than in the stable angina pectoris group and the control group. However, serum IL-10 levels were significantly lower than in the stable angina pectoris group and the control group.After one month of treatment, the serum IL-18 levels decreased significantly and the serum IL-10 levels increased significantly in all patients with acute coronary syndrome, but the changes of serum IL-18 and IL-10 levels were more pronounced in the fluvastatin group. No relationship was observed between the rate of decrease of serum IL-18 or the rate of increase of serum IL-10 and serum lipids levels.. Inflammation plays an important role in the initiation of acute coronary syndromes. Fluvastatin possesses an anti-inflammatory effect, independent of its lipid-lowering action.

Topics: Acute Coronary Syndrome; Angina Pectoris; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Interleukin-10; Interleukin-18; Lipids; Male; Middle Aged; Treatment Outcome

This prospective registered study was conducted to investigate the impact of statins (pravastatin, fluvastatin, atorvastatin) on clopidogrel platelet inhibition in patients with acute coronary syndrome (ACS) or stable angina.. A total of 1015 consecutive patients with ACS or stable angina underwent coronary angiography/percutaneous coronary intervention (PCI) were allocated to pravastatin group (n = 228), fluvastatin group (n = 179), atorvastatin group (n = 481) or placebo control group (n = 127). Baseline characteristics, coronary angiography/PCI features and acute stent thrombosis, platelet aggregation induced by 2, 5, 10 and 20 micromol adenosine diphosphate (ADP) at 1 minute (ADP-1), 5 minutes (ADP-5) and maximal platelet aggregation (ADP-M) were compared among groups.. Baseline and procedural characteristics were comparable among the four groups. Acute stent thrombosis (pravastatin group 0.9%, fluvastatin group 1.1%, atorvastatin group 1.0% and control group 0.8%, all P > 0.05), ADP-1, ADP-5, and ADP-M (all P > 0.05) were also similar among groups. Multivariate liner and ordinal logistic analysis revealed that age (B = 0.21, P = 0.001), dose of clopidogrel (B = 7.30, P = 0.002) and use of low-molecular heparin (OR = 6.71, P = 0.01) were independent factors for platelet aggregation inhibition efficacy by clopidogrel.. Inhibition of platelet aggregation with clopidogrel was influenced by age, clopidogrel dose and low-molecular heparin but not by various statin treatments.

Topics: Acute Coronary Syndrome; Adenosine Diphosphate; Aged; Angina Pectoris; Atorvastatin; Clopidogrel; Drug Interactions; Fatty Acids, Monounsaturated; Female; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Count; Platelet Function Tests; Pravastatin; Prospective Studies; Pyrroles; Ticlopidine

It is widely assumed that acute benefit of statin therapy is mediated especially by non-lipid effects. The immediate influence of statins on lipid levels in patients with acute coronary syndrome (ACS) is, however, not clear. A total of 64 consecutive patients with ACS were randomized at admission to fluvastatin 80 mg (Group 1, N = 32) or standard therapy without statin (Group 2, N = 32). The levels of total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), and triglycerides (TG) were examined at admission and after 24 h. Baseline characteristics were comparable in both groups. In Group 1, fluvastatin significantly decreased the levels of TC by 14.5%, LDL-C by 17.2%, and HDL-C by 10.0% (P < 0.001); TG were not influenced. In Group 2 only marginal reductions in TC (by 4.1%, P = 0.03) and HDL-C (by 7.5%, P < 0.01) were detected; the levels of LDL-C and TG were not changed. As compared with Group 2, in Group 1 the final levels of TC (P = 0.02) and LDL-C (P = 0.01) were significantly lower. Fluvastatin therapy, when started at admission in patients with ACS, significantly reduces TC and LDL-C already after 24 h. We suggest that the lipid-lowering effect of statins in the therapy of ACS is probably as prompt as non-lipid effects.

Topics: Acute Coronary Syndrome; Antioxidants; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Male; Middle Aged; Treatment Outcome; Triglycerides