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

Patients with acute coronary syndrome (ACS) are at high risk for recurrent coronary events, sudden death, and all-cause mortality. Conventional revascularization therapies reduce the risk of further ischemia but do not affect the underlying atherosclerotic disease. Statins have a proven record in the secondary prevention of coronary heart disease. Furthermore, statins have been shown to exert varying degrees of pleiotropic effects, which may stabilize vulnerable atherosclerotic plaques. A compelling body of evidence from randomized controlled trials demonstrates that high-dose, potent statin therapy initiated immediately after an acute coronary event can significantly reduce early as well as longer-term morbidity and mortality. Furthermore, high-dose, potent statin therapy displays a reasonable safety profile. National guidelines now recommend that in patients with ACS, statin therapy should be initiated in hospital prior to discharge, irrespective of baseline low-density lipoprotein cholesterol levels, to improve clinical outcomes. Every effort should be made to ensure all eligible patients with ACS are initiated and maintained on statin therapy.

Topics: Angina, Unstable; Atorvastatin; Cholesterol, HDL; Cholesterol, LDL; Fatty Acids, Monounsaturated; Fluvastatin; Heptanoic Acids; Hospitalization; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Myocardial Ischemia; Pravastatin; Pyrroles; Syndrome; Treatment Outcome

To investigate the effect of fluvastatin on blood levels of c-reactive protein (CRP), tumor necrosis factor alpha (TNFalpha) and cardiac troponin I (cTnI) in patients with unstable angina undergoing percutaneous coronary intervention (PCI).. Sixty patients who underwent PCI from July 2002 to April 2004 in our hospital were randomized into two groups: control group; fluvastatin group (40 mg/d). Serum levels of CRP, TNFalpha and cTnI were measured before and after two weeks treatment (in the early morning of the procedure) and at 24 hours after the procedure.. The serum levels of CRP, TNFalpha and cTnI in fluvastatin group were distinctly lower than those in control group before (P < 0.01) and after the procedure (P < 0.01), respectively.. The result suggested that PCI could lead to a detectable increase in serum levels of CRP, TNFalpha and cTnI in patients with coronary heart disease; Fluvastatin could significantly decrease the serum levels of CRP, TNFalpha and cTnI in patients with coronary heart disease; Fluvastatin could also decrease the serum levels of CRP, TNFalpha and cTnI in patients with PCI.

Topics: Angina, Unstable; Anticholesteremic Agents; C-Reactive Protein; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Indoles; Troponin I; Tumor Necrosis Factor-alpha

To investigate the effect on risk of major adverse cardiac events (MACE) of lipid lowering treatment with fluvastatin 80 mg/day after a first percutaneous coronary intervention in patients with stable and unstable angina.. This prespecified subgroup analysis of the LIPS (Lescol intervention prevention study) analysed 1658 patients with documented diagnosis; 824 had unstable angina (417 randomly assigned to fluvastatin, 407 to placebo) and 834 had stable angina (including silent ischaemia; fluvastatin, 418; placebo, 416). Median follow up was 3.9 years. There was no significant effect of anginal status on long term risk of MACE. Fluvastatin treatment reduced the risk of MACE by 28% compared with placebo (p = 0.03) among patients with unstable angina, with no difference between patients with stable and patients with unstable angina (relative risk 1.07, 95% confidence interval 0.87 to 1.30, p = 0.53). Fluvastatin reduced coronary atherosclerotic events (MACE excluding restenosis) by 36% (p = 0.006) among patients with unstable angina and 31% (p = 0.02) among patients with stable angina. Fluvastatin caused similar reductions in total cholesterol and low density lipoprotein cholesterol concentrations in both patient groups.. Treatment with fluvastatin 80 mg/day produced significant reductions in MACE and coronary atherosclerotic events after percutaneous coronary intervention in patients with average cholesterol concentrations. The beneficial effects of fluvastatin are observed in patients with unstable or stable angina alike.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angina Pectoris; Angina, Unstable; Angioplasty, Balloon, Coronary; Cardiovascular Diseases; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hypolipidemic Agents; Indoles; Male; Middle Aged; Postoperative Period; Prospective Studies

BACKGROUND--Patients with coronary artery disease (CAD) commonly have low HDL cholesterol (HDL-C) and mildly elevated LDL cholesterol (LDL-C), leading to uncertainty as to whether the appropriate goal of therapy should be lowering LDL-C or raising HDL-C. METHODS AND RESULTS--Patients in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) had mildly to moderately elevated LDL-C; many also had low HDL-C, providing an opportunity to compare angiographic progression and the benefits of the HMG-CoA reductase inhibitor fluvastatin in patients with low versus patients with higher HDL-C. Of the 339 patients with biochemical and angiographic data, 68 had baseline HDL-C <0.91 mmol/L (35 mg/dL), mean 0.82+/-0.06 mmol/L (31. 7+/-2.2 mg/dL), versus 1.23+/-0.29 mmol/L (47.4+/-11.2 mg/dL) in patients with baseline HDL-C >/=0.91 mmol/L. Among patients on placebo, those with low HDL-C had significantly more angiographic progression than those with higher HDL-C. Fluvastatin significantly reduced progression among low-HDL-C patients: 0.065+/-0.036 mm versus 0.274+/-0.045 mm in placebo patients (P=0.0004); respective minimum lumen diameter decreases among higher-HDL-C patients were 0. 036+/-0.021 mm and 0.083+/-0.019 mm (P=0.09). The treatment effect of fluvastatin on minimum lumen diameter change was significantly greater among low-HDL-C patients than among higher-HDL-C patients (P=0.01); among low-HDL-C patients, fluvastatin patients had improved event-free survival compared with placebo patients. CONCLUSIONS--Although the predominant lipid-modifying effect of fluvastatin is to decrease LDL-C, patients with low HDL-C received the greatest angiographic and clinical benefit.

Topics: Adult; Aged; Angina, Unstable; Angioplasty, Balloon, Coronary; Apolipoproteins; Cholesterol, HDL; Cholesterol, LDL; Coronary Angiography; Coronary Artery Bypass; Coronary Disease; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Male; Middle Aged; Myocardial Infarction; Survival Analysis

In the LIPS (Lescol Intervention Prevention Study), fluvastatin 80 mg/day reduced the risk of major adverse cardiac events (MACE) by 22% versus placebo (p = 0.01) following successful first percutaneous coronary intervention (PCI) in patients with stable or unstable angina or silent ischemia. The cost-effectiveness of such therapy is unknown.. To evaluate the cost-effectiveness of fluvastatin following successful first PCI from a US healthcare system perspective.. We used a Markov model to estimate expected outcomes and costs of 2 alternative treatment strategies following successful first PCI in patients with stable or unstable angina or silent ischemia: (1) diet/lifestyle counseling plus immediate fluvastatin 80 mg/day; and (2) diet/lifestyle counseling only, with initiation of fluvastatin 80 mg/day following occurrence of future nonfatal MACE. The model was estimated with data from LIPS and other published sources. Cost-effectiveness was calculated as the ratio of the difference in expected medical-care costs to the expected difference in life-years (LYs) and quality-adjusted life-years (QALYs) alternatively.. Treatment with fluvastatin following successful first PCI was found to increase life expectancy by 0.78 years (QALYs 0.68). Cost-effectiveness of fluvastatin following successful first PCI is 13 505 dollars per LY (15 454 dollar per QALY) saved. Ratios are lower for patients with diabetes (9396 dollar per LY; 10 718 dollar per QALY) and those with multivessel disease (9662 dollar per LY; 11 076 dollar per QALY). Findings were robust with respect to changes in key model parameters and assumptions.. Fluvastatin therapy following PCI is cost-effective compared with other generally accepted medical interventions.

Topics: Aged; Angina, Unstable; Atherectomy, Coronary; Cost-Benefit Analysis; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Indoles; Markov Chains; Middle Aged; Quality of Life; Risk Reduction Behavior