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

Individuals with chronic kidney disease are at high risk for cardiovascular disease and have a high prevalence of hyperlipidemia. Lipid-lowering therapy may help patients with renal disease reduce their risk for cardiovascular events.. A pooled analysis of 30 completed clinical trials compared the efficacy and safety profiles of fluvastatin in subgroups of patients with moderate to severe renal insufficiency (creatinine clearance < 50 ml/min) and patients with normal renal function or mild renal insufficiency (creatinine clearance > or = 50 ml/min).. Changes in lipid parameters with fluvastatin treatment were similar for the compared patient subgroups. Fluvastatin treatment reduced combined cardiac death and myocardial infarction by 41% compared with placebo among patients with moderate to severe renal insufficiency (hazard ratio, 0.59; p=0.007) and by 30% among patients with normal renal function or mild renal insufficiency (hazard ratio, 0.70; p=0.009). The relative reduction in the risk of major adverse cardiac events, a composite endpoint comprising cardiac death, nonfatal myocardial infarction, and coronary intervention procedures, with fluvastatin treatment was not significant for patients with moderate to severe renal insufficiency (hazard ratio, 0.83; p=0.18); in this patient subgroup, the incidence of coronary intervention procedures was similar between treatment groups. The safety profiles were similar for fluvastatin- and placebo-treated patients.. The results of this pooled analysis indicate that fluvastatin is safe and effective for reducing cardiac death and nonfatal myocardial infarction in patients with moderate to severe renal insufficiency. Fluvastatin did not reduce the rate of coronary intervention procedures.

Topics: Anticholesteremic Agents; Cholesterol, LDL; Comorbidity; Death, Sudden, Cardiac; Dose-Response Relationship, Drug; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hyperlipidemias; Incidence; Indoles; Male; Middle Aged; Myocardial Infarction; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Risk Factors; Survival Analysis; Treatment Outcome

Patients with systemic lupus erythematosus (SLE), with or without end-stage renal failure, are at increased risk of premature cardiovascular disease. Although statin therapy has been found to reduce cardiovascular risk in the general population, its effectiveness in kidney transplant recipients with SLE has not been examined. This study was undertaken to investigate the effect of fluvastatin on cardiac end points in a randomized controlled trial of renal transplant patients with SLE.. Patients with SLE were identified from among participants in the Assessment of Lescol in Renal Transplantation trial, a randomized, double-blind, placebo-controlled study of the effect of fluvastatin (40-80 mg/day) on cardiovascular outcomes in renal transplant recipients. Patients were randomized to either a group receiving fluvastatin or a placebo group for the duration of the 5-6-year trial, and then invited to continue in a 2-year open-label extension during which all participants, regardless of original group, received fluvastatin. Patients were followed up for a total of 7-8 years for assessment of the primary end point of major cardiac events, comprising nonfatal myocardial infarction, cardiac death, and coronary intervention procedures.. Fluvastatin reduced low-density lipoprotein cholesterol levels by 29.2% (95% confidence interval [95% CI] 18.3-40%), from a mean +/- SD of 4.0 +/- 0.9 mmoles/liter to 2.8 +/- 1.1 mmoles/liter, and total cholesterol by 19.6% (95% CI 11.7-27.5%), from 6.4 +/- 0.9 mmoles/liter to 5.1 +/- 1.1 mmoles/liter. Compared with placebo-treated patients, patients randomized to receive fluvastatin exhibited a 73.4% reduction in the risk of major cardiac events (relative risk 26.6 [95% CI 5.9-119.4], P = 0.064).. Our results indicate that the effect of fluvastatin on cardiac events in renal transplant recipients with SLE is similar to that observed with statin therapy in the renal transplant population as a whole.

Topics: Adult; Anticholesteremic Agents; Cholesterol, LDL; Coronary Artery Disease; Death, Sudden, Cardiac; Fatty Acids, Monounsaturated; Fluvastatin; Follow-Up Studies; Humans; Indoles; Kaplan-Meier Estimate; Kidney Transplantation; Lupus Erythematosus, Systemic; Lupus Nephritis; Middle Aged; Morbidity; Myocardial Infarction; Placebos; Postoperative Complications; Proportional Hazards Models; Risk Factors

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

Renal transplantation is associated with an increased risk for premature cardiovascular disease. We analyzed the data in the placebo arm of Assessment of Lescol in Renal Transplantation (ALERT) to improve our understanding of the relationship between cardiovascular risk factors and outcomes in this unique population.. We performed Cox survival analysis for myocardial infarction, cardiac death, and noncardiac death in 1,052 patients recruited to the placebo arm of ALERT. These subjects were aged 30 to 75 years, had stable graft function at least 6 months after transplantation, had a serum total cholesterol level between 155 and 348 mg/dL (4 and 9 mmol/L), and were receiving cyclosporine-based immunosuppression.. The results confirm previous studies. In multivariate analysis, preexisting coronary heart disease (hazard ratio [HR], 3.69; P < 0.001), total cholesterol level (HR, 1.55 per 50 mg/dL; P = 0.0045), and prior acute rejection (HR, 2.36; P = 0.0023) were independent risk factors. Conversely, independent risk factors for cardiac death were age (HR, 1.58 per decade; P = 0.0033), diabetes (HR, 3.35; P = 0.0002), ST-T changes on the ECG (HR, 3.17; P = 0.0004), and serum creatinine level (HR, 2.65 per milligram per deciliter; P < 0.0001).. This analysis confirms that renal transplant recipients share risk factors for myocardial infarction and cardiac death with the general population. However, the pattern of risk factors and their relationship with outcomes is atypical, highlighting the unique nature of cardiovascular risk in transplant recipients.

Topics: Adult; Aged; Cardiovascular Diseases; Creatinine; Death, Sudden, Cardiac; Diabetes Mellitus; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Immunosuppressive Agents; Indoles; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mortality; Myocardial Infarction; Obesity; Proportional Hazards Models; Randomized Controlled Trials as Topic; Risk Factors; Smoking; Survival Analysis