Risk reduction and tolerability of fluvastatin in patients with the metabolic syndrome: a pooled analysis of thirty clinical trials

Clin Ther. 2007 Sep;29(9):1987-2000. doi: 10.1016/j.clinthera.2007.09.026.

Abstract

Objective: This pooled analysis of 30 completed clinical trials assessed the efficacy and safety profile in reducing cardiovascular disease (CVD) risk of fluvastatin in the treatment of dyslipidemia in patients with and without the metabolic syndrome (metS).

Methods: Data from 30 double-blind, randomized, placebo-controlled or fluvastatin-controlled trials with > or =6 weeks of active treatment and daily fluvastatin doses of 20, 40, and 80 mg were pooled. Patients received fluvastatin or placebo. Linear contrasts from an analysis of covariance model containing factors for trial and treatment group (immediate-release fluvastatin 20, 40, 80 mg; extended-release fluvastatin 80 rag; or placebo), and using the baseline value as covariate, were used to compare the percentage changes from baseline to the first postbaseline assessment of all lipid parameters. A Cox regression analysis compared the all-fluvastatin group to the placebo group with regard to the time to occurrence of clinical end points from 5 pooled studies, each with a mean treatment duration >1 year wherein clinical end points were reviewed by an adjudication committee. These analyses were performed separately for patients with and without metS.

Results: This pooled analysis included data from 7043 patients (4095 men, 2948 women; all-fluvastatin group with and without metS, 2529 and 2052 patients, respectively; placebo group with and without metS, 1514 and 948 patients, respectively). Patients with metS in the pooled fluvastatin group had a greater mean reduction in triglyceride levels (24.1% vs 6.7%), a greater mean increase in high-density lipoprotein cholesterol levels (10.3% vs -0.6%), and a similar mean reduction in low-density lipoprotein cholesterol levels (26.8% vs 26.7%) compared with the subgroup of patients without metS. Treatment with fluvastatin was associated with a significantly lower incidence of major adverse cardiovascular events (MACEs) (16.4% vs 22.0%) and an increase in the time to first MACE in patients with metS compared with placebo (hazard ratio = 0.728; P = 0.001). The incidences of adverse events, particularly those of concern (ie, myalgia and/ or increased blood creatine phosphokinase, alanine aminotransferase, and/or aspartate aminotransferase) with lipid-lowering therapy, were statistically similar between the patients who received fluvastatin and those who received placebo in the 2 subgroups.

Conclusion: The results from this pooled analysis found that fluvastatin was effective in reducing CVD risk in the treatment of dyslipidemia in these patients with metS.

Publication types

  • Meta-Analysis

MeSH terms

  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Dyslipidemias / complications
  • Dyslipidemias / drug therapy
  • Fatty Acids, Monounsaturated* / adverse effects
  • Fatty Acids, Monounsaturated* / therapeutic use
  • Female
  • Fluvastatin
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Incidence
  • Indoles* / adverse effects
  • Indoles* / therapeutic use
  • Male
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / prevention & control*
  • Middle Aged
  • Triglycerides / blood

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Fatty Acids, Monounsaturated
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Indoles
  • Triglycerides
  • Fluvastatin