Both Fenofibrate and Atorvastatin Improve Vascular Reactivity in Combined Hyperlipidemia (Fenofibrate Versus Atorvastatin Trial) - FAT
The fenofibrate versus atorvastatin trial (FAT) was a single-center, randomized, single-blind study to evaluate the effects of fenofibrate and atorvastatin on endothelium-dependent vascular reactivity in male patients with mixed hyperlipidemia.
Fibrinate monotherapy will have a similar effect on vascular endothelium compared to statin monotherapy, the latter having been widely studied while fibrates have not. Also, there is a relationship between biochemical changes caused by these drugs and vascular endothelial changes.
Patients Screened: 29
Patients Enrolled: 29
Mean Follow Up: 10 weeks
Mean Patient Age: 40-60 years
Male patients referred to a university-based lipid clinic with nontreated combined hyperlipidemia (fasting plasma cholesterol >6.2 mmol/l and triglycerides >1.5 mm/l)
Secondary hyperlipidemia, body mass index >32 kg/m2, impaired glucose tolerance, alcohol abuse, or apo E2/E2 genotype
PBF, FMD, and BFI through the brachial artery, as detected by ultrasound after ischemia induced by blood pressure cuff inflation. PBF was calculated as the velocity time integral multiplied by the vessel cross-sectional area during the early post-ischemic period. BFI was calculated as the percentage increase of resting blood flow. FMD was calculated as the percentage increase in diameter after ischemia compared to rest.
Changes in biochemical parameters of subjects including total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, non-HDL cholesterol, apolipoprotein A-I, apolipoprotein B, fibrinogen, CRP, homcysteine, and insulinemia
Patients were randomized into two treatment arms: micronized fenofibrate (200 mg daily) or atorvastatin (10 mg daily). The groups were treated for 10 weeks. A group of 15 healthy male volunteers was used as a control.
A total of 29 males were randomized. The baseline characteristics for the entire group were mean age 47.4 ± 7.8 years, mean body mass index 27.8 ± 2.7 kg/m2, and mean systolic blood pressure 124.8 ± 12 mm Hg.
Both drugs significantly increased peak blood flow (PBF) compared to baseline (448 ml/min ± 216 to 536 ± 172 for fenofibrate, p=0.04, and 448 + 216 to 570 ± 180, p=0.03 for atorvastatin). The effects of both drugs on PBF did not differ significantly. Blood flow increase (BFI) increased significantly in the atorvastatin group, but not in the fenofibrate group (497% ± 247 to 664 ± 270 for fenofibrate, p=0.06, and 497 ± 247 to 671 ± 293 for atorvastatin, p=0.01). Flow-mediated dilation (FMD) was not significantly increased by either drug. Both drugs resulted in significant decreases in total cholesterol, triglycerides, and non-high-density lipoprotein (HDL) cholesterol and a significant increase in apolipoprotein A-I.
Atorvastatin was superior to fenofibrate at reducing serum total cholesterol, low-density lipoprotein (LDL) cholesterol, and non-HDL cholesterol. Fenofibrate was superior to atorvastatin at reducing triglycerides, and raising HDL cholesterol levels. Fenofibrate significantly decreased C-reactive protein (CRP), insulin, and uric acid levels while atorvastatin did not. Fenofibrate also significantly increased HDL cholesterol and homocysteine levels while atorvastatin did not. Atorvastatin significantly decreased LDL cholesterol levels and apolipoprotein B levels while fenofibrate did not. Atorvastatin also significantly increased fibrinogen levels while fenofibrate did not.
The only significant correlation found between biochemical and vascular changes was that decrease in CRP and insulinemia correlated with improvement in vascular reactivity for fenofibrinate. No other significant correlations between biochemical changes and vascular changes were found.
Among male patients with mixed hyperlipidemia, both fenofibrate and atorvastatin were associated with significantly improved endothelium-dependent vascular reactivity without mutual differences. The PBF measurement is superior to FMD at detection of this improvement, as the latter had significant intra-subject variability.
Malik J, Melenovsky V, Wichterle D, et al. Both fenofibrate and atorvastatin improve vascular reactivity in combined hyperlipidaemia (fenofibrate versus atorvastatin trial—FAT). Cardiovasc Res 2001;52:290-8.
Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Primary Hyperlipidemia, Statins, Diet
Keywords: Fenofibrate, Hyperlipidemia, Familial Combined, Volunteers, Insulin, Cholesterol, LDL, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Apolipoprotein A-I, Blood Pressure, Heptanoic Acids, Hypercholesterolemia, Single-Blind Method, Uric Acid, Pyrroles, Fibric Acids, C-Reactive Protein, Body Mass Index, Endothelium, Vascular, Cholesterol, HDL, Fibrinogen, Triglycerides, Fasting
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