A 16-week fenofibrate treatment increases LDL particle size in type IIA dyslipidemic patients.

OBJECTIVE: The objective of the present study was to compare the effects of a 16-week pharmacotherapy with fenofibrate (200 mg) or pravastatin (initially 20 mg for 8-weeks and, if necessary, increased to 40 mg) on low density lipoprotein (LDL) particle size assessed by gradient gel electrophoresis among patients with type IIa dyslipidemia. METHODS: For that purpose, type IIa dyslipidemic patients (cholesterol, 7.45+/-1.18 (S.D.) mmol/l; LDL cholesterol, 5.57+/-1.16 mmol/l; triglycerides (TGs), 1.66+/-0.43 mmol/l) were randomized to either fenofibrate (n=36) or pravastatin (n=43) therapy for 16 weeks. Fasting plasma lipoprotein levels as well as the LDL peak particle size (using 2-16% polyacrylamide gel electrophoresis) were assessed at baseline and after the 16-week treatment period. RESULTS: Whereas significant improvements in the plasma lipoprotein-lipid variables were observed with both fenofibrate and pravastatin treatments, LDL peak particle size was only significantly increased with fenofibrate therapy (+2.11+/-5.18 A, P<0.05). Among patients under fenofibrate therapy, changes in TG levels were negatively associated with changes in LDL peak particle size (r=-0.54, P<0.0007), whereas no such association was found in pravastatin-treated patients. The prevalence of patients with small, dense LDL particles (as defined by LDL particle diameter <255.5 A) was reduced from 69.4 to 30.6% (P<0.05) among fenofibrate-treated patients as opposed to 81.4 to 72.1% (NS) in patients who received pravastatin. CONCLUSION: As pravastatin treatment had no effect on LDL size, it is suggested that the additional effect of fenofibrate therapy on LDL size may contribute to reduce the risk of coronary heart disease (CHD) beyond what can be expected from the reduction in LDL cholesterol concentration in type IIa dyslipidemic patients.

ACE Inhibitors as First-Line Treatment Agents: A Comparative Study of Trandolapril and Enalapril on Casual and Ambulatory Blood Pressures.

This double-blind, randomized, parallel-ground study was designed to compare the efficacy of the angiotensin-converting enzyme inhibitors, trandolapril and enalapril, in 65 patients with mild to moderate primary hypertension. After a 4-week, single-blind, placebo run-in period, patients were randomized to receive either trandolapril 0.5 mg or enalapril 2.5 mg once daily. At 2-week intervals, trandolapril was titrated to 1, 2, or 4 mg and enalapril to 5, 10, or 20 mg in order to achieve a goal supine diastolic blood pressure (BP) of <90 mm Hg. In addition to casual BP measurement, 24-h ambulatory BP monitoring was performed at the end of the placebo period (baseline) and after 10 weeks of stable therapy at optimal and/or maximal dosage. Both drugs induced significant and comparable decreases in clinic systolic and diastolic BPs. The mean doses used were 3.2 mg for trandolapril and 16.6 mg of enalapril. The maximal effect was obtained at the highest dosage for both drugs in most patients with a mean decrease in supine diastolic BP of 8.6 mm Hg and 7.3 mm Hg for trandolapril 4 mg and enalapril 20 mg, respectively. Moreover, both agents significantly and similarly reduced mean 24-h as well as awake and sleep ambulatory BPs. Heart rates remained unchanged throughout the study. Our results demonstrate that both trandolapril and enalapril given at high dose exhibited significant decreases in clinic as well as in 24-h, awake, and sleep ambulatory BPs with no clear-up difference between the two treatment regimens. Moreover, our results emphasize the role of ambulatory BP monitoring when assessing the efficacy as well as the duration of action of new antihypertensive agents.