Comparison of lipid-lowering effects of low-dose fluvastatin and conventional-dose gemfibrozil in patients with primary hypercholesterolemia.

A total of 123 patients with primary hypercholesterolemia were randomized on a 2:1 ratio to receive either fluvastatin at 20 mg once daily at night (n = 82) or gemfibrozil at 600 mg twice daily (n = 41) in a double-blind, double-dummy comparison of the effects on plasma lipid parameters and tolerability over 8 weeks. All patients had either low-density lipoprotein cholesterol (LDL-C) concentrations > or = 160 mg/dL (4.1 mmol/L) in association with definite coronary artery disease (CAD) or > or = 2 risk factors, or LDL-C > or = 190 mg/dL (4.9 mmol/L) with no CAD and < 2 risk factors. All had triglyceride (TG) levels < or = 350 mg/dL (4.0 mmol/L). After 8 weeks of treatment, fluvastatin produced significant reductions from baseline of 17.4% (p < 0.001) in LDL-C, 13.2% (p < 0.001) in total cholesterol (TC), 13.8% (p < 0.001) in very low-density lipoprotein cholesterol (VLDL-C), and 6.4% (NS) in TG. High-density lipoprotein cholesterol (HDL-C) was increased by 5.6% (p < 0.001), and the ratio of LDL-C:HDL-C (Friedewald) was decreased by 21.2% (p < 0.001). Gemfibrozil reduced LDL-C by 15.8%, TC by 13.4%, VLDL-C by 32.2%, LDL-C:HDL-C by 24.8%, and TG by 34.2%, and increased HDL-C by 13.9% (all changes were statistically significant, p < 0.001) compared with baseline. Gemfibrozil produced significantly greater changes in VLDL-C (p < 0.01), HDL-C (p < 0.001), and TG (p < 0.001), but not in LDL-C: HDL-C, compared with fluvastatin. Both drugs significantly reduced apolipoprotein (apo) B and lipoparticles (Lp) E:B, and increased apo A-I but had divergent effects on LpA-I (increased with fluvastatin and reduced with gemfibrozil; p < 0.05). At the end of the study, 43.8% of fluvastatin patients and 45% of gemfibrozil patients achieved a reduction of > 20% in LDL-C levels. Normalization of LDL-C levels was achieved (according to European Atherosclerosis Society guidelines) by 13.4% of fluvastatin- and 14.6% of gemfibrozil-treated patients. Both drugs were well tolerated; adverse events occurred in 36.6% of fluvastatin recipients compared with 58.5% of patients taking gemfibrozil. No clinically notable elevations of aspartate or alanine aminotransferases, alkaline phosphatase, or creatine phosphokinase occurred. No patient developed new or worsening lens opacities associated with a reduction in optically corrected visual acuity. The most commonly reported adverse events were headache and gastrointestinal upset. There were no serious drug-related adverse events.

A multicentre multidose study of the efficacy and safety of spirapril in mild-to-moderate essential hypertension. UK Study Group of Spirapril in Hypertension.

This was a randomized double-blind parallel-group study of 283 patients who had mild-to-moderate [diastolic blood pressure (DBP) > 100 mmHg and < or = 115 mmHg] hypertension. After a 3 (or 4)-week placebo wash-out period followed by 6 weeks of active treatment with spirapril at either 3, 6, 12 or 24 mg once daily (or placebo), DBP decreased by approximately 10 mmHg in the (pooled) spirapril-treated patients compared with approximately 5 mmHg with placebo. There were statistically significant differences between all active-treatment groups (except the 24-mg dose group) and placebo, but not among the spirapril groups at the end of the +24-hour dosing interval. Reported adverse events were mostly not study drug-related and were similar to those with placebo except for headache, which was more frequent with spirapril than placebo (5.8% vs 1.7%, respectively). Similarly, the number and severity of the changes in laboratory variables did not differ between placebo vs spirapril, and none of these changes were dose-related. In conclusion, the studied dosages of spirapril were equally effective in reducing DBP, and the overall good decrease in blood pressure at the end of the dosing interval indicates that once-daily administration is effective in patients with mild-to-moderate hypertension.

Comparison of bevantolol and atenolol for systemic hypertension.

In an international, randomized, double-blind trial involving 229 patients, 400 mg of bevantolol was compared with 100 mg of atenolol (both in single daily doses) in the management of mild to moderate hypertension (diastolic blood pressure [BP] 95 to 115 mm Hg after a 4-week placebo washout period). Patients were then randomized to 12 weeks of treatment with either drug. Patients were evaluated at 2, 4, 8 and 12 weeks during the drug treatment period. Efficacy measurements were based on sitting and standing BP and heart rate. Adverse experiences were recorded on patient checklists, by spontaneous complaints and by 12-lead electrocardiography and funduscopy. A subgroup of 104 patients had heart rate and BP determinations every 24 to 26 hours after drug ingestion. Overall results showed both drugs to be comparably effective; no real difference was shown after 12 weeks of treatment. Bevantolol caused a more gradual BP decrease than atenolol. Both regimens were associated with decreased heart rate (less marked with bevantolol, p less than 0.001). Data from the 24-hour assessment subgroup showed similar results for both drugs, with a somewhat lower decrease in BP for bevantolol, which persisted throughout the study. Both drugs lowered sitting BP; the decrease was significantly less with bevantolol after the second week of therapy. The mean number of adverse experiences was similar for both drugs; cardiovascular side effects were less frequent with bevantolol. Patients taking bevantolol showed a higher incidence of digestive system side effects. Bevantolol maintained a 24-hour antihypertensive effect.(ABSTRACT TRUNCATED AT 250 WORDS)