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Objectives: The primary objective of this study was to determine the percentage of patients who reached the reduction goal in LDL-cholesterol (LDL-C) with fluvastatin dosage titration, if necessary combined with gemfibrozil, in an unselected patient population with primary hyperlipidaemia, after appropriate dietary intervention. A secondary objective of the study was to determine long-term safety in terms of liver and muscle enzymes and tolerability in terms of spontaneously reported adverse effects.
Patients and Study Design: In this open-label, dosage titration study in 1501 male and female patients, we compared the 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitor fluvastatin in four possible dosage regimens - 20mg, 40mg, 80mg and, if necessary, 80mg combined with gemfibrozil 1200mg - over a period of 1 year.
Results: In total, 61.8% of the patients recruited reached the desired LDL-C level for their coronary heart disease (CHD) risk category, i.e. <3.5 mmol/Lfor patients without CHD and <3.0 mmol/L for patients with CHD. The safety parameters ALT, AST and CPK were, in comparison with baseline, slightly higher in the fluvastatin 40mg, 80mg and 80mg plus gemfibrozil 1200mg groups. There was no difference in tolerability in terms of type of complaints and total number of complaints between the different treatment regimens.
Conclusion: This study shows that fluvastatin is an effective and well tolerated cholesterol-lowering compound in patients with mild hypercholesterolaemia.
Evidence for the reversibility of coronary heart disease (CHD) risk through the modification of risk factors has had a strong effect on clinical practice. Earlier lipid-lowering angiographic 'regression' trials demonstrated the benefits of reducing low-density lipoprotein cholesterol (LDL-C) levels by diet, drugs or non-pharmacological methods. These studies involved serial coronary angiography and, in most instances, demonstrated arrest of progression rather than actual regression of disease. Although encouraging, the results of regression studies had major limitations both in terms of analytical interpretation and clinical relevance. The situation was clarified in 1994 when results were published from the Scandinavian Simvastatin Survival Study (4S). This secondary prevention trial showed that patients treated with simvastatin 20 to 40 mg/day achieved a 35% decrease in serum LDL-C levels, which was associated with a 42% decrease in CHD mortality and a 30% decrease in total mortality. Similar, albeit slightly less impressive, results were published later from trials of other statins, in both the primary (WOSCOPS and AFCAPS/ TexCAPS) and secondary (CARE and LIPID) prevention of CHD.
Fluvastatin, a second generation synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin), has been investigated in more than 20 000 patients in a large number of clinical trials; the majority of these were double-blind, randomised studies in which lipid-lowering diets were followed. In dose-finding studies with fluvastatin, statistically significant reductions in LDL-C levels were achieved with doses of 20 to 40mg daily.
Fluvastatin 20 and 40 mg/day reduced serum LDL-C levels by 22 to 24% and 29.5%, respectively. On average, fluvastatin 80mg (40mg twice daily) has been shown to reduce LDL-C levels by as much as 36%, with no difference in tolerability compared with fluvastatin 40mg administered once daily.
The primary objective of this study was to determine the percentage of patients with hypercholesterolaemia who reached goal LDL-C levels with stepwise fluvastatin dosage titration at 3-month intervals. Goal serum LDL-C levels were <3.5 mmol/L for patients without CHD, and <3.0 mmol/L for patients with CHD. To address these objectives, fluvastatin dose titration from 20 to 80 mg/day was given to a large population of patients. Combination therapy with fluvastatin 80 mg/day and twice-daily gemfibrozil 600mg was also investigated in a subpopulation with combined dyslipidaemia.
The secondary aim was to determine safety in terms of liver and muscle enzymes and tolerability in terms of spontaneously reported complaints with each of the four dosage regimens.
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