Results of intensive long-term treatment of familial hypercholesterolemia.

Fifty-seven patients with familial hypercholesterolemia (FH) with mean age of 48 years (range 30 to 69), participated in a follow-up examination 5.5 years after the completion of a 1-year trial with lovastatin, cholestyramine, probucol, or omega-3 fatty acids. The goals were to record quality of life, compliance to treatment, adverse effects, and clinical outcome. The quality of life was similar to that in a Norwegian reference population. The factors causing most distress to patients were keeping a diet low in saturated fats, taking medication, and fear of death. The medication was mostly prescribed in maximum dosages. At follow-up, the reduction in total cholesterol was 36% (p < 0.05), low-density lipoprotein (LDL) cholesterol 38% (p < 0.05), triglycerides 20% (p < 0.05) compared with being on diet therapy only. High-density lipoprotein (HDL) cholesterol increased 8% (p < 0.05). Intake of saturated and monounsaturated fat increased 1.5% and 1.7% (p < 0.05), respectively; polyunsaturated fat was unchanged. Three patients experienced myocardial infarction, of whom 2 died and 1 developed angina pectoris. Before the start of lovastatin treatment, 27 coronary events occurred per 1,000 patient-years in this group compared with 12 events per 1,000 patient-years thereafter. Of 28 patients reporting adverse events, 4 discontinued lovastatin and 3 discontinued cholestyramine. Several practical and psychological difficulties were associated with FH. Long-term intensive lipid-lowering therapy was possible in FH outpatients without loss of effect and with good compliance to therapy. Intensive therapy, today is, however, not sufficient for many FH patients to reach a therapeutic goal of LDL cholesterol < 4.0 mmol/L. More potent lipid-lowering agents are needed.

Effectiveness of low-dose lovastatin combined with low-dose colestipol in moderate to severe primary hypercholesterolaemia.

The effect of the combination of low-dose lovastatin and low-dose colestipol was studied among 57 subjects with moderate to severe primary hypercholesterolaemia (total cholesterol > or = 7.0 mmol l-1). Following an 8-week dietary phase, participants were randomized to treatment with 20 mg of lovastatin combined with 5 g or with 10 g of colestipol, or to matching placebo. Baseline total cholesterol was 7.7 +/- 0.9 mmol l-1 after dietary stabilization. Total cholesterol levels were reduced to 5.6 +/- 0.7 mmol l-1 and 5.8 +/- 0.7 mmol l-1 after 4 and 8 weeks of treatment in the lovastatin 5 g-1 colestipol group, and 74% of the subjects achieved the goal of low density lipoprotein (LDL) cholesterol levels of > or = 4.0 mmol l-1. Among the lovastatin 10 g-1 colestipol group, total cholesterol was reduced to 5.4 +/- 0.5 mmol l-1 and 5.5 +/- 0.9 mmol l-1 following 4 and 8 weeks, and 80% of subjects achieved the LDL cholesterol goal. No change was seen in the placebo group. Thus, low-dose combination therapy with lovastatin and colestipol, in conjunction with dietary treatment, is effective in moderate to severe primary hypercholesterolaemia, and is well tolerated.