Atorvastatin plus pravastatin for the treatment of heterozygous familial hypercholesterolaemia--a pilot study.
The most common side-effect of statins, mainly during dose titration, is liver toxicity, In these cases, sufficient control of low density lipoprotein cholesterol (LDL-C) in patients with heterozygous familial hypercholesterolaemia (HFH) becomes problematical. In patients with intolerance to resins as well, especially in the presence of coronary artery disease (CAD), it is practically impossible to reach the LDL-C treatment goal. This study included seven HFH patients with CAD, who presented with alanine amino transferase levels greater than three times the upper normal limit during dose titration of atorvastatin or simvastatin of from 20 mg/day to 40 mg/day. They could not tolerate concomitant cholestyramine administration, and presented with LDL-C levels significantly higher than the treatment goal (100 mg/dl; 2.6 mmol/l). In these patients, a combination of two statins with different pharmacokinetics (20 mg/day of atorvastatin plus 40mg/day of pravastatin) was administered for a mean period of one year. Efficacy was compared with that of monotherapy with each drug alone and with that of 40 mg of atorvastatin in 13 patients, who could also not tolerate resin co-administration, and that of 40 mg/day of atorvastatin plus 12 g of cholestyramine in 30 patients, with similar pretreatment LDL-C levels. No increase in serum transaminases and no symptom or sign of myopathy was recorded during the administration of the combination of the two statins for a mean period of 12 months. The atorvastatin plus pravastatin regimen was more effective than both monotherapies and equally effective with the 40 mg of atorvastatin and the 40 mg of atorvastatin plus 12 g of cholestyramine regimens in reducing LDL-C (59% vs. 57% and 61%, respectively) and triglyceride levels (31% vs. 32% and 28%, respectively), while it also had a better effect on high density lipoprotein cholesterol (13% vs. 7% and 8%). The data suggest that the atorvastatin-pravastatin combination has a highly beneficial effect on all lipid parameters, without causing hepatotoxicity, in HFH patients with CAD who are sensitive to higher doses of statins in monotherapy. These results require confirmation in larger studies.
Athyros
V G
VG
Second Propedeutic Department of Internal Medicine, Aristotelian University, Hippocration Hospital, Thessaloniki, Greece. athyros@med.auth.gr
Papageorgiou
A A
AA
Demitriadis
D S
DS
Kontopoulos
A G
AG
D000704:Analysis of Variance; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D004359:Drug Therapy, Combination; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D017035:Pravastatin / Q000627:therapeutic use*; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin; D017035:Pravastatin