Treatment of primary hypercholesterolaemia. Short-term efficacy and safety of increasing doses of simvastatin and pravastatin: a double-blind comparative study.
OBJECTIVE
To compare the efficacy and safety of increasing doses (0, 10, 20 and 40 mg day-1, each dose for 6 weeks) of the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, simvastatin and pravastatin, in the treatment of primary hypercholesterolaemia.


METHODS
Randomized, double-blind study with two parallel groups.


METHODS
Two specialist lipid clinics in the Netherlands.


METHODS
Forty-eight patients aged 25-66 years with primary hypercholesterolaemia (mean serum cholesterol 10.2 mmol-1).


METHODS
Total serum cholesterol, triglycerides, lipoproteins, apolipoproteins A-I and B, laboratory safety parameters and sleep questionnaires.


RESULTS
Both drugs induced a dose-dependent reduction in the mean total and low-density lipoprotein cholesterol concentration (P < 0.001); low-density lipoprotein cholesterol decreased from 32 to 43% by simvastatin and from 23 to 33% by pravastatin. There was an overall difference in the mean relative change from baseline in favour of simvastatin (total cholesterol, P < 0.01; LDL cholesterol P < 0.001). Both drugs reduced serum triglycerides by 10-15%. The changes in apolipoprotein B and the differences in efficacy between the two drugs paralleled those of total and low-density lipoprotein cholesterol. Adverse experiences were mild and did not differ between treatment groups; in each group, one subject discontinued medication because of complaints of dizziness. Sleep questionnaires revealed different degrees of sleep problems, unaffected by active treatment.


CONCLUSIONS
Simvastatin appeared to be more potent than pravastatin in lowering total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B, whereas both drugs had the same short-term safety profile.
Stalenhoef
A F
AF
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Lansberg
P J
PJ
Kroon
A A
AA
Kortmann
B
B
De Haan
A F
AF
Stuyt
P M
PM
Kastelein
J J
JJ
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D008148:Lovastatin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019821:Simvastatin; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D008148:Lovastatin; D019821:Simvastatin; D017035:Pravastatin