Antiplatelet effects of policosanol (20 and 40 mg/day) in healthy volunteers and dyslipidaemic patients.
1. The present study was undertaken to compare the effects of a higher dose of policosanol, a cholesterol-lowering drug, (40 mg/day) with the effects of 20 mg/day policosanol on platelet aggregation in healthy volunteers and type II hypercholesterolaemic patients. 2. Study subjects were randomized to receive, under double-blind conditions, placebo or policosanol (20 or 40 mg/day) for 30 days once a day. Blood sampling was performed at baseline and after 30 days on therapy. 3. Platelet aggregation was induced with three aggregating agents: arachidonic acid (AA), collagen and low doses of ADP. 4. Policosanol (20 and 40 mg/day) moderately yet significantly reduced platelet aggregation, but no differences were observed in the effects produced by either dose of policosanol. In healthy volunteers, policosanol at 20 and 40 mg/day inhibited aggregation induced by 2 mmol/L AA (28.2 and 24.9%, respectively), 1 micro g/mL collagen (21.1 and 20.2%) and 1 micro mol/L ADP (30.9 and 29.1%). Changes that occurred following the administration of placebo were not significant, although an upward trend for collagen- and ADP-induced aggregation occurred in normal and hypercholesterolaemic subjects, respectively, thus partially masking the effects of policosanol on these responses. 5. The antiplatelet effects of policosanol at 20 and 40 mg/day in hypercholesterolaemic patients were also similar, so that both doses inhibited aggregation induced by 1.5 mmol/L AA (20.1 and 33.0%, respectively), 0.5 micro g/mL collagen (22.7 and 21.1%) and 1 micro mol/L ADP (40.5 and 34.7%). 6. In addition, after 30 days of therapy, 20 and 40 mg/day policosanol significantly (P < 0.01) reduced low-density lipoprotein-cholesterol (15.9 and 17.0%, respectively) and total cholesterol (12.4 and 12.3%, respectively; P < 0.05), yet increased high-density lipoprotein-cholesterol values by 5% in both groups (P < 0.05). 7. Triglycerides were decreased compared with baseline, but not with respect to the placebo. 8. We conclude that the antiplatelet effects induced by 40 mg/day policosanol administered for 30 days to healthy volunteers and to hypercholesterolaemic patients were similar to the effects induced by 20 mg/day policosanol. Thus, no enhancement of the response was achieved with the use of a higher dose of policosanol in study patients.
Center of Natural Products, National Center for Scientific Research Cubanacán, Havana City, Cuba.
María Lourdes
ML
Arruzazabala
Vivian
V
Molina
Rosa
R
Mas
Lilia
L
Fernández
Daisy
D
Carbajal
Suria
S
Valdés
Gladys
G
Castaño
D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005233:Fatty Alcohols / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D018709:Statistics, Nonparametric
D005233:Fatty Alcohols; D010975:Platelet Aggregation Inhibitors; C080710:policosanol