Int. Journal Clin. Pharmacol.
Volume 12 No. 4
July/August 1995
Pgs. 245-254

One-Year Study of the Effect of Policosanol on Lipid Profile in Patients With Type II Hypercholesterolemia

M. Canetti, M.D., M. Moreira, M.D., J. Illnait, Ph.D., R. Más, Ph.D., L. Fernández, M.Sc., J. C. Fernández, G. Castaño, Ph.D.

ABSTRACT

A 1-year, double-blind, placebo-controlled study of the efficacy, safety, and tolerability of policosanol 5 mg twice a day was conducted in 97 patients with type II hypercholesterolemia whose total and low-density lipoprotein (LDL) cholesterol was inadequately controlled by diet. After 2 months of policosanol therapy, significant reductions in total and LDL cholesterol were noted that persisted during the 1-year follow-up. Twelve months after therapy, LDL-C and total cholesterol decreased by 27.5% and 16.3%, respectively. Ratios of LDL to high-density lipoprotein (HDL) and total cholesterol to HDL were also signifi-cantly decreased after 2 months; reductions of 37.1% and 28%, respectively, were apparent 1 year after treatment. HDL increased during the study, but the increase (25.9%) reached statistical significance only after 12 months of therapy. Triglycerides changed nonsignificantly compared with baseline and placebo. Six patients (4 from the placebo group and 2 from the policosanol group) withdrew from the trial; no patient withdrew because of adverse experiences. No drug-related clinical or biochemical disturbances were observed. Adverse experiences reported were mild and transient and did not differ significantly from those seen with placebo. Policosanol (10 mg/d) administered for 1 year showed sustained efficacy, as well as very good safety and tolerability.

1. Dalmer Laboratory. (1990): Policosanol: Experimental Pharmacokinetics. Data on file.
2. Menindez R., Sotolongo V., Fraga V., et al. (1996): Niveles plasmaticus y cxcrecion de la radiactividad total en voluntariois sanos tras la administracion ora de octacosanol-3H. Rev. CENIC Cicn. Biol. 27:32-35.
3. Arruzazabala M. L., Carbajal D., Mas R., et al. (1994): Cholesterol-lowering effects of policosanol in rabbits. Biol. Res. 27:205-209.
4. Menindez R., Arruzazabala M.L., Mas R., et al. (1997): Cholesterol-lowering effect of policosanol on rabbits with hypercholesterolemia induced by a wheat starch-casein diet. Br. J. Nutr. 77:323-932.
5. Menindez R., Fernandez L, Del Rio A., et al. (1994): Policosanol inhibits cholesterol biosynthesis and enhances LDL processing in cultured human fibroblasts. Biol. Res. 27:199-203.
6. Menindez R., Amor A.M. Gonzilez R.M. Fraga V. and Mds R. (1996): Effect of policosanol on the hepatic cholesterol biosynthesis of normocholesterolcmic rats. Biol. Res. 29:253-257.
7. Cruz Bustillo D., Mederos C.M. Mas R., et al. (1991): Efecto hipocolesterol mico del Ateromixol (PPG) en el cerdo en ceba. Rev. CENIC Cien. Biol. 22:62-63.
8. Arruzazabala M. L., Valdes S., Mas R., et al. (1995): Effect of policosanol succesive dose increase in platelet aggregation healthy volunteers. Pharmacol. Res. 34:181-185.
9. Valdes S., Arruzazabala M.L., Carbajal D., et al. (1996): Effect of policosanol on platelet aggregation in healthy volunteers. Intern. J. Clin. Pharmacol. Res. 16:67-72.
10. Carbajal D, Arruzazabala M. L., Mas R., et al. (1998): Effect of policosanol on platelet aggregation and serum levels of arachidonic acid metabolites in healthy volunteers. Prostaglandins Leuko. Essent. Fatty Acids 58(1):61-4.
11. Noa M., Herrera M., Magrancr J. and Mas R. (1994): Effect of policosanol on isoprenaline-induccd myocardial necrosis in rats. J. Pharm. Pharmacol. 46:282-285.
12. Carbajal D, Arruzazabala M. L., Mas R., et al. (1994). Effects of policosanol on experimental thrombosis models. Prostaglandins Leuko. Essent. Fatty Acids 50:249-251.
13. Arruzazabala M.L., Carbajal D., Molina V., et al. (1993): Effect of policosanol on cerebral ischcmia in mongolian gerbils: Role of prostacyclin and thromboxane Az. Prostaglandins Leuko. Essent. Fatty Acids 49:695-697.
14. Noa M., Mas R., and Magraner J. (1994): Effect of policosanol on lipofundin-induced lesions in rats. J. Pharm. Pharmacol. 47:289-291.
15. Noa M., Mas R. and Mesa A. del R. (1997): Effect of policosanol in circulating endothelial cell in experimental models in Sprague-Dawley rats and in rabbits. Br. J. Nutr. 49:999-1002.
16. Noa M, Mas R, Mesa R. (1998): Effect of policosanol on intimal thickening in rabbit cuffed carotid artery. Int. J. Cardiol. 67(2):125-32,
17. Batista J., Stusser I. L., Penichet M. and Uguet E. (1995): Doppler-ultrasound pilot studyof thecffects of long-term policosanol therapy on carotid-vertebral atherosclerosis. Curr. Ther. Res. 56:906-914.
18. Fraga V., Menindez R., Anior A.M., et al. (1997): Effect of policosanol on in vivo and in vitro rat liver microsomal lipid pcroxidation. Arch. Medical Res. 28:355-360.
19. Mas R., Menindez R., Fraga V., etal. (1997): Modification of rat lipoprotein peroxidation by oral administration of policosanol. Abstract from the 4th International Conference on Preventive Cardiology, June 29-July3. Can. J. Cardiol. 13:Suppl. B. 310B.
20. Hernendez F., Illnait J., Mas R., et al. (1992): Effects of policosanol on serum lipids and lipoproteins in healthy volunteers. Curr. Ther. Res. 51:568-575.
21. Pons P., Mas R., Illnait J., et al. (1992): Efficacy and safety of policosanol in patients with primary hypercholesterolemia. Curr. Ther. Res. S2:507-513.
22. Pons P., Rodriguez M., Robaina C., et al. (1994): Effects of succesive dose increases of policosanol on lipid profile of patients with type-II hypercholesterolemia and tolerability to treatment. J. Clin. Pharmacol. Res. 14:27-33.
23. Soltero I., Fuenmayor I., Colmenares J. (1993): Ensayo doble ciego para la evalaucion del policosanol en el tratamiento de la hiperlipoproteinemia tipo II. Arch. Venezol. Farmacol. Terap. 12:65-70.
24. Aneiros E. Calderon B., Mas R., et al. (1993): Effects of successive dose increases of policosanol on the lipid profile and tolerability of treatment. Curr. Ther. Res. 54:304-312.
25. Aneiros E. Calderon B., Mas R., et al. (1995), Effect of policosanol in cholesterol-lowering levels in patients with type-II hypercholesterolemia. Curr. Ther. Res. 56:176-182.
26. Pons P., Rodriguez M., Mas R., et al. (1994): One-year efficacy and safety of policosanol in patients with type-II hypercholesterolemia. Curr. Ther. Res. 55:1084-1092.
27. Castano G., Mas R., Nodarse M., et al. (1995): One-year study of the efficacy and safety of policosanol (5 mg twice daily) in the treatment of type II hypercholesterolemia. Curr. Ther. Res., 56:296-304.
28. Canetti M., Morera M., Illnait J., et al. (1995): One year study on the effect of policosanol (5 mg-twice-a-day) on lipid profile in patients with type II hypercholesterolemia. Adv. Ther. 12:245-254.
29. Canetti M., Morera M., Illnait J., et al. (1995): A two year study on the efficacy and tolerability of policosanol in patients with type II hypercholesterolemia. Intern. J. Clin. Pharmacol. Res. 15:159-165.
30. Canetti M., Morera M., Mas R., et al. (1997): Effects of policosanol on primary hypercholesterolemia: A 3-year open follow-up. Curr. Ther Res. 58:868-75.
31. Castano G., Nodarse M., Mas R., et al. (1996): Comparaciones de los efectos del policosanol y la lovastatina en pacicntes con hipercolesterolemia primiaria tipo II. Rev. CENIC Cicn. Biol. 27:57-63.
32. Dalmer Laboratory. Policosanol vs lovastatin: Comparative study on efficacy, safety and tolerability in the treatment of type-II hypercholesterolemia. Data on file.
33. Benitez M., Romero C., Mas R., et al. (1997): A comparative study of policosanol vs pravastatin in patients with type-II hypercholesterolemia. Curr. Ther. Res. 58:859-67.
34. Ortensi G., Gladstein J., Vail H. and Tesone P.A. (1997): A comparativc study of policosanol vs. simvastatin in elderly patients with hypercholesterolemia. Curr. Ther. Res. 58:390-401.
35. Illnait J., Castano G., Mas R. and Fernandez J.C. (1997): A comparative study on the efficacy and tolerability of policosanol and simvastatin for treating type II hypercholesterolemia. Abstract front the 4th International Confereiicc on Preventive Cardiology. June 29-July 3. Can. J. Cardiol. 13:Suppl. B, 342B.
36. Canetti M., Morera M., Illnait J., et al. (1996): Estudio coniparativo de los efectos del policosanol y cl gemfibrozil cn pacientes con hipercolesterolemia primaria tipo II. Rev. CENIC Cicn. Biol. 27:64-70.
37. Soltero I., Fuenmayor I., Colmenares J. (1993): Estudio comparativo doble ciego de la eficacia y tolcrancia del policosanot vs. bezafibrato en pacientes con hiperlipidemia tipo II. Arch. Venezol. de Farmacol. Terap. 12:71-76.
38. Pons P., Fernandez L., Mas R. et al. (1996): Estudio coniparativo de los efectos del policosanol y el bezafibrato en pacientes con hipercolesterolemia primaria tipo II. Rev. CENIC Cien. Biol. 27:71-77
39. Alcocer L, Campos A., Mas R. and Fernandez L. (1997): A comparative study of policosanol vs acipimox in patients with type II hypercholesterolemia. Data on file.
40. Pons P., Illnait J., Mas R., et al. (1997): A comparativc study of policosanol versus probucol in patients with hypercholesterolemia. Curr. Ther. Res. 58:26-35.
41. Torres O., Agramonte A. J., Illnait J., et al. (1995): Treatment of hypercholesterolemia in NIDDM with policosanol. Diabetes Care 18:393-397.
42. Crespo N., Alvarez R., Mas R., et al. (1997): Effect of policosanol on patients with non-insulin-dependent diabetes mellitus and hypercholesterolemia: A pilot study. Curr. Ther. Res. 58:44-51.
43. Castano G., Tula L., Canetti M., et al. (1996): Effects of policosanol in hypertensive patients with type II hypercholesterolemia. Curr. Ther. Res. 57:691-699.
44. Pons P., Jimenez A., Rodriguez M., et al. (1993): Effects of policosanol in elderly hypercholesterolemic patients. Curr. Ther. Res. 53:265-269.
45. Castano G., Canetti M., Morera M., et al. (1995): Efficacy and tolerability of policosanol in elderly patients with type-II hypercholesterolemia: A 12 months study. Curr. Ther. Res. 56:819-828.
46. Zordoya R., Tula L., Castano G., Mas R., et al. (1996): Effects of policosanol on hypercholesterolemic patients with disturbances on serum biochemical indicators of hepatic function. Curr. Ther. Res. 57:568-577.
47. Davalos J.M., Mederos H., Rodriguez J., et al. (1996): Effect of policosanol in hypercholesterolemia due to nephrotic syndrome. X Latinciamerican Congress of Nephrology and Hypertension, 14 September, Santiago de Chile, Chile.
48. Arruzazabala M. L., Carbajal D., Mas R. and Valdes S. (1997): Comparative study of policosanol, aspirin and the combination therapy policosanol-aspirin on platelet aggregation in healthy volunteers. Pharmacol Res 36(4):293-7.
49. Stusser R., Batista J., Padron R. et al. (1998): Long-term therapy with policosanol improves treadmill exercise-ECG testing performance of coronary heart disease patients. Int J Clin Pharmacol Ther 36(9):469-73.
50. Fernandez L., Mas R., Illnait J., Fernandez J.C. (1998): Policosanol: Results of a postmarketing survellance study of 27,879 patients. Curr. Ther. Res. 59:7717-22.
51. Aleman C.L., Mas R., Rodeiro L., et al. (1991): Toxicologia aguda del Ateromixol (PPG) en roedores. Rev. CENIC Cien. Biol. 22:102-105.
52. Aleman C.L., Mas R., Rodeiro I., et al. (1992): Acute, subchronic and chronic toxicology of policosanol in rats. Toxicol. Letters. Suppl.2:248.
53. Rodriguez C., Mesa R., Mas R., et al. (1994): Study of policosanol oral chronic toxicity in male monkeys (Maraca arctoidcs). Food and Chem. Toxicol. 32:565-575.
54. Mesa A. del R., Mas R., Noa M., et al. (1994): Toxicity of policosanol in Beagle dogs: one year study. Toxicol. Letters. 73:131-90.
55. Aleman C.L., Mas R., Hernandez C., et al. (1994): A 12 months study of policosanol oral toxicity in Sprague-Dawley rats. Toxicol. Lett. 70:77-87.
56. Aleman C.L., Noa M., Cerejido E., Mis R., Rodeiro L Hcrnindez C. and Briffis F. (1995): Carcinogenicity of policosanol in mice: A 18 months study. Fd. and Client. Toxicol., 33:573-578.
57. Aleman C.L., Mas R., Noa M., et al. (1994): Carcinogenicity of policosanol in Sprague Dawley rats: A 24 months study. Teratog. Carcinog. and Mutag., 14:239-249.
58. Rodriguez M.D. and Garcia H. (1994): Teratogenic and reproductive studies of policosanol in the rat and rabbit. Teratog., Carcinog. and Mutag., 14:107-113.
59. Rodriguez M.D., Garcia H. (1998): Evaluation of peri- and post-natal toxicity of Policosanol in rats. Teratog Carcinog Mutagen 18(1):1-7.
60. Rodriguez M.D., Sanchez M., Garcia H. (1997): Multigeneration reproduction study of policosanol in rats. Toxicol. Lett. 90:97-106. 61. Carbajal D, Arruzazabala M. L., Mas R., et al. (1998): Interaction policosanol-warfarin on bleeding time and thrombosis in rats. Pharmacol Res 38(2):89-91.
61. Batista, J., Stusser, R., Saez, F. et al. (1996): Effect of policosanol on hyperlipidemia and coronary heart disease in middle-aged patient. A 14 month pilot study. International Journal of Clinical Pharmacology Research 34, 134-137.
62. Castano, G., Mas, R., Roca, J. et al. (1999): A double-blind, placebo-controlled study of the effects of policosanol in patients with intermittent claudication. Angiology 50, 123-130.
63. Fontani, G., Maffei, D. and Lodi, L. (2000): Policosanol, reaction time and event-related potentials. Neuropsychobiology 41, 158-165.
64. Mas, R., Castano, G., Illnait, J. et al. (1999): Effects of policosanol in patients with type II hypercholesterolemia and additional coronary risk factor. Clinical Pharmacology and Therapeutics 65, 439-447.