[Long-term effect of policosanol on the functional recovery of non-cardioembolic ischemic stroke patients: a one year study]. / Efecto a largo plazo del policosanol en la recuperacion funcional de pacientes con ictus isquemico no cardioembolico: estudio de un año.

INTRODUCTION: Stroke is a leading cause of mortality and disability. Policosanol has been effective in brain ischemia models. The aim of this study is to investigate whether policosanol, added to aspirin therapy within 30 days of stroke onset, is better than placebo + aspirine for the long-term recovery of non-cardioembolic ischemic stroke subjects. PATIENTS AND METHODS: Randomized, double-blind, placebo-controlled study. Eighty patients (mean age: 69 years) within 30 days of onset, with a modified Rankin Scale score (mRS) 2 to 4, were included. They were randomized in two groups (policosanol + aspirine or placebo + aspirine) for 12 months. RESULTS: Policosanol + aspirine decreased significantly mean mRS from the first interim check-up (1.5 months). The treatment even improved after long-term therapy. More policosanol + aspirin (87.5%) than placebo + aspirine (0%) patients achieved mRSs <= 1. Policosanol + aspirine increased significantly Barthel Index, lowered LDL-cholesterol and increased HDL-cholesterol versus placebo + aspirin. CONCLUSIONS: Long-term (12 months) administration of policosanol + aspirin given after suffering non-cardioembolic ischemic stroke was shown to be better than placebo + aspirin in improving functional outcomes when used among patients with non-cardioembolic ischemic stroke of moderate severity.

TITLE: Efecto a largo plazo del policosanol en la recuperacion funcional de pacientes con ictus isquemico no cardioembolico: estudio de un año.Introduccion. El ictus es una causa principal de mortalidad y discapacidad. El policosanol ha sido eficaz en modelos de isquemia cerebral. Este estudio investiga si el tratamiento a largo plazo con policosanol, añadido a la terapia con acido acetilsalicilico (AAS), dentro de los 30 dias posteriores a un ictus, es mejor que el placebo + AAS en la recuperacion de los pacientes. Pacientes y metodos. Estudio aleatorizado, doble ciego, controlado con placebo. Se incluyeron 80 pacientes (edad media: 69 años) que sufrieron un ictus en los 30 dias previos y con una puntuacion de 2-4 en la escala de Rankin modificada (mRS). Se distribuyeron aleatoriamente en dos grupos y recibieron policosanol + AAS o placebo + AAS durante 12 meses. Resultados. El tratamiento con policosanol + AAS disminuyo significativamente la puntuacion en la mRS desde el primer control intermedio (1,5 meses). El efecto del tratamiento incluso mejoro con la terapia a largo plazo. El numero de pacientes que alcanzaron valores de mRS menores o iguales a 1 fue superior en el grupo de policosanol + AAS (87,5%) que en el de placebo + AAS (0%). El tratamiento con policosanol + AAS aumento significativamente el indice de Barthel, disminuyo el colesterol LDL y aumento el colesterol HDL frente a placebo + AAS. Conclusiones. El tratamiento a largo plazo (12 meses) con policosanol + AAS fue mas efectivo que el tratamiento con placebo + AAS en la recuperacion funcional de los pacientes despues de sufrir un ictus isquemico no cardioembolico de moderada gravedad.

Effects of policosanol on patients with ischemic stroke: a pilot open study.

Stroke is a major health problem worldwide. Its pharmacological management includes thrombolytic therapy for the acute phase and antiplatelet drugs for stroke recovery and prevention. Statins can help in the acute phase and in preventing stroke in secondary prevention patients. Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects, with protective effects in stroke models. This observational study investigated the effects of policosanol (20 mg/day) administered during the acute phase and for 5 years later on the neurological recovery of patients with ischemic stroke treated with antiplatelets and vitamins. After hospital discharge, patients were followed up every 3 (first year) and 6 (thereafter) months. Neurological improvement was assessed with the modified Canadian Neurological Scale. Adverse events were recorded. Fifty patients were included; all completed the study. Neurological score improved throughout the study. No patient died, and most [40 (80.0%)] did not experience new vascular events; only one (2.0%) suffered a new stroke, and two (4.0%) suffered more than one transient ischemic attack. The time to the first recurrent event was 46.2 months. Policosanol persistently lowered serum total cholesterol, with such reduction correlating with the neurological improvement (R = 0.995253301). Triglycerides were unchanged. Treatment was well tolerated. Policosanol administered to patients suffering ischemic stroke treated with aspirin and vitamins showed good results on neurological outcomes and recurrent events. This study, however, has limitations, since it was open and uncontrolled, and patients also consumed aspirin and vitamins. New randomized, controlled studies are needed to assess the usefulness of policosanol in stroke management.

Effects of addition of policosanol to omega-3 fatty acid therapy on the lipid profile of patients with type II hypercholesterolaemia.

BACKGROUND: Policosanol is a mixture of higher aliphatic primary alcohols purified from sugar-cane wax. The mixture has cholesterol-lowering efficacy, its specific effects being to reduce serum total (TC) and low-density lipoprotein cholesterol (LDL-C), and to increase high-density lipoprotein cholesterol (HDL-C). The effects of policosanol on triglycerides (TG) are modest and inconsistent. Omega-3 fatty acids (FA) from fish oil protect against coronary disease, mainly through antiarrhythmic and antiplatelet effects. Omega-3 FA also have lipid-modifying effects, mostly relating to TG reduction. Thus, potential benefits could be expected from combined therapy with omega-3 FA and policosanol. OBJECTIVE: To investigate whether combined therapy with omega-3 FA + policosanol offers benefits compared with omega-3 FA + placebo with respect to the lipid profile of patients with type II hypercholesterolaemia. METHODS: This randomised, double-blind study was conducted in 90 patients with type II hypercholesterolaemia. After 5 weeks on a cholesterol-lowering diet, patients were randomised to omega-3 FA + placebo, omega-3 FA + policosanol 5 mg/day or omega-3 FA + policosanol 10 mg/day for 8 weeks. Omega-3 FA was supplied as 1g capsules (two per day); placebo and policosanol were provided in tablet form. Physical signs and laboratory markers were assessed at baseline and after 4 and 8 weeks on therapy. Drug compliance and adverse experiences (AEs) were assessed at weeks 4 and 8. The primary efficacy variable was LDL-C reduction; other lipid profile markers were secondary variables. RESULTS: After 8 weeks, omega-3 FA + policosanol 5 and 10 mg/day, but not omega-3 FA + placebo, significantly reduced LDL-C by 21.1% and 24.4%, respectively (both p < 0.0001). Omega-3 FA + policosanol 5 mg/day also significantly lowered TC (12.7%; p < 0.01) and TG (13.6%; p < 0.05), and significantly increased HDL-C (+14.4%; p < 0.001). Omega-3 FA + policosanol 10 mg/day significantly decreased TC (15.3%; p < 0.001) and TG (14.7%; p < 0.01), and significantly increased HDL-C (+15.5%; p < 0.0001). Omega-3 FA + placebo significantly reduced TG (14.2%; p < 0.05) but had no significant effect on other lipid profile variables. The proportion of randomised patients in the omega-3 FA + policosanol 5 or 10 mg/day groups that achieved LDL-C targets or reductions 15% was significantly greater than in the omega-3 FA + placebo group (p < 0.001). Combined therapy with omega-3 FA + policosanol 5 or 10 mg/day resulted in significantly greater changes in LDL-C, TC and HDL-C than treatment with omega-3 FA + placebo, but did not modify the TG response compared with the omega-3 FA + placebo group. Four patients (two in the omega-3 FA + placebo group and two in the omega-3 FA + policosanol 10 mg/day group) withdrew from the study; none of these withdrawals was due to AEs. Two patients reported mild AEs, namely nausea/headache (one in the omega-3 FA + placebo group) and heartburn (one in the omega-3 FA + policosanol 5 mg/day group). CONCLUSIONS: Policosanol 5 or 10 mg/day administered concomitantly with omega-3 FA 1 g/day improved LDL-C, TC and HDL-C, maintained the reduction in TG attributable to omega-3 FA monotherapy, and was well tolerated. Treatment with omega-3 FA + policosanol could be useful for regulating lipid profile in patients with type II hypercholesterolaemia, but further studies involving larger sample sizes are needed before definitive conclusions can be drawn.

Effects of D-003, a mixture of very long chain fatty acids purified from sugar cane wax, at 5 and 10 mg/day on platelet aggregation in healthy volunteers.

D-003 is a mixture of high molecular weight aliphatic primary acids purified from sugar cane wax with antiplatelet and cholesterol-lowering effects. Previous studies showed that D-003 (10-20 mg/day) administered for a short time inhibits platelet aggregation, 14 days being the longest duration investigated. This study was conducted to investigate the effects of D-003 (5 and 10 mg/day) for 30 days on platelet aggregation in normocholesterolemic subjects. This report shows the effects of D-003 on platelet aggregation to arachidonic acid (AA) (1.5 mM), collagen (2 microg/ml) and adenosine 5'-diphosphate ADP (2 microM) assessed at baseline and at treatment completion. Fifty-four subjects were randomized to placebo or D-003 (5 or 10 mg/day) for 30 days. Platelet aggregation to AA, collagen and ADP were assessed. D-003 at the lowest dose (5 mg/day) significantly but modestly inhibited (p < 0.01) platelet aggregation to AA (5.0%) and (p < 0.01) to collagen (7.5%). D-003 at 10 mg/day inhibited (p < 0.001) platelet aggregation to AA and collagen (p < 0.01) by 20.3% and 14.7%, respectively. ADP-induced aggregation, however, was unchanged. D-003 at 10 mg/day, but not at 5 mg/day, lowered (p < 0.01) plasma fibrinogen. D-003 (5 and 10 mg/day) reduced low-density lipoprotein cholesterol (LDL-C) by 17.7% and 26.4%, respectively, and total cholesterol (TC) by 14.5% and 18.5%, while at 10 mg/day, but not at 5 mg/day, it increased high-density lipoprotein cholesterol (HDL-C) by 9.6%. Triglycerides, however, were unchanged with D-003. No disturbances in safety indicators were induced with D-003. One subject (D-003 5 mg/day) discontinued the study and four patients (three taking D-003 and one taking placebo) reported adverse effects (AE) (headache in two patients taking D-003 and one patient taking placebo, and polyphagia in one patient taking D-003). In conclusion, D-003 (5-10 mg/day) for 30 days inhibited platelet aggregation to AA and collagen but not to ADP Therefore, the antiplatelet effect was present with the longer treatment, even at a dose of 5 mg/day. The cholesterol-lowering effects of D-003 were consistent with those expected for such a short treatment. In addition, D-003 at 10 mg/day significantly lowered plasma fibrinogen. The treatment was well tolerated.

The effect of D-003 (10 mg/day) on biochemical parameters of bone remodelling in postmenopausal women: a randomized, double-blind study.

Biphosphonates, which are antiresorptive agents used to treat osteoporosis, inhibit the mevalonate pathway, preventing protein prenylation and inhibiting osteoclast activity. Statins decrease cholesterol biosynthesis by blocking the mevalonate pathway and have been reported to have beneficial effects on bone. D-003 is a mixture of high molecular weight acids purified from sugarcane wax that inhibits cholesterol biosynthesis before mevalonate production. D-003 prevents bone loss and resorption in rats with osteoporosis induced with ovariectomy or corticoids. Biochemical markers of bone turnover are used to monitor the short-term efficacy of antiosteoporotic therapy. This randomized, double-blind, placebo-controlled study was undertaken to investigate the short-term effects of D-003 (10 mg/day) on biochemical markers of bone turnover in postmenopausal women with low bone mineral density (BMD). After 4 weeks on a low-fat diet, 34 women were randomized to D-003 (10 mg/day) or placebo for 6 months. Pre- and post-treatment samples were analyzed for urinary excretion of deoxypyridinoline (DPD)/creatinine (Cr), a marker of bone resorption, and serum bone specific alkaline phosphatase (BSAP), a marker of bone formation. The effects on lipid profile and safety indicators, as well as adverse events (AE), were investigated. D-003 (10 mg/day) lowered urinary excretion of tDPD/Cr versus baseline (20.6%) (p < 0.001) and placebo (33.7%) (p < 0.01), but did not modify serum BSAP. D-003 decreased low-density lipoprotein-cholesterol (LDL-C) (32.8%), total cholesterol (TC) (16.4%) and the TC/high-density lipoprotein-cholesterol (HDL-C) ratio (34.7%), increased HDL-C (30.3%) (p < 0.001) and did not modify triglycerides. The effects on these variables were significant as early as 3 months after treatment initiation. D-003 was well tolerated. Three patients (one in the placebo group and two in the D-003 group) withdrew from the study. Two of these withdrawals were due to AE: abdominal pain (placebo) and heartburn (D-003). Five patients (four in the placebo group [22.2%] and one in the D-003 group [6.3%]) reported mild AE. In conclusion, D-003 (10 mg/day) reduced urinary excretion of tDPD/Cr, a bone resorption marker and did not change serum BSAP, a bone formation marker, while it lowered cholesterol in study patients. These preliminary results suggest that D-003 could be useful in treating postmenopausal women with low BMD. However, the potential value of D-003 in treating or preventing osteoporosis deserves further clinical investigation.

A comparison of the effects of D-003 and policosanol (5 and 10 mg/day) in patients with type II hypercholesterolemia: a randomized, double-blinded study.

The main goal of hypercholesterolemia management for coronary prevention is to reduce serum low-density lipoprotein cholesterol (LDL-C) levels. D-003 is a mixture of high molecular weight aliphatic acids purified from sugarcane wax, while policosanol is a cholesterol-lowering drug purified from the same source, consisting in a mixture of higher aliphatic alcohols. No previous comparative study of both drugs in humans has been reported. This randomized, double-blind study compares the efficacy and tolerability of D-003 and policosanol (5 and 10 mg/day) in patients with type II hypercholesterolemia. After a baseline period, 100 patients were randomized to D-003 or policosanol both at 5 mg/day and 10 mg/day, for 8 weeks. D-003 and policosanol 5 mg/day reduced (p < 0.0001) LDL-C by 26.9% and 20.9%, respectively. These reductions increased with 10 mg/day (35.1% for D-003, 25.1% for policosanol. The reductions of LDL-C achieved with D-003 5 mg/day and 10 mg/day were greater (p < 0.05 and p < 0.001, respectively) than with policosanol. The frequency of patients treated with D-003 (5 mg/day) reaching LDL-C reductions > or = 15% (22/25, 88%) was greater (p < 0.01) than with policosanol (5 mg/day) (19/25, 76%), and the same was true for D-003 10 mg/day (25/25, 100%) and policosanol (22/25, 88%; p < 0.01). D-003 and policosanol (5 mg/day) also lowered (p < 0.001) total cholesterol (TC) (16.2% and 13.5%, respectively), and increased high-density lipoprotein cholesterol (HDL-C) by 15.3% (D-003) and 6.7% (policosanol). At 10 mg/day, D-003 and policosanol reduced (p < 0.001) TC (21.3% and 16.0%, respectively), while HDL-C was increased by 17.3% and 9.8%, respectively, D-003 being more effective than policosanol. Treatments did not affect triglycerides. Both drugs were well tolerated, with D-003 tolerated as well as policosanol. Three patients discontinued the study, none due to adverse events (AEs). Seven patients (three from the D-003 group and four from the policosanol group) experienced mild AEs. In conclusion, D-003 (5 and 10 mg/day) administered to patients with type II hypercholesterolemia was more effective than policosanol in lowering LDL-C and TC, and in increasing HDL-C. D-003 could be useful for treating type II hypercholesterolemia, but this subject deserves further clinical research.

Effects of d-003, a new substance purified from sugar cane wax, on platelet aggregation and plasma levels of arachidonic acid metabolites in healthy volunteers.

D-003 is a mixture of very high molecular weight aliphatic acids purified from sugar cane wax showing cholesterol-lowering and antiplatelet effects proven in experimental and clinical studies. Experimental evidence indicates that inhibition of platelet aggregation induced by D-003 is associated with a reduction of thromboxane B2 (TxB2) and an increase of prostacyclin (Pgl2) serum levels. This double-blinded, randomized, placebo-controlled study was undertaken to investigate whether D-003 (20 mg/day) modifies serum levels of TxB2 and Pgl2 and inhibits platelet aggregation in human healthy volunteers. Thirty-one subjects were randomized to placebo or D-003 at 20 mg/day for 14 days. Serum levels of TxB2 and Pgl2 and platelet aggregation to arachidonic acid (AA) (1.75 mM) and collagen (1 microg/ml) were assessed. D-003 (20 mg/day) significantly reduced (p < 0.001) TxB2by 36.4% and increased Pgl2 serum levels by 31% compared with baseline, and these changes were different from placebo. As expected, D-003 significantly inhibited (p < 0.001) platelet aggregation to AA (81.9-65.6%) and to collagen (75.3-62.3%). No subject withdrew from the study. No drug-related disturbances were observed. We conclude that D-003 at 20 mg/day for 14 days significantly inhibited platelet aggregation to AA and collagen and reduced TxB2 and increased Pgl2 serum levels. These results are consistent with those observed in experimental models, indicating that the antiplatelet effect of D-003 is associated with the observed changes on the levels of AA metabolites. Further studies, however, should explore the mechanism involved in this action in greater depth.

Concomitant use of policosanol and beta-blockers in older patients.

Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. It is safe and well tolerated, even in populations with high consumption of concomitant drugs. These data suggest that adverse events (AE) due to drug-to-drug interactions (DDI) with policosanol are not relevant. Experimental data indicate that potential DDI between policosanol and drugs metabolized through the cytochrome P450 hepatic system are not expected, but pharmacodynamic DDI cannot be excluded. Several clinical studies have shown that policosanol decreased arterial pressure compared with placebo, and a pharmacological interaction with beta-blockers was experimentally proven. Therefore, clinical DDI between policosanol and beta-blockers can be expected. This study investigated whether policosanol reinforces the antihypertensive effects of beta-blockers and/or whether this combination impairs some safety indicators or induces specific AE in older patients. After 5 weeks on a diet-only baseline period, 205 older hypercholesterolemic patients taking beta-blockers were randomized to policosanol 5 mg/day or placebo for 3 years. After 1 year on therapy, policosanol significantly reduced (p < 0.00001 versus placebo) low-density lipoprotein-cholesterol (LDL-C) (20.9%), total cholesterol (TC) (19.3%) and triglycerides (TG) (25.7%), whereas it increased (p < 0.01 and p < 0.001 versus placebo) high-density lipoprotein-cholesterol (HDL-C) levels (4.1%). Treatment effects did not to wear off during the 3-year follow-up. At study completion, policosanol lowered (p < 0.00001 versus placebo) LDL-C (34.3%), TC (23.2%) and TG (21.2%) and raised (p < 0.00001 versus placebo) HDL-C (12.3%). Thirty-one patients (15.1%) discontinued the study, 22 in the placebo group (20.6%) and nine in the policosanol group (9.2%). Of these, 20 patients (16 in the placebo group and four in the policosanol group) withdrew from the study due to AE. The frequency of serious adverse events (SAE), mostly vascular, in policosanol patients (3/98, 3.1%) was lower than in the placebo group (15/107, 14.0%). No impairment of safety indicators was observed. Nevertheless, reductions in systolic and diastolic blood pressure were observed in policosanol patients compared with those in the placebo group. The frequency of policosanol patients reporting mild or moderate AE (18/98, 18.4%) was also lower than in the placebo group (30/107, 28.0%). In conclusion, policosanol was well tolerated in elderly patients taking beta-block- ers and did not increase AE. Additional reduction of blood pressure and a lower frequency of SAE were observed in policosanol patients compared with those taking placebo. The cholesterol-lowering efficacy of policosanol was that expected. These results provide support that policosanol therapy added to hypercholesterolemic elderly individuals taking beta-blockers could provide additional benefits in lowering blood pressure; SAE were not more frequent in the policosanol group than in the placebo group and there was no increase in AE.

Comparison of the efficacy, safety and tolerability of original policosanol versus other mixtures of higher aliphatic primary alcohols in patients with type II hypercholesterolemia.

This randomized, double-blind study was undertaken to compare the efficacy and tolerability of policosanol and Octa-60 in patients with type II hypercholesterolemia. After 4 weeks on a diet, 110 patients were randomized to policosanol or Octa-60 5 mg tablets once a day for 5 weeks. The dose was then doubled to 10 mg/day for the next 5 weeks. Policosanol 5 and 10 mg/day significantly lowered low-density lipoprotein-cholesterol (LDL-C) (p<0.0001 and p<0.00001), the main efficacy variable, by 18.6% and 30.2%, while Octa-60 significantly reduced (p<0.05) LDL-C by 10.0% at study completion only. The frequency of policosanol patients reaching reductions of LDL-C > or = 15% after 5 mg/day (37/55; 67.3%) and 10 mg/day (47/55; 88.7%) was greater (p<0.01 and p<0.01) than in the Octa-60 group, which was 5/55 (9.1%) and 20/55 (36.4%). Likewise, the frequency of patients reaching LDL-C values of <3.4 mmol/l at study completion was greater (p<0.001) in the policosanol group (39/55, 70.9%) than in the Octa-60 group (6/55, 10.9%). Policosanol 5 and 10 mg/day significantly lowered (p<0.00001) total cholesterol (TC) (13.4% and 20.4%), LDL-C/high-density lipoprotein-cholesterol (HDL-C) (22.1% and 37.0%) and TC/HDL-C (17.2% and 28.2%). Octa-60 at 10 mg/day lowered (p<0.05) TC (8.7%), LDL-C/HDL-C (12.6%) and TC/HDL-C (9.4%). HDL-C was increased (p<0.001 and 0.0001) by policosanol 5 and 10 mg/day (5.6% and 12.5%) but was unchanged by Octa-60. In both groups, triglycerides remained unchanged. Both treatments were safe and well tolerated. Octa-60, but not policosanol, significantly increased glucose and alanine aminotransferase, but individual values were within the normal range. Four patients (two from each group) discontinued the trial, but only one (in the Octa-60 group) did so because of an adverse event (AE) (skin rash). Overall, three patients (all from the Octa-60 group) reported AEs. In conclusion, original policosanol at 5 and 10 mg/day, but not Octa 60, was effective in patients with type II hypercholesterolemia. Thus, policosanol reached the efficacy criterion for LDL-C reduction in both steps, while Octa-60 failed to reach this goal. In addition, policosanol was better tolerated than Octa-60.

Effects of policosanol 20 versus 40 mg/day in the treatment of patients with type II hypercholesterolemia: a 6-month double-blind study.

Policosanol is a well defined mixture of higher aliphatic primary alcohols isolated from sugar cane wax with cholesterol-lowering effects proven for a dose range from 5-20 mg/day in patients with type II hypercholesterolemia and dyslipidemia associated with noninsulin dependent diabetes mellitus. This randomized, double-blind study investigated the cholesterol-lowering efficacy and tolerability of policosanol 20 mg/day compared with 40 mg/day. Changes in low-density lipoprotein (LDL)-cholesterol levels were predefined as the primary efficacy endpoint. Patients with type II hypercholesterolemia were enrolled in the study and instructed to continue a step I cholesterol-lowering diet for 6 weeks and those eligible to be included (89) were randomly allocated to receive under double-blind conditions placebo (n = 30), policosanol 20 mg/day (n = 29) or 40 mg/day (n = 30). After 24 weeks, policosanol at 20 and 40 mg/day significantly (p < 0.00001) lowered LDL-cholesterol by 27.4% and 28.1%, total cholesterol (p < 0.00001) by 15.6% and 17.3%, and the LDL-cholesterol/high-density lipoprotein (HDL)-cholesterol ratio by 37.2% and 36.5%, respectively The ratio of total cholesterol/HDL-cholesterol was lowered by 27.1% and 27.5%, while HDL-cholesterol levels increased (p < 0.001) by 17.6% and 17.0%, respectively. Compared with baseline, policosanol 20 mg/day lowered triglycerides (p < 0.05) by 12.7%, while they were lowered (p < 0.01) by 15.6% at a dose of policosanol 40 mg/day All the above-mentioned significant differences were also different from placebo and no significant changes occurred in any lipid profile parameters in the placebo group. Based on the mean values of LDL-cholesterol levels at study completion, the mean percent reductions from baseline were 27.4% and 28.1% for the 20 and 40 mg/day groups, respectively. Thus, the effects of both policosanol doses on the main efficacy variable were practically identical. Consistent with the data obtained for LDL-cholesterol, both doses were similarly effective in changing all the other lipid profile parameters. No unexpected adverse effects were observed and there were no significant between-group differences regarding safety indicator values or reported adverse effects. In conclusion, although the tolerability profile remains excellent, according to the present results policosanol at a dose of 40 mg/day does not offer significant additional cholesterol-lowering efficacy over the 20 mg/day dose.

A long-term study of policosanol in the treatment of intermittent claudication.

Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. This study was undertaken to investigate the long-term effects of policosanol administered to patients with moderately severe intermittent claudication. The study consisted of a 6-week single-blind, placebo-controlled run in phase, followed by a 2-year double-blind, randomized treatment step. Fifty-six patients who met study entry criteria were randomized to receive placebo or policosanol 10 mg twice daily. Walking distances on a treadmill (constant speed 3.2 km/h, slope 10 degrees, temperature 25 degrees C) were assessed before and after 6, 12, 18, and 24 months of treatment. Both groups were similar at randomization. After 6 months of therapy, policosanol significantly increased (p < 0.01) the initial claudication distance from 125.9 +/- 8.7 m to 201.1 +/- 24.8 m and the absolute claudication distance from 219.5 +/- 14.1 m to 380.7 +/- 50.2 m. Both variables remained unchanged in the placebo group (p < 0.01). These effects did not wear off but improved after long-term therapy, so that final values were 333.5 +/- 28.6 m (initial claudication distance) and 648.9 +/- 54.1 m (absolute claudication distance); both significantly greater (p < 0.0001) than those obtained in the placebo group, which showed values of 137.9 +/- 21.8 m (initial claudication distance) and 237.7 +/- 28.1 m (absolute claudication distance), respectively. At study completion, 21 policosanol and 5 placebo patients attained increases in claudication distance values > 50% (p < 0.001). Policosanol, but not placebo, significantly increased the ankle/arm pressure index. In addition, from month 6 up to study completion, the frequency of patients reporting improvement of lower limb symptoms was greater in the policosanol group than in the placebo group. The treatment was tolerated well. There were 16 withdrawals (12 placebo, 4 policosanol) from the study. Eight patients in the placebo group experienced a total of 10 serious adverse events, 8 of which were vascular events, compared with none in the policosanol group (p < 0.01). In addition, 3 patients in the policosanol group and 3 patients in the placebo group reported mild adverse events during the study. The present results demonstrate the long-term usefulness of policosanol therapy to treat patients with intermittent claudication.

Effects of policosanol in older patients with type II hypercholesterolemia and high coronary risk.

BACKGROUND: The present study was undertaken to investigate the effects of policosanol in older patients with type II hypercholesterolemia and more than one concomitant atherosclerotic risk factor. METHODS: After 6 weeks on a lipid-lowering diet, 179 patients randomly received a placebo or policosanol at doses of 5 followed by 10 mg per day for successive 12-week periods of each dose. Policosanol (5 and 10 mg/d) significantly (p < .001) reduced low-density lipoprotein cholesterol (LDL-C; 16.9% and 24.4%, respectively) and total cholesterol (TC; 12.8% and 16.2%, respectively), while significantly (p < .01) increasing (p < .001) high-density lipoprotein cholesterol (HDL-C) by 14.6% and 29.1%, respectively. RESULTS: Policosanol significantly decreased (p < .01) the ratios of LDL-C to HDL-C (29.1%) and TC to HDL-C (28%) at study completion, although triglycerides remained unchanged. Policosanol, but not the placebo, significantly improved (p .01) cardiovascular capacity, which was assessed using the Specific Activity Scale. No serious adverse experiences occurred in policosanol patients (p < .01), compared with seven adverse experiences (7.9%) reported by placebo patients. CONCLUSIONS: This study shows that policosanol is effective, safe, and well tolerated in older hypercholesterolemic patients.

Effects of D-002 on Lipid Peroxidation in Older Subjects.

D-002 is a mixture of higher aliphatic alcohols isolated from beeswax that inhibits rat microsomal lipid peroxidation in vitro and in vivo. This study was undertaken to investigate whether D-002 also inhibits lipid peroxidation in older subjects. The free radical theory of aging suggests that progressive defects in the protection against free radical reactions leads to progressive deleterious effects of free radicals on cells and tissues. This free radical damage has been implicated in several pathophysiological processes associated with the chronic degenerative diseases that occur with aging. Forty-eight older subjects were randomly assigned, in a double-blind fashion, to receive placebo or D-002 tablets (50 mg/day) once daily. At baseline, D-002 and placebo groups were well matched regarding several variables. D-002 significantly reduced the susceptibility of nonfractionated plasma samples to copper-mediated lipid peroxidation. It also significantly increased the length of the lag phase (P <.001) and the total antiioxidant status (P <.05) compared with baseline and placebo. In addition, D-002 significantly decreased malondialdehyde levels (expressed in terms of thiobarbituric acid reactive substances (TBARS, P <.001) compared with baseline, but not with placebo. No significant changes on lipid peroxidation parameters were observed in the placebo group. We conclude that D-002 treatment may be useful to prevent or manage certain pathophysiological conditions in the elderly.

Effects of policosanol on postmenopausal women with type II hypercholesterolemia.

This randomized, double-blind, placebo-controlled study was conducted to investigate the efficacy, safety and tolerability of policosanol, a cholesterol-lowering drug purified from sugar-cane wax, in postmenopausal women with type II hypercholesterolemia. A total of 244 women who had experienced the menopause and showed elevated serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels despite 6 weeks on a standard lipid-lowering diet were randomized to receive placebo or policosanol 5 mg/day for 12 weeks, after which the dose was doubled to 10 mg/day for the next 12 weeks. Policosanol (5 and 10 mg/day) significantly lowered LDL-C levels (17.7% and 25.2%, respectively) and total cholesterol (12.6% and 16.7%, respectively), as well as the ratios of LDL-C to high-density lipoprotein cholesterol (HDL-C) (17.0% and 29.3%, respectively) and total cholesterol to HDL-C (16.7% and 27.2%, respectively), compared to the baseline and placebo; at the same time, policosanol significantly raised HDL-C levels by 16.5% and 29.3%, respectively. The drug was safe and well tolerated. No drug-related adverse events were observed, and even the extent of adverse events was less in the policosanol group than in the placebo group. Four serious adverse events occurred in the placebo group (one myocardial infarction, two cases of hypertensive status and one surgical intervention) compared to none in the policosanol group. In conclusion, policosanol is effective, safe and well tolerated in hypercholesterolemic postmenopausal women.

Effects of policosanol in patients with type II hypercholesterolemia and additional coronary risk factors.

INTRODUCTION: This study was undertaken to evaluate the efficacy, safety, and tolerability of policosanol, a new cholesterol-lowering drug, in patients with type II hypercholesterolemia and additional coronary risk factors. PATIENTS AND METHODS: After 5 weeks of a standard step-1 lipid-lowering diet, 437 patients were randomized to receive, under double-blind conditions, 5 mg policosanol or placebo once a day with the evening meal for 12 weeks and 10 mg policosanol or placebo for the next 12 weeks. RESULTS: Both groups were similar at randomization. Policosanol (5 and 10 mg/day) significantly reduced (P < .001) serum low-density lipoprotein cholesterol (18.2% and 25.6%, respectively) and cholesterol (13.0% and 17.4%), and it significantly raised (P < .01) high-density lipoprotein cholesterol (15.5% and 28.4%). Triglycerides remained unchanged after the first 12 weeks and lowered significantly (5.2%; P < .01) at study completion. Policosanol was safe and well tolerated, and no drug-related disturbances were observed. Two male patients who received placebo died during the study--one because of a myocardial infarction and the other because of a cardiac arrest that occurred during a surgical intervention. There were 11 serious adverse events (5.1%) in 10 patients who received placebo (4.6%), 7 of which were vascular, compared with no serious adverse events reported in patients receiving policosanol (P < .01). CONCLUSIONS: Subjects in the group treated with policosanol did not have serious adverse events during the 24-week study. This study shows that policosanol is effective, safe, and well tolerated in patients with hypercholesterolemia and concomitant coronary risk factors.

A double-blind, placebo-controlled study of the effects of policosanol in patients with intermittent claudication.

This study was undertaken to evaluate the efficacy and tolerability of policosanol, a new cholesterol-lowering drug with concomitant antiplatelet effects, in patients with intermittent claudication. After a baseline period of 6 weeks, 62 patients were randomized to receive, under double-blind conditions, either placebo (31 patients) or policosanol (31), 10 mg twice daily. Walking distances in a treadmill (constant speed 3.2 km/hr, slope 10 degrees) were assessed before and after 6 months of treatment. Both groups were similar at randomization. Policosanol increased significantly (p < 0.01) the initial claudication distance from 132.5+/-13.5 m (baseline) to 205.7+/-36.3 m (after therapy) and the absolute claudication distance (p<0.0001) from 229.5+/-22.0 m to 365.4+/-46.9 m; meanwhile both variables remained unchanged in the placebo group (p<0.05). The reduction of lower limb symptoms showed a greater benefit in the policosanol group. There was no significant change in either group in the ankle/arm pressure ratio. The treatment was well tolerated. There were 10 discontinuations (seven placebo, three policosanol) from the study. Six withdrawals occurred because of adverse events (AE); all were in placebo patients. There were five serious vascular AEs in the placebo group but none in the policosanol group (p<0.05). Overall, 12/31 (38.7%) placebo patients and 3/31 (9.7%) policosanol patients experienced AEs after randomization, which showed a lesser incidence of AEs in the policosanol group (p<0.01). The present study demonstrates a beneficial effect of policosanol in patients with intermittent claudication.

Effects of policosanol and pravastatin on lipid profile, platelet aggregation and endothelemia in older hypercholesterolemic patients.

This randomized, double-blind study was undertaken to compare the effects of policosanol and pravastatin administered at 10 mg/day on lipid profile, platelet aggregation and endothelemia in older patients with type II hypercholesterolemia and high coronary risk. After 6 weeks on a lipid-lowering diet, patients with low-density lipoprotein (LDL) cholesterol levels > 3.4 mmol/l were randomized to receive, under double-blind conditions, policosanol or pravastatin 10 mg tablets that were taken with the evening meal for 8 weeks. Policosanol significantly (p < 0.00001) lowered LDL-cholesterol (19.3%), total cholesterol (13.9%) and the ratios of LDL-cholesterol/high-density lipoprotein (HDL)-cholesterol (28.3%) and total cholesterol/HDL-cholesterol (24.4%). Pravastatin significantly (p < 0.00001) lowered LDL-cholesterol (15.6%), total cholesterol (11.8%) and the ratios (p < 0.0001) of LDL-cholesterol/HDL-cholesterol (18.9%) and total cholesterol/HDL-cholesterol (15.7%). Policosanol, but not pravastatin, significantly increased (p < 0.001) levels of HDL-cholesterol (18.4%) and reduced (p < 0.01) triglycerides (14.1%). Policosanol was more effective (p < 0.05) than pravastatin in inhibiting platelet aggregation induced by all agonists and it significantly reduced (p < 0.0001) platelet aggregation induced by arachidonic acid at 1.5 and 3 mmol/l by 42.2% and 69.5%, respectively, platelet aggregation induced by collagen 0.5 microgram/ml (p < 0.05) (16.6%) and that induced by adenosine diphosphate 1 mumol/l (p < 0.01) (20.3%). Pravastatin significantly reduced (p < 0.001) (27%) only platelet aggregation induced by arachidonic acid 3 mmol/l. Both drugs significantly decreased (p < 0.00001) endothelemia levels but final values were significantly lower (p < 0.001) in the policosanol than in the pravastatin group. Both treatments were safe and well tolerated. Pravastatin significantly (p < 0.01) increased serum levels of alanine amine transferase but individual values remained within normal. Two patients on pravastatin discontinued the study because of adverse experiences (myocardial infarction and jaundice, respectively). In conclusion, the effects of policosanol (10 mg/day) on lipid profile, platelet aggregation and endothelemia in older patients with type II hypercholesterolemia and high coronary risk are more favorable than those induced by the same doses of pravastatin.

Comparative study of the efficacy and tolerability of policosanol and lovastatin in patients with hypercholesterolemia and noninsulin dependent diabetes mellitus.

This randomized, double-blind study was undertaken to compare the efficacy and tolerability of policosanol (10 mg/day) and lovastatin (20 mg/day) in patients with hypercholesterolemia and noninsulin dependent diabetes mellitus. After 6 weeks on a lipid lowering diet, 53 patients were randomized to receive either policosanol or lovastatin tablets that were taken o.i.d. for 12 weeks under double-blind conditions. Both groups were similar at randomization. Policosanol significantly (p < 0.001) lowered low-density lipoprotein (LDL)-cholesterol (20.4%), total cholesterol (14.2%) and the ratio of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol (23.7%). Lovastatin significantly (p < 0.01) lowered LDL-cholesterol (16.8%), total cholesterol (14.0%) and the ratio (p < 0.05) of LDL-cholesterol to HDL-cholesterol (14.9%). Triglyceride levels did not significantly change after therapy. Policosanol, but not lovastatin, significantly increased (p < 0.01) levels of HDL-cholesterol (7.5%). Comparison between groups showed that changes in HDL-cholesterol induced by policosanol were significantly greater (p < 0.01) than those induced by lovastatin. Both treatments were safe and well tolerated. Lovastatin moderately but significantly (p < 0.05) increased levels of aspartate aminotransferase, creatine phosphokinase and alkaline phosphatase. Adverse reactions were more frequent in the lovastatin group (p < 0.01) than in the policosanol group. In conclusion, policosanol administered at 10 mg/day produces more advantageous changes in HDL-cholesterol and has a better safety and tolerability profile than lovastatin 20 mg/day.

Cholesterol-lowering effect of policosanol on rabbits with hypercholesterolaemia induced by a wheat starch-casein diet.

The effect of policosanol, a mixture of high-molecular-weight aliphatic alcohols isolated from sugarcane wax, on casein-induced hypercholesterolaemia in rabbits was studied. When policosanol was administered by the oral route once daily for 30 d (50 mg/kg) the increases in plasma total cholesterol and LDL-cholesterol (LDC-C) were significantly reduced when compared with the control group. The incorporation of 3H2O into sterols in the liver was significantly depressed, suggesting inhibition of hepatic cholesterol biosynthesis. The oral administration of policosanol raised the rate of removal of 125I-labelled LDL from serum. Kinetic parameters calculated following injection of [125I]LDL showed than in casein-fed rabbits, the terminal half-life (t1/2) was significantly decreased after policosanol treatment. The hepatic LDL-binding activity was increased after policosanol administration which suggested that the enhanced clearance was due, at least in part, to increased receptor-mediated uptake of LDL by the liver. Considered together, these results suggest that policosanol can significantly reduce the increase of plasma LDL-C in rabbits fed on a wheat starch-casein diet by reducing cholesterol biosynthesis in the liver. Such an effect could account for the enhancement of LDL catabolism through the receptor-mediated pathway.

Treatment of hypercholesterolemia in NIDDM with policosanol.

OBJECTIVE: To determine whether elevated levels of cholesterol and low-density lipoprotein (LDL) cholesterol in non-insulin-dependent diabetes mellitus (NIDDM) patients could be decreased by policosanol, a new cholesterol-lowering drug. NIDDM predisposes patients to coronary artery disease (CAD) through the direct action of hyperglycemia on the arteries as well as the dyslipidemia induced by NIDDM. RESEARCH DESIGN AND METHODS: This double-blind placebo-controlled trial was performed in 29 patients with NIDDM and hypercholesterolemia. After stable glycemic control was achieved by diet and/or oral hypoglycemic drugs, patients were instructed to follow a cholesterol-lowering diet for 6 weeks. Patients who met entry criteria received, under double-blind conditions, policosanol (5 mg) or placebo tablets twice a day for 12 weeks. RESULTS: Policosanol (10 mg/day) significantly reduced total cholesterol by 17.5% and LDL cholesterol by 21.8% compared with baseline and placebo. Furthermore, high-density lipoprotein (HDL) cholesterol was raised by 11.3% (not significant), and triglycerides showed a statistically nonsignificant decrease of 6.6%. These changes in lipid profile were similar to those induced by policosanol in nondiabetic patients with type II hyperlipoproteinemia. CONCLUSIONS: Glycemic control was unaffected by treatment. No clinically or biochemically adverse effects attributable to treatment were observed. Only one patient (placebo) withdrew from the trial because of an adverse experience (erythema). We concluded that policosanol is effective and safe in patients with NIDDM and hypercholesterolemia.