Comparison of the Efficacy, Safety and Tolerability of Policosanol and Atorvastatin in Patients with Type II Hypercholesterolemia

Revista CENIC Ciencias Biológicas, Vol. 36, No. 3, 2005.

Comparison of the efficacy, safety and tolerability of policosanol and atorvastatin in patients with type II hypercholesterolemia

Gladys Castaño, Rosa Más,* Lilia Fernández,* José Illnait,* Julio Fernández,* Meylin Mesa and Sarahí Mendoza.*

Medical Surgical Research Center, *Center of Natural Products from the National Center for Scientific Research, Havana City, Cuba.

Recibido: 12 de diciembre de 2003. Aceptado: 10 de noviembre de 2004.

Palabras clave: policosanol, atorvastatina, hipercolesterolemia tipo II, drogas reductoras de colesterol. Key words: policosanol, atorvastatin, type II hypercholesterolemia, cholesterol-lowering drugs.

RESUMEN. La hipercolesterolemia es uno de los más importantes factores de ries- C. El policosanol, pero no la atorvastatina go coronario. El principal objetivo en el control de la dislipidemia es la disminución fue efectivo en el incremento de la con- de las concentraciones elevadas de LDL C. El policosanol es un medicamento centración en el suero de HDL C. El hipocolesterolemizante purificado de la cera de la caña de azúcar con un intervalo policosanol fue mejor tolerado que la terapéutico entre 5 y 20 mg ⁄ d, que reduce significativamente la concentración de atorvastatina de acuerdo con los indica- LDL C en el suero sanguíneo. La atorvastatina es un inhibidor de la HMGCoA dores bioquímicos de seguridad y el re- reductasa, el cual a través de su intervalo terapéutico (10 a 80 mg/d) muestra un porte de EA. marcado efecto hipolipemiante, superior a otras estatinas hasta ahora disponibles. Este estudio se lleva a cabo para comparar la eficacia, seguridad y tolerabilidad del policosanol y la atorvastatina en pacientes con hipercolesterolemia tipo II. Este estu- ABSTRACT. Hypercholesterolemia is a dio se realizó en pacientes de ambos sexos de forma aleatorizada y a simple ciegas major coronary risk factor. The main goal con grupos paralelos. Después de 5 semanas de dieta baja en colesterol, 175 pacien- of dyslipidemia control in is to lower ≥ ⁄ tes con valores de colesterol 3,4 mmol L se trataron aleatoriamente con policosanol elevated LDL-C levels. Policosanol is a o atorvastatina ( 10 mg ) una vez al día en horario de la cena y durante 8 semanas. Se cholesterol-lowering drug purified from realizó la evaluación del perfil de los lípidos del suero y de los indicadores de seguri- sugar cane wax with a therapeutic range dad, así como de los eventos adversos (EA). Después de 8 semanas el policosanol (10 from 5 to 20 mg/d, which significantly re- ⁄ mg d) disminuyó significativamente (p < 0,000 001 vs línea de base) la LDL C (27,0 duces LDL-C levels. Atorvastatin is an %), TC (19,6 %), LDL-C/colesterol de lipoproteina de alta densidad (HDL-C) (30,1 %) HMGCoA reductase inhibitor, which y TC/HDL-C (23,9 %), así como TG (12,4 %). (p < 0,000 1 vs valores basales). Por otra across its dose range (10 - 80 mg/d) shows parte, la atorvastatina (10 mg /d) redujo significativamente (p < 0,000 001 vs valores significantly greater lipid-lowering basales) la LDL C (35,2 % ), TC (26,2 %), LDL-C/HDL-C (34,5 %), TC/HDL-C (25,9 %) effects than previously available statins. y (p < 0,000 1) TG (10,2 %). La atorvastatina fue más efectiva que el policosanol (p < This study was undertaken to compare 0,001) para reducir la LDL-C y TC (p< 0,000 1). El policosanol, pero no la atorvastatina the efficacy, safety and tolerability of po- incrementó las HDL C de manera significativa (p < 0,000 1) en un 10,4 %. (En el licosanol and atorvastatin on patients chequeo intermedio realizado a las 4 semanas, los cambios inducidos por ambos with type II hypercholesterolemia. This medicamentos sobre el perfil de los lípidos del suero eran ya significativos, siendo el randomized, single-blinded, parallel- efecto de la atorvastatina similar al obtenido a las 8 semanas, mientras que el polico- group study was conducted in patients sanol continuó incrementando su efecto a lo largo del tratamiento. Tanto el policosa- of both sexes with type II hypercholes- nol como la simvastatina fueron bien tolerados. La atorvastatina incremento signifi- terolemia. After 5 weeks on cholesterol- cativamente (p < 0,01) la CPK y la ALAT mientras que el policosanol disminuyó lowering diet, 175 patients showing LDL- estos valores (p < 0,01) en relación a los basales, pero los individuales permanecieron C values³ 3.4 mmol/L were randomized dentro del intervalo normal. Seis pacientes resultaron baja del estudio debido a even- to policosanol or atorvastatin 10-mg tos adversos, todos del grupo de la atorvastatina . De 17 pacientes que reportaron EA tablets once daily with the evening meal durante el estudio, tres fueron del grupo policosanol y 14 del grupo atorvastatina (p for 8 weeks. Assessment of lipid profile, < 0,01), que reportaron un total de 4 y 23 AE, respectivamente. La atorvastatina (10 safety indicators and adverse events (AE) mg/d) por 8 semanas fue más efectiva que el policosanol en igual dosis para reducir was done. After 8 weeks, policosanol 10 LDL-C y TC en pacientes con hipercolesterolemia tipo II, pero similarmente efecti- mg/d significantly (p < 0.000 001 vs vos para reducir las concentraciones en suero de TG , LDL - C/HDL C y CT/HDL baseline) lowered LDL-C (27.0 %), TC

Address for correspondence: Rosa Más, Ph.D., Center of Natural Products, National Center for Scientific Research, P.O. Box 6414, Havana City, Cuba. 171 Revista CENIC Ciencias Biológicas, Vol. 36, No. 3, 2005.

(19.6 %), LDL-C/high-density lipoprotein- viduals at highest risk, such as shown that policosanol is long-term cholesterol (HDL-C) (30.1 %) and TC/ those at secondary prevention, dia- safe and well tolerated. HDL-C (23.9 %) ratios, as well as (p < betics and patients with several risk Two previous studies compared 0.000 01) TG (12.4 %). In turn, atorvastatin factors.2,3 the effects of both policosanol and 10 mg/d decreased (p < 0.000 001 vs The adherence to a step I cho- atorvastatin administered at 10 mg/ baseline) LDL-C (35.2 %), TC (26.2 %), lesterol-lowering diet is the first- d for 8 weeks to older hypercholes- LDL-C/HDL-C (34.5 %), TC/HDL-C choice therapy for hypercholester- terolemic and diabetic patients, re- (25.9 %) and (p < 0.000 1) TG (10.2 %). olemia management,2,3 but such spectively.45,46 Atorvastatin has been Atorvastatin was more effective than po- measures alone are often not enough more effective than policosanol for licosanol (p < 0.001) to reduce LDL-C and TC (p< 0.0001) Policosanol, but not to reach a desirable control. Then, lowering LDL-C and TC, TG being atorvastatin, significantly increased cholesterol-lowering drugs must be similarly reduced by both drugs. HDL-C by 10.4 % (p < 0.000 1). At the indicated to these patients, HMG- Policosanol, but not atorvastatin, interim check-up performed at week 4, CoA reductase inhibitors (statins) has increased HDL-C levels. Both the changes induced by both drugs on being a first-choice pharmacologi- policosanol and atorvastatin were lipid profile were yet significant, the cal alternative and the most pre- well tolerated, policosanol being effects of atorvastatin being similar to scribed drugs worldwide for lower- better tolerated than atorvastatin.45,46 those achieved at week 8, while polico- ing elevated LDL-C levels.2,3 Taking into account this back- sanol increased the effects with treat- Atorvastatin is a member of ground, the present study was un- ment duration. Both policosanol and statin class that, across its dosage dertaken to compare the efficacy atorvastatin were safe and well tolerated. range (10 - 80 mg/d), induces marked and tolerability of policosanol and Atorvastatin significantly increased (p < reductions of plasma LDL-C, greater atorvastatin on a broad population 0.01) CPK and ALAT levels respect to than those induced by simvastatin, of patients with type II hypercho- baseline, while policosanol decreased (p pravastatin, lovastatin, fluvastatin lesterolemia. < 0.01) such values. Policosanol, but not and cerivastatin.14-22 Thus, it is a atorvastatin, decreased systolic pressure suitable reference to compare the PATIENTS AND METHODS (p < 0.01) compared with baseline, but cholesterol-lowering effects of any Design individual values remained within normal ranges. Six patients withdrew from other hypocholesterolemic drug. This randomized, single-blinded, the study due to AE, all from atorvastatin Atorvastatin is generally well toler- parallel-group, comparative study group, reported 12 AE during the study. ated and most drug-related adverse was conducted at the Medical Sur- Seventeen patients reported some AE events (AE) are mild and transient, gical Research Center, the patients during the study: three policosanol and gastrointestinal symptoms being being recruited at Ramón Gonzá- 14 atorvastatin patients (p < 0.01) who the most frequent. As occurs with lez Coro Policlinics (Havana City, reported a total of 4 and 23 AE, respec- other statins, persistent increases Cuba). The study protocol received tively. Atorvastatin (10 mg/d) for 8 weeks on serum transaminases and creatin- ethical approval by the independent was more effective than similar doses of phosphokinase (CPK), myalgia and ethics committee from such centre, policosanol to reduce LDL-C and TC in myopathy have been associated to written informed consent being ob- patients with type II hypercholestero- atorvastatin treatment.14-22 tained from all participants before lemia, but similarly effective to reduce Policosanol is a mixture of higher enrolment. TG and both LDL-C/HDL-C and TC/ aliphatic primary alcohols purified At recruitment (visit 1) patients HDL-C ratios. Policosanol, however, but from sugar cane (Saccharum offici- entered in a 5 weeks run-in period not atorvastatin, was effective to increase narum, L.) wax with cholesterol-low- and were instructed to follow a HDL-C levels. Policosanol was better ering effects.23 Policosanol lowers NCEP step 1 cholesterol-lowering tolerated than atorvastatin as indicated cholesterol by inhibiting cholesterol diet.16,18 Then, patients attended for blood biochemistry safety indicators and AE report. biosynthesis in a step between ac- lab analyses, being assessed lipid etate consumption and mevalonate profile variables and blood safety in- INTRODUCTION production,24-26 through an indirect dicators. One-week later patients as- Coronary heart disease (CHD) is regulation of HMG CoA reductase sisted to visit 2 and those who met the major cause of mortality in activity.26 LDL receptor-dependent study inclusion criteria were random- adult population.1 Hypercholester- processing is also increased by ized, under single-blind conditions, to olemia, mainly that associated with policosanol treatment.24 policosanol (10 mg) or atorvastatin elevated plasma levels of low-den- The cholesterol-lowering effi- (10 mg) tablets. Study medications sity lipoprotein cholesterol (LDL-C) cacy of policosanol has been proven were randomized by a fixed random- is a major risk factor for CHD,2-6 and on patients with type II hypercho- ization method using a block size of endpoint clinical studies have proven, lesterolemia and on patients with 10 and allocation ratio 1:1. beyond any doubt, the clinical ben- Type 2 diabetes mellitus.2742 Results The authors used atorvastatin efits of lowering LDL-C levels.7-13 show that policosanol reduces LDL- 10 mg tablets (CardylR). (Pfizer, SA, Hence, expert guidelines recom- C, total cholesterol (TC) and the ra- Madrid). Policosanol 10 mg-tablets mend hypercholesterolemia man- tios of TC/high-density lipoprotein- were manufactured to obtain an agement in middle-aged and elderly cholesterol (HDL-C) and LDL-C/ appearance identical to that of ator- patients as a part of the coronary HDL-C, whereas increases HDL-C vastatin tablets (Laboratorios Dalmer prevention strategy.2,3 Coexistence values.2742 Although frequently S.A., Havana City, Cuba). of hypercholesterolemia with other policosanol reduces triglycerides Patients were instructed to take non-lipid risk factors increases the (TG), its effects have been gener- study medications once a day with global coronary risk and updated ally modest and not always consis- the evening meal for 8 weeks. After coronary prevention places LDL-C tent. 4 weeks on therapy, an interim goals as the cornerstone of hyperc- Postmarketing surveillance checkup was performed (visit 3) and holesterolemia management, which studies conducted in more than the final checkup was performed at become more restrictive for indi- 30 000 individuals,43,44 have also week 8 (visit 4). 172 Revista CENIC Ciencias Biológicas, Vol. 36, No. 3, 2005.

Patients based in enzymatic methods using dent samples; while comparisons The study enrolled women patients reagent kits from Roche (Switzer- between groups were done using of both sexes, aged 35 to 75 years, land). All laboratory tests were the t test for independent samples. with documented hypercholester- performed in the Hitachi 719 auto- Comparison of categorical variables olemia. All patients provided written analyzer (Tokyo, Japan) located at were done using the Fishers Exact informed consent before enrolling the laboratory of the Center for Sur- Test. All tests were two tailed. A in the trial. Inclusion criteria estab- gical and Medical Research (Ha- value of α = 0.05 was assumed for lished the following values after the vana City, Cuba). statistical significance. Statistical diet-only period: serum LDL-C lev- Systematic quality control was analyses were performed using the els ≥ 3.4 mmol/L and triglycerides performed throughout the study, so Statistica for Windows package pro- < 4.52 mmol/L . To be included, pa- that the precision and accuracy of gram. tients needed to stop any cholesterol- the methods were followed. lowering drug for at least 4 weeks RESULTS before to start the baseline diet only Efficacy variables Baseline characteristics period. Changes on serum LDL-C lev- One hundred eighty five (185) Patients with active renal or he- els were considered as primary ef- patients were enrolled for the study, patic diseases, diagnosed neoplastic ficacy variable. The treatments but only 175 were included. Ten pa- diseases and severe hypertension were considered effective only if tients were not included because (diastolic pressure ≥ 120 mm Hg) LDL-C levels were reduced by at their LDL-C values were below in- were excluded from the study. In least 15 % compared with baseline.49 clusion criteria after the diet-only addition, patients who had had a Analyses of the frequency of cases baseline period (7) and TG values history of unstable angina, myocar- reaching LDL-C goals were also per- remained above 4.52 mmol/L (three dial infarction, stroke, transient formed. Other lipid profile variables patients). ischemic attacks or any major sur- were considered as secondary effi- The two groups were well matched gery within the 3 months prior to cacy variables. with respect all baseline character- the study were also excluded. istics (Table 1). Study patients Tolerability showed a very high frequency (≥ 50 %) Assessments Data from the physical examina- of arterial hypertension, and a high At enrollment, a complete medi- tion, laboratory tests and interview frequency (≥ 20 %) of diabetes mel- cal history and physical examination for AE were included for the analy- litus, smoking. Consumption of were performed. Physical examina- sis of drug tolerability. AE pre- concomitant medications was high tion was done from visits 1 to 4. At defined as serious were fatal or (> 85 %) and consistent with patient visits 3 and 4, patients were re- disabling experiences, leading to or characteristics, since antihyper- quested about AE and assessed for prolonging hospitalization, moder- tensive drugs (diuretics, β-adreno- compliance with study medications. ate were those requiring discon- receptor blockers, angiotensin Compliance was assessed by tablet tinuation of therapy according to converting enzyme inhibitors (ACEI), counts and patient interview. Labo- the physician and(or) specific treat- calcium channel blockers) and oral ratory tests were reported at ba- ment of the AE. Mild AE were hypoglycaemic drugs were among seline and 4 and 8 weeks. those not requiring withdrawal of the drugs most frequently con- study drugs and(or) specific treat- sumed by study patients. Concomitant medications ment of the AE. AE were also clas- The use of any other lipid-low- sified as unlikely, doubtfully, possi- Effects on lipid profile ering drug different than those in- bly or probably drug-related accord- Table 2 summarizes the effects vestigated was prohibited during ing to their estimated relationship on lipid profile, both groups being the study, but no other special pro- with study medications. well-matched respect all lipid pro- hibition about concomitant medica- file variables at randomisation. Af- tions was established. Statistical analysis ter 8 weeks, policosanol 10 mg/d sig- All data were analyzed by Inten- nificantly (p < 0.000 001 vs baseline) Laboratory analysis tion-to-Treat, meaning that data of lowered LDL-C (27.0 %), TC (19.6 %), Blood samples were drawn from randomised patients were analysed LDL-C/high-density lipoprotein- after a 12 h fast and aliquots were as randomised, so that data of with- cholesterol (HDL-C) (30.1 %) and taken for laboratory determinations. drawals were also included. TC/HDL-C (23.9 %) ratios, as well as Lipid profile. Serum TC and For the primary efficacy variable (p < 0.000 01) TG (12.4 %). In turn, triglycerides were determined by the authors assumed that atorvas- atorvastatin 10 mg/d decreased (p < colorimetric enzymatic methods tatin at 10 mg/d would show a dif- 0.000 001 vs baseline) LDL-C (35.2 %), using reagent kits from Roche ference in serum LDL-C reduction TC (26.2 %), LDL-C/HDL-C (34.5 %), (Switzerland). Levels of serum of 20 % compared with policosanol TC/HDL-C (25.9 %) and (p < 0.000 1) HDL-C were determined according administered at the same dosage. TG (10.2 %). Atorvastatin was more to the cholesterol content present For that, and based in 95 % test effective than policosanol (p < 0.001) in the supernatant obtained after β- power and 5 % of significance level, to reduce LDL-C and TC (p< 0.000 1). lipoproteins precipitation.47 LDL-C a sample size of 160 patients would Policosanol, but not atorvastatin, values were calculated using the be enough. Allowing for an esti- significantly increased HDL-C by Friedewald formula (in mmol/L).48 mated dropout rate of 10 %, recruit- 10.4 % (p < 0.000 1). Safety indicators. Other labora- ment of at least 170 patients was At the interim check-up per- tory tolerability tests included de- needed. formed at week 4, the changes in- terminations of glucose, creatinine, Within group comparisons of duced by both drugs on lipid pro- CPK, AST and ALT and were per- continuous variables were per- file were yet significant, the effects formed by routine laboratory tests formed using the t test for depen- of atorvastatin being similar to 173 Revista CENIC Ciencias Biológicas, Vol. 36, No. 3, 2005.

Table 1. Baseline characteristics of study patients.

Characteristics Policosanol Atorvastatin (n = 88) (n = 87) Age (years) (X ± SD) 674 ± 7 63± Bodymassindex(kg/m2)4(X±SD)226.62±3.26.44±4. Sex:Female/Males743/1573/1

Personalhistory

H5ypertension55612.5658. D6iabetesmellitus 26289.2232. S8moking 14280.1720. Obesity(kg/m2≥340) 19155.1217. C3HD 18124.1813. H45DL-C<0,9mmol/L 423.2. FamilyhistoryofCHD 334364 336348.6 334314 3139.1

Concomitantmedications*(CM)

Patientsconsuming≥17CM 75847.7185. D4iuretics 36388.2232. β-6Blockers 12178.1519. A6ngiotensinconvertingenzymeinhibitors12138.1914. O4ralhypoglycemicdrugs 19145.1116. C92alciumchannelblockers 110.1612. M92uscularrelaxant 100.1511. V92itamin 100.1511. A0spirine 141571. 5. N68itratesvasodilators 646.4.

n Number of patients. CHD Coronary heart disease. (X ± SD) (mean ± standard deviation). The table includes only those CM consumed by ≥ 10 study patients. All comparisons were not significant (Fishers Exact Probability Test).

those achieved at week 8, while tal of 4 and 23 AE, respectively Thus, the effects here reported for policosanol increased the effects (Table 4). atorvastatin on HDL-C values are with treatment duration. over those expected for such dose DISCUSSION and treatment duration. Safety and tolerability This study demonstrates that As expected, atorvastatin effec- Both policosanol and atorvastatin policosanol and atorvastatin, ad- tively lowered TG, the decrease ob- were well tolerated (Table 3). Poli- ministered at 10 mg/d were effective tained being near to that reported cosanol, but not atorvastatin, mildly, to lower LDL-C, the main efficacy for the dose of 10 mg/d .14-20 In turn, but significantly lowered systolic variable, on patients with type II the effects of policosanol on TG blood pressure, but no patient hypercholesterolemia. have been variable, so that they have showed symptoms of hypotension Atorvastatin was more effective been significantly reduced in some and all individual values remained than policosanol for lowering LDL- studies, but unchanged in others.27-42 within normal limits. Atorvastatin C and TC, a logical result consider- As previously reported, atorvastatin significantly increased, while poli- ing that it is more effective than and policosanol were similarly ef- cosanol lowered, ALAT and CPK lovastatin, simvastatin, fluvastatin fective for decreasing TG.45,39 levels respect to baseline. and pravastatin across all dosage Both drugs were well tolerated. Six patients withdrew from the ranges,14-22 and that policosanol 10 mg/ Atorvastatin significantly, but mod- study, all from atorvastatin group. d was as effective as starting doses erately increased AST and CPK, Of them, experienced some AE of these statins.2742 The changes on both changes being expected ac- (skin rash, nauseas and vomiting, LDL-C and TC here described are cording to atorvastatin safety and other dyspnea, perspiration and ta- consistent with those indepen- tolerability profile.14-22 Policosanol, chycardia, meanwhile the other re- dently reported for both atorvasta- by the contrary, significantly reduced ported skin rash, myalgia, ab- tin21 and policosanol.33-35 both variables, a result consistent dominal pain, uncontrolled hyper- As occurred in the two previous with data obtained in previous stud- tension, gastritis, abdominal reports, only policosanol signifi- ies. The significant, but slight re- cramps). cantly increased HDL-C.45,46 In such duction of systolic arterial pressure Seventeen patients reported regard, the effects of atorvastatin induced by policosanol, not by some AE during the study: three 10 mg/d on HDL-C are controver- atorvastatin, also agrees with pre- policosanol and 14 atorvastatin pa- sial, so have ranged from modest in- vious results. This effect, however, tients (p < 0.01) who reported a to- creases14-17 to unchanged values.15-20 is not considered as a potential AE 174 Revista CENIC Ciencias Biológicas, Vol. 36, No. 3, 2005.

Table 2. Effects of policosanol (10 mg/d) and atorvastatin (10 mg/d) on lipid profile.

Tereatment B4aselinWseekChangeWseek8Change (%) (%) LDL-C (mmol/L) P8olicosanol4*.42±0.63.52±0.69***++++−18.9++++3.18±0.58****++−27.0+ A6torvastatin4*.41±0.62.91±0.63***−33.12.82±0.55****−35.2 TC (mmol/L) +++ P7olicosano6*.33±0.65.40±0.63***++++−14.15.05±0.56****+++−19.6++ A8torvastatin6*.32±0.64.74±0.69***−24.34.63±0.61****−26.2 HDL-C (mmol/L) P5olicosanol12.15±0.219.20±0.2+*5.14.24±0.23*+10. A2torvastatin10.15±0.214.17±0.3+61.11.17±0.2+4. Triglycerides (mmol/L) P8olicosanol2*.06±0.51.79±0.49−8.41.71±0.48***−12.4 A1torvastatin2*.05±0.61.89±0.58−1.41.72±0.48**−10.2 LDL-C/HDL-C P8olicosanol4*.02±1.03.06±0.88***−18.62.68±0.72****−30.1 A7torvastatin3*.99±0.92.64±0.83***−30.72.52±0.72****−34.5 TC/HDL-C P2olicosanol5*.72±1.24.63±1.01***−15.04.21±0.85****−23.9 A4torvastatin5*.68±1.14.29±1.02***−21.94.10±0.83****−25.9

(X ± SD) X Mean. SD Standard deviation. *p < 0.05; *p< 0.001; **p < 0.000 1; ***p < 0.000 01; ****p < 0.000 001 Comparison with baseline (T-test for dependent samples). +p < 0.01; ++p < 0.000 1; +++ p < 0.000 01; ++++ p < 0.000 001 Comparison with atorvastatin (T-test for independent samples).

since no policosanol-related hy- fective than similar doses of polico- book for Clinical Practice. Blood Lip- potension has been reported and sanol to reduce LDL-C and TC, but ids and Coronary Heart Disease. Sec- because the control of arterial pres- similarly effective to reduce TG and ond Edition International Lipid Infor- sure is another important goal of both LDL-C/HDL-C and TC/HDL-C mation Bureau (ILIB), New York, 2000. 4. Lipid Research Clinics Program. The coronary prevention. Then, this ef- ratios. Policosanol, however, but not lipid research clinics coronary primary fect could potentially be an advan- atorvastatin, was effective to in- prevention trial results I. Reduction in tage of policosanol, mainly in a po- crease HDL-C levels. Policosanol, the incidence of coronary heart dis- pulation with high frequency of however, was better tolerated than ease. JAMA, 251, 351-364, 1984. patients with concomitant hyper- atorvastatin, as indicated by the 5. Lipid Research Clinics Program. The tension and hypercholesterole- changes of ALAT and CPK as well lipid research clinics coronary primary mia. as the AE pattern. prevention trial results II. The relation- The frequency of AE reported in ship of reduction in the incidence of atorvastatin group was higher than ACKNOWLEDGEMENTS coronary heart disease to cholesterol- lowering. JAMA, 251, 365-374, 1984. that reported by policosanol pa- This study was supported by a 6. Frick M.H., Elo O., Happa K., Heinonen tients. Thus, the frequency of research grant from the West Ha- O.P., Heinsalmi P., Helo P. Helsinki atorvastatin patients experiencing vana Scientific Pole. Heart Study: primary-prevention with AE was 14/87 (16.1 %), various pa- gemfibrozil in middle-aged men with tients reporting several AE. Thus, BIBLIOGRAPHY dyslipidemia. New England Journal of these 14 patients reported 23 AE, 1. World Health Organization. World Medicine, 317, 1237-1245, 1987. indicating that they did not tolerate Health Report: Life in the 21st Cen- 7. Scandinavian Simvastatin Survival well the drug. Most of these AE were tury-A Vision of All Geneva, World Study Group. Randomised trial of cho- of gastrointestinal nature, which Health Organization, Switzerland, lesterol lowering in 4 444 patients with coronary heart disease: the Scandina- agrees with the tolerability profile 1998. 2. Expert Panel of Detection, Evaluation vian Simvastatin Survival Study (4S): of this drug. Nevertheless, only 3/88 and Treatment of High Blood Choles- Lancet, 344, 1383-1389, 1994. patients randomised to policosanol terol in Adults: Executive Summary of 8. Sacks FM, Pfeffer MA, Moyé LA for the (3.4 %) referred four AE. the Third Report of the National Cho- Cholesterol and Recurrent Events Trial lesterol Education Program (NCEP) Investigators: The effect of pravastatin CONCLUSIONS Expert Panel on Detection, Evaluation, on coronary events after myocardial infarction in patients with average cho- The present study shows that and Treatment of High Blood Choles- terol in Adults (Adult Treatment Panel lesterol levels. New England Journal atorvastatin (10 mg/d) administered III). JAMA, 285, 2486-2497, 2001. of Medicine, 335, 1001-1009, 1996. for 8 weeks to patients with type II 3. Gotto, A.M., Assman G., Carmena R., 9. The Long-Term Intervention with hypercholesterolemia was more ef- Davignon J. et al. The ILIB Lipid Hand- pravastatin in ischaemic disease (LIPID) 175 Revista CENIC Ciencias Biológicas, Vol. 36, No. 3, 2005.

Table 3. Effects of policosanol and atorvastatin on safety indicators.

Tereatment B4aselinW8eekWeek Bodyweight (kg) P3olicosanol668.76±8.4698.69±8.268.63±8.2 A1torvastatin699.01±11.2609.42±11.069.73±13.7 Pulserate (beats/min) P9olicosanol772.35±6.971.67±5.4+72.14±5.52+ A1torvastatin754.02±6.7793.52±5.674.38±5.8 SBP (mmHg) P9olicosanol1*29.83±15.61*27.39±14.50127.61±14.93* A8torvastatin1029.31±15.61227.76±19.3129.26±14.1 DBP (mmHg) P5olicosanol7*8.92±8.8797.73±7.8478.58±6.9 A7torvastatin758.02±10.595.10±8.478.95±7.4 ALT (U/L) P1olicosanol129.98±7.319.17±6.0+++18.15±6.20*++++ A0torvastatin2*0.16±7.82*3.00±7.5023.05±9.17 AST (U/L) P7olicosanol2*4.06±7.421.59±6.51*+++20.61±6.81***+++ A9torvastatin294.43±6.9215.71±7.424.51±6.2 CPK (UI/L) P0olicosanol9*9.54±45.889.85±36.09+++86.73±35.29*+++++ A5torvastatin1*02.76±57.71*17.30±58.68121.18±54.39* Glucose (mmol/L) P5olicosanol54.27±0.950.14±0.95.14±1.0 A7torvastatin57.22±0.954.19±1.05.13±1.0 Creatinine (µmol/L) P7olicosanol960.54±14.4849.17±17.588.43±13.8 A7torvastatin970.64±13.9869.95±13.589.88±16.5

*p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.000 1 Comparison with baseline (T-test for dependent samples). + p < 0.05; ++ p < 0.01; +++ p < 0.001; ++++p < 0.000 1; +++++ p < 0.000 01 Comparison with atorvastatin (T-test for independent samples).

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RESULTADOS CIENTIFICOS DESTACADOS MINISTERIO DE EDUCACION SUPERIOR DE CUBA

EMPLEO GENERALIZADO DE LA CORALINA® HAP-200 EN TODO EL PAIS EN ESTOMATOLOGIA Y CIRUGIA MAXILOFACIAL Laboratorio de Biomateriales, Centro Nacional de Investigaciones Científicas.

La hidroxiapatita porosa Coralina® HAP-200 es un biomaterial para implantes óseos desarrollado a finales de la década del ochenta, el cual constituye el primer biomaterial grado III según la clasificación internacional que se desarrolla y aplica en Cuba. En 1992, este producto obtuvo certificado de registro sanitario en el país para aplicaciones en Estomatología y Cirugía Maxilofacial. Actualmente, se cuenta con las instalaciones adecuadas y la capacidad productiva necesaria para satisfacer toda la GRANULADOS demanda nacional y los planes de exportación en condiciones de Buenas Prácticas de Producción. Se produce a partir de corales marinos, los cuales han resultado excelentes fuentes para la obtención de materiales biocompatibles con los huesos, ya que los procesos biológicos que tienen lugar en ellos constituyen modelos de perfecta organización ana- tómica y fisiológica. Todo el proceso de prospección y colecta de corales se realiza a través de los organismos especializados y autorizados para el control del medio ambien- te, con lo cual, se garantiza su explotación de forma sostenible sin dañar el ecosistema. RECTANGULARES No se conocen contraindicaciones en el uso de Coralina® HAP-200. A partir de 1990, se comenzó a suministrar estos biomateriales a hospitales de varias provincias del país con vistas realizar diferentes protocolos de ensayos y estu- dios clínicos y a partir de 2000, se inició su comercialización. Los volúmenes del producto puesto a disposición de las instituciones de Salud del país han permitido tratar un número creciente de pacientes cada año. En los dos últimos, se apreció un incremento considerable en su aplicación. Hasta el presente, se han tratado unos 9 600 pacientes, de ellos, 4 300 en los dos últimos años. Las lesiones tratadas en esta especialidad abarcan desde pequeños defectos de CIRCULARES los huesos en el maxilar y la mandíbula, hasta grandes pérdidas óseas en la regiones facial y craneal con grandes deformaciones y secuelas estéticas y funcionales. Cuba es uno de los pocos países en el mundo que pone este tipo de producto a plena disposición de toda la población, lo que eleva la calidad de los servicios médicos especializados en implantología y cirugía reconstructiva y contribuye a mejorar la calidad de vida de aquella. En el desarrollo y generalización de este producto, se ha contado con la colabo- ración de especialistas, estomatólogos, cirujanos maxilofaciales y autoridades de importantes instituciones de Salud Pública del país. ESFERICAS 178