Comparative efficacy, safety and tolerability of policosanol versus statins in patients with type II hypercholesterolemia: emphasis on muscle function indicators

Lowering elevated total (TC) and low-density lipo-protein-cholesterol (LDL-C) reduces the frequency of coronary events, so that cholesterol-lowering drugs are indicated to prevent coronary heart disease (CHD). Nevertheless, myo-pathy and rhabdomyolysis are related with the use of these drugs, mainly with HMGCoA reductase inhibitors (statins). Policosanol is a cholesterol-lowering drug purified from sugar cane wax, which inhibits cholesterol biosynthesis through the regulation of the activity of HMGCoA reductase. Short and long-term satisfactory efficacy of policosanol (5 – 20 mg/d) has been demonstrated, being notorious its excellent safety and tolerability, so that no drug-related adverse experiences (AE) have proven up to date. Nevertheless, considering its effects on cholesterol biosynthesis, it is convenient to discard whether policosanol can induce muscular AE similarly to statins. This study was undertaken to compare the effects of policosanol and statins on patients with Type II Hypercholesterolemia (HC), with emphasis on safety and effects on muscle function indi-cators. After 4 weeks on a baseline cholesterol-lowering diet period, 411 eligible patients randomly re-ceived, under double-blind con-ditions, policosanol 10 mg/d or statins (lovastatin 20 mg/d or simvastatin 10 mg/d). Tablets were taken once a day with the evening meal for 8 weeks. Physical examination and laboratory tests were done at baseline and study completion, while requests for AE and compliance assessment were done at final visit. Policosanol at 10 mg/d for 8 weeks significantly (p < 0.00001) lowered LDL-C (23.3 %), TC (16.5 %) and triglycerides (p < 0.0001) (10.1 %), while statins reduced (p < 0.00001) LDL-C (21.8 %), TC (17.4 %) and triglycerides (p < 0.001) (5.5 %). Policosanol, but not statins, significantly increased (p < 0.001) HDL-C (9.6 %). The frequency of patients reaching LDL-C reductions ≥ 15 % was sig-nificantly greater (p < 0.05) in policosanol (144/206, 70.0 %) than in statins group (120/205,58.5 %) Both treatments were well tolerated. None of them affected physical safety indicators. Policosanol signi-ficantly lowered (p < 0.05) aspartate aminotransferase (AST) and (p < 0.01) creatinphosphokinase (CPK) values, while unchanged other blood biochemistry indicators. Statins significantly (p < 0.05) increased CPK levels. Twenty-eight (28) patients (7 policosanol, 21 statin) discontinued from the study, Two policosanol patients withdrew from the trial due to AE consisting of abdominal pain and lower limb edema, respectively. Eleven (11) statin-patients discontinued the study due to a serious AE (unstable angina) and other 10 non-serious AE. Three patients reported mus-cular AE (cramps and/or myalgia), 5 suffered gastrointestinal distur-bances (abdominal pain; diarrhea, nauseas, gastric discomfort and/or vomiting), 2 referred cardiovascular AE (arrythmia, uncontrolled hyper-tension) and other patient reported dizziness + headache. In addition, three of these patients concomitantly reported asthenia; skin rash and uncontrolled diabetes. The fre-quency of AE in policosanol (14, 6.8%) was lower (p < 0.05) than in statin group (29, 14.1 %). It is concluded that short-term efficacy of policosanol (10 mg/d) to reduce LDL-C in patients with type II HC was similar to that of starting doses of statins. Effects of both treatments on TC and triglycerides were also equivalent. Policosanol, but not statins, significantly increased HDL-C. Both drugs were safe, but only statins increased CPK, an indicator of muscle function. Policosanol was better tolerated than statins as revealed AE and withdrawal analysis, including reports related with muscle-related AE. Never-theless, long-term studies invest-tigating policosanol effects on muscle function variables through specific algorithm will be needed to definitively discard its potential risk to induce such effects