EFFECTS OF POLICOSANOL IN OLDER PATIENTS CONSUMING NITRATES VASODILATORS

Abstract

Background: Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. The efficacy and safety of policosanol have been investigated in clinical studies and post-marketing surveillance. Policosanol is very safe and no drug-related adverse events have been demonstrated, even in population subsets with high consumption of concomitant therapy, indicating that the potential risk of drug-drug interaction for policosanol is low. Vasodilators are used in geriatric populations mainly to treat congestive heart failure and acute decompensating of heart failure, although associated to other anti-hypertensive are also used for manage hypertension. Vasodilators, however, have considerable risk of drug-related toxicity, the most frequent symptoms being those derived from excessive vasodilation and hypotension, such as nausea, vomiting, loss of consciousness and reflex tachycardia. Vasodilators show important drug-drug interaction derived from pharmacodynamic interactions with several drugs, those associated to concomitant use of other vasodilators and diuretics being the most relevant. Considering such facts, the interest to study putative drug-drug interaction between policosanol and vasodilators is supported. Objective: To investigate whether policosanol administered to older patients consuming vasodilators induces any specific disturbance on safety indicators and/or increase the frequency or severity of adverse events in such patients. Methods: This report was based in the analysis of the records of all patients (185) taking nitrates vasodilators included in a Prevention Study in the Elderly randomised to policosanol 5 mg/d or placebo for 3 years. Analysis was by Intention-to-treat. Results: Baseline characteristics were well balanced in both groups. After one year on treatment, policosanol lowered significantly low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC) and triglycerides (TG), whereas raised high-density lipoprotein-cholesterol (HDL-C). Policosanol effects persisted, even increased, during the 3 years treatment. At the end of the study, policosanol reduced LDL-C (35%), TC (25%), TG (19,3%) and raised HDL-C (16,7%). Of 185 randomised patients taking vasodilators, 44 (23,8 %) withdrew from the trial. The frequency of withdrawals in placebo (31/95; 32,6 %) was greater (p<0,01) than in policosanol group (13/90; 14,4

%). Overall, 26/185 (14,1 %) patients discontinued due to some adverse events: 23 placebo (24,2 %) and 3 (3,3 %) policosanol patients (p<0,01). Policosanol did not impair safety indicators compared with placebo, but induced additional decreases of systolic pressure compared with placebo, but no individual value or clinical symptom of hypotension was reported. The frequency of policosanol patients experiencing serious adverse events (3/90; 3,3 %) was lower (p<0,01) than in respective placebo (23/95; 24,2 %). Likewise, the frequency of policosanol patients who experienced some mild or moderate adverse events during the study (10/90; 11,1 %) was lower (p<0,05) than in matched placebo (28/95; 29,5 %). Conclusions: These results indicate that policosanol can be administered to older patients taking vasodilators without risk of relevant adverse drug-drug interaction.