Abstract P62: Efficacy of Ezetimibe 2.5 Milligrams Utilizing a Novel Tablet Splitting Strategy

Abstract

Background: Ezetimibe's excellent tolerability and approximately 20% LDL lowering effect have made it the most commonly prescribed 2 nd line lipid lowering agent after statins. Ezetimibe is available only in a 10 mg form, either as a stand-alone tablet or in combination with simvastatin as ezetimibe/simvastatin (Vytorin). During clinical development, a wide range of ezetimibe doses were evaluated, including 0.25, 1, and 5 mg. A 2.5 mg dose of ezetimibe was never evaluated. Prospective and retrospective studies have demonstrated that splitting a 10 mg ezetimibe tablet, which provides approximately 5 mg of ezetimibe, is clinically equivalent to a whole 10 mg tablet. On the basis of these results, along with others that demonstrated 1 mg of ezetimibe significantly lowered LDL by approximately 13 to 15%, we prospectively randomized patients to either a simvastatin 20 mg tablet or an ezetimibe/simvastatin 10/80 tablet (10 mg ezetimibe plus 80 mg simvastatin) split into 4 to yield an estimated daily dose of ezetimibe 2.5 mg and simvastatin 20 mg. The efficacy of the two strategies on lipid parameters was compared. We selected ezetimibe/simvastatin 10/80 as a means of obtaining 2.5 mg of ezetimibe, as this tablet size can be readily split into 4 relatively equal parts with a commercially available tablet splitter. Study design: Thirty three subjects were randomized to either simvastatin 20 mg or an ezetimibe/simvastatin 10/80 tablet divided into 4. Lipid panels were collected at baseline and after 6 weeks of therapy. Results: Twenty nine of the 33 subjects successfully completed the study. Conclusion: From a comparative effectiveness perspective, ezetimibe 2.5 mg, delivered by splitting an ezetimibe/simvastatin10/80 tablet into 4, provides the greatest value and delivers LDL lowering comparable to full dose ezetimibe 10 mg. This novel tablet splitting strategy may be applicable to other medications and provide significant additional cost-reduction. Lipid Value (mg/dL) ES 2.5/20 * (n=14) Simvastatin 20 (n=15) P (between groups) % change from baseline (p ** ) % change from baseline (p ** ) Low density lipoprotein -44.7 ± 19.0% (<.001) -27.1 ± 22.4% (<.001) 0.03 High density lipoprotein -5.1 ± 7.4% (<.05) -0.7 ± 9.3% (ns) 0.17 Triglycerides -23.3 ± 3.8% (<.01) -11.9 ± 6.0% (.03) 0.18 Total cholesterol -34.2 ± 13.0% (<.001) -19.9 ± 14.6% (<.001) 0.001 Data is expressed as mean ± SD. * ES: Ezetimibe/simvastatin 10/80 tablet split into 4 parts, supplying ezetimibe 2.5 and simvastatin 20. ** P-value for the change in the lipid parameter from the baseline value.