Efficacy and safety of ezetimibe co-administered with ongoing atorvastatin therapy in achieving low-density lipoprotein goal in patients with hypercholesterolemia and coronary heart disease

Abstract

This randomised, double-blind, placebo (PBO)-controlled study evaluated the efficacy and safety of ezetimibe (EZE) co-administered with ongoing atorvastatin (ATV) therapy in 450 hypercholesterolemic patients with coronary heart disease (CHD) who had not achieved their low-density lipoprotein cholesterol (LDL-C) goal < or =2.60 mmol/l while on a stable dose of ATV 10 or 20 mg/day for > or =6 weeks. After a 4-week diet/baseline active run-in period, patients with LDL-C >2.60 mmol/l and < or =4.20 mmol/l were stratified by ATV dose and randomised (1 : 1) to EZE 10 mg or PBO for 6 weeks while continuing open-label ATV. Significantly more patients achieved an LDL-C goal < or =2.6 mmol/l with EZE than PBO (81.3 vs. 21.8%; p < or = 0.001). Compared to PBO, co-administration of EZE with ongoing ATV led to significantly (p < or = 0.001) greater reductions in LDL-C, total cholesterol, triglycerides, non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B; HDL-C was significantly (p < or = 0.05) increased. Co-administration of EZE and ATV was well tolerated, with an overall safety profile similar to ATV alone.

Treatment With Ezetimibe Plus Low-Dose Atorvastatin Compared With Higher-Dose Atorvastatin Alone

“…Changes in serum lipid levels by lipid-lowering treatment. The extent of LDL-C reduction and the number of patients achieving the LDL-C goal of Յ2.5 mmol/l by the ezetimibe-atorvastatin combination in this study were comparable with data from previous studies evaluating the safety and tolerability of ezetimibe and atorvastatin coadministration (21,23). Although ⌬LDL-C did not differ significantly between the 2 groups, LDL-C tended to be more reduced by the combined treatment than by the 40 mg/day of atorvastatin.…”

“…Moreover, combining the 2 substances eliminates side effects such as statin-associated myopathy and hepatotoxicity and ezetimibe-induced compensatory-elevated hepatic cholesterol synthesis (18,20). Although the combination of ezetimibe with a low atorvastatin dosage provides a very potent tool for reducing LDL-C, it is not known whether the combined treatment strategy achieves the same platelet inhibitory and anti-inflammatory effects as therapy with higher atorvastatin dosages (21)(22)(23). We therefore investigated patients with CAD to determine whether combined treatment with ezetimibe plus low-dose atorvastatin had different effects on platelet function and plasma chemokine levels than higher-dose therapy with atorvastatin alone.…”

An evaluation of alanine transaminase and creatine kinase elevations with the use of ezetimibe in an ambulatory care setting

“…Of note, all 17 cases also were on concomitant statin therapy which in clinical trials has shown to have a greater incidence of transaminase or CK elevations. [11][12][13][14][15][16][17][18] Of these 17 cases, only 5 (0.1%) patients had no other causes noted, aside from the use of a statin in combination with ezetimibe, for the elevation. In our study, even with concomitant statin therapy, we had rates of ALT and/or CK elevations similar to that of placebo in previously published studies.…”

The lipid-lowering effect of ezetimibe in pure vegetarians

“…Although it has been reported that beneficial changes can occur (21,22), they are generally small, and this study was not powered to detect such small effects.…”