Efficacy and Safety of Ezetimibe Added to Atorvastatin Versus Atorvastatin Uptitration or Switching to Rosuvastatin in Patients With Primary Hypercholesterolemia

Abstract

Hypercholesterolemic patients (n= 1,547) at high atherosclerotic cardiovascular disease risk with low-density lipoprotein cholesterol (LDL-C) levels ≥100 and ≤160mg/dl while treated with atorvastatin 10mg/day entered a multicenter, randomized, double-blind, active-controlled, clinical trial using two 6-week study periods. Period I compared the efficacy/safety of (1) adding ezetimibe 10mg (ezetimibe) to stable atorvastatin 10mg, (2) doubling atorvastatin to 20mg, or (3) switching to rosuvastatin 10mg. Subjects in the latter 2 groups who persisted with elevated LDL-C levels (≥100 and ≤160mg/dl) after period I, entered period II; subjects on atorvastatin 20mg had ezetimibe added to their atorvastatin 20mg, or uptitrated their atorvastatin to 40mg; subjects on rosuvastatin 10mg switched to atorvastatin 20mg plus ezetimibe or uptitrated their rosuvastatin to 20mg. Some subjects on atorvastatin 10mg plus ezetimibe continued the same treatment into period II. At the end of period I, ezetimibe plus atorvastatin 10mg reduced LDL-C significantly more than atorvastatin 20mg or rosuvastatin 10mg (22.2% vs 9.5% or 13.0%, respectively, p <0.001). At the end of period II, ezetimibe plus atorvastatin 20mg reduced LDL-C significantly more than atorvastatin 40mg (17.4% vs 6.9%, p <0.001); switching from rosuvastatin 10mg to ezetimibe plus atorvastatin 20mg reduced LDL-C significantly more than uptitrating to rosuvastatin 20mg (17.1% vs 7.5%, p<0.001). Relative to comparative treatments, ezetimibe added to atorvastatin 10mg (periodI) or atorvastatin 20mg (period II) produced significantly greater percent attainment of LDL-C targets <100 or <70mg/dl, and significantly greater percent reductions in total cholesterol, non-high-density lipoprotein cholesterol, most lipid and lipoprotein ratios, and apolipoprotein B (except ezetimibe plus atorvastatin 20 vs atorvastatin 40mg). Reports of adverse experiences were generally similar among groups. In conclusion, treatment of hypercholesterolemic subjects at high cardiovascular risk with ezetimibe added to atorvastatin 10 or 20mg produced significantly greater improvements in key lipid parameters and significantly greater attainment of LDL-C treatment targets than doubling atorvastatin or switching to (or doubling) rosuvastatin at thecompared doses.