Low dose of ROSuvastatin in combination with EZEtimibe effectively and permanently reduce low density lipoprotein cholesterol concentration independently of timing of administration (ROSEZE): A randomized, crossover study - preliminary results

Abstract

Background: In an attempt to improve low density lipoprotein-cholesterol (LDL-C) level control in patients ineffectively treated with statins, we evaluated the effectiveness of a fixed-dose combination (FDC) of 10 mg rosuvastatin and ezetimibe and its relation to the timing of drug administration.

Methods: A randomized, open label, single center, crossover study involving 83 patients with coronary artery disease and hypercholesterolemia with baseline LDL-C ≥ 70 mg/dL. In arm I the FDC drug was administered in the morning for 6 weeks, then in the evening for the following 6 weeks and vice versa in arm II. The primary endpoint was the change in LDL-C after 6 and 12 weeks.

Results: The median LDL-C concentration at baseline, after 6 and 12 weeks respectively was: 98.10 mg/dL (Q1;Q3: 85.10;116.80), 63.14 mg/dL (50.70;77.10) and 59.40 mg/dL (49.00;73.30); p < 0.001. LDL-C levels were similar regardless of the timing of drug administration (morning 62.50 mg/dL [50.70;76.00] vs. evening 59.70 mg/dL [48.20;73.80]; p = 0.259], in both time points: 6 week: 63.15 mg/dL (50.75;80.65) vs. 63.40 mg/dL (50.60;74.00), p = 0.775; and 12 week: 62.00 mg/dL (50.20;74.40) vs. 59.05 mg/dL (47.65;66.05), p = 0.362. The absolute change in LDL-C concentration for the morning vs. evening drug administration was - 6 week: -34.6 mg/dL (-56.55; -19.85) (-34.87%) vs. -31.10 mg/dL (-44.20; -16.00) (-35.87%) (p not significant); 12. week: -34.20 mg/dL (-47.8; -19.0) (-37.12%) vs. -37.20 mg/dL (-65.55; -23.85) (-40.06%) (p not significant). The therapy was safe and well tolerated.

Conclusions: Fixed-dose combination of rosuvastatin and ezetimibe significantly and permanently decreases LDL-C regardless of the timing of drug administration.

Keywords: adherence; apolipoprotein B; fixed-dose; hypercholesterolemia; lipoprotein(a); secondary prevention; timing of administration.

Figure 1

Primary endpoint: Change in low density lipoprotein cholesterol (LDL-C) after 6 and 12 weeks of therapy.

Figure 2

Low density lipoprotein cholesterol (LDL-C) concentration depending on time of day of study drug administration.

Figure 3

Morning administration of the study drug: change in low density lipoprotein cholesterol (LDL-C) concentration depending of time of testing.

Figure 4

Evening administration of the study drug: change in low density lipoprotein cholesterol (LDL-C) concentration depending of time of testing.

Figure 5

Change in total cholesterol (TC) concentration after 6 and 12 weeks of therapy.