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.