Rosuvastatin 10 mg Plus Ezetimibe vs Rosuvastatin 20 mg in Patients with ASCVD & T2DM

30 Mar, 26

Introduction

Patients with type 2 diabetes (T2DM) are burdened with poor outcomes following acute coronary syndrome (ACS) and are at an increased risk of developing coronary artery disease (CAD). These patients therefore require more intensive low-density lipoprotein- cholesterol (LDL-C) lowering therapy. A combination of moderate-intensity statin plus ezetimibe is used increasingly to achieve the LDL-C target in T2DM patients. Nevertheless, there is scarcity of studies comparing efficacy and safety of moderate-intensity statin plus ezetimibe vs. high-intensity statin in patients with atherosclerotic cardiovascular disease (ASCVD) and T2DM.

Aim

To compare the efficacy and safety of moderate-intensity rosuvastatin plus ezetimibe vs. high-intensity rosuvastatin monotherapy in patients with ASCVD and T2DM.

Patient Profile

Patients with ASCVD [defined as one of the following: stable angina, unstable angina, myocardial infarction (MI), stroke or transient ischemic attack (TIA), peripheral artery disease, and history of percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG)] and T2DM (N=223, age >19 years).
All patients were on oral hypoglcemic agents for at least 3 months

Methods

Study Design

A multicenter, open-label, non-inferiority randomized trial.

Treatment Strategy and Assessments

After a 4 week run-in phase, in addition to the standard treatment, the study subjects were randomly assigned to receive either rosuvastatin 20 mg once daily (R20 group) or single-pill combination of rosuvastatin 10 mg plus ezetimibe 10 mg once daily (R10Z group) for a period of 24 weeks.
Patients that completed the study in the full analysis set (FAS) was 111 patients in the R10Z group and 112 patients in the R20 group.
The per protocol (PP) set included 195 patients (97 patients in the R10Z group and 98 patients in the R20 group) after excluding patients from FAS who violated the protocols.

Outcomes

Primary Efficacy Outcome

The least square mean percent (LSM %) change of LDL-C level at 24 weeks from baseline.

Secondary Efficacy Outcomes

LDL-C change at 12 weeks from baseline, changes in total cholesterol, high density lipoprotein cholesterol (HDL-C), TG, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), and homeostasis model assessment-insulin resistance (HOMA-IR) at 12 and 24 weeks from baseline, and changes of apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), apolipoprotein B48 (ApoB48), and apolipoprotein B/apolipoprotein A1 ratio (Apo B/A1) at 24 weeks.

Safety Outcomes

The incidence of patient-reported symptoms/signs, and laboratory tests
The incidence of adverse events

Results

A previous history of ACS was seen in 74.4% of the study population. The mean DM duration was 7.2 years.
The mean LDL-C level at randomization was 72.1 mg/dL in the R10Z group and 69.8 mg/dL in the R20 group (p = 0.65). The medication adherence was similar in both the study groups.
After 24 weeks of treatment, The LDL-C decreased significantly from baseline to week 24 in both groups (-20.5% in R10Z group and − 13.5% in R20 group, p-value < 0.001 in both groups, Fig. 1). The LSM % difference between R10Z and R20 groups was 7.0% (p for non-inferiority = 0.06).

Fig. 1: Change in LDL-C during the study period

In the PP set, patients in the R10Z group had greater reduction in LDL-C as compared to those in the R20 group (− 14.1% vs. −26.5%, p < 0.001; the LSM difference between the two groups: 12.4%, Fig. 2)

Fig. 2: Changes in LDL-C in the PP set analysis

Patients in the R10Z group had significantly higher decreases in apolipoprotein B level at 24 weeks from baseline, as compared to those in the R20 group (−15.6% vs. −9.9%, p-value = 0.008) (Table 1).

Table 1: Changes in Apolipoprotein during the study period

Parameters			R20 Group	R10Z Group		LSM Diff		P value
Apolipoprotein A1	Baseline	Mean (mg/dL)	140.2	139.3
	Week 24	Mean (mg/dL)	134.4	137.2
	Week 24	LSM change %	-1.2	0.5		-1.8		0.29
Apolipoprotein B	Baseline	Mean (mg/dL)	74.0	76.2
	Week 24	Mean (mg/dL)	68.6	65.4
	Week 24	LSM change %	-9.9	-15.6		5.7		0.008
Apolipoprotein B48	Baseline	Mean (mg/dL)	0.7	0.7
	Week 24	Mean (mg/dL)	0.7	0.6
	Week 24	LSM change %	26.2	6.3		19.9		0.17
Apolipoprotein B/A1	Baseline	Mean (mg/dL)	0.5	0.6
	Week 24	Mean (mg/dL)	0.5	0.5
	Week 24	LSM change %	-5.5	-13.2		7.6		0.004
HbA1c	Baseline	Mean (%)	6.8		7.0
	Week 12	Mean (%)	6.9		7.11
	Week 24	Mean (%)	7.1		7.3
	Week 12	LSM change %	-0.3		-0.2		-0.07		0.95
	Week 24	LSM change %	2.9		4.0		-1.1		0.47
FPG	Baseline	Mean	131.9		136.9
	Week 12	Mean	139.8		135.3
	Week 24	Mean	138.0		140.6
	Week 12	LSM change %	1.5		-0.5		2.0		0.52
	Week 24	LSM Change %	2.2		4.3		-2.2		0.51
HOMA-IR	Baseline	Mean	3.9		4.7
	Week 12	Mean	4.3		3.6
	Week 24	Mean	4.7		4.5
	Week 12	LSM Change %	46.4		2.9		43.6		0.27
	Week 24	LSM Change %	37.1		32.1		5.0		0.85

Higher proportion of patients in the R10Z group achieved LDL-C < 55 mg/dL vs. those in R20 group (significant difference at 12 weeks; p = 0.01). The difference at 24 weeks was not statistically significant (p = 0.09).
The incidence of total adverse events was lower in the patients in the R10Z group vs. those in the R20 group (p = 0.048).

Conclusion

Single-pill combination of moderate-intensity rosuvastatin plus ezetimibe was non-inferior to high-intensity rosuvastatin in LDL-C lowering efficacy with good safety profile in ASCVD patients with T2DM.

Sci Rep. 2025 May 8;15(1):16012. doi: 10.1038/s41598-025-00298-7.