3 Key Takeaways
Plain English Summary- 01Core Finding
Lipid-lowering therapy was adjusted according to a predefined protocol to achieve LDL-C targets.
- 02Study Evidence
Tested in a randomized controlled trial (n=1525) at the randomized clinical trial stage.
- 03Practical Meaning
Controlled trial findings show causal benefit under protocol rules; real-world effectiveness can vary across patients.
What This Means for You
Within a target-directed LDL-C-lowering strategy, cardiovascular efficacy (real-world effectiveness in the trial) and safety did not differ significantly, whether initiated as statin-ezetimibe combination therapy or as statin monotherapy, but combination therapy facilitated achievement of a lower LDL-C target.
The Discovery
In a target-directed low-density lipoprotein cholesterol (LDL-C)-lowering strategy, the impact of the initial treatment regimen has not been investigated in patients with atherosclerotic cardiovascular disease. We compared the efficacy (real-world effectiveness in the trial) and safety of initial statin-ezetimibe combination therapy versus statin monotherapy within intensive or conventional LDL-C-targeting strategies. In this prespecified second randomization of the randomized Ez-PAVE trial (Effects of Ezetimibe Combination Therapy for Patients With Atherosclerotic Cardiovascular Disease: Randomized Comparison of LDL Cholesterol Targeting <70 versus <55 mg/dL) conducted at 17 centers in South Korea, a total of 3048 patients with atherosclerotic cardiovascular disease were enrolled between January 2021 and July 2022. Following the first randomization to either an intensive (<55 mg/dL) or conventional (<70 mg/dL) LDL-C-targeting strategy, patients underwent subsequent randomization (initial statin-ezetimibe combination therapy [n=1525] versus statin monotherapy [n=1523]) and were followed up for 3 years. Lipid-lowering therapy was adjusted according to a predefined protocol to achieve LDL-C targets. The primary end point was a 3-year composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, any revascularization, or hospitalization for unstable angina. The mean±SD age was 64.4±9.0 years, and 638 patients (20.9%) were female. The incidence of the primary end point did not differ between statin-ezetimibe combination therapy (128 patients [8.5%]) and statin monotherapy (119 patients [7.9%]; hazard ratio, 1.07 [95% CI, 0.83-1.37]; P =0.596). Patients who received statin-ezetimibe combination therapy achieved lower median LDL-C levels during follow-up than those who received statin monotherapy in both the intensive-targeting (53 mg/dL [interquartile range, 45-62 mg/dL] versus 62 mg/dL [interquartile range, 53-74 mg/dL]) and conventional-targeting (63 mg/dL [interquartile range, 55-73 mg/dL] versus 70 mg/dL [interquartile range, 62-81 mg/dL]) strategies. During follow-up, ezetimibe was added to the treatment regimen of 241 patients (34.3%) and 177 patients (24.8%) who initially received statin monotherapy in the intensive- and conventional-targeting strategies, respectively. The treatment effect of intensive-targeting versus conventional-targeting strategies was consistent regardless of therapy regimens without significant heterogeneity ( P interaction =0.583). The safety end points were similar between the groups.
How It Works, Simply
This cardiology research focuses on LDL cholesterol. Researchers evaluated it using a randomized controlled trial (n=1525) at the randomized clinical trial stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
Lipid-lowering therapy was adjusted according to a predefined protocol to achieve LDL-C targets.
- 02Study Evidence
Tested in a randomized controlled trial (n=1525) at the randomized clinical trial stage.
- 03Practical Meaning
Controlled trial findings show causal benefit under protocol rules; real-world effectiveness can vary across patients.
Key Numbers
Biological Mechanism & Study Design
Study Design & Cohort
Randomized controlled trial
Randomized controlled trial (n=1525) · Randomized Clinical Trial
Biological Pathway & Modality
LDL cholesterol
Intervention: Statin-Ezetimibe Combination Therapy
Experimental Findings & Endpoints
In a target-directed low-density lipoprotein cholesterol (LDL-C)-lowering strategy, the impact of the initial treatment regimen has not been investigated in patients with atherosclerotic cardiovascular disease.
We compared the efficacy and safety of initial statin-ezetimibe combination therapy versus statin monotherapy within intensive or conventional LDL-C-targeting strategies. In this prespecified second randomization of the randomized Ez-PAVE trial (Effects of Ezetimibe Combination Therapy for Patients With Atherosclerotic Cardiovascular Disease: Randomized Comparison of LDL Cholesterol Targeting <70 versus <55 mg/dL) conducted at 17 centers in South Korea, a total of 3048 patients with atherosclerotic cardiovascular disease were enrolled between January 2021 and July 2022.
Following the first randomization to either an intensive (<55 mg/dL) or conventional (<70 mg/dL) LDL-C-targeting strategy, patients underwent subsequent randomization (initial statin-ezetimibe combination therapy [n=1525] versus statin monotherapy [n=1523]) and were followed up for 3 years. Lipid-lowering therapy was adjusted according to a predefined protocol to achieve LDL-C targets.
The primary end point was a 3-year composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, any revascularization, or hospitalization for unstable angina. The mean±SD age was 64.4±9.0 years, and 638 patients (20.9%) were female.
The incidence of the primary end point did not differ between statin-ezetimibe combination therapy (128 patients [8.5%]) and statin monotherapy (119 patients [7.9%]; hazard ratio, 1.07 [95% CI, 0.83-1.37]; P =0.596). Patients who received statin-ezetimibe combination therapy achieved lower median LDL-C levels during follow-up than those who received statin monotherapy in both the intensive-targeting (53 mg/dL [interquartile range, 45-62 mg/dL] versus 62 mg/dL [interquartile range, 53-74 mg/dL]) and conventional-targeting (63 mg/dL [interquartile range, 55-73 mg/dL] versus 70 mg/dL [interquartile range, 62-81 mg/dL]) strategies.
During follow-up, ezetimibe was added to the treatment regimen of 241 patients (34.3%) and 177 patients (24.8%) who initially received statin monotherapy in the intensive- and conventional-targeting strategies, respectively. The treatment effect of intensive-targeting versus conventional-targeting strategies was consistent regardless of therapy regimens without significant heterogeneity ( P interaction =0.583).
The safety end points were similar between the groups.
Clinical Translation & Practice Context
Within a target-directed LDL-C-lowering strategy, cardiovascular efficacy and safety did not differ significantly, whether initiated as statin-ezetimibe combination therapy or as statin monotherapy, but combination therapy facilitated achievement of a lower LDL-C target.
The Bottom Line · Clinical Pearl
“Within a target-directed LDL-C-lowering strategy, cardiovascular efficacy and safety did not differ significantly, whether initiated as statin-ezetimibe combination therapy or as statin monotherapy, but combination therapy facilitated achievement of a lower LDL-C target.”
Published in Circulation · Current Stage: Randomized Clinical Trial
