Intensive versus conventional LDL-c targeting in ASCVD
ACC.26 – In the open-label, randomized Ez-PAVE trial among patients with ASCVD, targeting an LDL-c of <55 mg/dL resulted in a lower risk of major cardiovascular events compared with targeting a level of <70 mg/dL.
This summary is based on the presentation of Byeong-Keuk Kim, MD, PhD (Seoul, South Korea) at the ACC.26 Scientific Session - Intensive LDL cholesterol targeting in atherosclerotic cardiovascular disease: The Ez-PAVE randomized clinical trial.
Introduction and methods
Despite guideline recommendations, randomized evidence evaluating the optimal LDL-c target for secondary prevention in patients with ASCVD remains limited. The aim of the current study was to compare the efficacy and safety of LDL-c targeting of <55 mg/dL versus <70 mg/dL in patients with ASCVD.
The Ez-PAVE trial (Effects of Ezetimibe Combination Therapy for Patients with Atherosclerotic Cardiovascular Disease — Randomized Comparison of LDL Cholesterol Targeting <70 mg per Deciliter vs. <55 mg per Deciliter) was an investigator-initiated, multicenter, randomized, open-label, superiority trial conducted at 17 sites in South Korea. A total of 3048 adults patients (age 19–80 years) with documented ASCVD, defined as previous ACS, stable angina with imaging or functional studies, coronary revascularization or other arterial revascularization, stroke or transient ischemic attack, or peripheral artery disease, were randomized in a 1:1 ratio to an LDL-c target level of <55 mg/dL (intensive-targeting group) or an LDL-c target level of <70 mg/dL (conventional-targeting group). Patients in each group underwent a second randomization in a 1:1 ratio to statin monotherapy or combination therapy with statin plus ezetimibe. Median follow-up was 3 years.
The primary endpoint was a composite of cardiovascular death, nonfatal MI, nonfatal stroke, any revascularization, or hospitalization for unstable angina at 3 years.
Safety endpoints included new-onset diabetes (among patients without diabetes at baseline), worsening of glycemic control (among patients with diabetes at baseline), statin-associated muscle symptoms leading to changes in therapy dose or regimen, diagnosis of cancer, cataract surgery, and elevation of the aminotransferase, creatinine, or creatine kinase level.
Main results
- At 3 years, the median LDL-c level was 56 mg/dL (IQR: 42–61) in the intensive-targeting group and 66 mg/dL (IQR: 55–74) in the conventional-targeting group.
- At 3 years, the cumulative incidence of the primary outcome was 6.6% in the intensive-targeting group and 9.7% in the conventional-targeting group (HR: 0.67; 95%CI: 0.52–0.86; P<0.002).
- The cumulative incidence of a composite of cardiovascular death, nonfatal MI, or nonfatal stroke (one of the key secondary endpoints) was 2.3% in the intensive-targeting group and 3.6% in the conventional-targeting group (HR: 0.63; 95%CI: 0.41–0.96; P<0.030).
- The rates of most prespecified safety endpoints were similar between the two groups. Elevation of creatine level occurred less frequently in the intensive-targeting group compared with the conventional targeting group (1.2% vs. 2.7%; P=0.004).
Conclusion
In patients with ASCVD, targeting an LDL-c level of <55 mg/dL was associated with a significantly lower 3-year risk of cardiovascular death, nonfatal MI, nonfatal stroke, any revascularization, or hospitalization for unstable angina than targeting an LDL-c level of <70 mg/dL. Dr. Kim concluded that “these findings provide randomized evidence supporting more intensive lipid-lowering strategies for secondary prevention, consistent with current guideline recommendations.”
- Our reporting is based on the information provided at the ACC.26 Scientific Session -