Meta Analysis of apoB Lowering and CV Risk Reduction Among Different LLTs

Key Takeaway

This meta-analysis included 254,828 participants from 20 RCTs Reported the association of 6 different classes (statins, ezetimibe, PCSK9-inhibitors, CETP-inhibitors, fibrates, and niacin) of LLT with apoB levels and major CV events and showed that:

• All 6 classes of LLT were associated with similar reduction in risk of major CV events for the same magnitude and duration of apoB lowering
• For 30 mg/dL absolute reduction in plasma apoB levels, 6 classes of LLTs were associated with a consistent reduction in major CV events:
  • 10%, 15%, 19% and 20% proportional reduction after 1, 2, 3, and 4 or 5 years of therapy, respectively
• Regardless of changes in other lipids, the therapeutic benefit of LLT was determined by changes in plasma apoB levels

Why This Matters

• LDL-C reduction therapies (statins, ezetimibe, and PCSK9 inhibitors) have demonstrated consistent reduction of major CV events in several RCTs
  • However, therapies that do not involve up-regulation of LDL-receptor pathway* or that lower triglycerides^† did not show a consistent reduction in risk of CV events
• Trapping of apoB molecule within the artery wall can cause progression of atherosclerotic plaque
• This study compared the association between the proportional reduction in major CV events and different classes of LLT for the same magnitude and duration of apoB lowering

Key Highlights

Methods:

• Meta-analysis of RCTs evaluating 6 different classes of LLTs
• Databases: MEDLINE and EMBASE were searched from inception to November 2022

Inclusion criteria:

• Placebo-controlled, double-blind RCTs reporting adjudicated clinical CV outcomes and enrolled ≥1,000 participants with a median follow-up duration of ≥1 year
• Reported absolute achieved differences in plasma apoB levels between treatment and control groups
• Provided cumulative event curves figure for the treatment and control groups that included number of participants remaining at risk at beginning of each year of follow-up

Analysis:

• Association between 30 mg/dL reduction in plasma apoB levels and risk of major CV events across classes of LLTs
• Summary estimates of the effect for an individual class of therapy were combined in an inverse variance-weighted random-effects meta-analysis iteratively after each year of follow-up
• Heterogeneity of effect among different LLT classes was assessed using the I² statistics

Results:

254,828 participants from 20 trials with major CV events (30,175) were included

• Mean age = 63 years
• Females = 26%

Association of Reduction in Plasma Apo-b Levels with Llt and Reduction in Major Cv Events

For each 30 mg/dL absolute reduction in plasma apoB levels, the 6 classes of LLT (statins, ezetimibe, PCSK9-inhibitors, CETP-inhibitors, fibrates, and niacin) were associated with a consistent reduction in major CV events after therapy