Association between Apolipoprotein B and cardiovascular risk: a meta-analysis of randomized controlled trials

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Abstract

Background and Aims

Recent evidence from Mendelian randomization studies suggests that the clinical benefit of any lipid-lowering therapy should be proportional to the absolute change in apolipoprotein B (apoB) containing lipoproteins. We sought to compare and to estimate the magnitude of the expected clinical benefit per unit reduction in apoB for several classes of lipid-lowering therapies.

Methods

We conducted a study-level meta-analysis of randomized trials evaluating statins, ezetimibe, PCSK9-inhibitors, CETP-inhibitors, niacin, and fibrates. We included all studies reporting apoB levels and cardiovascular (CV) outcomes, with at least 1000 participants and 1-year follow-up. The primary outcome was major CV events (MACEs). We estimated the relative risk (RR) of MACEs, adjusted for study duration, for each class and in a combined analysis.

Results

Twenty-five trials that enrolled 285,241 participants (mean age: 63.3 years; female sex: 24.7%) who experienced 40,244 first MACEs were included. The mean absolute difference in apoB between the treatment and comparison groups at 1 year was 24.1 mg/dL. The pooled RR per 30 mg/dL reduction in apoB levels was 0.79 (95% confidence intervals (CI) 0.77-0.81) for MACEs, consisting of significant risk reduction in non-fatal myocardial infarction (RR 0.76; 95%CI 0.73-0.79), coronary revascularisation (0.78; 0.73-0.82), stroke (0.79; 0.76-0.81), and CV death (0.87; 0.82-0.92).

Conclusions

All the lipid-lowering therapies are associated with very similar reductions in the risk of major CV events per unit change in apoB, suggesting that the clinical benefit may be proportional to the achieved absolute reduction in apoB, regardless of the observed changes in other lipids.

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