Effect of apolipoprotein B reduction on major adverse cardiovascular events in randomized controlled trials of triglyceride-lowering therapies: systematic review and exploratory meta-regression
M Sobral Domingues, A Garcia, A Ferreira, J FerreiraAbstract
Background
Randomized controlled trials (RCTs) of triglyceride (TG)-lowering therapies show inconsistent benefits on major adverse cardiovascular events (MACE). Because TGs poorly reflect atherogenic particle burden, apolipoprotein B (ApoB) may be a better marker of treatment effect. It remains unclear how often ApoB is reported in these trials or weather data are sufficient for pooled analyses.
Aim
To systematically assess how fully ApoB is reported in TG-lowering RCTs and weather ApoB reduction correlates with MACE reduction.
Methods
We performed a systematic review of RCTs evaluating TG-lowering therapies (EPA and/or DHA, fibrates, and niacin/nicotinic acid) in high-risk populations reporting MACE. MEDLINE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials were searched. After screening and inclusion, we performed an exploratory meta-regression assessing the association between absolute ApoB reduction and risk ratio (RR) for a composite and individual outcome of cardiovascular death, myocardial infarction (MI), stroke, and coronary revascularization.
Results
Twenty-nine RCTs met inclusion criteria, but only 8 adequately reported ApoB values at baseline and end of study, or provided absolute ApoB change, allowing quantitative analysis. These trials included 86,216 participants and 10,285 MACE. ApoB reduction was associated with a lower risk of MACE (RR 0.90 per 10 mg/dL reduction; 95% CI [0.80-1.01]; p = 0.084; I² = 61%), although this did not reach statistical significance – Figure 1A. ApoB reduction significantly correlated with a reduced risk of MI (RR 0.84; 95% CI [0.71-1.00]; p=0.048; I²=42%) – Figure 1B. For coronary revascularization, there was a trend toward risk reduction (RR 0.87; 95% CI [0.75-1.00]; p=0.057; I²=42%). No significant associations were observed for CV death (RR 1.07; 95% CI [0.91-1.26]; p=0.42; I²=61%) or stroke (RR 0.96; 95% CI [0.83-1.11]; p=0.57; I²=60%).
Conclusions
ApoB reporting in TG-lowering RCTs was limited, constraining evaluation of effects on atherogenic particle burden. Still, available data suggest greater ApoB reduction aligns with lower CV risk, especially MI, highlighting ApoB potential to reveal benefits not captured by TG levels. Larger trials with consistent ApoB reporting are needed to define the true cardioprotective impact of TG-lowering therapies.