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Effect of apolipoprotein B reduction on major adverse cardiovascular events in trials of triglyceride-lowering therapies: systematic review and exploratory meta-regression
Session:
Sessão de Comunicações Orais 05 – Para além do LDL: determinantes metabólicos do risco cardiovascular
Speaker:
Miguel Sobral Domingues
Congress:
CPC 2026
Topic:
J. Preventive Cardiology
Theme:
28. Risk Factors and Prevention
Subtheme:
28.4 Lipids
Session Type:
Comunicações Orais
FP Number:
---
Authors:
Miguel Sobral Domingues; André Garcia; António Ferreira; Jorge Ferreira
Abstract
<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Aptos,sans-serif"><strong><span style="font-family:"Calibri",sans-serif"><span style="color:black">Background:</span></span></strong><span style="font-family:"Calibri",sans-serif"><span style="color:black"> 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.</span></span></span></span></p> <p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Aptos,sans-serif"><strong><span style="font-family:"Calibri",sans-serif"><span style="color:black">Aim:</span></span></strong><span style="font-family:"Calibri",sans-serif"><span style="color:black"> To systematically assess how fully ApoB is reported in TG-lowering RCTs and weather ApoB reduction correlates with MACE reduction.</span></span></span></span></p> <p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Aptos,sans-serif"><strong><span style="font-family:"Calibri",sans-serif"><span style="color:black">Methods:</span></span></strong><span style="font-family:"Calibri",sans-serif"><span style="color:black"> We performed a systematic review (CRD420251207909) 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.</span></span></span></span></p> <p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Aptos,sans-serif"><strong><span style="font-family:"Calibri",sans-serif"><span style="color:black">Results:</span></span></strong><span style="font-family:"Calibri",sans-serif"><span style="color:black"> 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 – <strong>Figure 1</strong>. ApoB reduction significantly correlated with a reduced risk of MI (RR 0.84; 95% CI [0.71-1.00]; p=0.048; I²=42%). 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%).</span></span></span></span></p> <p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Aptos,sans-serif"><strong><span style="font-family:"Calibri",sans-serif"><span style="color:black">Conclusions:</span></span></strong><span style="font-family:"Calibri",sans-serif"><span style="color:black"> 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.</span></span></span></span></p>
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