National Lipid Association Highlights New Meta-Analysis Supporting LDL-C Lowering in Primary Prevention

The National Lipid Association (NLA) today announced the publication of a new meta-analysis evaluating the impact of low-density lipoprotein cholesterol (LDL-C) lowering on major adverse cardiovascular events (MACE) in primary prevention populations. The study synthesizes data from randomized trials of both statin and non-statin therapies and updates a landmark 2012 analysis conducted by the Cholesterol Treatment Trialists’ Collaboration (CTTC).

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality worldwide. Elevated LDL-C is a well-established causal driver of atherosclerotic cardiovascular disease (ASCVD). Numerous clinical trials have demonstrated that lowering LDL-C reduces the risk of myocardial infarction, stroke, and coronary revascularization. This updated analysis examined the magnitude of MACE risk reduction per unit decrease in LDL-C among individuals without established ASCVD, or in trials where at least 80% of participants were free of ASCVD at baseline.

“Reducing LDL-C is one of the most powerful strategies available to prevent heart attacks and strokes across diverse patient populations,” said Dinesh K. Kalra, MD, MBA, lead author of the study, preventive cardiologist, Chief of Cardiology at the University of Louisville, and incoming NLA President. “Our findings reinforce the view that LDL-C lowering should be considered a cornerstone of comprehensive risk reduction — including dietary and other lifestyle modification — not only in patients with established ASCVD, but also in individuals without manifest disease. Notably, we observed even greater relative risk reductions among primary prevention populations who were at lower risk of developing ASCVD.”

Key findings include:

• In cardiovascular outcomes trials composed solely or predominantly of primary prevention participants, each 1 mmol/L (38.7 mg/dL) reduction in LDL-C was associated with a 30% relative risk reduction for 4-point MACE.
• The magnitude of benefit was greatest among individuals with lower baseline ASCVD risk and in trials that included patients with inflammatory conditions.
• These results further strengthen the evidence supporting LDL-C lowering as an effective strategy for primary prevention and underscore the importance of early intervention.

“Importantly, these findings remind us that atherosclerosis develops over decades, and risk reduction efforts should begin early,” said Kevin C. Maki, PhD, CLS, MNLA, Co-Editor-inChief of the Journal of Clinical Lipidology and senior author of the paper. “Although our analysis focused on cholesterol lowering medications, early and sustained lifestyle intervention remains critical for maintaining optimal LDL-C levels. The totality of evidence for LDL-C and ASCVD risk continues to support the principle that ‘lower for longer is better’.” The full article, “Low-Density Lipoprotein Cholesterol Lowering and Risk of Major Adverse Cardiovascular Events in Primary Prevention Trials: A Meta-Analysis,” is available open access in the Journal of Clinical Lipidology HERE.

Authors

Dinesh K. Kalra, MD, MBA; Kausik K. Ray, MD, MPhil; Archna Bajaj, MD, MSCE; Pamela R. Kushner, MD; Meredith L. Wilcox, MPH; Mary R. Dicklin, PhD; Carol F. Kirkpatrick, PhD, MPH, RDN; Kevin C. Maki, PhD, CLS