Background The American College of Cardiology/American Heart Association updated cholesterol treatment guidelines dropped treatment recommendations based on elevated low-density lipoprotein (LDL) levels. Yet some experts cite the benefit of early statins in patients with elevated LDL for preventing atherosclerosis. We sought clinical evidence for this early LDL treatment hypothesis.

Methods and results A review of the clinical evidence examining the relationship between LDL reduction and outcomes (excluding LDL >190). We found three arguments proposed in the literature citing clinical evidence supporting the early LDL treatment hypothesis: (1), lower risk patients get relatively more primary prevention benefit from statins than higher risk patients, (2), statins demonstrate a legacy effect with prolonged risk reduction even after stopping treatment, and (3), genetic studies illustrate the benefit of lifelong LDL reduction for lowering CV risk. A review of the primary evidence found little clinical evidence supporting the first two arguments, but strong grade B+ evidence for the third. However, we found no evidence for or against whether intervening before 10-year risk exceeds 7.5-12.5% would result in substantial incremental net clinical benefit. If early intervention is practiced, evidence to date suggests that overall CV risk should be the primary indication.

Conclusions We found consistent grade B+ evidence that the effectiveness of LDL reduction on risk reduction will increase over time, however, we found no clinical evidence for or against whether starting before 10-year CV risk is 7.5–12.5% provides substantive additional net patient benefit, and grade A- evidence that elevated age-adjusted CV risk should be the primary indication for early treatment, but found no evidence for or against whether degree of LDL elevation should be a secondary factor. Additional clinical research is needed, especially with regard the long-term safety of statins and how long it takes for LDL reduction to reach full effectiveness.