The negative results of numerous trials call into question the validity of using low density lipoprotein (LDL) cholesterol as a surrogate target for the prevention of cardiovascular disease (CVD), say the authors of a review of published evidence.
The systematic review included randomised controlled trials (RCTs) of cholesterol reduction with a statin, ezetimibe, or a PCSK9 inhibitor. LDL-C reduction targets were ≥30 per cent for moderate-risk and ≥50 per cent for high-risk individuals.
The majority of studies were of “excellent quality and had a low overall risk of bias”.
Of 13 RCTs that met the target, only one reported a mortality benefit and five reported a reduction in CVD events. Of 22 that did not meet the target, four reported a mortality benefit and 14 reported a reduction in CVD events.
A beneficial reduction in cardiovascular events was seen with reductions as little as 11-15 per cent, while a lack of cardiovascular benefit was seen with reductions of ≥50 per cent.
“This analysis highlights the discordance between a well-researched clinical guideline written by experts and empirical evidence gleaned from dozens of clinical trials of cholesterol reduction,” say the authors.
The review has a number of limitations that must be considered when interpreting the results.