Effect of lipid-lowering therapies on lipoprotein(a) levels: a meta-analysis of randomized controlled trials

Cardiovascular disease (CVD) is one of the leading causes of death and disability. The prevalence of total CVD cases doubled from 271 million cases in 1990 to 607 million cases in 2020, and the number of CVD deaths steadily rose from 12.1 million cases in 1990 to 19.0 million cases in 2020. Atherosclerosis, a condition where fatty deposits accumulate inside of the arteries and decrease blood flow to the heart muscle, is considered to be the principal driver. Several lipid-lowering therapies (LLTs) were developed for treating this type of disease. But despite administration of the evidence-based therapies, substantial residual risk persists particularly among individuals with known CVDs. Residual cardiovascular (CV) risk has been defined as the risk of CV events that remains despite treatment for or achievement of targets for risk factors such as low-density lipoprotein cholesterol (LDL-C). Several epidemiological studies, Mendelian randomization studies and randomized controlled trials illustrated that lipoprotein(a) [Lp(a)] is a casual risk factor leading to the residual risk in CV prevention. In the attempt of reducing cardiovascular risk, the role of Lp(a) as pharmaceutical target seems to be of great interest. However, no approved therapy for patients with elevated Lp(a) levels is currently available. From this point of view, it is crucial to understand whether available lipid-lowering therapies have an effect also on Lp(a) and how much this could be eventually linked to the reduction of other lipids. According to the Oxford CEBM Levels of Evidence, the systematic reviews and meta-analysis of published randomized controlled trials is considered as the first-level evidence. Since the evidence from literature is conflicting, we will conduct a comprehensive meta-analysis to summarize the data from different sources, provide updated results with increased statistic power and greater accuracy.