Statin therapy and lipoprotein(a) levels: a systematic review and meta-analysis

Aims: Lipoprotein(a) [Lp(a)] is a causal and independent risk factor for cardiovascular disease (CVD). People with elevated Lp(a) are often prescribed statins as they also often show elevated low-density lipoprotein cholesterol (LDL-C) levels. While statins are well-established in lowering LDL-C, their effect on Lp(a) remains unclear. We evaluated the effect of statins compared to placebo on Lp(a) and the effects of different types and intensities of statin therapy on Lp(a). Methods and results: We conducted a systematic review and meta-analysis of randomized trials with a statin and placebo arm. Medline and EMBASE were searched until August 2019. Quality assessment of studies was done using Cochrane risk-of-bias tool (RoB 2). Mean difference of absolute and percentage changes of Lp(a) in the statin vs. the placebo arms were pooled using a random-effects meta-analysis. We compared effects of different types and intensities of statin therapy using subgroup- and network meta-analyses. Certainty of the evidence was determined using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Overall, 39 studies (24 448 participants) were included. Mean differences (95% confidence interval) of absolute and percentage changes in the statin vs. the placebo arms were 1.1 mg/dL (0.5-1.6, P < 0.0001) and 0.1% (-3.6% to 4.0%, P = 0.95), respectively (moderate-certainty evidence). None of the types of statins changed Lp(a) significantly compared to placebo (very low- to high-certainty evidence), as well as intensities of statin therapy (low- to moderate-certainty evidence). Conclusion: Statin therapy does not lead to clinically important differences in Lp(a) compared to placebo in patients at risk for CVD. Our findings suggest that in these patients, statin therapy will not change Lp(a)-associated CVD risk.