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

Abstract

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.

Effect of an increase in Lp(a) following statin therapy on cardiovascular prognosis in secondary prevention population of coronary artery disease

“…An ILLUMINATE trial showed that Lp(a) levels are positively and dose-dependently correlated with atorvastatin dosage [ 9 ]. De Boer et al reported that statins are associated with approximately 1.1 mg/dL increases in Lp(a) levels compared to placebo, whereas high-intensity statins are associated with 2.6 mg/L increases in Lp(a) levels [ 29 ]. Several systematic reviews and meta-analyses most recently indicated that statins increase Lp(a) levels by 10–20% [ 13 , 14 ].…”

Lipoprotein(a) in Atherosclerotic Diseases: From Pathophysiology to Diagnosis and Treatment

“…Accordingly, kits that aim to quantify the mass concentration of Lp(a) are more prone to variation compared to molarity-measuring tests, leading to diverging values of different mass-targeting kits, even within the same population with a standard Lp(a) molar concentration [ 60 , 61 ]. Despite this issue and the apo(a)-insensitive quantifying methods, [ 61 , 62 ] commercial kits measuring Lp(a) in mg/dL instead of estimating its molarity in nmol/L are still amply encountered in practice and the literature [ 63 , 64 ]. Moreover, converting the mass concentration of Lp(a) to its molar equivalent (mg/dL to nmol/L) cannot produce accurate results, although attempts have been made and a rough 2–2.5× conversion factor has been proposed [ 65 ].…”

“…According to recent evidence, conflicting data exist regarding the effect of statins on Lp(a). Although statins remain one the most effective and safest drug category for primary prevention of ASCVD, a recent study revealed a mean 11% increase in Lp(a) levels with their use [ 63 , 243 , 244 ]. Moreover, the ILLUMINATE trial revealed that, in high-risk CVD patients, Lp(a) levels are positively and dose-dependently correlated with atorvastatin dosage [ 245 ].…”

Atherogenic Lipoproteins for the Statin Residual Cardiovascular Disease Risk

“…In an individual-patient data meta-analysis of statin-treated patients, associations of baseline and on-statin treatment Lp(a) with CVD risk were approximately linear, with an increased risk at Lp(a) values equal to or greater than 30 mg/dL for baseline lipoprotein(a) and equal to or greater than 50 mg/dL for on-statin Lp(a) [ 56 ].…”