Comparison of the effects of fibrates versus statins on plasma lipoprotein(a) concentrations: a systematic review and meta-analysis of head-to-head randomized controlled trials

BACKGROUND Raised plasma lipoprotein(a) (Lp(a)) concentration is an independent and causal risk factor for atherosclerotic cardiovascular disease. Several types of pharmacological approaches are under evaluation for their potential to reduce plasma Lp(a) levels. There is suggestive evidence that statins and fibrates, two frequently employed lipid-lowering drugs, can lower plasma Lp(a). The present study aims to compare the efficacy of fibrates and statins in reducing plasma concentrations of Lp(a) using a meta-analysis of randomized head-to-head trials. METHODS Medline and Scopus databases were searched to identify randomized head-to-head comparative trials investigating the efficacy of fibrates versus statins in reducing plasma Lp(a) levels. Meta-analysis was performed using a random-effects model, with inverse variance weighted mean differences (WMDs) and 95% confidence intervals (CIs) as summary statistics. The impact of putative confounders on the estimated effect size was explored using random effects meta-regression. RESULTS Sixteen head-to-head comparative trials with a total of 1388 subjects met the eligibility criteria and were selected for this meta-analysis. Meta-analysis revealed a significantly greater effect of fibrates versus statins in reducing plasma Lp(a) concentrations (WMD, -2.70 mg/dL; 95% CI, -4.56 to -0.84; P = 0.004). Combination therapy with fibrates and statins had a significantly greater effect compared with statin monotherapy (WMD, -1.60 mg/dL; 95% CI, -2.93 to -0.26; P = 0.019) but not fibrate monotherapy (WMD, -1.76 mg/dL; 95% CI, -5.44 to +1.92; P = 0.349) in reducing plasma Lp(a) concentrations. The impact of fibrates versus statins in reducing plasma Lp(a) concentrations was not found to be significantly associated with treatment duration (P = 0.788). CONCLUSIONS Fibrates have a significantly greater effect in reducing plasma Lp(a) concentrations than statins. Addition of fibrates to statins can enhance the Lp(a)-lowering effect of statins.