Systematic review and meta-analysis deciphering the impact of fibrates on paraoxonase-1 status

Objective A significant residual cardiovascular risk is consistently observed in patients treated with statins. A combined treatment with fibrates reduces cardiovascular events in very high-risk patients. Because this is apparently unconnected to an improvement in lipid-related outcomes we hypothesized that the cardioprotective effects of fibrates might be associated with an improvement in paraoxonase-1 (PON1) status. Method The search for existing evidence, using the Medline, Scopus and Cochrane databases, was systematic and followed the PRISMA statement without restrictions on publication date. We excluded non-clinical and observational studies and we extracted data on baseline and post-treatment values of serum PON1 activity and other measurements of PON1 status. Results Nine studies (including 12 treatment arms) in patients with hyperlipidemia, diabetes or metabolic syndrome treated with fibrates, alone or in combination with statins, were included to synthesize results. A meta-analysis of the data using a random-effects model revealed a significant increase in serum PON1 activity following fibrate therapy (WMD: 15.64 U/L, 95% CI: 6.94, 24.34, p < 0.001), an effect that was robust and not sensitive to any particular study. Subgroup analysis indicated differences in the effect size among types of fibrates and that PON1 alterations were associated with high-density lipoprotein cholesterol changes following fibrate therapy. Conclusions Results indicate a significant PON1-enhancing effect of fibrates. Whether this effect is associated with a clinical benefit, although likely, remains to be further investigated.