Impact of fibrate therapy on plasma plasminogen activator inhibitor-1: a systematic review and meta-analysis of randomized controlled trials

Sahebkar, Amirhossein, Simental-Mendía, Luis E., Watts, Gerald F., and Golledge, Jonathan (2015) Impact of fibrate therapy on plasma plasminogen activator inhibitor-1: a systematic review and meta-analysis of randomized controlled trials. Atherosclerosis, 240 (1). pp. 284-296.

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Objective: The aim of this systematic review was to perform a meta-analysis of randomized controlled trials (RCTs) examining the efficacy of fibrate therapy in reducing plasma concentration or activity of plasminogen activator inhibitor 1 (PAI-1).

Methods: Scopus and MEDLINE databases were searched (up to October 15, 2014) to identify RCTs investigating whether fibrates lower plasma PAI-1 concentration or activity. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. Sensitivity analyses were conducted using the one-study remove approach. Random-effects meta-regression was performed to assess the impact of potential moderators on the estimated effect sizes.

Results: A total of 14 RCTs examining the effects of gemfibrozil (6 trials), bezafibrate (4 trials), and fenofibrate (5 trials) were included. Meta-analysis suggested that fibrate therapy did not significantly reduce plasma PAI-1 concentration (weighed mean difference [WMD]: −11.39 ng/mL, 95% CI: −26.64, 3.85, p = 0.143) or activity (WMD: 2.02 U/mL, 95% CI: −0.87, 4.90, p = 0.170). These results remained unchanged after subgroup analysis according to duration of treatment (<12 and ≥12 weeks) and type of fibrate administered (fenofibrate, bezafibrate or gemfibrozil). The estimated effects of fibrate therapy on plasma concentration and activity of PAI-1 were independent of treatment duration and changes in plasma triglyceride levels in the meta-regression analysis.

Conclusion: This meta-analysis of RCTs suggested that fibrate therapy does not reduce plasma concentration or activity of PAI-I. The putative benefits of fibrate therapy in patients with cardiovascular disease appear to be exerted via mechanisms independent of effects on PAI-1.

Item ID: 39225
Item Type: Article (Research - C1)
ISSN: 1879-1484
Keywords: coronary heart disease; fibric acid; Peroxisome proliferator-activated receptor; plasminogen; thrombosis
Funders: Iran National Science Foundation (INSF), National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: NHMRC grant 1019921, NHMRC grant 1079369, NHMRC grant 1003707, NHMRC grant 1000967, NHMRC grant 1020955
Date Deposited: 18 Jun 2015 03:53
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl Cardiovascular Diseases) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 100%
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