Effect of statin therapy on plasma proprotein convertase subtilisin kexin 9 (PCSK9) concentrations: a systematic review and meta‐analysis of clinical trials. Issue 11 (14th September 2015)

• Record Type: Journal Article
• Authors: Sahebkar, A.; Simental‐Mendía, L. E.; Guerrero‐Romero, F.; Golledge, J.; Watts, G. F.
• Is Part Of: Diabetes, obesity & metabolism. Volume 17:Issue 11(2015:Nov.)
• Page Start: 1042
• Page End: 1055
• Publication Date: 2015-09-14
• Subjects: Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.12536
• Languages: English
• ISSNs: 1462-8902

Abstract

<abstract abstract-type="main" id="dom12536-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="dom12536-sec-0001" sec-type="section"> <title>Aims</title> <p id="dom12536-para-0001">To evaluate the magnitude of the effect of statin therapy on plasma proprotein convertase subtilisin kexin 9 (PCSK9) levels through a systematic review and meta‐analysis of clinical trials.</p> </sec> <sec id="dom12536-sec-0002" sec-type="section"> <title>Methods</title> <p id="dom12536-para-0002">A random‐effects model (using DerSimonian‐Laird method) and the generic inverse variance method were used for quantitative data synthesis. Heterogeneity was quantitatively assessed using the I<sup>2</sup> index. Sensitivity analyses were conducted using the one‐study remove approach. Random‐effects meta‐regression was performed using an unrestricted maximum likelihood method to evaluate the association between statin‐induced elevation of plasma PCSK9 concentrations with duration of treatment and magnitude of LDL cholesterol reduction.</p> </sec> <sec id="dom12536-sec-0003" sec-type="section"> <title>Results</title> <p id="dom12536-para-0003">A total of 15 clinical trials examining the effects of statin therapy on plasma PCSK9 levels were included. Meta‐analysis of data from single‐arm statin treatment arms [weighted mean difference (WMD) 40.72 ng/ml, 95% confidence interval (CI) 34.79, 46.65; p < 0.001] and randomized placebo‐controlled trials (WMD 22.98 ng/ml, 95% CI 17.95, 28.01; p < 0.001) showed a significant increase in plasma PCSK9 concentrations after statin therapy, irrespective of the type of statin administered in either of the analyses (single‐arm or randomized placebo‐controlled trial). There was no significant elevation of plasma PCSK9 levels with statin/ezetimibe combination therapy compared with statin monotherapy (WMD 23.14 ng/ml, 95% CI −1.97, 48.25; p = 0.071); however, removal of one study in the meta‐analysis yielded a significant result in the sensitivity analysis (WMD 31.41 ng/ml, 95% CI 7.86, 54.97; p = 0.009).</p> </sec> <sec id="dom12536-sec-0004" sec-type="section"> <title>Conclusions</title> <p id="dom12536-para-0004">This meta‐analysis suggests that statin therapy causes a significant increase in plasma PCSK9 concentrations.</p> </sec> </abstract>