A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials investigating the effects of statin therapy on plasma lipid concentrations in HIV-infected patients

Abstract

Statin therapy may lower plasma lipid concentrations, but the evidence in HIV-infected patients is still unclear. Therefore, we aimed to investigate the impact of statin therapy on plasma lipid concentrations through a systematic review of the literature and meta-analysis of available randomized controlled trials (RCTs). The literature search included PUBMED, SCOPUS, Web of Science and Google Scholar up to October 30, 2015. The meta-analysis was performed using either a fixed-effects or random-effect model according to I(2) statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Two investigators independently reviewed the title or abstract, further reviewed the full-texts and extracted information on study characteristics and study outcomes. Meta-analysis of 12 RCTs with 697 participants suggested significant reductions in plasma concentrations of low density lipoprotein (LDL) cholesterol (WMD: -0.72mmol/L [-27.8mg/dL], 95%CI: -1.04, -0.39, p<0.001; I(2)=85.7%), total cholesterol (WMD: -1.03mmol/L [-39.8mg/dL], 95%CI: -1.42, -0.64, p<0.001; I(2)=94.7%) and non-high density lipoprotein cholesterol (non-HDL-C) (WMD: -0.81mmol/L [-31.3mg/dl], 95%CI: -1.32, -0.30, p=0.002; I(2)=76.5%), and elevations in HDL-C (WMD: 0.072mmol/L [2.8mg/dL], 95%CI: 0.053, 0.092, p<0.001; I(2)=0%) following treatment with statins (mostly of moderate-intensity). No significant alteration in plasma triglycerides (TG) concentrations was found (WMD: -0.16mmol/L [-14.2mg/dL], 95%CI: -0.61, 0.29, p=0.475; I(2)=90.2%). All these effects were robust in sensitivity analysis, suggesting that the computed effect is not driven by any single study. In subgroup analysis, no significant difference was found among different statins in terms of changing plasma concentrations of LDL-C, HDL-C and TG. However, atorvastatin was found to be more efficacious in reducing plasma total cholesterol concentrations (p<0.001). In conclusion, the meta-analysis suggested significant reductions in plasma concentrations of LDL-C, total cholesterol and non-HDL-C, and elevations in HDL-C, but no significant alteration in plasma TG following treatment with statins.

HIV-1–Associated Atherosclerosis

“…More recent studies have focused on therapies that reduce immune activation, as well as cholesterol, which may be of benefit, particularly for HIV + individuals because the CVD is driven by traditional and inflammatory factors (3,123). Statins, which are both lipid-lowering and anti-inflammatory, were used in the INTREPID (HIV+ Patients and Treatment with Pitavastatin vs Pravastatin for Dyslipidemia) and the current REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) trial.…”

“…Recent trials (127) indicate that rosuvastatin decreases oxLDL levels early after initiation and is associated with decreased monocyte activation (3,123). This early improvement in oxLDL is linked with improved CIMT, a measurement for atherosclerotic plaque in treated HIV infection (3,123).…”

“…This early improvement in oxLDL is linked with improved CIMT, a measurement for atherosclerotic plaque in treated HIV infection (3,123). There has been a report of a positive effect of rosuvastatin in reducing LDL levels without a substantial modification of activated T cells and levels of CRP, a general immune marker (128).…”

PCSK9 and infection: A potentially useful or dangerous association?

“…Dyslipidemia is a leading risk factor for cardiovascular morbidities and mortalities. In spite of the established role of statins as the mainstay of lipid management (Banach & Serban, et al, ; Banach et al, , ) and numerous pleiotropic actions of these drugs (Chrusciel et al, ; Ferretti, Bacchetti, & Sahebkar, ; Parizadeh et al, ; Sahebkar & Kotani, et al, ; Sahebkar & Serban, et al, ; Serban et al, ), statin‐treated patients have a considerable residual cardiovascular risk that calls for additional LDL lowering (Banach & Aronow, et al, ; Sahebkar & Watts, , ). PCSK9 inhibitors such as evolocumab (formerly AMG 145) and alirocumab (formerly REGN727/SAR236553), are human monoclonal antibodies (mABs) that bind with a high affinity to PCSK9 and suppress its function resulting in a reduction of LDL‐cholesterol levels (Blom et al, ; Giugliano et al, ) and cardiovascular events (Sabatine et al, ).…”

Hepatitis C virus and proprotein convertase subtilisin/kexin type 9: a detrimental interaction to increase viral infectivity and disrupt lipid metabolism

“…Specifically, concern on the use of PCSK9 inhibitors in HCV-infected patients cannot be easily translated to HIV patients, where cholesterol-lowering treatment is often indicated (e.g. statins) and in some cases hampered by drug-to-drug interactions [90]. Conversely, preclinical and clinical studies showed that PCSK9 inhibition promotes pathogen lipid clearance by LDLR, reduces inflammatory signals and improves prognosis among patients with sepsis [15,91].…”