Systematic Review and Network Meta-Analysis on the Efficacy of Evolocumab and Other Therapies for the Management of Lipid Levels in Hyperlipidemia

Peter P. Toth*, Gillian Worthy, Shravanthi R. Gandra, Naveed Sattar, Sarah Bray, Lung-I Cheng, Ian Bridges, Gavin M. Worth, Ricardo Dent, Carol A. Forbes, Sohan Deshpande, Janine Ross, Jos Kleijnen, Erik S. G. Stroes

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

44 Citations (Web of Science)

Abstract

Background-The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab substantially reduce low-density lipoprotein cholesterol (LDL-C) when added to statin therapy in patients who need additional LDL-C reduction.

Methods and Results-We conducted a systematic review and network meta-analysis of randomized trials of lipid-lowering therapies from database inception through August 2016 (45 058 records retrieved). We found 69 trials of lipid-lowering therapies that enrolled patients requiring further LDL-C reduction while on maximally tolerated medium-or high-intensity statin, of which 15 could be relevant for inclusion in LDL-C reduction networks with evolocumab, alirocumab, ezetimibe, and placebo as treatment arms. PCSK9 inhibitors significantly reduced LDL-C by 54% to 74% versus placebo and 26% to 46% versus ezetimibe. There were significant treatment differences for evolocumab 140 mg every 2 weeks at the mean of weeks 10 and 12 versus placebo (-74.1%; 95% credible interval -79.81% to -68.58%), alirocumab 75 mg (-20.03%; 95% credible interval -27.32% to -12.96%), and alirocumab 150 mg (-13.63%; 95% credible interval -22.43% to -5.33%) at >= 12 weeks. Treatment differences were similar in direction and magnitude for PCSK9 inhibitor monthly dosing. Adverse events were similar between PCSK9 inhibitors and control. Rates of adverse events were similar between PCSK9 inhibitors versus placebo or ezetimibe.

Conclusions-PCSK9 inhibitors added to medium-to high-intensity statin therapy significantly reduce LDL-C in patients requiring further LDL-C reduction. The network meta-analysis showed a significant treatment difference in LDL-C reduction for evolocumab versus alirocumab.

Original languageEnglish
Article numbere005367
Number of pages13
JournalJournal of the American Heart Association
Volume6
Issue number10
DOIs
Publication statusPublished - Oct 2017

Keywords

  • alirocumab
  • evidence-based medicine
  • evolocumab
  • ezetimibe
  • lipids
  • low-density lipoprotein cholesterol
  • meta-analysis
  • proprotein convertase subtilisin/kexin type 9 inhibitor
  • statin therapy
  • HIGH CARDIOVASCULAR-RISK
  • SUBTILISIN/KEXIN TYPE 9
  • HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA
  • RANDOMIZED CONTROLLED-TRIAL
  • TREATED JAPANESE PATIENTS
  • ACUTE CORONARY SYNDROMES
  • ODYSSEY OPTIONS I
  • ISPOR TASK-FORCE
  • MONOCLONAL-ANTIBODY
  • STATIN THERAPY

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