• Eliano Pio Navarese, Michalina Kolodziejczak, Volker Schulze, Paul A Gurbel, Udaya Tantry, Yingfeng Lin, Maximilian Brockmeyer, David E Kandzari, Julia M Kubica, Ralph B D'Agostino, Jacek Kubica, Massimo Volpe, Stefan Agewall, Dean J Kereiakes, and Malte Kelm.
• Ann. Intern. Med. 2015 Jul 7; 163 (1): 405140-51.

BackgroundGuidelines recommend statins as first-line therapy for dyslipidemia. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new lipid-lowering approach.PurposeTo assess the efficacy and safety of PCSK9 antibodies in adults with hypercholesterolemia.Data SourcesMEDLINE, PubMed Central, and Google Scholar; conference proceedings; and the ClinicalTrials.gov registry through 4 April 2015.Study SelectionPhase 2 or 3 randomized, controlled trials (RCTs) comparing treatment using PCSK9 antibodies with no anti-PCSK9 therapy in adults with hypercholesterolemia.Data ExtractionTwo investigators independently extracted data on study characteristics and lipid and clinical outcomes, and rated risk of bias of trials. Prespecified primary end points were all-cause and cardiovascular mortality.Data SynthesisTwenty-four RCTs comprising 10 159 patients were included. Compared with no antibody, treatment with PCSK9 antibodies led to marked reductions in low-density lipoprotein cholesterol levels (mean difference, -47.49% [95% CI, -69.64% to -25.35%]; P < 0.001] and other atherogenic lipid fractions, and it reduced all-cause mortality (odds ratio [OR], 0.45 [CI, 0.23 to 0.86]; P = 0.015; heterogeneity P = 0.63; I2 = 0%) and cardiovascular mortality (OR, 0.50 [CI, 0.23 to 1.10]; P = 0.084; heterogeneity P = 0.78; I2 = 0%). The rate of myocardial infarction was significantly reduced with use of PCSK9 antibodies (OR, 0.49 [CI, 0.26 to 0.93]; P = 0.030; heterogeneity P = 0.45; I2 = 0%), and increases in the serum creatine kinase level were reduced (OR, 0.72 [CI, 0.54 to 0.96]; P = 0.026; heterogeneity P = 0.65; I2 = 0%). Serious adverse events did not increase with administration of PCSK9 antibodies.LimitationResults were derived from study-level data rather than patient-level data, and clinical outcome data are rare.ConclusionPCSK9 antibodies seem to be safe and effective for adults with dyslipidemia.Primary Funding SourceCRC 1116 Masterswitches in Myocardial Ischemia, German Research Council DFG.

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