Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies in Adults With Hypercholesterolemia: A Systematic Review and Meta-analysis.
BACKGROUND
Guidelines recommend statins as first-line therapy for dyslipidemia. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new lipid-lowering approach.


OBJECTIVE
To assess the efficacy and safety of PCSK9 antibodies in adults with hypercholesterolemia.


METHODS
MEDLINE, PubMed Central, and Google Scholar; conference proceedings; and the ClinicalTrials.gov registry through 4 April 2015.


METHODS
Phase 2 or 3 randomized, controlled trials (RCTs) comparing treatment using PCSK9 antibodies with no anti-PCSK9 therapy in adults with hypercholesterolemia.


METHODS
Two 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.


RESULTS
Twenty-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.


CONCLUSIONS
Results were derived from study-level data rather than patient-level data, and clinical outcome data are rare.


CONCLUSIONS
PCSK9 antibodies seem to be safe and effective for adults with dyslipidemia.


BACKGROUND
CRC 1116 Masterswitches in Myocardial Ischemia, German Research Council DFG.
Eliano Pio
EP
Navarese
Michalina
M
Kolodziejczak
Volker
V
Schulze
Paul A
PA
Gurbel
Udaya
U
Tantry
Yingfeng
Y
Lin
Maximilian
M
Brockmeyer
David E
DE
Kandzari
Julia M
JM
Kubica
Ralph B
RB
D'Agostino
Jacek
J
Kubica
Massimo
M
Volpe
Stefan
S
Agewall
Dean J
DJ
Kereiakes
Malte
M
Kelm
D000789:Angina, Unstable / Q000517:prevention & control; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control; D002423:Cause of Death; D002784:Cholesterol / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D017270:Lipoprotein(a) / Q000097:blood; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000276:immunology*; D012697:Serine Endopeptidases / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000924:Anticholesteremic Agents; D017270:Lipoprotein(a); D002784:Cholesterol; D003402:Creatine Kinase; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases