BACKGROUND: Guidelines recommend statins as first-line therapy for dyslipidemia. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) are a new lipid-lowering approach. PURPOSE: To assess the efficacy and safety of PCSK9 antibodies in adults with hypercholesterolemia. DATA SOURCES: MEDLINE, PubMed Central, and Google Scholar; conference proceedings; and the ClinicalTrials.gov registry through 4 April 2015. STUDY SELECTION: Phase 2 or 3 randomized, controlled trials (RCTs) comparing treatment using PCSK9 antibodies with no anti-PCSK9 therapy in adults with hypercholesterolemia. DATA EXTRACTION: 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. DATA SYNTHESIS: 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. LIMITATIONS: Results were derived from study-level data rather than patient-level data, and clinical outcome data are rare. CONCLUSION: PCSK9 antibodies seem to be safe and effective for adults with dyslipidemia.
Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies in Adults With Hypercholesterolemia: A Systematic Review and Meta-analysis / Navarese, Ep; Kolodziejczak, M; Schulze, V; Gurbel, Pa; Tantry, U; Lin, Y; Brockmeyer, M; Kandzari, De; Kubica, Jm; D'Agostino RB, Sr; Kubica, J; Volpe, Massimo; Agewall, S; Kereiakes, Dj; Kelm, M.. - In: ANNALS OF INTERNAL MEDICINE. - ISSN 0003-4819. - (2015). [10.7326/M14-2957]
Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies in Adults With Hypercholesterolemia: A Systematic Review and Meta-analysis.
VOLPE, Massimo;
2015
Abstract
BACKGROUND: Guidelines recommend statins as first-line therapy for dyslipidemia. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) are a new lipid-lowering approach. PURPOSE: To assess the efficacy and safety of PCSK9 antibodies in adults with hypercholesterolemia. DATA SOURCES: MEDLINE, PubMed Central, and Google Scholar; conference proceedings; and the ClinicalTrials.gov registry through 4 April 2015. STUDY SELECTION: Phase 2 or 3 randomized, controlled trials (RCTs) comparing treatment using PCSK9 antibodies with no anti-PCSK9 therapy in adults with hypercholesterolemia. DATA EXTRACTION: 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. DATA SYNTHESIS: 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. LIMITATIONS: Results were derived from study-level data rather than patient-level data, and clinical outcome data are rare. CONCLUSION: PCSK9 antibodies seem to be safe and effective for adults with dyslipidemia.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
