Subject(s)
Cardiovascular Diseases , Hypertriglyceridemia/blood , Triglycerides/blood , Biomarkers/blood , Cardiovascular Diseases/blood , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cholesterol, VLDL/blood , Humans , Hypertriglyceridemia/complications , Morbidity/trends , United States/epidemiologySubject(s)
Atrial Fibrillation/drug therapy , Adrenergic beta-Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Anti-Arrhythmia Agents/therapeutic use , Anticoagulants/therapeutic use , Atrial Fibrillation/physiopathology , Biomarkers/blood , Catheter Ablation , Diabetes Mellitus/physiopathology , Diastole/physiology , Dilatation, Pathologic/physiopathology , Heart Atria/physiopathology , Heart Failure/physiopathology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Medication Adherence , Postoperative Complications , Risk Assessment , Stroke/etiology , Stroke/prevention & control , Stroke Volume/physiology , Systole/physiologySubject(s)
Angioplasty, Balloon, Coronary , Coronary Disease/therapy , Drug-Eluting Stents , Acetanilides/therapeutic use , Acute Coronary Syndrome/physiopathology , Acute Coronary Syndrome/therapy , Angina Pectoris/diagnosis , Angioplasty, Balloon, Coronary/economics , Angiotensin Receptor Antagonists/economics , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/economics , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antithrombins/economics , Antithrombins/therapeutic use , C-Reactive Protein/analysis , Cholesterol, LDL/blood , Clinical Trials as Topic , Coronary Angiography , Coronary Artery Bypass , Coronary Circulation , Coronary Disease/physiopathology , Coronary Thrombosis/diagnosis , Coronary Thrombosis/therapy , Cost-Benefit Analysis , Diabetes Mellitus/epidemiology , Enzyme Inhibitors/therapeutic use , Heart/diagnostic imaging , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/economics , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Life Style , Medical History Taking , Medication Adherence , Multidetector Computed Tomography , Myocardial Ischemia/diagnosis , Myocardial Ischemia/therapy , Piperazines/therapeutic use , Platelet Aggregation Inhibitors/economics , Platelet Aggregation Inhibitors/therapeutic use , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Radionuclide Imaging , Ranolazine , Risk Factors , Troponin/bloodABSTRACT
CONTEXT: Ustekinumab and briakinumab, monoclonal antibodies to the shared p40 subunit of interleukin (IL)-12 and IL-23, have shown efficacy in treating chronic plaque psoriasis (CPP). Preliminary reports of major adverse cardiovascular events (MACEs) in psoriasis patients receiving anti-IL-12/23 agents have prompted concern. OBJECTIVE: To evaluate a possible association between biologic therapies for CPP and MACEs via meta-analysis. DATA SOURCES: Randomized controlled trials (RCTs) of anti-IL-12/23 (ustekinumab and briakinumab) agents and anti-tumor necrosis factor α (TNF-α) agents (adalimumab, etanercept, and infliximab) used in treating CPP were reviewed using the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Ovid MEDLINE from database inception to May 2011. The results of registered nonpublished completed studies were procured through abstract publications or poster presentations. STUDY SELECTION: Randomized, placebo-controlled, double-blind, monotherapy studies (with safety outcome data for MACE) of IL-12/23 antibodies and anti-TNF-α agents in adults. Studies of psoriatic arthritis were excluded. DATA EXTRACTION: Two investigators independently searched data while 6 investigators reviewed the abstracted data. RESULTS: A total of 22 RCTs comprising 10 183 patients met the predefined inclusion criteria. The primary outcome measure was MACE, a composite end point of myocardial infarction, cerebrovascular accident, or cardiovascular death during the placebo-controlled phase of treatment in patients receiving at least 1 dose of study agent or placebo. Absolute risk differences were used as an effect measure. There was no evidence of statistical heterogeneity across the studies using the I(2) statistic (I(2) = 0), allowing for combination of trial results using the Mantel-Haenszel fixed-effects method. During the placebo-controlled phases of the anti-IL-12/23 studies, 10 of 3179 patients receiving anti-IL-12/23 therapies experienced MACEs compared with zero events in 1474 patients receiving placebo (Mantel-Haenszel risk difference, 0.012 events/person-year; 95% confidence interval [CI], -0.001 to 0.026; P =.12). In the anti-TNF-α trials, only 1 of 3858 patients receiving anti-TNF-α agents experienced a MACE compared with 1 of 1812 patients receiving placebo (Mantel-Haenszel risk difference, -0.0005 events/person-year; 95% CI, -0.010 to 0.009; P = .94). CONCLUSIONS: Compared with placebo, there was no significant difference in the rate of MACEs observed in patients receiving anti-IL-12/IL-23 antibodies or anti-TNF-α treatments. This study may have been underpowered to identify a significant difference.
Subject(s)
Antibodies, Monoclonal/adverse effects , Cardiovascular Diseases/chemically induced , Immunoglobulin G/adverse effects , Immunologic Factors/adverse effects , Myocardial Infarction/chemically induced , Psoriasis/drug therapy , Stroke/chemically induced , Adalimumab , Adolescent , Adult , Aged , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Double-Blind Method , Etanercept , Humans , Immunoglobulin G/therapeutic use , Immunologic Factors/therapeutic use , Infliximab , Interleukin-12 , Interleukin-23 , Middle Aged , Placebos , Randomized Controlled Trials as Topic , Receptors, Tumor Necrosis Factor/therapeutic use , Risk , Tumor Necrosis Factor-alpha , Ustekinumab , Young AdultSubject(s)
Contrast Media/adverse effects , Kidney Diseases/chemically induced , Aged , Aged, 80 and over , Coronary Angiography , Creatinine/blood , Female , Glomerular Filtration Rate , Humans , Kidney Diseases/diagnosis , Kidney Diseases/physiopathology , Male , Osmolar Concentration , Practice Guidelines as Topic , Risk FactorsSubject(s)
Fluorobenzenes/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Sulfonamides/therapeutic use , C-Reactive Protein/analysis , Cholesterol, LDL/blood , Clinical Trials as Topic , Female , Humans , Male , Middle Aged , Myocardial Infarction/prevention & control , Rosuvastatin CalciumSubject(s)
Death, Sudden, Cardiac/prevention & control , Defibrillators, Implantable , Heart Failure/therapy , Primary Prevention , Ventricular Dysfunction, Left/therapy , Anti-Arrhythmia Agents/therapeutic use , Education, Medical, Continuing/organization & administration , Heart Failure/diagnosis , Humans , Primary Prevention/methods , Risk Assessment , Risk Factors , Treatment OutcomeSubject(s)
Arthritis, Rheumatoid/complications , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Cardiovascular Diseases/diagnosis , Humans , Randomized Controlled Trials as Topic , Risk Assessment , Risk FactorsSubject(s)
Cardiology/organization & administration , Cardiovascular Diseases/therapy , Health Care Reform/organization & administration , Canada , Cardiology/legislation & jurisprudence , Congresses as Topic , Health Care Reform/legislation & jurisprudence , Humans , Insurance Coverage/organization & administration , Liability, Legal , Medically Uninsured/legislation & jurisprudence , Poverty , Single-Payer System/organization & administration , United States , Universal Health Insurance/organization & administrationSubject(s)
Angioplasty, Balloon, Coronary , Hyperbaric Oxygenation/methods , Myocardial Infarction/therapy , Myocardial Reperfusion/methods , Oxygen/therapeutic use , Humans , Radiopharmaceuticals , Technetium Tc 99m Sestamibi , Tomography, Emission-Computed, Single-Photon , Ventricular Dysfunction, Left/prevention & control , Ventricular Function, LeftABSTRACT
ACKNOWLEDGMENT: This Editors' Consensus is supported by an educational grant from Colgate-Palmolive, Inc., New York, New York, and is based on a meeting of the authors held in Boston, Massachusetts, on January 9, 2009. DISCLOSURE: Dr. Friedewald has received honoraria for speaking from Novartis, East Hanover, New Jersey. Dr. Kornman is a full-time employee and shareholder of Interleukin Genetics, Waltham, Massachusetts, which owns patents on genetic biomarkers for chronic inflammatory diseases. Dr. Genco is a consultant to Merck, Whitehouse Station, New Jersey. Dr. Ridker has received research support from AstraZeneca, Wilmington, Delaware; Novartis; Pfizer, New York, New York; Roche, Nutley, New Jersey; Sanofi-Aventis, Bridgewater, New Jersey; and Abbott Laboratories, Abbott Park, Illinois. Dr. Ridker has received non-financial research support from Amgen, Thousand Oaks, California. Dr. Ridker is a co-inventor on patents held by Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease. Dr. Ridker is a research consultant for Schering-Plough, Kenilworth, New Jersey; Sanofi-Aventis; AstraZeneca; Isis, Carlsbad, California; Novartis; and Vascular Biogenics, Tel Aviv, Israel. Dr. Van Dyke is a co-inventor on patents held by Boston University, Boston, Massachusetts, that relate to inflammation control, including consulting fees. Dr. Roberts has received honoraria for speaking from Merck, Schering-Plough, AstraZeneca, and Novartis. All other individuals in a position to control content disclosed no relevant financial relationships.