Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomised controlled trial
| Autor: | Paul M Ridker, Jean G MacFadyen, Brendan M Everett, Peter Libby, Tom Thuren, Robert J Glynn, John Kastelein, Wolfgang Koenig, Jacques Genest, Alberto Lorenzatti, John Varigos, Peter Siostrzonek, Peter Sinnaeve, Francisco Fonseca, Jose Nicolau, Nina Gotcheva, Huo Yong, Miguel Urina-Triana, Davor Milicic, Renata Cifkova, Riina Vettus, Stephan D Anker, Athanasios J Manolis, Fernando Wyss, Tamas Forster, Axel Sigurdsson, Prem Pais, Alessandro Fucili, Hisao Ogawa, Hiroaki Shimokawa, Irina Veze, Birute Petrauskiene, Leon Salvador, Jan Hein Cornel, Tor Ole Klemsdal, Felix Medina, Andrzej Budaj, Luminita Vida-Simiti, Zhanna Kobalava, Petar Otasevic, Daniel Pella, Mitja Lainscak, Ki-Bae Seung, Patrick Commerford, Mikael Dellborg, Marc Donath, Juey-Jen Hwang, Hakan Kultursay, Marcus Flather, Christie Ballantyne, Seth Bilazarian, William Chang, Cara East, Les Forgosh, Barry Harris, Monica Ligueros |
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| Přispěvatelé: | ACS - Atherosclerosis & ischemic syndromes, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Interleukin-1beta Myocardial Infarction 030204 cardiovascular system & hematology Placebo Antibodies Monoclonal Humanized law.invention 03 medical and health sciences 0302 clinical medicine Randomized controlled trial law Internal medicine medicine Humans Myocardial infarction cardiovascular diseases Mortality Randomized Controlled Trials as Topic biology business.industry C-reactive protein Hazard ratio Confounding Antibodies Monoclonal General Medicine Middle Aged medicine.disease Thrombosis Lipids Surgery Canakinumab 030104 developmental biology C-Reactive Protein biology.protein Female business medicine.drug |
| Zdroj: | Lancet, 391(10118), 319-328. Elsevier Limited |
| ISSN: | 1474-547X 0140-6736 |
| Popis: | Background: Canakinumab, a monoclonal antibody targeting interleukin-1β reduces inflammation and cardiovascular event rates with no effect on lipid concentrations. However, it is uncertain which patient groups benefit the most from treatment and whether reductions in the inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) correlate with clinical benefits for individual patients. Methods: The Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) used computer-generated codes to randomly allocate 10 061 men and women with a history of myocardial infarction to placebo or one of three doses of canakinumab (50 mg, 150 mg, or 300 mg) given subcutaneously once every 3 months. In a prespecified secondary analysis designed to address the relationship of hsCRP reduction to event reduction in CANTOS, we evaluated the effects of canakinumab on rates of major adverse cardiovascular events, cardiovascular mortality, and all-cause mortality according to on-treatment concentrations of hsCRP. We used multivariable modelling to adjust for baseline factors associated with achieved hsCRP and multiple sensitivity analyses to address the magnitude of residual confounding. The median follow-up was 3·7 years. The trial is registered with ClinicalTrials.gov, number NCT01327846. Findings: Baseline clinical characteristics did not define patient groups with greater or lesser cardiovascular benefits when treated with canakinumab. However, trial participants allocated to canakinumab who achieved hsCRP concentrations less than 2 mg/L had a 25% reduction in major adverse cardiovascular events (multivariable adjusted hazard ratio [HRadj]=0·75, 95% CI 0·66–0·85, p |
| Databáze: | OpenAIRE |
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