Abstract:
Aims:Canakinumab, a monoclonal antibody targeting interleukin (IL)-1β, reduces rates of recurrent cardiovascular events without lowering lipids. It is uncertain, however, to what extent these beneficial cardiovascular outcomes are mediated through interleukin-6 (IL-6) signalling, an issue with substantial pathophysiologic consequences and therapeutic implications. Methods and results:A total of 4833 stable atherosclerosis patients in the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) had IL-6 levels measured before randomization and after treatment with placebo or one of three doses of canakinumab (50 mg, 150 mg, or 300 mg) given subcutaneously once every 3 months. Participants were followed for up to 5 years (median follow-up 3.7 years). Compared with those allocated to placebo, CANTOS participants receiving canakinumab who achieved on-treatment IL-6 levels below the study median value of 1.65 ng/L experienced a 32% reduction in major adverse cardiovascular events [MACE, multivariable adjusted hazard ratio (HRadj) 0.68, 95% confidence interval (CI) 0.56-0.82; P < 0.0001], a 30% reduction in MACE plus the additional endpoint of hospitalization for unstable angina requiring urgent revascularization (MACE+, HRadj 0.70, 95% CI 0.59-0.84; P < 0.0001), a 52% reduction in cardiovascular mortality (HRadj 0.48, 95% CI 0.34-0.68; P < 0.0001), and a 48% reduction in all-cause mortality (HRadj 0.52, 95% CI 0.40-0.68; P < 0.0001) with prolonged treatment. In contrast, those with on-treatment IL-6 levels equal to or above 1.65 ng/L after taking the first dose of canakinumab had no significant benefit for any of these endpoints. These differential findings based on the magnitude of IL-6 response were seen in analyses alternatively based on tertiles of on-treatment IL-6 levels, and in analyses using a statistical inference approach to estimate the effect of treatment among individuals who would achieve a targeted IL-6 level. Conclusion:CANTOS provides proof of concept evidence in humans that modulation of the IL-6 signalling pathway, at least with canakinumab, associates with reduced cardiovascular event rates, independent of lipid lowering. Clinical trial registration:ClinicalTrials.gov NCT01327846.
journal_name
Eur Heart Jjournal_title
European heart journalauthors
Ridker PM,Libby P,MacFadyen JG,Thuren T,Ballantyne C,Fonseca F,Koenig W,Shimokawa H,Everett BM,Glynn RJdoi
10.1093/eurheartj/ehy310subject
Has Abstractpub_date
2018-10-07 00:00:00pages
3499-3507issue
38eissn
0195-668Xissn
1522-9645pii
5078464journal_volume
39pub_type
杂志文章,随机对照试验abstract::Cardiac beta-adrenoceptor density and subtype distribution has been determined in different kinds of heart failure. A decrease in cardiac beta-adrenoceptor function appears to be a general phenomenon in all kinds of heart failure. However, cardiac beta 1- and beta 2-adrenoceptors seem to be differentially affected in ...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/10.suppl_b.38
更新日期:1989-06-01 00:00:00
abstract:AIMS:The effect of statins on risk of heart failure (HF) hospitalization and HF death remains uncertain. We aimed to establish whether statins reduce major HF events. METHODS AND RESULTS:We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized controlled endpoint statin trials...
journal_title:European heart journal
pub_type: 杂志文章,meta分析,评审
doi:10.1093/eurheartj/ehv072
更新日期:2015-06-21 00:00:00
abstract::We have evaluated overall and cardiac sympathetic activity in 47 patients undergoing coronary angiography, 27 with stable angina of at least 3 months duration, and 20 with unstable ischaemic symptoms within this period. Cardiac and overall sympathetic activity were assessed using radiotracer noradrenaline kinetic tech...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/14.6.751
更新日期:1993-06-01 00:00:00
abstract::The alterations of the beta-adrenoceptor adenylyl cyclase are reviewed. In failing myocardium, the down-regulation of beta 1-adrenoceptors is accompanied by a decrease in steady state mRNA levels, as studied with quantitative polymerase chain reactions in dilated and ischaemic cardiomyopathy. The density of beta 2-adr...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/15.suppl_d.30
更新日期:1994-12-01 00:00:00
abstract:AIMS:To investigate the effects of secretory phospholipase A2 (sPLA(2)) inhibition on plasma lipoproteins. Secretory phospholipase A2 isoenzymes promote atherosclerosis by mechanisms that include lipoprotein modification, retention, and oxidation. METHODS AND RESULTS:Phospholipase Levels And Serological Markers of Ath...
journal_title:European heart journal
pub_type: 杂志文章,随机对照试验
doi:10.1093/eurheartj/ehq374
更新日期:2011-04-01 00:00:00
abstract:AIMS:The coefficient of variation is a popular measure for describing the amount of repeat variability present in ECG measurements from recording to recording. However, it can be misleading. The aim of the present study was to assess repeat variation (reclassification) in computer measured ECG criteria, i.e. positive t...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1053/euhj.1997.0741
更新日期:1998-02-01 00:00:00
abstract::The evaluation for European Union market approval of coronary stents falls under the Medical Device Directive that was adopted in 1993. Specific requirements for the assessment of coronary stents are laid out in supplementary advisory documents. In response to a call by the European Commission to make recommendations ...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/ehv203
更新日期:2015-10-07 00:00:00
abstract::619 patients with suspected acute myocardial infarction (MI) were randomized to receive either a high-dose short-term intravenous infusion of streptokinase (1.5 MU over one hour) or placebo. Using a '2 X 2 X 2 factorial' design, patients were also randomized to receive either oral aspirin (325 mg on alternate days for...
journal_title:European heart journal
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1987-06-01 00:00:00
abstract:AIMS:To examine the relations between genetic loci, plasma lipoprotein(a) [Lp(a)] levels, and cardiovascular disease (CVD) risk among diabetic patients and compare with the observations in the general population. METHODS AND RESULTS:In two prospective cohorts of patients with type 2 diabetes (n= 2308) from the Nurses'...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehr350
更新日期:2012-02-01 00:00:00
abstract::A case of severe iatrogenic fibrous left main coronary artery stenosis following aortic valve replacement (Hall-Kaster prosthesis) is documented clinically, angiographically and histologically. Reported histological data of this rare complication of valve replacement are reviewed. The onset of ischaemic symptoms in th...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a062413
更新日期:1988-10-01 00:00:00
abstract:OBJECTIVE:The purpose of this study was to determine the sensitivity and specificity of new criteria proposed by Duke University for case definition of infective endocarditis as compared to the previously accepted Von Reyn criteria. PATIENTS:A total of 143 consecutive suspected cases of infective endocarditis in 137 f...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a015411
更新日期:1997-07-01 00:00:00
abstract::The haemodynamic side-effects of ionic (amidotrizoate) and non-ionic (iopamidol) contrast media after injection into the right atrium were compared in experimental and clinical studies. Pulmonary hypertension was induced in 10 dogs by embolization of the pulmonary vascular bed with agar-agar solution (mean pulmonary a...
journal_title:European heart journal
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1093/oxfordjournals.eurheartj.a062219
更新日期:1987-12-01 00:00:00
abstract::Left ventricular volume and ejection fraction were measured by 2-dimensional echocardiography from 2 orthogonal apical long axis views in 90 patients admitted with acute transmural myocardial infarction. Results were correlated with worst Killip class during hospital stay, enzymatic infarct size (peak CK-MB) and morta...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a061638
更新日期:1984-03-01 00:00:00
abstract::Left ventricular flow patterns were studied at rest by colour flow Doppler echocardiography in 33 patients with mitral tilting-disc prostheses (group 1), in 38 patients with mitral tissue prostheses (group 2) and in 18 healthy volunteers (controls). A 'crossed' flow pattern was seen in 14 patients with mechanical (42%...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a060494
更新日期:1994-03-01 00:00:00
abstract::Chronic kidney disease (CKD) is associated with high cardiovascular risk. CKD patients exhibit a specific lipoprotein pattern termed 'uraemic dyslipidaemia', which is characterized by rather normal low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, and high triglyceride plasma levels. All t...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehaa1050
更新日期:2021-01-04 00:00:00
abstract:AIMS:To examine the extent of platelet inhibition by prasugrel vs. clopidogrel in a TRITON-TIMI 38 substudy. METHODS AND RESULTS:TRITON-TIMI 38 randomized acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) to prasugrel or standard dose clopidogrel. Selected sites prospectively e...
journal_title:European heart journal
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1093/eurheartj/ehp159
更新日期:2009-07-01 00:00:00
abstract::This study has compared the effect on heart rate control of the addition of pindolol 15 mg bd or verapamil 40 mg tds to maintenance digoxin therapy in 12 patients with chronic atrial fibrillation. The study was performed in a randomized cross-over fashion. Treatment effects were assessed by 24-h ambulatory electrocard...
journal_title:European heart journal
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1093/oxfordjournals.eurheartj.a059386
更新日期:1989-01-01 00:00:00
abstract::A patient with a three-year history of recurrent pulmonary embolism is presented. Thromboembolic pulmonary hypertension was proven in the final stage of disease in the presence of repeated episodes of systemic embolic events. Paradoxical embolism was assumed to be present on the basis of blood-gas analysis and contras...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a062561
更新日期:1988-06-01 00:00:00
abstract:AIMS:Benefits and complications of postoperative implantable cardioverter-defibrillator tests are controversial matters. This study sought to assess the necessity of defibrillation function tests after implantation. METHODS AND RESULTS:We retrospectively analysed 1007 implantable cardioverter-defibrillator tests in 58...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1053/euhj.1999.1716
更新日期:2000-01-01 00:00:00
abstract::The natriuretic peptides are important tools to establish diagnosis and prognosis in heart failure (HF). With application of therapies for HF, changes in both B-type natriuretic peptide (BNP) and its amino terminal cleavage fragment (NT-proBNP) parallel the benefits of the HF therapy applied. This dynamic nature of BN...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/eht463
更新日期:2014-01-01 00:00:00
abstract:AIMS:Quantitative analysis of rest-stress myocardial perfusion magnetic resonance imaging (MRI) can provide assessments of regional myocardial perfusion reserve (MPR). The purpose of this study was to compare regional MPR determined by myocardial perfusion MRI with coronary flow reserve (CFR) by intracoronary Doppler f...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehn521
更新日期:2009-02-01 00:00:00
abstract:Aims:Optimal blood pressure for prevention of cardiovascular (CV) events in patients with Type 2 diabetes mellitus (T2DM) remains uncertain and there is concern for increased risk with low diastolic blood pressure (DBP). This study analysed the association between blood pressure and CV outcomes in high-risk patients wi...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehx809
更新日期:2018-06-21 00:00:00
abstract:AIMS:We evaluated the accuracy of 64-slice computed tomography (CT) to identify ischaemic aetiology of heart failure (IHF). METHODS AND RESULTS:Ninety-three consecutive patients in sinus rhythm with dilated cardiomyopathy but without suspicion of coronary artery disease (CAD) were enrolled when admitted for angiograph...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehn072
更新日期:2008-09-01 00:00:00
abstract:AIMS:Valve compliance might determine the onset of symptoms better than resting measures of aortic stenosis. This study compared valve compliance measured by dobutamine stress echocardiography with resting haemodynamic variables against the end-point of symptoms at low workload during exercise testing. METHODS AND RES...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1016/s0195-668x(03)00235-5
更新日期:2003-07-01 00:00:00
abstract:AIMS:Subjects with lipoprotein(a) [Lp(a)] elevation have increased arterial wall inflammation and cardiovascular risk. In patients at increased cardiovascular risk, arterial wall inflammation is reduced following lipid-lowering therapy by statin treatment or lipoprotein apheresis. However, it is unknown whether lipid-l...
journal_title:European heart journal
pub_type: 杂志文章,随机对照试验
doi:10.1093/eurheartj/ehy862
更新日期:2019-09-01 00:00:00
abstract::The effects of dexamethasone on cultured rat beating heart cells experimentally infected with coxsackievirus B2 were investigated at an early stage (1-3 days) post challenge. Changes in the release of the cardiac enzyme, aspartate amino-transferase (AST), beating %, cytopathic effect (CPE), virus titre, ultrastructure...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/12.suppl_d.39
更新日期:1991-08-01 00:00:00
abstract::The non-invasive quantification of mitral and aortic regurgitation using the left-to-right stroke count ratio (SCR) calculated with gated equilibrium radionuclide ventriculography (RNV), is affected by the overlap of atria and ventricles and the consequent difficult definition of the ventricular regions of interest (R...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a062176
更新日期:1987-10-01 00:00:00
abstract:AIMS:Habitual cigarette smokers, paradoxically, present improved short-term prognosis after acute myocardial infarction, a phenomenon often termed "smoker's paradox". We sought to examine cigarette smokers' post-infarction survival advantage in a countrywide survey of unselected, consecutive patients presenting with ac...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1053/euhj.2000.2315
更新日期:2001-05-01 00:00:00
abstract::The efficacies and safety of nicorandil, 20 mg b.d., and diltiazem, 60 mg t.d., in the treatment of stable angina pectoris were compared in a double-blind randomized parallel group study involving 123 patients. The duration of the study was 3 months. Exercise tolerance tests were performed by the patients when on plac...
journal_title:European heart journal
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1093/eurheartj/14.suppl_b.30
更新日期:1993-07-01 00:00:00
abstract:AIMS:The aim of the study was to evaluate the long-term results of allograft and prosthetic valve replacement in the treatment of infective aortic valve endocarditis with periannular abscess. METHODS:Between March 1988 and March 1996, 65 patients underwent surgery for active aortic valve endocarditis and paravalvular ...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1053/euhj.1999.1877
更新日期:2000-03-01 00:00:00