Mehta S.R.,Hamilton Health Sciences |
Bassand J.-P.,University Hospital Jean Minjoz |
Chrolavicius S.,Hamilton Health Sciences |
Diaz R.,Estudios Clinicos Latinoamerica |
And 10 more authors.
New England Journal of Medicine | Year: 2010
Background: Clopidogrel and aspirin are widely used for patients with acute coronary syndromes and those undergoing percutaneous coronary intervention (PCI). However, evidence-based guidelines for dosing have not been established for either agent. Methods: We randomly assigned, in a 2-by-2 factorial design, 25,086 patients with an acute coronary syndrome who were referred for an invasive strategy to either double-dose clopidogrel (a 600-mg loading dose on day 1, followed by 150 mg daily for 6 days and 75 mg daily thereafter) or standard-dose clopidogrel (a 300-mg loading dose and 75 mg daily thereafter) and either higher-dose aspirin (300 to 325 mg daily) or lower-dose aspirin (75 to 100 mg daily). The primary outcome was cardiovascular death, myocardial infarction, or stroke at 30 days. Results: The primary outcome occurred in 4.2% of patients assigned to double-dose clopidogrel as compared with 4.4% assigned to standard-dose clopidogrel (hazard ratio, 0.94; 95% confidence interval [CI], 0.83 to 1.06; P = 0.30). Major bleeding occurred in 2.5% of patients in the double-dose group and in 2.0% in the standard-dose group (hazard ratio, 1.24; 95% CI, 1.05 to 1.46; P = 0.01). Double-dose clopidogrel was associated with a significant reduction in the secondary outcome of stent thrombosis among the 17,263 patients who underwent PCI (1.6% vs. 2.3%; hazard ratio, 0.68; 95% CI, 0.55 to 0.85; P = 0.001). There was no significant difference between higher-dose and lower-dose aspirin with respect to the primary outcome (4.2% vs. 4.4%; hazard ratio, 0.97; 95% CI, 0.86 to 1.09; P = 0.61) or major bleeding (2.3% vs. 2.3%; hazard ratio, 0.99; 95% CI, 0.84 to 1.17; P = 0.90). Conclusions: In patients with an acute coronary syndrome who were referred for an invasive strategy, there was no significant difference between a 7-day, double-dose clopidogrel regimen and the standard-dose regimen, or between higher-dose aspirin and lower-dose aspirin, with respect to the primary outcome of cardiovascular death, myocardial infarction, or stroke. (Funded by Sanofi-Aventis and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00335452.) Copyright © 2010 Massachusetts Medical Society. All rights reserved.
Mega J.L.,Harvard University |
Braunwald E.,Harvard University |
Wiviott S.D.,Harvard University |
Bassand J.-P.,University Hospital Jean Minjoz |
And 14 more authors.
New England Journal of Medicine | Year: 2012
BACKGROUND: Acute coronary syndromes arise from coronary atherosclerosis with superimposed thrombosis. Since factor Xa plays a central role in thrombosis, the inhibition of factor Xa with low-dose rivaroxaban might improve cardiovascular outcomes in patients with a recent acute coronary syndrome. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned 15,526 patients with a recent acute coronary syndrome to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months. The primary efficacy end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke. RESULTS: Rivaroxaban significantly reduced the primary efficacy end point, as compared with placebo, with respective rates of 8.9% and 10.7% (hazard ratio in the rivaroxaban group, 0.84; 95% confidence interval [CI], 0.74 to 0.96; P = 0.008), with significant improvement for both the twice-daily 2.5-mg dose (9.1% vs. 10.7%, P = 0.02) and the twice-daily 5-mg dose (8.8% vs. 10.7%, P = 0.03). The twice-daily 2.5-mg dose of rivaroxaban reduced the rates of death from cardiovascular causes (2.7% vs. 4.1%, P = 0.002) and from any cause (2.9% vs. 4.5%, P = 0.002), a survival benefit that was not seen with the twice-daily 5-mg dose. As compared with placebo, rivaroxaban increased the rates of major bleeding not related to coronary-artery bypass grafting (2.1% vs. 0.6%, P<0.001) and intracranial hemorrhage (0.6% vs. 0.2%, P = 0.009), without a significant increase in fatal bleeding (0.3% vs. 0.2%, P = 0.66) or other adverse events. The twice-daily 2.5-mg dose resulted in fewer fatal bleeding events than the twice-daily 5-mg dose (0.1% vs. 0.4%, P = 0.04). CONCLUSIONS: In patients with a recent acute coronary syndrome, rivaroxaban reduced the risk of the composite end point of death from cardiovascular causes, myocardial infarction, or stroke. Rivaroxaban increased the risk of major bleeding and intracranial hemorrhage but not the risk of fatal bleeding. (Funded by Johnson & Johnson and Bayer Healthcare; ATLAS ACS 2-TIMI 51 ClinicalTrials.gov number, NCT00809965.) Copyright © 2011 Massachusetts Medical Society.
Gibson C.M.,Beth Israel Deaconess Medical Center |
Gibson C.M.,Harvard University |
Chakrabarti A.K.,Beth Israel Deaconess Medical Center |
Mega J.,Harvard University |
And 11 more authors.
Journal of the American College of Cardiology | Year: 2013
Objectives The aim of this study was to determine if rivaroxaban is associated with a reduction in stent thrombosis among patients with acute coronary syndromes (ACS) in the ATLAS-ACS 2 TIMI 51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects With Acute Coronary Syndrome - Thrombolysis in Myocardial Infarction 51) trial. Background Dual antiplatelet therapy (DAPT) has been the mainstay of efforts to prevent stent thrombosis. Because thrombin is a potent stimulant of platelet activation, we hypothesized that inhibition of thrombin generation via factor Xa inhibition may further reduce the risk of stent thrombosis. Methods The ATLAS-ACS 2 TIMI 51 study was a placebo-controlled trial that randomly assigned 15,526 patients with recent ACS to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months. Results Among patients who had a stent placed before or at the time of the index event, rivaroxaban significantly reduced independently adjudicated Academic Research Consortium definite and probable stent thrombosis in the pooled (1.9% vs. 1.5%; hazard ratio [HR]: 0.65; p = 0.017) and the 2.5 mg twice-daily (1.9% vs. 1.5%; HR: 0.61; p = 0.023) treatment groups when compared with placebo, with a trend toward a reduction in the 5 mg twice-daily treatment group (1.9% vs. 1.5%; HR: 0.70; p = 0.089). Among patients who received both aspirin and a thienopyridine (stratum 2), the benefit of rivaroxaban emerged during the period of active treatment with DAPT (HR: 0.68; 95% CI: 0.50 to 0.92, combined rivaroxaban group vs. placebo). Among stented patients who were treated with dual antiplatelet therapy, there was a mortality reduction among those treated with twice-daily rivaroxaban 2.5 mg (HR: 0.56; 95% CI: 0.35 to 0.89; p = 0.014). Conclusions Among stented patients with ACS treated with DAPT, the administration of twice-daily rivaroxaban 2.5 mg was associated with a reduction in stent thrombosis and mortality. (An Efficacy and Safety Study for Rivaroxaban in Patients With Acute Coronary Syndrome; NCT00809965) © 2013 by the American College of Cardiology Foundation.
Toussirot E.,University Hospital Jean Minjoz |
Toussirot E.,University of Franche Comte |
Toussirot E.,University Hospital St Jacques
Drugs and Aging | Year: 2010
Ankylosing spondylitis (AS) and spondylarthritis (SpA) are generally observed in young male patients but can be diagnosed in the elderly. These cases correspond to late-onset or late-diagnosed AS or SpA. The clinical presentation may be either typical axial disease with a more severe illness compared with young-onset disease, or peripheral oligoarthritis of the lower limbs with pitting oedema (late-onset peripheral spondylarthropathy). New criteria for axial SpA including MRI-determined modifications of the sacroiliac joints may help the clinician with diagnosis. The treatment options for late-onset-diagnosed AS include the same drugs as those taken by patients with young-onset AS, i.e. NSAIDs, sulfasalazine and anti-tumour necrosis factor (TNF)-α agents. Anti-TNFα agents are very effective drugs in young-onset AS and SpA. However, the effectiveness and safety of this drug class has not been specifically evaluated in elderly ASSpA patients, and caution is therefore required with use of these drugs in elderly patients with co-morbidities andor polypharmacy. In particular, careful evaluation for the risk of infection and cardiovascular events is recommended before initiating anti-TNFα agents in this age category. However, safety data from elderly patients with rheumatoid arthritis seem reassuring. With the increasing life expectancy and the new diagnostic modalities for axial (and peripheral) SpA, it is likely that the number of patients (diagnosed) with late-onset ASSpA will increase. Thus, the clinician must be familiar with the clinical characteristics and particularities of this group of inflammatory rheumatic diseases. © 2010 Adis Data Information BV. All rights reserved.
Gallinet D.,Saint Vincent Private Hospital |
Adam A.,University Hospital Jean Minjoz |
Gasse N.,University Hospital Jean Minjoz |
Rochet S.,University Hospital Jean Minjoz |
Obert L.,University Hospital Jean Minjoz
Journal of Shoulder and Elbow Surgery | Year: 2013
Hypothesis: Reverse shoulder arthroplasty in complex shoulder fractures is now a common practice. Unfortunately, loss of rotation is observed when tuberosity excision is used, impairing function and patient satisfaction. The purpose of this study was to evaluate the advantage of tuberosity repair in terms of the functional result. Materials and methods: We reviewed 41 patients, with a mean age at trauma of 76.9 years, at a mean follow-up of 24 months. Tuberosities were repaired in 27 patients and totally removed in the other 14 cases. Results: Two-thirds of the repaired tuberosities consolidated in anatomic position. We compared a group with tuberosity healing in anatomic position versus a group without repair and with malunion or nonunion of the tuberosities. In the first group, all sectors of motion, especially external rotation (49° vs 10°), were improved and both Constant scores (65 vs 50) and Disabilities of the Arm, Shoulder and Hand scores (30 vs 40) were significantly better. Conclusion: Management of complex fractures of the superior extremity of the humerus by reverse shoulder arthroplasty is an accepted approach, but such treatment is restricted to elderly patients. Shoulder rotational ability is improved by systematically repairing the tuberosities around the implant. However, their consolidation should be anatomic; otherwise, the result is impaired by the lack of rotation. Nonunion or malunion does not lead to a functional disaster, as is sometimes the case with hemiarthroplasty without tuberosity healing. © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees.
Toussirot E.,University Hospital Jean Minjoz |
Toussirot E.,University of Franche Comte |
Toussirot E.,St Jacques Hospital
Inflammation and Allergy - Drug Targets | Year: 2010
Functional disability in rheumatoid arthritis (RA) reflects the cumulative effects of the disease over time and is an important outcome measure. Various factors are responsible for functional disability, such as pain, swollen joints, joint tenderness and damage, deformities but also fatigue and depression. The most commonly used instrument for evaluating functional disability in RA is the health assessment questionnaire (HAQ), a self reported questionnaire. Numerous longitudinal studies have attempted to identify predictors of disability in RA and their results show that the most common variables associated with future disability are baseline HAQ or its variation during the first year of follow-up, female sex and old age. The HAQ score is a valuable indicator of disability in RA and has been shown to be predictive of loss of employment and mortality in RA. It may therefore be regarded as a relevant outcome variable in clinical trials and for the management of patients with RA in clinical practice. © 2010 Bentham Science Publishers Ltd.
Meneveau N.,University Hospital Jean Minjoz
Current Opinion in Cardiology | Year: 2010
PURPOSE OF REVIEW: Acute pulmonary embolism remains associated with high morbidity and mortality rates despite currently available therapeutic options. This review outlines the most recent changes in this field and summarizes the main indications for thrombolytic therapy and surgical or catheter-based embolectomy in patients with high-risk pulmonary embolism. RECENT FINDINGS: There have been no major advances in therapy for high-risk pulmonary embolism over the past few years. The main change concerns risk stratification, which now classifies patients as high risk versus intermediate or low risk, replacing the former terminology of acute massive, submassive or nonmassive pulmonary embolism. Risk stratification is now oriented toward evaluation of the risk of early pulmonary embolism-related death. Thrombolysis is the mainstay of therapy in high-risk pulmonary embolism. Surgical embolectomy has become more frequent, due to the reduction in mortality risk associated with this technique. However, it remains limited to patients unsuitable for thrombolysis. Catheter-based embolectomy is reserved for situations in which neither thrombolysis nor surgical embolectomy is possible. SUMMARY: Thrombolytic treatment should be first-line therapy in patients with high-risk pulmonary embolism presenting with cardiogenic shock and/or persistent arterial hypotension, with very few absolute contraindications. Both surgical and catheter pulmonary embolectomy are valuable therapeutic options in patients in whom thrombolysis is absolutely contraindicated or has failed. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Bassand J.-P.,University Hospital Jean Minjoz
Europace | Year: 2012
Atrial fibrillation (AF) is strongly associated with cardioembolic stroke, and thromboprophylaxis is an established means of reducing stroke risk in patients with AF. Oral vitamin K antagonists such as warfarin have been the mainstay of therapy for stroke prevention in patients with AF. However, they are associated with a number of limitations, including excessive bleeding when not adequately controlled. Antiplatelet agents do not match vitamin K antagonists in terms of their preventive efficacy. Dual-antiplatelet therapy (clopidogrel and acetylsalicylic acid) or combined antiplateletvitamin K antagonist therapy in AF has also failed to provide convincing evidence of their additional benefit over vitamin K antagonists alone. Novel oral anticoagulants, including the direct thrombin inhibitor dabigatran and direct Factor Xa inhibitors such as rivaroxaban, apixaban, and edoxaban, have now been approved or are currently in late-stage clinical development in AF. These newer agents may provide a breakthrough in the optimal management of stroke risk. © The Author 2011.
Bassand J.-P.,University Hospital Jean Minjoz
EuroIntervention | Year: 2014
Despite widespread adoption of acetylsalicylic acid and P2Y12 receptor inhibitor therapy as the standard of care for secondary event prevention in patients with acute coronary syndrome (ACS), the rate of cardiovascular death or myocardial infarction following discharge is approximately 24-31% over five years, indicating an important unmet need to reduce further the risk of recurrent ACS events. Because thrombin has a role in arterial thrombus generation, a mechanistic rationale exists for adding an anticoagulant to dual antiplatelet therapy to reduce cardiovascular event rates and mortality. The direct thrombin inhibitor dabigatran and the direct Factor Xa inhibitors rivaroxaban and apixaban have been investigated for this application, with only rivaroxaban successfully completing a phase III trial. These results suggest that dose selection is of paramount importance in this indication, with lower anticoagulant doses (relative to those used in other indications, such as stroke prevention in atrial fibrillation) plus low-dose acetylsalicylic acid potentially improving cardiovascular outcomes. This article reviews clinical trial data of anticoagulants for secondary event prevention in patients with ACS; it also discusses the mechanistic reasons that may underlie these observations and looks towards the potential impact of findings from the ATLAS ACS 2 TIMI 51 trial on clinical practice. © Europa Digital & Publishing 2014. All rights reserved.
Servagi-Vernat S.,Catholic University of Louvain |
Servagi-Vernat S.,University Hospital Jean Minjoz |
Differding S.,Catholic University of Louvain |
Hanin F.-X.,Catholic University of Louvain |
And 4 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2014
Purpose: Hypoxia in head and neck squamous cell carcinoma (HNSCC) is associated with poor prognosis and outcome. 18F-Fluoroazomycin arabinoside (FAZA) is a positron emission tomography (PET) tracer developed to enable identification of hypoxic regions within tumor. The aim of this study was to evaluate the use of 18 F-FAZA-PET for assessment of hypoxia before and during radiation therapy. Methods: Twelve patients with locally advanced HNSCC underwent 18 F-FAZA-PET scans before and at fraction 7 and 17 of concomitant chemo-radiotherapy. A hypoxic voxel was defined as a voxel expressing a standardized uptake value (SUV) equal or above the SUV mean of the posterior contralateral neck muscles plus three standard deviations. The fractional hypoxic volume fraction (FHV) and the spatial move of hypoxic volumes during treatment were analyzed. Results: A hypoxic volume could be identified in ten patients before treatment. FAZA-PET FHV varied from 0 to 54.3 % and from 0 to 41.4 % in the primary tumor and in the involved node, respectively. Six out of these ten patients completed all the FAZA-PET-computed tomography (CT) during the radiotherapy. In all patients, FHV and SUV max values decreased. All patient presented a spatial move of hypoxic volume, but only three patients had newborn hypoxic voxels after 17 fractions. Conclusion: This study indicated that 18F-FAZA-PET could be used to identify and quantify tumor hypoxia before and during concomitant radio-chemotherapy in patients with locally advanced HNSCC. In addition to the information on prognostic value, the use of 18F-FAZA-PET allowed the delineation of hypoxic volumes for dose escalation protocols. However, due to fluctuation of hypoxia during treatment, repeated scan will have to be performed (i.e. adaptive radiotherapy). © 2014 Springer-Verlag.