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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. Source

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. Source

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. Source

Toussirot E.,University Hospital Jean Minjoz | Toussirot E.,University of Franche Comte
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. Source

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. Source

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