Patrick Mismetti

Unité Inserm U1077, Caen, Lower Normandy, France

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Publications (227)1070.26 Total impact

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    Laurent Bertoletti, Patrick Mismetti, Hervé Decousus
    Circulation 09/2014; 130(12):e108. · 15.20 Impact Factor
  • Philippe Girard, Guy Meyer, Patrick Mismetti
    The American journal of medicine. 07/2014; 127(7):e21.
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    ABSTRACT: Two enoxaparin dosage regimens are used as comparators to evaluate new anticoagulants for thromboprophylaxis in patients undergoing major orthopaedic surgery, but so far no satisfactory direct comparison between them has been published. Our objective was to compare the efficacy and safety of enoxaparin 3,000 anti-Xa IU twice daily and enoxaparin 4,000 anti-Xa IU once daily in this clinical setting by indirect comparison meta-analysis, using Bucher's method. We selected randomised controlled trials comparing another anticoagulant, placebo (or no treatment) with either enoxaparin regimen for venous thromboembolism prophylaxis after hip or knee replacement or hip fracture surgery, provided that the second regimen was assessed elsewhere versusthe same comparator. Two authors independently evaluated study eligibility, extracted the data, and assessed the risk of bias. The primary efficacy outcome was the incidence of venous thomboembolism. The main safety outcome was the incidence of major bleeding. Overall, 44 randomised comparisons in 56,423 patients were selected, 35 being double-blind (54,117 patients). Compared with enoxaparin 4,000 anti-Xa IU once daily, enoxaparin 3,000 anti-Xa IU twice daily was associated with a reduced risk of venous thromboembolism (relative risk [RR]: 0.53, 95% confidence interval [CI]: 0.40 to 0.69), but an increased risk of major bleeding (RR: 2.01, 95% CI: 1.23 to 3.29). In conclusion, when interpreting the benefit-risk ratio of new anticoagulant drugs versus enoxaparin for thromboprophylaxis after major orthopaedic surgery, the apparently greater efficacy but higher bleeding risk of the twice-daily 3,000 anti-Xa IU enoxaparin regimen compared to the once-daily 4,000 anti-Xa IU regimen should be taken into account.
    Thrombosis and haemostasis. 06/2014; 112(3).
  • B Tardy, E Chalayer, C Chapelle, P Mismetti
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    ABSTRACT: We read with interest the article by Sanford and al (1) reporting through a meta-analysis the effect of low-molecular-weight heparin on survival in cancer patients. The authors found 9 studies that met their inclusion criteria (one-year survival outcomes). Then, after reporting the results of LMWH on overall survival in patients with cancer, they extracted also data on venous thromboembolism (VTE) for the 9 trials.This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 06/2014; · 6.08 Impact Factor
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    ABSTRACT: To assess the efficacy of low-molecular-weight heparin (LMWH) venous thromboprophylaxis in patients with transient reduced mobility in the non-major orthopaedic setting. A meta-analysis was conducted using data from all available randomized trials comparing LMWH with placebo or no prophylactic treatment in patients with leg immobilization for fracture or soft-tissue injury of the lower limb or in patients undergoing knee arthroscopy. The primary endpoint was the incidence of major venous thromboembolic events (VTEs), including asymptomatic proximal deep-vein thrombosis, symptomatic VTEs, and VTE-related death. The Mantel-Haenszel method was used to generate the summary statistics for the overall effect of LMWH. Fourteen studies were included (4,726 patients). The weighted rate of major VTEs was estimated to be 2.9% (95% confidence interval [CI], 2.2% to 3.7%) without LMWH prophylaxis. Overall, a significant 68% reduction in the risk of major VTEs was observed with LMWH prophylaxis (relative risk [RR], 0.32; 95% CI, 0.20 to 0.51; P < .001). The treatment effect was not modified by the clinical setting, that is, distal lower limb injury (7 studies; 1,711 patients; RR, 0.42; 95% CI, 0.20 to 0.86) or knee arthroscopy (6 studies; 2,428 patients; RR, 0.27; 95% CI, 0.15 to 0.49). A nonsignificant 35% increase in the risk of major bleeding was observed in the LMWH prophylaxis group (RR, 1.35; 95% CI, 0.53 to 3.47). This meta-analysis indicates potential efficacy of LMWH in preventing thromboembolic events in patients with reduced mobility in the non-major orthopaedic setting compared with placebo or no treatment. However, the decision of whether to implement LMWH prophylaxis in each specific setting should also take into account the risk of VTEs in the absence of prophylaxis, the potential adverse effects of LMWH, and the cost. Level II, meta-analysis of Level II studies or Level I studies with inconsistent results.
    Arthroscopy The Journal of Arthroscopic and Related Surgery 05/2014; · 3.10 Impact Factor
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    ABSTRACT: Purpose To report the implantation and retrieval vena cava filter success rate of the ALN filter in a the setting of a prospective randomized trial (PREPIC 2) trial filter subgroup. Materials and Methods Prepic 2 is a prospective open randomized study with a blind evaluation that compared retrievable ALN vena cava filter (ALN Implant Chirurgicaux) maintained for 3 months with no filter insertion in patients receiving anticoagulant therapy for acute symptomatic pulmonary embolism (PE) associated to deep vein thrombosis. The filter retrieval was systematically scheduled at 3 months. The primary goal of this ancillary study is to report the technical success rate of filter implantation and removal. The secondary goal is to report filter related complications. Results Between 08-2006 and 07-2012; 399 patients (median 76 years) with acute PE and no contradiction to anticoagulation were enrolled in 18 centres. 193 patients received an ALN filter after randomization in the filter arm in addition to anticoagulation therapy, using femoral (162) basilic (15) or jugular vein (16), access. Filter wasn’t implanted because of 2(1%) technical failure; 3 (1.5%) non confirmation of PE diagnosis after randomization; and 2 (1%) patients’ death before implantation. post implantation cavogram showed >15° tilting in 19 (9.8%) cases. Minor complications were observed in 20 cases (11.9%): 4 (2%) <20 mm migration; 10 (5.2%) >3 mm filters struts penetration outside the cavogram and 3 1.6%) puncture site hematoma; 5 (2.6%) tilt increase were reported. Among the 166 (92.2%) patients who were referred for extraction after 3 months (93 days [89-98]), retrieval was successfully performed in 92.2% (153). 3 (1.8%) asymptomatic filter thrombosis were observed. Failure of extraction was observed in 13 (7.8%) case, because of >15° tilt (n=9, 5.4%) or non removable fibrotic bridge to IVC n=4/2.4%. Filter removal was successfully performed in an median of 20 min [15-40]. Conclusion The ALN filter was successfully extracted in 92.2% in this multicenter experience with a little complication rate.
    SIR 2014, 3S84; 03/2014
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    Annales francaises d'anesthesie et de reanimation 03/2014; · 0.77 Impact Factor
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    ABSTRACT: Dabigatran and warfarin have been compared for the treatment of acute venous thromboembolism (VTE) in a previous trial. We undertook this study to extend those findings. In a randomized, double-blind, double-dummy trial of 2589 patients with acute VTE treated with low-molecular-weight or unfractionated heparin for 5 to 11 days, we compared dabigatran 150 mg twice daily with warfarin. The primary outcome, recurrent symptomatic, objectively confirmed VTE and related deaths during 6 months of treatment occurred in 30 of the 1279 dabigatran patients (2.3%) compared with 28 of the 1289 warfarin patients (2.2%; hazard ratio, 1.08; 95% confidence interval [CI], 0.64-1.80; absolute risk difference, 0.2%; 95% CI, -1.0 to 1.3; P<0.001 for the prespecified noninferiority margin for both criteria). The safety end point, major bleeding, occurred in 15 patients receiving dabigatran (1.2%) and in 22 receiving warfarin (1.7%; hazard ratio, 0.69; 95% CI, 0.36-1.32). Any bleeding occurred in 200 dabigatran (15.6%) and 285 warfarin (22.1%; hazard ratio, 0.67; 95% CI, 0.56-0.81) patients. Deaths, adverse events, and acute coronary syndromes were similar in both groups. Pooled analysis of this study RE-COVER II and the RE-COVER trial gave hazard ratios for recurrent VTE of 1.09 (95% CI, 0.76-1.57), for major bleeding of 0.73 (95% CI, 0.48-1.11), and for any bleeding of 0.70 (95% CI, 0.61-0.79). Dabigatran has similar effects on VTE recurrence and a lower risk of bleeding compared with warfarin for the treatment of acute VTE. www.clinicaltrials.gov. Unique identifiers: NCT00680186 and NCT00291330.
    Circulation 02/2014; 129(7):764-72. · 15.20 Impact Factor
  • Xavier Delavenne, Silvy Laporte, Patrick Mismetti
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    ABSTRACT: New oral anticoagulants target specific factors in the coagulation cascade by directly inhibiting thrombin for dabigatran and Factor Xa for -xatrans. Pharmacological progresses with these anticoagulants allow the use of fixed doses without any therapeutic drug monitoring. Their pharmacokinetic specificity is the key role of the transporter proteins P-glycoprotein (P-gp) for all these drugs and the metabolism mediated by CYP3A4 for -xabans. Dose adjustment is recommended for decreasing creatinine clearance or in case of drug-drug interaction. New oral anticoagulants are promising but their safety needs further investigations in particular populations such as elderly patients, patients with renal or hepatic impairment, or patients on polymedication.
    Revue médicale suisse 02/2014; 10(416):319-24.
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    ABSTRACT: Introduction.– Les essais randomisés en ouvert avec évaluation à l’aveugle (PROBE) permettent de limiter les biais d’évaluation par rapport aux études en ouvert simple, et sont parfois considérés comme aussi performants que les essais en double insu pour l’évaluation d’une stratégie thérapeutique. Cependant, si l’exagération de l’effet traitement liée aux études en ouvert est bien estimée, celle liée aux études PROBE n’a jamais été estimée. Nous avons cherché à quantifier le biais d’estimation lié au schéma d’études PROBE par rapport aux études en double insu à partir des essais évaluant un nouvel anticoagulant oral dans la fibrillation atriale. Me´thodes.– Tous les essais randomisés évaluant un nouvel anticoagulant par rapport au traitement de référence (anti-vitamine K) dans la prévention des événements emboliques dans la fibrillation atriale ont été inclus. Les bases de données consultées étaient MEDLINE, EMBASE, la library Cochrane, les sites web de l’ « US National Institute of Health, Meta-Embol » et les registres d’essais cliniques. Le critère principal d’évaluation et les critères secondaires étaient communs à toutes les études : accidents vasculaires cérébraux et embolies systémiques (AVC-ES), AVC hémorragiques, hémorragies majeures, hémorragies intracrâniennes, et mortalité cardiovas- culaire. L’effet traitement commun a été estimé pour les études PROBE et pour les études en double insu en combinant le logarithme des risques relatifs (RR) de chacune des études pondéré par l’inverse de la variance, selon un modèle à effets fixes ou à effets aléatoires. L’exagération de l’effet traitement a été estimée par le rapport des effets communs entre les études PROBE et les études en double insu ; le test d’interaction a été considéré comme significatif au seuil de 0,10. Re´sultats.– Au total, 8 études (59 238 patients) ayant comparé l’apixaban, l’edoxaban, le dabigatran, l’AZD0837, le ximelagatran, ou le rivaroxaban aux anti-vitamine K ont été incluses. De fac¸on globale, une réduction significative est observée avec les nouveaux anticoagulants oraux sur le critère principal AVC-ES (RR = 0,84 ; IC95 % 0,76–0,92) ainsi que sur tous les autres critères. L’estimation de l’efficacité des nouveaux anticoagulants oraux sur le critère primaire était plus importante à partir des études PROBE (5 essais, 22 947 patients ; RR = 0,76, IC95 % 0,65–0,90) comparé aux études en double insu (3 essais, 36 387 patients ; RR = 0,88, IC95 % 0,78–0,98), soit une majoration non significative de 16 % (test d’interaction p = 0,17). L’interaction était évidente pour les AVC hémorragiques (test d’interaction p = 0,05) avec une majoration de 72 % de l’effet traitement dans les études PROBE (RR = 0,32 ; IC95 % 0,20–0,49) par rapport études en double insu (RR = 0,55 ; IC95 % 0,41–0,73). Aucune autre interaction n’a été significative sur les autres critères. Conclusions.– Les études PROBE peuvent influencer les résultats d’un essai clinique en faveur du nouveau traitement. Cependant, l’influence d’un facteur confondant comme la classe pharmacologique ne peut être exclue. L’étude avec l’edoxaban dont le suivi est en cours, devrait permettre d’affiner les estimations. Il s’agit de rester prudent lors des comparaisons indirectes de ces molécules entre elles lors des méta-analyses en réseau.
    Revue d Épidémiologie et de Santé Publique 02/2014; 62:S38–S39. · 0.69 Impact Factor
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    ABSTRACT: Aim To evaluate the magnitude of venous and arterial thrombosis risk associated with antiphospholipid antibodies (APLs) in adults without systemic lupus erythematosus (SLE). Case-control and cohort studies were selected from the MEDLINE and Cochrane Library databases. Two investigators independently extracted data on study design, patient characteristics, venous and arterial events and exposure to APLs, including lupus anticoagulant (LA), anticoardiolipin (aCL), anti-β2 Glycoprotein I (β2GpI), anti-prothrombin (aPT), anti-phosphatidyl serine (aPS), and anti-phosphatidyl ethanolamine (aPE). 30 studies were included (16,441 patients). The odds ratio (OR) for venous thrombosis was 6.14 (95% confidence interval [CI] 2.74-13.8) in LA-positive patients (5 studies, 1650 patients) and 1.46 (CI 1.06-2.03) in aCL positive patients (12 studies, 5375 patients). None of the associations with more recently identified APLs was significant, but fewer studies were available. For arterial thrombosis, the OR for LA and aCL was 3.58 (CI 1.29-9.92) and 2.65 (CI 1.75-4.00) respectively. The associations between β2GpI, aPT and aPS and the risk of arterial thrombosis were also significant, the OR being 3.12 (CI 1.51- 6.44), 2.95 (CI 1.31-6.66) and 6.00 (CI 3.07- 11.7), respectively. Owing to the heterogeneity of cut-off values for each APL assay, we were unable to perform any sensitivity analysis to determine the optimal value. The presence of low-quality studies may have led to overestimation of the magnitude of the associations. LA and aCL were significantly associated with an increased risk of thrombosis, especially arterial, in patients without SLE. Systematic thromboprophylaxis in high-risk patients with APL should be evaluated.
    Autoimmunity reviews 01/2014; · 6.37 Impact Factor
  • G Meyer, P Girard, P Mismetti
    La Revue de Médecine Interne 01/2014; · 0.90 Impact Factor
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    ABSTRACT: The well-known limitations of vitamin K antagonists (VKA) led to development of new oral anticoagulants (NOAC) in non-valvular atrial fibrillation (NVAF). The aim of this meta-analysis was to determine the consistency of treatment effects of NOAC irrespective of age, comorbidities, or prior VKA exposure. All randomized, controlled phase III trials comparing NOAC to VKA up to October 2012 were eligible provided their results (stroke/systemic embolism (SSE) and major bleeding (MB)) were reported according to age (≤ or >75 years), renal function, CHADS2 score, presence of diabetes mellitus or heart failure, prior VKA use or previous cerebrovascular events. Interactions were considered significant at p <0.05. Three studies (50,578 patients) were included, respectively evaluating apixaban, rivaroxaban, and dabigatran versus warfarin. A trend towards interaction with heart failure (p = 0.08) was observed with respect to SSE reduction, this being greater in patients not presenting heart failure (RR = 0.76 [0.67-0.86]) than in those with heart failure (RR = 0.90 [0.78-1.04]); Significant interaction (p = 0.01) with CHADS2 score was observed, NOAC achieving a greater reduction in bleeding risk in patients with a score of 0-1 (RR 0.67 CI 0.57-0.79) than in those with a score ≥2 (RR 0.85 CI 0.74-0.98). Comparison of MB in patients with (RR 0.97 CI 0.79-1.18) and without (RR 0.76 CI 0.65-0.88) diabetes mellitus showed a similar trend (p = 0.06). No other interactions were found. All subgroups derived benefit from NOA in terms of SSE or MB reduction. NOAC appeared to be more effective and safer than VKA in reducing SSE or MB irrespective of patient comorbidities. Thromboembolism risk, evaluated by CHADS2 score and, to a lesser extent, diabetes mellitus modified the treatment effects of NOAC without complete loss of benefit with respect to MB reduction.
    PLoS ONE 01/2014; 9(3):e91398. · 3.53 Impact Factor
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    ABSTRACT: Objectives The purpose of this study was to investigate the survival effects of inferior vena cava filter in patients with venous thromboembolism (VTE) and a significant bleeding risk. Background The effectiveness of inferior vena cava filter use among patients with acute symptomatic VTE and known significant bleeding risk remains unclear. Methods In this prospective cohort study of patients with acute VTE identified from the RIETE registry, we assessed the association between inferior vena cava filter insertion placed for known significant bleeding risk and the outcomes of all-cause mortality, pulmonary embolism (PE)-related mortality, and VTE rates through 30 days after initiation of VTE treatment. We used propensity score matching to adjust for the likelihood of receiving a filter. Results Of the 40,142 eligible patients that had acute symptomatic VTE, 371 underwent filter placement because of known significant bleeding risk. Three hundred and forty four patients treated with a filter were matched with 344 patients treated without a filter. Propensity score-matched pairs showed a non-significant trend toward lower risk of all-cause death for filter insertion compared with no insertion (6.6% vs. 10.2%, P = 0.12). The risk-adjusted PE-related mortality rate was lower for filter insertion than no insertion (1.7% vs. 4.9%, P = 0.03). Risk-adjusted recurrent VTE rates were higher for filter insertion than no insertion (6.1% vs. 0.6%, P > 0.001). Conclusions In patients presenting with VTE and a significant bleeding risk, compared to anticoagulant therapy, IVC filter insertion was associated with a lower risk of PE-related death, while it was associated with a higher risk of recurrent VTE. However, study design limitations do not imply a causal relationship between filter insertion and outcome.
    Journal of the American College of Cardiology 01/2014; · 14.09 Impact Factor
  • G. Meyer, P. Girard, P. Mismetti
    La Revue de Médecine Interne. 01/2014;
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    ABSTRACT: Purpose To compare magnetic resonance imaging (MRI) brain feature in cryptogenic stroke patients with patent foramen ovale (PFO), cryptogenic stroke patients without PFO and patients with cardioembolic stroke. Materials and methods The ethics committee required neither institutional review board approval nor informed patient consent for retrospective analyses of the patients’ medical records and imaging data. The patients’ medical files were retrospectively reviewed in accordance with human subject research protocols. Ninety-two patients under 60 years of age were included; 15 with cardioembolic stroke, 32 with cryptogenic stroke with PFO and 45 with cryptogenic stroke without PFO. Diffusion-weighted imaging of brain MRI was performed by a radiologist blinded to clinical data. Univariate, Fischer's exact test for qualitative data and non-parametric Wilcoxon test for quantitative data were used. Results There was no statistically significant difference found between MRI features of patients with PFO and those with cardioembolic stroke (p<.05). Patients without PFO present more corticosubcortical single lesions (p<.05) than patients with PFO. Patients with PFO have more often subcortical single lesions larger than 15 mm, involvement of posterior cerebral arterial territory and intracranial occlusion (p<.05) than patient with cryptogenic stroke without PFO. Conclusion Our study suggests a cardioembolic mechanism in ischemic stroke with PFO.
    European journal of radiology 01/2014; · 2.65 Impact Factor
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    ABSTRACT: Purpose To assess the efficacy of low-molecular-weight heparin (LMWH) venous thromboprophylaxis in patients with transient reduced mobility in the non-major orthopaedic setting. Methods A meta-analysis was conducted using data from all available randomized trials comparing LMWH with placebo or no prophylactic treatment in patients with leg immobilization for fracture or soft-tissue injury of the lower limb or in patients undergoing knee arthroscopy. The primary endpoint was the incidence of major venous thromboembolic events (VTEs), including asymptomatic proximal deep-vein thrombosis, symptomatic VTEs, and VTE-related death. The Mantel-Haenszel method was used to generate the summary statistics for the overall effect of LMWH. Results Fourteen studies were included (4,726 patients). The weighted rate of major VTEs was estimated to be 2.9% (95% confidence interval [CI], 2.2% to 3.7%) without LMWH prophylaxis. Overall, a significant 68% reduction in the risk of major VTEs was observed with LMWH prophylaxis (relative risk [RR], 0.32; 95% CI, 0.20 to 0.51; P < .001). The treatment effect was not modified by the clinical setting, that is, distal lower limb injury (7 studies; 1,711 patients; RR, 0.42; 95% CI, 0.20 to 0.86) or knee arthroscopy (6 studies; 2,428 patients; RR, 0.27; 95% CI, 0.15 to 0.49). A nonsignificant 35% increase in the risk of major bleeding was observed in the LMWH prophylaxis group (RR, 1.35; 95% CI, 0.53 to 3.47). Conclusions This meta-analysis indicates potential efficacy of LMWH in preventing thromboembolic events in patients with reduced mobility in the non-major orthopaedic setting compared with placebo or no treatment. However, the decision of whether to implement LMWH prophylaxis in each specific setting should also take into account the risk of VTEs in the absence of prophylaxis, the potential adverse effects of LMWH, and the cost. Level of Evidence Level II, meta-analysis of Level II studies or Level I studies with inconsistent results.
    Arthroscopy The Journal of Arthroscopic and Related Surgery 01/2014; · 3.10 Impact Factor
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    ABSTRACT: To compare efficacy and safety of thromboprophylaxis with semuloparin started postoperatively versus enoxaparin started preoperatively in major abdominal surgery. Venous thromboembolism is an important complication following major abdominal surgery. Semuloparin is a novel ultra-low-molecular-weight heparin with high antifactor Xa and minimal antifactor IIa activity. In this double-blind noninferiority trial, adult patients undergoing major abdominal or pelvic operation under general anesthesia lasting more than 45 minutes were assigned to either daily enoxaparin 40 mg commenced preoperatively or daily semuloparin 20 mg commenced postoperatively, for 7 to 10 days. Patients underwent bilateral leg venography between 7 and 11 days postsurgery. The primary efficacy end point was the composite of any deep vein thrombosis, nonfatal pulmonary embolism, or all-cause death. The primary safety outcome was bleeding. Both were independently adjudicated. In total, 4413 patients were randomized; 3030 (1499 in the enoxaparin and 1531 in the semuloparin groups) were evaluable for the primary efficacy end point, which occurred in 97 patients (6.3%) in the semuloparin group and 82 patients (5.5%) in the enoxaparin group [odds ratio (OR) = 1.16, 95% confidence interval (CI): 0.84-1.59]. On the basis of a noninferiority margin of 1.25, postoperative semuloparin did not demonstrate noninferiority to preoperative enoxaparin. Major bleeding occurred in 63 of 2175 patients (2.9%) in the semuloparin group and 98 of 2177 patients (4.5%) in the enoxaparin group (OR = 0.63, 95% CI: 0.46-0.87). Semuloparin commenced postoperatively did not demonstrate noninferiority to enoxaparin initiated preoperatively for thromboprophylaxis after major abdominal surgery. Study registered with clinicaltrials.gov: NCT00679588.
    Annals of surgery 12/2013; · 7.90 Impact Factor
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    ABSTRACT: Introduction: Fondaparinux sodium (pentasaccharide) was the first of a new class of antithrombotic agents developed for the prevention and treatment of venous thromboembolism (VTE), blocking thrombin generation by selectively inhibiting factor Xa. Areas covered: This review focuses on the currently available information evaluating the pharmacokinetics, pharmacodynamics, clinical efficacy and safety of fondaparinux in the prevention and treatment of VTE and treatment of acute coronary syndromes (ACS). Expert opinion: Fondaparinux is an alternative to low-molecular-weight heparins (LMWH) for thromboprophylaxis in various clinical settings (major orthopedic surgery of the lower limbs, major abdominal surgery, immobilized medical patients at high risk of VTE), as well as for the treatment of VTE (deep venous thrombosis, pulmonary embolism). It is currently challenged, in the context of both surgical thromboprophylaxis and acute VTE treatment, by the new oral anticoagulants. Fondaparinux remains the sole drug validated in patients with isolated superficial vein thrombosis of the lower limbs, and at prophylactic doses is a good alternative to LMWH at anticoagulant doses for patients with ACS, especially those ineligible for percutaneous coronary intervention.
    Expert Opinion on Drug Metabolism &amp Toxicology 12/2013; · 2.94 Impact Factor
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    ABSTRACT: The use of new oral anticoagulants (NOACs) in patients with impaired renal function raised major concerns, in particular the possibility of an increased bleeding risk due to accumulation. The aims of this work were to assess the safety of NOAC in patients with renal failure and described the relationship between clinical events and drug renal excretion magnitude. All phase III trials comparing NOACs to vitamin K antagonists (VKA) in patients with estimated glomerular filtration (eGFR) rate <50 mL/min were eligible. The main safety and efficacy outcomes were major bleeding and thrombosis. A meta-regression was performed to estimate the correlation between the treatment effect estimate and the percent of renal excretion. Nine studies (12272 patients) were included. A significantly greater relative reduction in major bleeding was seen for NOACs with eGFR <50 mL/min (RR 0.61; CI 0.51-0.74) than those with high renal excretion (RR 0.96; CI 0.85-1.07) (interaction test: p <0.0001). A linear relationship between the relative risk of major bleeding and the magnitude of renal excretion was found by meta-regression (R(2) =0.66, p =0.03). For thrombosis, a greater treatment effect of NOA versus INR-adjusted VKA was observed in patients with eGFR <50 mL/min (RR 0.78, CI 0.67-0.92), but no correlation between treatment effect and renal excretion was found. New oral anticoagulants were at least as effective as VKA with reduced risks of major bleeding and thrombosis in patients with eGFR <50 mL/min. The renal excretion of these new drugs seemed to modify the safety profile, contrary to the efficacy. This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 12/2013; · 6.08 Impact Factor

Publication Stats

3k Citations
1,070.26 Total Impact Points

Institutions

  • 2014
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 1999–2014
    • Université Jean Monnet
      • • Faculté de Médecine
      • • Groupe de Recherche sur la Thrombose (GRT)
      Saint-Étienne, Rhône-Alpes, France
  • 2013
    • Institute Mutualiste Montsouris
      Lutetia Parisorum, Île-de-France, France
    • McGill University Health Centre
      • Division of Orthopaedic Surgery
      Montréal, Quebec, Canada
    • The Thrombosis & Atherosclerosis Research Institute
      Hamilton, Ontario, Canada
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
  • 2003–2013
    • Centre Hospitalier Universitaire de Saint-Étienne
      • Department of Medicine and Therapeutics
      Saint-Étienne, Rhône-Alpes, France
  • 2012
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
    • Université de Montpellier 1
      Montpelhièr, Languedoc-Roussillon, France
  • 2009–2012
    • University of Lyon
      Lyons, Rhône-Alpes, France
    • Region Hovedstaden
      Hillerød, Capital Region, Denmark
    • McMaster University
      • Department of Medicine
      Hamilton, Ontario, Canada
  • 2011
    • Centre Hospitalier Régional Universitaire de Lille
      Lille, Nord-Pas-de-Calais, France
    • Hôtel-Dieu de Paris – Hôpitaux universitaires Paris Centre
      Lutetia Parisorum, Île-de-France, France
  • 2007
    • Centre Hospitalier Universitaire de Nice
      Nice, Provence-Alpes-Côte d'Azur, France
  • 2003–2006
    • Bellevue University
      Bellevue, Nebraska, United States
  • 2005
    • Claude Bernard University Lyon 1
      Villeurbanne, Rhône-Alpes, France