Patrick Mismetti

University of Lille Nord de France, Lille, Nord-Pas-de-Calais, France

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Publications (246)1280.05 Total impact

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    Patrick Mismetti · Laurent Bertoletti
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    ABSTRACT: The optimal duration of anticoagulation after a first episode of unprovoked pulmonary embolism is uncertain. To determine the benefits and harms of an additional 18-month treatment with warfarin vs placebo, after an initial 6-month nonrandomized treatment period on a vitamin K antagonist. Randomized, double-blind trial (treatment period, 18 months; median follow-up, 24 months); 371 adult patients who had experienced a first episode of symptomatic unprovoked pulmonary embolism (ie, with no major risk factor for thrombosis) and had been treated initially for 6 uninterrupted months with a vitamin K antagonist were randomized and followed up between July 2007 and September 2014 in 14 French centers. Warfarin or placebo for 18 months. The primary outcome was the composite of recurrent venous thromboembolism or major bleeding at 18 months after randomization. Secondary outcomes were the composite at 42 months (treatment period plus 24-month follow-up), as well as each component of the composite, and death unrelated to pulmonary embolism or major bleeding, at 18 and 42 months. After randomization, 4 patients were lost to follow-up, all after month 18, and 1 withdrew due to an adverse event. During the 18-month treatment period, the primary outcome occurred in 6 of 184 patients (3.3%) in the warfarin group and in 25 of 187 (13.5%) in the placebo group (hazard ratio [HR], 0.22; 95% CI, 0.09-0.55; P = .001). Recurrent venous thromboembolism occurred in 3 patients in the warfarin group and 25 patients in the placebo group (HR, 0.15; 95% CI, 0.05-0.43); major bleeding occurred in 4 patients in the warfarin group and in 1 patient in the placebo group (HR, 3.96; 95% CI, 0.44 to 35.89). During the 42-month entire study period (including the study treatment and follow-up periods), the composite outcome occurred in 33 patients (20.8%) in the warfarin group and in 42 (24.0%) in the placebo group (HR, 0.75; 95% CI, 0.47-1.18). Rates of recurrent venous thromboembolism, major bleeding, and unrelated death did not differ between groups. Among patients with a first episode of unprovoked pulmonary embolism who received 6 months of anticoagulant treatment, an additional 18 months of treatment with warfarin reduced the composite outcome of recurrent venous thrombosis and major bleeding compared with placebo. However, benefit was not maintained after discontinuation of anticoagulation therapy. clinicaltrials.gov Identifier: NCT00740883.
    JAMA The Journal of the American Medical Association 07/2015; 314(1):31-40. DOI:10.1001/jama.2015.7046 · 30.39 Impact Factor
  • C. Chapelle · P. Mismetti · M. Cucherat · S. Laporte
    Revue d Épidémiologie et de Santé Publique 05/2015; 63. DOI:10.1016/j.respe.2015.03.041 · 0.66 Impact Factor
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    ABSTRACT: Although retrievable inferior vena cava filters are frequently used in addition to anticoagulation in patients with acute venous thromboembolism, their benefit-risk ratio is unclear. To evaluate the efficacy and safety of retrievable vena cava filters plus anticoagulation vs anticoagulation alone for preventing pulmonary embolism recurrence in patients presenting with acute pulmonary embolism and a high risk of recurrence. Randomized, open-label, blinded end point trial (PREPIC2) with 6-month follow-up conducted from August 2006 to January 2013. Hospitalized patients with acute, symptomatic pulmonary embolism associated with lower-limb vein thrombosis and at least 1 criterion for severity were assigned to retrievable inferior vena cava filter implantation plus anticoagulation (filter group; n = 200) or anticoagulation alone with no filter implantation (control group; n = 199). Initial hospitalization with ambulatory follow-up occurred in 17 French centers. Full-dose anticoagulation for at least 6 months in all patients. Insertion of a retrievable inferior vena cava filter in patients randomized to the filter group. Filter retrieval was planned at 3 months from placement. Primary efficacy outcome was symptomatic recurrent pulmonary embolism at 3 months. Secondary outcomes were recurrent pulmonary embolism at 6 months, symptomatic deep vein thrombosis, major bleeding, death at 3 and 6 months, and filter complications. In the filter group, the filter was successfully inserted in 193 patients and was retrieved as planned in 153 of the 164 patients in whom retrieval was attempted. By 3 months, recurrent pulmonary embolism had occurred in 6 patients (3.0%; all fatal) in the filter group and in 3 patients (1.5%; 2 fatal) in the control group (relative risk with filter, 2.00 [95% CI, 0.51-7.89]; P = .50). Results were similar at 6 months. No difference was observed between the 2 groups regarding the other outcomes. Filter thrombosis occurred in 3 patients. Among hospitalized patients with severe acute pulmonary embolism, the use of a retrievable inferior vena cava filter plus anticoagulation compared with anticoagulation alone did not reduce the risk of symptomatic recurrent pulmonary embolism at 3 months. These findings do not support the use of this type of filter in patients who can be treated with anticoagulation. clinicaltrials.gov Identifier: NCT00457158.
    JAMA The Journal of the American Medical Association 04/2015; 313(16):1627-1635. DOI:10.1001/jama.2015.3780 · 30.39 Impact Factor
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    ABSTRACT: Epidemiological evidence that the risk of coronary heart disease is inversely associated with the level of high-density lipoprotein cholesterol (HDL-C) has motivated several phase III programmes with cholesteryl ester transfer protein (CETP) inhibitors. To assess alternative methods to predict clinical response of CETP inhibitors. Meta-regression analysis on raising HDL-C drugs (statins, fibrates, niacin) in randomised controlled trials. 51 trials in secondary prevention with a total of 167 311 patients for a follow-up >1 year where HDL-C was measured at baseline and during treatment. The meta-regression analysis showed no significant association between change in HDL-C (treatment vs comparator) and log risk ratio (RR) of clinical endpoint (non-fatal myocardial infarction or cardiac death). CETP inhibitors data are consistent with this finding (RR: 1.03; P5-P95: 0.99-1.21). A prespecified sensitivity analysis by drug class suggested that the strength of relationship might differ between pharmacological groups. A significant association for both statins (p<0.02, log RR=-0.169-0.0499*HDL-C change, R(2)=0.21) and niacin (p=0.02, log RR=1.07-0.185*HDL-C change, R(2)=0.61) but not fibrates (p=0.18, log RR=-0.367+0.077*HDL-C change, R(2)=0.40) was shown. However, the association was no longer detectable after adjustment for low-density lipoprotein cholesterol for statins or exclusion of open trials for niacin. Meta-regression suggested that CETP inhibitors might not influence coronary risk. The relation between change in HDL-C level and clinical endpoint may be drug dependent, which limits the use of HDL-C as a surrogate marker of coronary events. Other markers of HDL function may be more relevant. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Heart (British Cardiac Society) 04/2015; 101(11). DOI:10.1136/heartjnl-2014-306691 · 6.02 Impact Factor
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    Patrick Mismetti · Laurent Bertoletti
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    ABSTRACT: The initial management or venous thromboembolism (VTE) corresponds to the first 3 months of treatment. Pulmonary embolism (PE) are mostly hospitalized. Serious PE associated with hemodynamic instability has to be admitted in intensive care unit due to the need for fibrinolytics. PE without any risk factor for VTE recurrences or death could be followed as outpatient. Conversely, deep vein thrombosis (DVT), including proximal DVT are not hospitalized with the xception of patients with serious risk factors. The therapeutic strategy is identical between DVT and PE treatment with an acute phase with either parenteral anticoagulants, especially low molecular weight heparins or fondaparinux, or by an intensive dose of direct oral anticoagulant such as rivaroxaban or apixaban. Then maintenance therapy has to be prescribed either with vitamin K antagonists with overlapping parenteral anticoagulants for at least 72 hours, or with a maintenance dose of apixaban or rivaroxaban.
    La Revue du praticien 02/2015; 65(2):193-8.
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    ABSTRACT: L’apixaban est un inhibiteur direct du facteur Xa de la coagulation. Il a montré une efficacité supérieure à celle de l’aspirine et supérieure à celle des antivitamines K sur la prévention des accidents vasculaires cérébraux (AVC) et des embolies systémiques au cours de la fibrillation atriale non valvulaire (FANV) avec un profil de tolérance plus favorable, même si le risque d’accident hémorragique demeure incontournable, compte tenu de son mécanisme d’action. La posologie recommandée est de 5 mg deux fois par jour pouvant être réduite à 2,5 mg deux fois par jour selon le risque de l’individu. Il est également indiqué dans le traitement de la maladie thromboembolique veineuse mais pas encore remboursé dans cette indication. Comme pour tous les anticoagulants oraux directs (AOD), il ne nécessite pas de surveillance biologique de routine, néanmoins il peut retentir sur tous les tests de coagulation rendant l’interprétation de ces derniers parfois difficile. Dans les circonstances cliniques particulières où la mesure de l’efficacité anticoagulante est jugée nécessaire, il convient alors de réaliser une mesure spécifique de l’activité anti-Xa, le résultat étant alors exprimé en concentration de l’anticoagulant utilisé. Il est donc nécessaire de préciser le nom du médicament pour lequel le dosage est demandé. L’absence d’antidote spécifique à ces nouveaux anticoagulants rend parfois la gestion des accidents hémorragiques complexe. L’utilisation de substances pro-hémostatiques, qui semble efficace sur des modèles animaux, reste insuffisamment documentée en pratique clinique. Les mesures d’hémostase locales ou locorégionales, lorsqu’elles sont possibles, sont un élément essentiel du traitement des accidents hémorragiques.
    Journal des Maladies Vasculaires 12/2014; 39(6). DOI:10.1016/j.jmv.2014.09.002 · 0.24 Impact Factor
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    ABSTRACT: Apixaban is a direct inhibitor of coagulation factor Xa. Superior efficacy over aspirin and antivitamin K has been shown in the prevention of stroke and systemic embolism during non-valvular atrial fibrillation with a more favorable safety profile, even though the risk of hemorrhage cannot be ignored, considering its mechanism of action. The recommended dose is 5mg twice daily which can be reduced to 2.5mg depending on the individual risk. Apixaban is also indicated for the treatment of venous thromboembolism but reimbursement has not yet been accepted in France for this indication. As with all direct oral anticoagulants, no routine biological monitoring is required, nevertheless their use may have an impact on all coagulation tests, eventually hampering interpretation. In particular clinical circumstances where a measure of anticoagulant efficacy is deemed necessary, specific assay of anti-Xa activity is appropriate, the result being expressed as concentration of the anticoagulant used. It is therefore necessary to state the name of the medicine for which the assay is requested. With these new anticoagulants, management of hemorrhagic events can be more difficult due to the lack of a specific antidote. Pro-hemostatic substances have exhibited efficacy in animal models but results are still insufficiently documented in clinical practice. Local or locoregional hemostasis measurements, when possible, are an essential factor in the treatment of hemorrhagic events. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
    Journal des Maladies Vasculaires 11/2014; · 0.24 Impact Factor
  • Value in Health 11/2014; 17(7):A493-A494. DOI:10.1016/j.jval.2014.08.1465 · 2.89 Impact Factor
  • Value in Health 11/2014; 17(7):A472-A473. DOI:10.1016/j.jval.2014.08.1345 · 2.89 Impact Factor
  • Value in Health 11/2014; 17(7):A496-A497. DOI:10.1016/j.jval.2014.08.1483 · 2.89 Impact Factor
  • Source
    Laurent Bertoletti · Patrick Mismetti · Hervé Decousus
    Circulation 09/2014; 130(12):e108. DOI:10.1161/CIRCULATIONAHA.113.007143 · 14.95 Impact Factor
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    Philippe Girard · Guy Meyer · Patrick Mismetti
    The American Journal of Medicine 07/2014; 127(7):e21. DOI:10.1016/j.amjmed.2014.01.042 · 5.30 Impact Factor
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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.
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    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; 12(9). DOI:10.1111/jth.12648 · 5.55 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; 30(8). DOI:10.1016/j.arthro.2014.03.009 · 3.19 Impact Factor
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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 05/2014; DOI:10.1016/j.ejrad.2014.01.022 · 2.16 Impact Factor
  • Thrombosis Research 05/2014; 133:S122. DOI:10.1016/S0049-3848(14)50383-0 · 2.43 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 04/2014; 63(16). DOI:10.1016/j.jacc.2014.01.058 · 15.34 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

Publication Stats

4k Citations
1,280.05 Total Impact Points

Institutions

  • 2015
    • University of Lille Nord de France
      Lille, Nord-Pas-de-Calais, France
  • 2008–2015
    • Unité de Recherche Clinique de Nanoro
      Wagadugu, Centre, Burkina Faso
  • 1995–2015
    • Centre Hospitalier Universitaire de Saint-Étienne
      • Department of Medicine and Therapeutics
      Saint-Etienne, Rhône-Alpes, France
  • 2012–2014
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2009–2014
    • Université Jean Monnet
      • • Faculté de Médecine
      • • Groupe de Recherche sur la Thrombose (GRT)
      Saint-Étienne, Rhône-Alpes, France
  • 2012–2013
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2009–2012
    • University of Lyon
      Lyons, Rhône-Alpes, France
  • 2011
    • Centre Hospitalier Régional Universitaire de Lille
      Lille, Nord-Pas-de-Calais, France
  • 2003–2006
    • Bellevue University
      Bellevue, Nebraska, United States
  • 2005
    • Claude Bernard University Lyon 1
      Villeurbanne, Rhône-Alpes, France
    • Hospital Centre University of Fort de France
      Fort Royal, Martinique, Martinique
    • Thomas Jefferson University
      • Department of Medicine
      Filadelfia, Pennsylvania, United States