Capecitabine efficacy after cycline-dependent-kinase 4/6 inhibitor plus endocrine therapy in metastatic hormone receptor-positive breast cancer.

BACKGROUND: The combination of endocrine treatment with cycline-dependent-kinase 4/6 inhibitor is the new standard of treatment in hormone receptor-positive HER2 negative metastatic breast cancer. The optimal subsequent treatment after CDK4/6 inhibitor remain unclear. As recommended by standard guidelines, capecitabine, an oral chemotherapy is a therapeutic option in endocrine resistant metastatic breast cancer. The objective of this study was to evaluate capecitabine efficacy after disease progression under combination of ET and CDK4/6 inhibitor in a hormone receptor positive metastatic breast cancer population. PATIENTS AND METHODS: Patients progressing under CDK 4/6 inhibitor plus ET and treated with capecitabine, between January 2016 and December 2020, were retrospectively included. Primary endpoint was time to treatment failure (TTF) on capecitabine. Logistic regression were used to identify predictive factors: exclusive bone versus visceral metastases, first-line versus ≥ 2 lines of combination therapy, aromatase inhibitor (AI) versus fulvestrant. RESULTS: Fifty-six patients with a 62-year median age (IC95% 42-81) were analyzed. The CDK 4/6 inhibitor and ET combination was prescribed in first-line setting in 26 patients (46%). Twenty-five patients (44%) had exclusive bone metastasis. Median TTF was 6.1 months. Six patients discontinued capecitabine due to toxicity. Outcomes were not significantly different regardless of metastases localization, ET, and treatment line of the combination of CDK 4/6 inhibitor and ET. Median PFS was 7.1 months. Median OS was 41.3 months. CONCLUSION: Compared to other data of capecitabine prescribed in patients with hormonal resistant MBC, this retrospective study suggests that capecitabine remains effective after CDK 4/6 inhibitor plus ET progression, regardless of therapeutic-line setting and metastases localization. MICRO ABSTRACT: Cycline dependant kinase 4/6 inhibitor plus endocrine therapy have become the standard of care in metastatic hormone receptor positive (HR+) breast cancer (BC). Few data reported the optimal subsequent therapy after progression under the combination. Capecitabine is a therapeutic option in endocrine resistant HR+/HER2- metastatic breast cancer. Data evaluating efficacy of capecitabine after disease progression on endocrine therapy plus cycline-dependant kinase 4/6 inhibitor are poor. This study showed a 6.1-month median time to treatment failure on capecitabine. Capecitabine remained effective regardless of therapeutic-line setting and metastases localization.

A propensity score-weighted study comparing a two- versus four-weekly pegylated liposomal doxorubicin regimen in metastatic breast cancer.

PURPOSE: A 4-weekly schedule of pegylated liposomal doxorubicin (PLD) has been approved for the treatment of metastatic breast cancer (MBC). Phase II trials have suggested interest in a 2-weekly regimen. This study aimed to compare the efficacy and safety of these two schedules. METHODS: Data from MBC patients treated with PLD between 2011 and 2021 were retrospectively collected. The objective was to demonstrate the noninferiority of the 2-weekly versus the 4-weekly schedule in terms of 6-month progression-free survival (PFS). The prespecified noninferiority margin was calculated as 1.20. A propensity score to receive either schedule was estimated using a gradient boosting algorithm. Survival analyses using Cox regression models weighted by the propensity score were performed to compare the schedules. RESULTS: Among the 192 patients included, 96 (50%) underwent each schedule. The median number of previous systemic therapies was 4 (IQR, 3 to 6). Anthracyclines were previously given in early breast cancer in 63.9% of patients. The median follow-up was 10.0 months (IQR, 5.0 to 20.1). A comparable distribution of adverse events was observed. The median PFS was 3.2 months (95% CI, 2.9 to 3.9), and the median overall survival was 12.1 months (95% CI, 10.8 to 14.9). The weighted hazard ratio for PFS was 1.12 (90% CI, 0.82 to 1.54), including the noninferiority boundaries. CONCLUSION: PLD appeared to be a well-tolerated drug in this heavily pretreated MBC population. The efficacy and safety of the 2-weekly schedule did not provide any advantage, suggesting no interest in changing the registered regimen.

[Endocarditis of mitral and aortic prosthetic heart valves caused by Aggregatibacter aphrophilus]. / Le cas clinique du mois. Endocardite à Aggregatibacter aphrophilus sur prothèses valvulaires.

We present the case of an acute endocarditis of mitral and aortic prosthetic heart valves caused by Aggregatibacter aphrophilus (Haemophilus aphrophilus-paraphrophilus). This third report in the literature emphasizes the diagnostic work-up and the role of positron emission tomography combined with computed tomography in this setting. The specificities of endocarditis due to the HACEK group (Haemophilus spp., Aggregatibacter, Cardiobacterium hominis, Eikenella corrodens and Kingella spp.) and the specific microbiological data and therapeutic options pertinent to this germ are discussed.

Nous rapportons la troisième observation clinique de la littérature d'une endocardite sur prothèses mécaniques mitrale et aortique due à l'Aggregatibacter aphrophilus (Haemophilus aphrophilus-paraphrophilus). Le pathogène récemment rebaptisé Aggregatibacter aphrophilus fait partie du groupe HACEK (Haemophilus spp., Aggregatibacter, Cardiobacterium hominis, Eikenella corrodens and Kingella spp.) impliqué dans des endocardites valvulaires de diagnostic difficile. Cette histoire clinique est l'occasion d'une revue de la littérature et des spécificités de ce pathogène. Elle met en exergue la contribution de la tomographie à émission de positons combinée à une tomodensitométrie dans le diagnostic et le suivi. Elle démontre, avec un recul de plus de deux ans, l'efficacité du traitement médical dans certaines endocardites sur prothèse.

[Cardiac rehabilitation, state of the art 2017]. / Revalidation cardiaque, état des lieux en 2017.

Cardiovascular disease remains the leading cause of death in western countries. Despite advances in acute management of patients, secondary prevention remains essential and should include cardiac rehabilitation. Recent data have confirmed the interest of this management in the various conventional indications : coronary disease, valvular heart disease, heart failure and heart transplantation. New indications emerge with some benefit that should be evaluated : ventricular assistance, pulmonary hypertension, trans-catheter aortic valve implantation. However, the different rehabilitation programs proposed are still too uneven in content and duration and the number of patients participating in these programs remains low. Home based cardiac rehabilitation technologies have already shown some effectiveness and could improve some of the weaknesses of rehabilitation programs. Again protocols and tools need to be improved and standardized. The budgetary impact will also have to be studied further.

Les maladies cardiovasculaires restent la première cause de mortalité. Malgré les progrès réalisés dans la prise en charge aiguë des patients, la prévention secondaire reste essentielle et doit inclure la prise en charge en revalidation cardiaque. Les données récentes confirment son intérêt dans les différentes indications classiques : maladie coronaire, valvulopathies, insuffisance cardiaque ou transplantation. Des nouvelles indications émergent avec également un certain bénéfice qu'il conviendra de vérifier : assistance ventriculaire, hypertension artérielle pulmonaire, remplacement valvulaire trans-cathéter (TAVI). Cependant, les différents programmes de revalidation proposés sont encore trop inégaux en contenu et en durée et le nombre de patients qui participent à ces programmes reste faible. Les technologies de télé revalidation ont déjà démontré une certaine efficacité et pourraient améliorer certaines limites des programmes de revalidation. De nouveau, les protocoles et les outils doivent être améliorés et standardisés. L'impact budgétaire devra également être davantage étudié.

[Coronary artery disease and sport practice]. / Maladie coronaire et pratique sportive.

Cardiovascular diseases are responsible for many deaths in our western societies. Practice of sport activities can decrease their occurrence and improve the prognosis of the patients already affected. The practice of a sport, however, presents an increased cardiovascular risk during its realization (sudden death, myocardial infarction, etc.). An assessment of the risk of complication is necessary before allowing patients with ischemic heart disease to practice a sport activity. Sport activities in competitions are discouraged for most patients, but for the majority, recreational activities should be encouraged. A regular medical follow-up is necessary as well as a respect of instructions of good sport practice.

Les maladies cardiovasculaires sont responsables de nombreux décès dans nos sociétés occidentales. La pratique d'une activité sportive permet de diminuer leur survenue et d'améliorer le pronostic des patients déjà atteints. La pratique d'un sport peut cependant être associée à un risque cardiovasculaire majoré lors de sa réalisation (mort subite, infarctus du myocarde, etc.). Une évaluation du risque des complications est nécessaire avant de permettre à un patient coronarien de pratiquer du sport. Les compétitions sportives sont déconseillées pour la plupart de ces patients, mais pour la grande majorité de ceux-ci, les activités de loisir doivent être encouragées. Un suivi médical régulier reste donc nécessaire, tout comme le respect des consignes des bonnes pratiques sportives.

[Increased heart rate as a risk factor and treatment target in patients with heart failure]. / Place du traitement médical bradycardisant dans l'insuffisance cardiaque.

Numerous epidemiological studies have shown that a high resting heart rate is associated with an increased cardiovascular morbidity and mortality, particularly in heart failure. The resting heart rate is not only a risk marker in heart failure, but it is also a risk factor, i.e., modifying heart rate also modifies the risk. Chronotropic drugs have shown benefits in terms of morbidity and mortality. Nevertheless, there is a major difference between the recommended heart rate and the patients’ everyday life heart rate. Indeed, even if the proportion of heart failure patients on beta-blockers is satisfactory, the number of patients with an optimal heart rate remains insufficient. The aim of this article is to examine the deleterious effect of an elevated resting heart rate in heart failure with systolic dysfunction, in order to overcome the therapeutic inertia and to improve the outcome in this patient group.

De nombreuses études épidémiologiques ont révélé qu'une fréquence cardiaque de repos supérieure à 75 battements par minute est associée à une morbi-mortalité cardiovasculaire augmentée, notamment chez les patients insuffisants cardiaques. La fréquence cardiaque de repos n'est pas seulement un marqueur de risque accru; elle est aussi un facteur de risque «modifiable¼. Plusieurs classes thérapeutiques chronotropes négatives ont démontré des bénéfices en termes de morbidité et mortalité. Néanmoins, il existe une différence majeure entre la fréquence cardiaque recommandée et celle de la vie de tous les jours. En effet, même si la proportion de patients insuffisants cardiaques sous bêta-bloquants est satisfaisante, le contrôle de la fréquence cardiaque demeure souvent insuffisant. L'objectif de cet article est de mettre en lumière le rôle délétère d'une fréquence cardiaque élevée au repos chez les insuffisants cardiaques souffrant de dysfonction systolique, afin de surmonter l'inertie thérapeutique et d'améliorer le devenir de ces patients.

[CONTRIBUTION OF CARDIAC CATHETERIZATION TO THE DIAGNOSIS AND TREATMENT OF CORONARY HEART DISEASE BEFORE AGE 40]. / APPORT DU CATHÉTÉRISME CARDIAQUE DANS LE DIAGNOSTIC ET LE TRAITEMENT DE LA MALADIE CORONARIENNE AVANT 40 ANS.

Coronary artery disease is the most frequent heart disease in our population. Its pathogenesis is well known and the first manifestation of the disease can occur in young adults. The main cause is atherosclerosis. The prevention and treatment of cardiovascular risk factors are key elements. The clinician's diagnosis is crucial before coronary arteriography, since the rate of percutaneous procedures decreases with the gravity of the starting diagnosis.

[How I TREAT AN ASYMPTOMATIC AORTIC STENOSIS?]. / COMMENT JE TRAITE... la sténose aortique asymptomatique.

Aortic stenosis (AS) is the most common valvular heart disease in adults. The most frequent aetiology is now degenerative AS. There is general agreement that, in the absence of serious co-morbidity, surgery must be recommended for patients with symptomatic disease. The management of asymptomatic patients with severe aortic disease remains controversial for several reasons: sudden death in asymptomatic patients has been reported with an incidence < 1 % per year. In addition, operative mortality is significantly higher in symptomatic, when compared with asymptomatic, patients. Patients should be carefully educated about the importance of follow-up and reporting symptoms as soon as they develop. Echocardiography confirms the diagnosis and the severity of aortic stenosis. Exercise testing may be helpful when the patient is asymptomatic. If the patient develops symptoms during test, he should be referred for surgery. The management of patients with AS in everyday practice is based on the guidelines developed by ESC in October 2012.

[Cardiovascular and renal protection of patients with type 2 diabetes : focus after EMPA-REG OUTCOME and LEADER]. / Protection cardiovasculaire et rénale du patient diabétique de type 2 : le point après EMPA-REG OUTCOME et LEADER.

Type 2 diabetes (T2D), often associated with arterial hypertension, represents a high risk of cardiovascular disease and nephropathy. Two clinical trials demonstrate the superiority versus a placebo of two antidiabetic drugs in patients with T2D and high cardiovascular risk : empagliflozin, an inhibitor of sodium-glucose type 2 (SGLT2) cotransporters, in EMPA-REG OUTCOME and liraglutide, an agonist of glucagon-like peptide-1 (GLP-1) receptors, in LEADER. Both medications showed a significant reduction in major cardiovascular events (-14 and -13 %, respectively), cardiovascular mortality (-38 and -22%), all-cause mortality (-32 and -15 %) and renal events (-39 et -22 %). The underlying protective mechanisms remain controverted. Ongoing studies should allow to decide whether the benefits are specific to each molecule or may be attributed to a class effect.

Le diabète de type 2 (DT2), souvent associé à une hypertension artérielle, expose à un risque élevé de cardiopathie et d'insuffisance rénale. Deux essais cliniques ont démontré la supériorité versus un placebo de deux médicaments antidiabétiques chez des patients DT2 à haut risque cardiovasculaire : l'empagliflozine, un inhibiteur sélectif des cotransporteurs sodium-glucose de type 2 (SGLT2), dans l'étude EMPA-REG OUTCOME et le liraglutide, un agoniste des récepteurs du glucagon-like peptide-1 (GLP-1), dans l'étude LEADER. Ces deux médicaments ont entraîné une réduction significative des événements cardiovasculaires majeurs (respectivement, -14 et -13 %), de la mortalité cardiovasculaire (-38 et -22 %), de la mortalité globale (-32 et -15 %) et des événements rénaux (-39 et -22 %). Les mécanismes sous-jacents expliquant le meilleur pronostic restent discutés. Des études en cours devraient permettre de savoir s'il s'agit d'un effet propre à la molécule ou d'un effet attribuable à la classe pharmacologique.

[European society of cardiology guidelines for the management of infective endocarditis (partim 1)]. / Recommandations européennes sur la prise en charge de l'endocardite infectieuse (partim 1).

Until recently, the recommendations of infective endocarditis were based on expert opinions, due to its low incidence and the absence of controlled trials. The update in 2015 of the new guidelines of the European Society of Cardiology (compared with 2009) relates to the publication of a randomised study on the surgical treatment, the innovations in imaging procedures (especially functional imaging in nuclear medicine) and the new concept of «Team Endocarditis¼ (multidisciplinary approach). Their aim is to remind the limitations of antibiotic prophylaxis and to insist on hospital hygiene measures. Future challenges will be to obtain a better understanding of the mechanisms associated with the contamination of the valve and to optimize the adaptation of the current epidemiological prophylaxis. In this first part, we will describe the preventive and diagnostic approaches of infective endocarditis.

Jusqu'à ce jour, les recommandations concernant le traitement de l'endocardite infectieuse étaient essentiellement basées sur l'opinion d'experts, à cause de sa faible incidence et de l'absence d'essais contrôlés. La mise à jour, en 2015, des recommandations de la Société Européenne de Cardiologie de 2009, est justifiée par la publication d'une première étude randomisée sur le traitement chirurgical, par les innovations concernant les procédures d'imagerie (particulièrement l'imagerie fonctionnelle en médecine nucléaire) et par le nouveau concept d'«Endocarditis Team¼ (approche multidisciplinaire). Ces directives européennes ont le mérite de rappeler les limitations de l'antibioprophylaxie et d'insister sur les mesures préventives à prodiguer. Les défis futurs seront de mieux comprendre les mécanismes associés à la contamination de l'endocarde valvulaire et de mieux adapter la prophylaxie à l'évolution épidémiologique. Dans cette première partie, nous décrivons la prophylaxie et les moyens diagnostiques de l'endocardite infectieuse.

[Myocardial infarction on spontaneous coronary dissection caused by fibromuscular dysplasia]. / Le cas clinique du mois : Infarctus du myocarde sur dissection coronaire spontanée secondaire à une dysplasie fibromusculaire.

Spontaneous Coronary Artery Dissection (SCAD) is a non-traumatic and non-iatrogenic separation of the coronary arterial wall. Although uncommon, it should be suspected in any young patient with acute myocardial infarction especially without risk factor of cardiovascular disease. Early coronary angiography is essential in the diagnosis of SCAD. Fibromuscular dysplasia is a rare cause of SCAD, particularly encountered in young women. This is a nonatherosclerotic and noninflammatory vascular disease. Fibromuscular dysplasia may cause stenosis, aneurysm, dissection and / or occlusion of arteries. It most commonly affects the renal and cerebral arteries.

La dissection spontanée d'une artère coronaire est définie comme une séparation non traumatique et non iatrogène de la paroi artérielle coronaire. Bien que rare, elle devrait être suspectée chez tout jeune patient qui présente un infarctus aigu du myocarde, surtout s'il ne présente aucun facteur de risque cardio-vasculaire. Le diagnostic est posé lors de la coronarographie réalisée en urgence. La dysplasie fibromusculaire est une cause rare de dissection spontanée d'une artère coronaire, particulièrement rencontrée chez les jeunes femmes. Il s'agit d'une maladie de la paroi artérielle, dont l'origine n'est ni athéromateuse ni inflammatoire, entraînant des sténoses, anévrismes, dissections et/ou occlusions, touchant particulièrement les artères à visée cérébrale et rénale.

Left ventricular regional function and maximal exercise capacity in aortic stenosis.

AIMS: The objective assessment of maximal exercise capacity (MEC) using peak oxygen consumption (VO2) measurement may be helpful in the management of asymptomatic aortic stenosis (AS) patients. However, the relationship between left ventricular (LV) function and MEC has been relatively unexplored. We aimed to identify which echocardiographic parameters of LV systolic function can predict MEC in asymptomatic AS. METHODS AND RESULTS: Asymptomatic patients with moderate to severe AS (n = 44, aortic valve area <1.5 cm(2), 66 ± 13 years, 75% of men) and preserved LV ejection fraction (LVEF > 50%) were prospectively referred for resting echocardiography and cardiopulmonary exercise test. LV longitudinal strain (LS) of each myocardial segment was measured by speckle tracking echocardiography (STE) from the apical (aLS) 4-, 2-, and 3-chamber views. An average value of the LS of the analysable segments was provided for each myocardial region: basal (bLS), mid (mLS), and aLS. LV circumferential and radial strains were measured from short-axis views. Peak VO2 was 20.1 ± 5.8 mL/kg/min (median 20.7 mL/kg/min; range 7.2-32.3 mL/kg/min). According to the median of peak VO2, patients with reduced MEC were significantly older (P < 0.001) and more frequently females (P = 0.05). There were significant correlations between peak VO2 and age (r = -0.44), LV end-diastolic volume (r = 0.35), LV stroke volume (r = 0.37), indexed stroke volume (r = 0.32), and E/e' ratio (r = -0.37, all P < 0.04). Parameters of AS severity and LVEF did not correlate with peak VO2 (P = NS for all). Among LV deformation parameters, bLS and mLS were significantly associated with peakVO2 (r = 0.43, P = 0.005, and r = 0.32, P = 0.04, respectively). With multivariable analysis, female gender (ß = 4.9; P = 0.008) and bLS (ß = 0.50; P = 0.03) were the only independent determinants (r(2) = 0.423) of peak VO2. CONCLUSION: In asymptomatic AS, impaired LV myocardial longitudinal function determines reduced MEC. Basal LS was the only parameter of LV regional function independently associated with MEC.

[ACUTE CORONARY SYNDROME AND LIPID-LOWERING THERAPY. DOES THE IMPROVE-IT STUDY MAKE ANY DIFFERENCE?]. / Syndrome coronarien aigu et traitement hypolipémiant. L'étude IMPROVE-IT change-t-elle la donne?

Statins reduce both LDL cholesterol (LDL-C) levels and the risk of cardiovascular events in patients with and without cardiovascular disease. Intensive statin therapy, compared with moderate-dose statin therapy, incrementally lowers LDL-C levels and rates of cardiovascular events in patients presenting with acute coronary syndrome. Ezetimibe, by diminishing the absorption of cholesterol from the intestine, additionally reduces LDL-C when added to statins. In this article, we discuss the potential benefits of the combination of simvastatin and ezetimibe for the long-term management of patients with acute coronary syndrome through an analysis of the IMPROVE-IT results (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial). This randomised double blind trial included 18,144 patients with a LDL-C of 50 to 100 (with statin) or 125 (without statin) mg/dl and had a median follow-up of 6 years. The objective of the study was to test the efficacy of simvastatin 40 mg versus simvastatin 40 mg and 10 mg ezetimibe. The primary endpoint included cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina and coronary revascularization. The addition of ezetimibe to simvastatin resulted in an incremental lowering of LDL-C (reached value 53.2 versus 69.9 mg/dl, p < 0.001) and a further improvement of the patient prognosis (relative reduction of primary endpoint: -6.4%, p = 0.016). In addition, the combined therapy showed no significant adverse effects, particularly regarding the risk of cancers, which confirms the safety of ezetimibe. In acute coronary syndrome, the prescription of ezetimibe should be considered (class HA, level of evidence B) in patients with a LDL-C a 70 mg/dl despite maximally tolerated dose of statin.

[Asymptomatic severe aortic stenosis with preserved left ventricular ejection fraction. Evaluation by exercise test: which results and which decision?]. / Sténose aortique sévère asymptomatique à fraction d'éjection ventriculaire gauche préservée. Évaluation à l'effort : quels résultats et quelles décisions ?

Aortic stenosis is the most common valvular heart disease in Europe and North America and it is a real public health problem. Its prevalence increases with population aging. Symptomatic patients require surgery (class I, level of evidence B). In asymptomatic patients, a stress test with or without imaging is recommended to unmask the false asymptomatic patients and refine risk stratification of occurrence of major events. This support remains difficult and makes the optimal timing for surgery controversial in the absence of prospective data on the determinants of aortic stenosis progression, multicenter studies on risk stratification or randomized studies on patient management. The complexity of care arises from the balance between the spontaneous disease risk (risk of sudden death and irreversible left ventricular dysfunction) and the risk of surgery and prosthetic complications. It is therefore crucial to identify subgroups of patients at risk of pejorative progression in whom prophylactic surgery may be considered. This article focuses on evaluating during exercise asymptomatic patients with severe aortic stenosis and preserved left ventricular ejection fraction. We will explain how to perform the test, determine which echocardiographic measurements should be obtained, focusing on the diagnostic and prognostic value of these measurements and discuss indications for surgery according to new practice guidelines.

[CT coronary angiography for the diagnosis of coronary heart disease]. / Contribution du scanner coronaire au diagnostic de maladie coronarienne.

Coronary computed tomography is an emerging technique for the diagnosis of coronary heart disease. Based on a clinical case, we discuss the diagnostic evaluation of chest pain and the role of coronary CT.

[Heart failure in the elderly]. / L'insuffisance cardiaque du sujet âgé.

Heart failure in the elderly represents a major public health problem.In this population, the general objective of therapy, defined by current guidelines, does not differ from that proposed for younger patients: the aims are to decrease symptoms, to improve quality of life, to decrease hospitalizations, and to increase survival. However, in this category of patients, respect for autonomy and quality of life remains a priority, and requires a personalized approach because of the geriatric characteristics of many patients.

[How I explore a case of suspected arrhythmogenic right ventricular dysplasia]. / Comment j'explore...une suspicion de dysplasie arythmogène du ventricule droit.

Arrhythmogenic right ventricular dysplasia is a rare, but not exceptional pathology combining the occurrence of potentially fatal arrhythmias with a gradual deterioration of the structure and function of the right ventricle. In this article, we discuss the etiopathology of the disease and emphasize the diagnostic approach.

[Perioperative management of direct oral anticoagulants: not much evidence but several different approaches]. / Gestion péri-opératoire des nouveaux anticoagulants oraux: peu de données mais plusieurs approches!

New oral anticoagulants (NOACs) are a major step forward in the field of anticoagulation. As a consequence, the number of patients treated with NOACs that have to undergo surgery constantly increases. The optimal management of such patients is not clearly determined so far as scientifically established data are lacking. A first proposal is to mimic the perioperative management of patients on vitamin-K antagonists. When the risk of perioperative bleeding is low, NOAC intake is stopped 24 hours before surgery. If the risk of postoperative hemorrhage is moderate or high, NOAC treatment is interrupted 5 days before surgery with a low molecular weight heparin bridging whenever necessary. A second option is based on pharmacokinetic data. When the risk of perioperative bleeding is low, NOAC intake is stopped the day before surgery. If the risk of perioperative bleeding is higher, NOAC intake is suspended for 5 half lives before surgery, 48-72 hours or more. This interruption should be for a longer period in the presence of renal failure. When an unforeseen surgery is needed, the procedure must be delayed as late as possible. In case of emergency, non specific pro-hemostatic agents such as prothrombin complexes or recombinant factor VIIa have not strongly proven useful and must only be used in last ditch effort.