Anticoagulation in Patients with Chronic Kidney Disease.

BACKGROUND: Both atrial fibrillation and venous thromboembolism (VTE) are highly prevalent among patients with chronic kidney disease (CKD). Until recently, warfarin was the most commonly prescribed oral anticoagulant. Direct oral anticoagulants (DOACs) have important advantages and have been shown to be noninferior to warfarin with respect to stroke prevention or recurrent VTE in the general population, with lower bleeding rates. This review article will provide available evidence on the use of DOACs in patients with CKD. SUMMARY: In post hoc analyses of major randomized studies with DOACs for stroke prevention in atrial fibrillation, in the subgroup of participants with moderate CKD, defined as a creatinine clearance (CrCl) of 30-50 mL/min, dabigatran 150 mg and apixaban were associated with lower rates of stroke and systemic embolism, whereas apixaban and edoxaban were associated with lower bleeding and mortality rates, compared with warfarin. In retrospective observational studies in patients with advanced CKD (defined as a CrCl <30 mL/min) and atrial fibrillation, DOACs had similar efficacy with warfarin with numerically lower bleeding rates. All agents warrant dose adjustment in moderate-to-severe CKD. In patients on maintenance dialysis, the VALKYRIE trial, which was designed initially to study the effect of vitamin K on vascular calcification progression, established superiority for rivaroxaban compared with a vitamin K antagonist (VKA) in the extension phase. Two other clinical trials using apixaban (AXADIA and RENAL-AF) in this population were inconclusive due to recruitment challenges and low event rates. In post hoc analyses of randomized studies with DOACs in patients with VTE, in the subgroup of participants with moderate CKD at baseline, edoxaban was associated with lower rates of recurrent VTE, whereas rivaroxaban and dabigatran were associated with lower and higher bleeding rates, respectively, as compared to warfarin. KEY MESSAGES: DOACs have revolutionized the management of atrial fibrillation and VTE, and they should be preferred over warfarin in patients with moderate-to-severe CKD with appropriate dose adjustment. Therapeutic drug monitoring with a valid technique may be considered to guide clinical management in individualized cases. Current evidence questions the need for oral anticoagulation in patients on maintenance dialysis with atrial fibrillation as both DOACs and VKAs are associated with high rates of major bleeding.

Utilizing synchronous care to improve cardiovascular and renal health among patients with type 2 diabetes: Proof-of-concept results from the DECIDE-CV clinical programme.

AIM: The management of patients with type 2 diabetes is asynchronous, i.e. not coordinated in time, resulting in delayed access to care and low use of guideline-directed medical therapy (GDMT). METHODS: We retrospectively analysed consecutive patients assessed in the 'synchronized' DECIDE-CV clinic. In this outpatient clinic, patients with type 2 diabetes and cardiovascular or chronic kidney disease are simultaneously assessed by an endocrinologist, cardiologist and nephrologist in the same visit. The primary outcome was use of GDMT before and after the assessment in the clinic, including sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, renin-angiotensin system blockers and mineralocorticoid receptor antagonists. Secondary outcomes included the baseline-to-last-visit change in surrogate laboratory biomarkers. RESULTS: The first 232 patients evaluated in the clinic were included. The mean age was 67 ± 12 years, 69% were men and 92% had diabetes. In total, 73% of patients had atherosclerotic cardiovascular disease, 65% heart failure, 56% chronic kidney disease and 59% had a urinary albumin-to-creatinine ratio ≥30 mg/g. There was a significant increase in the use of GDMT:sodium-glucose cotransporter 2 inhibitors (from 44% to 87% of patients), glucagon-like peptide 1 receptor agonists (from 8% to 45%), renin-angiotensin system blockers (from 77% to 91%) and mineralocorticoid receptor antagonists (from 25% to 45%) (p < .01 for all). Among patients with paired laboratory data, glycated haemoglobin, urinary albumin-to-creatinine ratio and N-terminal proB-type natriuretic peptide levels significantly dropped from baseline (p < .05 for all). CONCLUSIONS: Joint assessment of patients with diabetes in a synchronized cardiometabolic clinic holds promise for enhancing GDMT use and has led to significant reductions in surrogate cardiovascular and renal laboratory biomarkers.

Cardiovascular phenotypes in type 2 diabetes: Latent class analysis of the CANVAS Program and CREDENCE trial.

AIM: To identify unique clinical phenotypes in type 2 diabetes (T2D) and investigate their treatment response to canagliflozin using latent class analysis. METHODS: This was a pooled latent class analysis of the individuals in the CANVAS Program and CREDENCE trial. The co-primary endpoints were hospitalization for heart failure (HHF) and the composite of cardiovascular death (CVD) or HHF. Secondary endpoints included three-point major adverse CV events, its individual components, and all-cause mortality. We completed Cox proportional hazards models to evaluate the effect of canagliflozin across phenotypes. RESULTS: Four distinct phenotypes were identified: Phenotype 1 (n = 966, 6.6%), with the lowest prevalence of heart failure, kidney dysfunction and hypertension; Phenotype 2 (n = 4169, 28.7%), primarily comprising females with a high prevalence of atherosclerotic vascular disease (ASCVD); Phenotype 3 (n = 7108, 48.9%), predominately males with a high prevalence of ASCVD; and Phenotype 4 (n = 2300, 15.8%), possessing the highest prevalences of HF and renal dysfunction. A hierarchical increase in the risk of the primary endpoint was observed across the phenotypes, with the highest CV risk observed for Phenotype 4 (hazard ratio for HHF: 7.57 [95% CI: 4.19-13.69]). Canagliflozin significantly reduced HHF and the composite CVD or HHF across phenotypes (all P values for interaction > .05). CONCLUSION: We identified four clinically distinct T2D phenotypes with differential CV risks. Canagliflozin reduced the risk of CV events, irrespective of the phenotype, emphasizing its broad therapeutic acceptability.

Epidemiology, thrombolytic management, and outcomes of acute stroke among patients with chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: The relative frequency of ischaemic versus haemorrhagic stroke among patients with chronic kidney disease (CKD) has not been clearly described. Moreover, no recent meta-analysis has investigated the outcomes of patients with CKD treated with thrombolysis for acute ischaemic stroke. We conducted a systematic review and meta-analysis to estimate the proportion of stroke subtypes and the outcomes of thrombolysis in CKD. METHODS: A PubMed, EMBASE and Cochrane literature research was conducted. The primary outcome was the proportion and incidence of ischaemic versus haemorrhagic strokes among patients with CKD. In addition, we assessed the impact of CKD on disability, mortality and bleeding among patients with acute ischaemic stroke treated with thrombolysis. The pooled proportion and the risk ratio were estimated using a random-effects model. RESULTS: Thirty-nine observational studies were included: 22 on the epidemiology of stroke types and 17 on the outcomes of thrombolysis in this population. In the main analysis (>99 281 patients), ischaemic stroke was more frequent than haemorrhagic among patients with CKD [78.3%, 95% confidence interval (CI) 73.3-82.5%]. However, among patients with kidney failure, the proportion of ischaemic stroke decreased and was closer to that of haemorrhagic stroke (59.8%, 95% CI 49.4-69.4%). CKD was associated with worse clinical outcomes in patients with acute ischaemic stroke compared with patients with preserved kidney function. CONCLUSIONS: The relative frequency of haemorrhagic stroke seems to increase as kidney function declines. Among patients with acute ischaemic stroke treated with thrombolysis, presence of CKD is associated with higher disability, mortality and bleeding, compared with patients with preserved kidney function.

Synchronous Health Care Delivery for the Optimization of Cardiovascular and Renal Care in Patients with Type 2 Diabetes.

PURPOSE OF REVIEW: The current care model of type 2 diabetes (T2D) and its complications appears to be "asynchronous" with patient care divided by specialty. This model is associated with low use of guideline-directed medical therapies. RECENT FINDINGS: The use of integrated care models has been well described in the management of patients with T2D; this usually includes an endocrinologist coupled with a nutritionist and nurse. However, physician-based care models are largely "asynchronous," whereby the patient requires multiple different siloed specialties to manage their health care. To date, there has been limited exploration of synchronous care delivery, i.e., whereby multi-comorbid patients with T2D are seen simultaneously by health care providers from endocrinology, cardiology, and nephrology to optimize use of guideline-directed medical therapies (GDMT). Given the rising complexity of patients with T2D, further research is needed on the role of synchronous health care delivery in optimizing the use of GDMT and improving patient outcomes.

Clinical Phenotypes in Patients With Type 2 Diabetes Mellitus: Characteristics, Cardiovascular Outcomes and Treatment Strategies.

PURPOSE OF REVIEW: With recent advances in the pharmacological management of type 2 diabetes mellitus (T2DM), there is a growing need to understand which patients optimally benefit from these novel therapies. Various clinical clustering methodologies have emerged that utilise data-agnostic strategies to categorise patients that have similar clinical characteristics and outcomes; broadly, this characterisation is termed phenotyping. In patients with T2DM, we aimed to describe patient characteristics from phenotype studies, their cardiovascular risk profiles and the impact of antihyperglycemic treatment. RECENT FINDINGS: Numerous phenotypic studies have been undertaken that have utilised a combination of clinical, biochemical, imaging and genetic variables. Each of these has produced phenotypes that display a spectrum of cardiovascular risk. Studies that aimed to describe pathophysiological phenotypes generally identified five phenotypes: autoimmune phenotype, insulin-related phenotypes (including permutations of insulin deficiency and resistance), obesity phenotype, ageing phenotype, and a sex-related phenotype. Studies examining risk profiles have demonstrated that across such phenotypes there is a spectrum of risk for diabetic complications. Few studies have examined treatment effects across these phenotypes, and thus provide little insights towards making phenotype-guided treatment decisions Clustering analyses in patients with T2DM have identified distinct phenotypes with unique risk profiles. Further studies are needed that harness the use of clinical, biochemical, imaging and genetic data to explore therapeutic heterogeneity and response to antihyperglycemic treatment across the spectrum of patient phenotypes.

[Oral anticoagulation in chronic kidney disease]. / Anticoagulation orale et insuffisance rénale chronique.

Non-vitamin K antagonist oral anticoagulants (NOAC) present several advantages over vitamin K antagonists, but data with respect to their use in patients with chronic kidney disease is limited. The decision to use oral anticoagulation as well as the choice of the molecule may be difficult in these patients. In patients with moderate kidney disease, NOACs appear to be safe and effective. In advanced kidney disease, they should be used with prudence, after careful assessment of risks and benefits, and at adapted doses. In end stage kidney disease, evidence is weak, suggesting an unfavourable risk benefit ratio. Prescription of oral anticoagulation in these patients has to be individualised in a shared decision making process.

Les anticoagulants oraux directs (ACOD) présentent plusieurs avantages sur les antivitamines K, mais les données concernant leur utilisation en cas d'insuffisance rénale avancée restent rares. Le choix d'anticoaguler et celui de la molécule sont particulièrement ardus chez ces patients. En cas d'insuffisance rénale légère à modérée, les ACOD présentent un profil de sécurité et d'efficacité satisfaisant. En cas d'insuffisance rénale sévère, leur utilisation doit être prudente, avec une évaluation soigneuse des risques et bénéfices, et en adaptant la posologie. Chez les patients avec insuffisance rénale terminale, l'évidence est faible et suggère un rapport bénéfice/risque défavorable pour l'anticoagulation orale. La décision d'anticoaguler et le choix de la molécule nécessiteront une approche individualisée et une décision partagée avec le patient.

[Internal medicine in 2020]. / 2020 en revue par les internistes hospitaliers.

2020: annus horribilis for hospital medicine? The past year, notable because of the current pandemic, has had a profound impact on multiple aspects of medical practice. Just as all medical staff and the general population, hospital internists were put under immense strain in 2020. This year has more than ever reinforced our belief in the importance of keeping a critical and scientific eye on the mass of new studies and data produced every year. The internists of the HUG propose a critical review of selected recent publications that may influence our daily management of patients.

2020 : annus horribilis pour la médecine hospitalière ? L'année écoulée, marquée par la pandémie en cours, a eu un impact majeur sur de multiples aspects de notre pratique. Comme l'ensemble du monde médico-soignant et de la population, les internistes hospitaliers ont été mis à rude épreuve en 2020. Cette année a plus que jamais renforcé notre conviction de l'importance de porter un regard scientifique sur la masse de nouveautés qui surviennent chaque année. Les internistes hospitaliers des HUG vous proposent de partager leur vision critique de publications scientifiques récentes utiles pour notre pratique quotidienne.

Direct oral anticoagulants in chronic kidney disease: an update.

PURPOSE OF REVIEW: Direct oral anticoagulants (DOACs) are variably eliminated by the kidneys rendering their use potentially problematic in patients with chronic kidney disease (CKD) or necessitating appropriate dose adjustment. RECENT FINDINGS: Both observational and limited randomized trial data for DOACs compared with no treatment or with warfarin for patients with atrial fibrillation on maintenance dialysis were recently published. In a randomized trial in patients on hemodialysis, there was no significant difference in vascular calcification between patients who received rivaroxaban with or without vitamin K2 or vitamin K antagonists. A randomized trial of apixaban versus warfarin was terminated owing to poor enrollment and preliminary results identified no difference in clinical outcomes between groups. However, valuable pharmacodynamic data will be forthcoming from that trial. In observational research, among patients newly diagnosed with atrial fibrillation, there were opposing trends in the associations of apixaban initiation versus no oral anticoagulation with ischemic versus hemorrhagic stroke and no association was present with the overall risk of stroke or embolism. In another study comparing apixaban with warfarin initiation, apixaban was associated with less bleeding. Regular-dose apixaban (5 mg twice daily) associated with reduced rates of ischemic stroke or systemic embolism, whereas no such association was present for those prescribed the reduced dose (2.5 mg twice daily). SUMMARY: DOACs may be used after appropriate dose adjustment for an established clinical indication in patients with advanced CKD. Quality evidence for oral anticoagulation, with any specific agent or dose, for stroke prevention in hemodialysis continues to be lacking.

Risk of Cardiovascular Events and Mortality Among Elderly Patients With Reduced GFR Receiving Direct Oral Anticoagulants.

RATIONALE & OBJECTIVE: Evidence for the efficacy of direct oral anticoagulants (DOACs) to prevent cardiovascular (CV) events and mortality in older individuals with a low estimated glomerular filtration rate (eGFR) is lacking. We sought to characterize the association of oral anticoagulant use with CV morbidity in elderly patients with or without reductions in eGFRs, comparing DOACs with vitamin K antagonists (VKAs). STUDY DESIGN: Population-based retrospective cohort study. SETTINGS & PARTICIPANTS: All individuals 66 years or older with an initial prescription for oral anticoagulants dispensed in Ontario, Canada, from 2009 to 2016. EXPOSURE: DOACs (apixaban, dabigatran, and rivaroxaban) compared with VKAs by eGFR group (≥60, 30-59, and<30mL/min/1.73m2). OUTCOMES: The primary outcome was a composite of a CV event (myocardial infarction, revascularization, or ischemic stroke) or mortality. Secondary outcomes were CV events alone, mortality, and hemorrhage requiring hospitalization. ANALYTICAL APPROACH: High-dimensional propensity score matching of DOAC to VKA users and Cox proportional hazards regression. RESULTS: 27,552 new DOAC users were matched to 27,552 new VKA users (median age, 78 years; 49% women). There was significantly lower risk for CV events or mortality among DOAC users compared with VKA users (event rates of 79.78 vs 99.77 per 1,000 person-years, respectively; HR, 0.82 [95% CI, 0.75-0.90]) and lower risk for hemorrhage (event rates of 10.35 vs 16.77 per 1,000 person-years, respectively; HR, 0.73 [95% CI, 0.58-0.91]). There was an interaction between eGFR and the association of anticoagulant class with the primary composite outcome (P<0.02): HRs of 1.01 [95% CI, 0.92-1.12], 0.83 [95% CI, 0.75-0.93], and 0.75 [95% CI, 0.51-1.10] for eGFRs of≥60, 30 to 59, and<30mL/min/1.73m2. No interaction was detected for the outcome of hemorrhage. LIMITATIONS: Retrospective observational study design limits causal inference; dosages of DOACs and international normalized ratio values were not available; low event rates in some subgroups limited statistical power. CONCLUSIONS: DOACs compared with VKAs were associated with lower risk for the composite of CV events or mortality, an association for which the strength was most apparent among those with reduced eGFRs. The therapeutic implications of these findings await further study.

Association of Chronic Kidney Disease with Preserved Ejection Fraction Heart Failure Is Independent of Baseline Cardiac Function.

BACKGROUND/AIMS: Chronic kidney disease (CKD) is common among patients with heart failure with preserved ejection fraction (HFpEF) and is associated with worse clinical outcomes. This study aims to identify whether the association of CKD with HFpEF is independent of underlying echocardiographic abnormalities. MATERIALS: We conducted a retrospective cohort study including patients without prevalent heart failure referred for echocardiography. Patients with serial echocardiograms, baseline left ventricular ejection fraction (LVEF) ≥50% and estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2 were matched 1:1 with patients with eGFR <60 mL/min/1.73 m2 for age (±5 years), sex, history of hypertension or diabetes, use of renin-angiotensin inhibitors, and LVEF (±5%). A secondary analysis included patients with preserved LVEF and normal left ventricular mass index matched for the same parameters except use of renin-angiotensin inhibitors. RESULTS: Patients with CKD were at increased risk for HFpEF admission: crude hazard ratio (HR) 1.79 (95% confidence interval [CI] 1.38-2.32, p < 0.001) and adjusted HR (for coronary disease, loop diuretics, left atrial diameter) 1.64 (95% CI 1.22-2.21, p = 0.001). LVEF and left ventricular diameter decreased over time in both groups but no difference was observed in rate of dropping. Results were similar in the secondary analysis (crude HR 1.99, 95% CI 1.07-3.71, p = 0.03 and HR adjusted for left atrial diameter 1.98, 95% CI 1.05-3.75, p = 0.04). Rate of change was similar for LVEF, pulmonary artery pressure, and left ventricular mass index in both groups. CONCLUSION: CKD is independently associated with incident HFpEF despite a similar change in relevant echocardiographic parameters in patients with or without CKD.

External validation of prediction models for mortality in an incident dialysis population
.

AIMS: Different prediction models have been established to estimate mortality in the dialysis population. This study aims to externally validate the different available mortality prediction models in an incident dialysis population. MATERIALS: This was a retrospective cohort study of incident hemodialysis and peritoneal dialysis patients at two academic tertiary care centers. METHODS: Three previously published prediction models were used: the Liu index, the Urea5 score, and a predictive model estimating the survival probability by Hemke et al. [6]. Models were compared using the C-statistic, net reclassification index, and integrated discrimination improvement. Only the subgroup of 193 patients with enough data to be included in all models was used. RESULTS: 377 patients were started on dialysis in both institutions between 2006 and 2011. Median follow-up was 787 days. 104 patients (27.6%) died during follow-up and 181 were admitted to the hospital (48.0%). All three models were predictive of mortality and hospital admissions. The survival probability model by Hemke et al. [6] performed better than the other two models for mortality (C-statistic 0.72). The Liu index had the highest performance for hospital admissions (C-statistic 0.65). Using reclassification statistics (reference = Urea5), the only model to improve discriminatory ability was the Liu index for the outcome of hospital admission. CONCLUSION: The survival probability model by Hemke et al. [6] may be preferred for mortality prediction in incident dialysis patients. The Liu index could be used to predict hospital admissions in the same population. Available models demonstrated only modest performance in predicting either outcome. Therefore, alternative models need to be developed.
.

Platelet reactivity in stable cardiovascular patients with chronic kidney disease.

The study aimed to evaluate antiplatelet drug responsiveness in stable outpatients with cardiovascular disease and chronic kidney disease (CKD) and examine whether impaired antiplatelet drug responsiveness is associated with worse clinical outcomes in this population. Stable cardiovascular patients (n = 771) were enrolled at least one month after an acute ischemic atherothrombotic event. Antiplatelet drug responsiveness was assessed with specific assays (serum TxA2 for aspirin, the VASP assay for clopidogrel) and other aggregation-based assays using different agonists. All patients were followed until the first occurrence of a major adverse cardiovascular event. The 133 CKD patients were found to have higher activity of von Willebrand factor and higher fibrinogen levels. After a median follow-up of 33 months, 88 events occurred in patients without CKD and 31 events in patients with CKD (5.0 events and 8.7 events per 100 patient years, respectively, HR = 1.75 (95% CI 1.16-2.63; p = 0.008). The prevalence of poor aspirin and clopidogrel responsiveness and high platelet reactivity as assessed with different aggregation-based assays was similar in patients with estimated GFR ≥ 60 ml/min, 45-59 ml/min, and < 45 ml/min. No significant interaction for CKD vs. non-CKD was observed for events occurrence in patients with or without high platelet reactivity on several assays, with the exception of collagen-induced aggregation. In stable cardiovascular patients, CKD is not associated with higher platelet reactivity. Decreased antiplatelet drug responsiveness is not associated with worse clinical outcomes in CKD patients.

Serial versus single troponin measurements for the prediction of cardiovascular events and mortality in stable chronic haemodialysis patients.

AIM: This study aims to describe the variability of pre-dialysis troponin values in stable haemodialysis patients and compare the performance of single versus fluctuating or persistently elevated troponins in predicting a composite of mortality and cardiac arrest, myocardial infarction or stroke. METHODS: A total of 128 stable ambulatory chronic haemodialysis patients were enrolled. Pre-dialysis troponin I was measured for three consecutive months. The patients were followed for 1 year. A troponin elevation (>0.06 µg/L) was considered high risk, and patients were classified into three risk groups: (i) patients who had normal troponin levels on all three measurements; (ii) patients with at least one elevated and one normal troponin value; and (iii) patients with elevated troponin values on all measurements. RESULTS: A total of 81 patients had all three troponin values in the normal range; 29 had fluctuating values; 18 had all three values elevated. Twenty-seven deaths or composite events were observed: eight in the first risk group, 10 in the second and nine in the third. Persistently elevated and fluctuating troponin values were associated with higher mortality and cardiovascular event rate. Serial troponin measurement had a higher sensitivity for the composite outcome than single troponin measurement when either fluctuating or persistently elevated values were considered to confer high risk. CONCLUSION: Most haemodialysis patients do not have elevated troponin levels at baseline. Troponin levels that remain elevated or fluctuate are associated with worse outcomes. A serial troponin measurement strategy is associated with better sensitivity and higher negative predictive value compared with single troponin measurement.

Echocardiographic parameters and renal outcomes in patients with preserved renal function, and mild- moderate CKD.

BACKGROUND: Echocardiographic characteristics across the spectrum of chronic kidney disease (CKD) have not been well described. We assessed the echocardiographic characteristics of patients with preserved renal function and mild or moderate CKD referred for echocardiography and determined whether echocardiographic parameters of left ventricular (LV) and right ventricular (RV) structure and function were associated with changes in renal function and mortality. METHODS: This retrospective cohort study enrolled all adult patients who had at least one trans-thoracic echocardiography between 2004 and 2014 in our institution. The composite outcome of doubling of serum creatinine or initiation of maintenance dialysis or kidney transplantation was the primary outcome. Mortality was the secondary outcome. RESULTS: 29,219 patients were included. Patients with worse renal function had higher prevalence of structural and functional LV and RV abnormalities. Higher estimated glomerular filtration rate (eGFR) was independently associated with preserved LV ejection fraction, preserved RV systolic function, and lower LV mass, left atrial diameter, pulmonary artery pressure, and right atrial pressure, as well as normal RV structure. 1041 composite renal events were observed. 8780 patients died during the follow-up. Pulmonary artery pressure and the RV, but not the LV, echocardiographic parameters were independently associated with the composite renal outcome. In contrast, RV systolic function, RV dilation or hypertrophy, LV ejection fraction group, LV diameter quartile, and pulmonary artery pressure quartile were independently associated with all-cause mortality. CONCLUSIONS: Echocardiographic abnormalities are frequent even in early CKD. Echocardiographic assessment particularly of the RV may provide useful information for the care of patients with CKD.

Apixaban Pharmacokinetics at Steady State in Hemodialysis Patients.

It is unclear whether warfarin is protective or harmful in patients with ESRD and atrial fibrillation. This state of equipoise raises the question of whether alternative anticoagulants may have a therapeutic role. We aimed to determine apixaban pharmacokinetics at steady state in patients on hemodialysis. Seven patients received apixaban 2.5 mg twice daily for 8 days. Blood samples were collected before and after apixaban administration on days 1 and 8 (nondialysis days). Significant accumulation of the drug was observed between days 1 and 8 with the 2.5-mg dose. The area under the concentration-time curve from 0 to 24 hours increased from 628 to 2054 ng h/ml (P<0.001). Trough levels increased from 45 to 132 ng/ml (P<0.001). On day 9, after a 2.5-mg dose, apixaban levels were monitored hourly during dialysis. Only 4% of the drug was removed. After a 5-day washout period, five patients received 5 mg apixaban twice daily for 8 days. The area under the concentration-time curve further increased to 6045 ng h/ml (P=0.03), and trough levels increased to 218 ng/ml (P=0.03), above the 90th percentile for the 5-mg dose in patients with preserved renal function. Apixaban 2.5 mg twice daily in patients on hemodialysis resulted in drug exposure comparable with that of the standard dose (5 mg twice daily) in patients with preserved renal function and might be a reasonable alternative to warfarin for stroke prevention in patients on dialysis. Apixaban 5 mg twice daily led to supratherapeutic levels in patients on hemodialysis and should be avoided.

[Recent advances in internal medicine]. / Médecine interne générale: l'année 2017 en revue par les internistes hospitaliers.

In medicine, there are progresses which radically transform practices, change recommendations and win unanimous support in the medical community. There are some which divide, questioning principles that seemed established. There are also small advances, which can answer the questions that internists ask themselves in the daily care of their patients. Here are several articles published in 2017, read and commented for you by hospitalists, selected according to their impact on the medical world.

En médecine, il y a des découvertes qui révolutionnent les pratiques, changent les recommandations et rassemblent toute la communauté médicale. Il y en a qui divisent, en remettant en question des principes qui semblaient établis. Il y a aussi de petites avancées qui permettent de répondre aux questions que se posent les internistes dans la prise en charge quotidienne de leurs patients. Voici quelques articles parus en 2017, lus et commentés pour vous par des internistes hospitaliers et sélectionnés en fonction de leur retentissement dans le monde médical.

Neutropenia in kidney and liver transplant recipients: Risk factors and outcomes.

No studies have directly compared the key characteristics and outcomes of kidney (KTx) and liver transplantation (LTx) recipients with neutropenia. In this single-center, retrospective, cohort study, we enrolled all adult patients who received a KTx or LTx between 2000 and 2011. Neutropenia was defined as 2 consecutive absolute neutrophil count (ANC) values <1500/mm3 in patients without preexisting neutropenia. The first neutropenia episode occurring during the first year post-transplantation was analyzed. A total of 663 patients with KTx and 354 patients with LTx met the inclusion criteria. Incidence of neutropenia was 20% in KTx and 38% in LTx, respectively. High-risk CMV status and valganciclovir (VGCV) use were significant predictors of neutropenia for KTx recipients, but only VGCV use vs nonuse in LTx recipients. Neutropenia was associated with worse survival in KTx recipients (adjusted HR 1.95, 95% CI 1.18-3.22, P<.01), but not in LTx recipients (adjusted HR 0.75, 95% CI 0.52-1.10, P=.15). Sixteen acute rejection episodes were associated with preceding neutropenia in KTx recipients (HR 1.77, 95% CI 1.16-2.68, P=.007) and 24 acute rejection episodes in LTx recipients (HR 1.41, 95% CI 0.97-2.04, P=.07). Incidence of infection was similar in patients with and without neutropenia among KTx and LTx recipients.

Cardiovascular complications in chronic dialysis patients.

PURPOSE OF REVIEW: This review article focuses on the most significant cardiovascular complications in dialysis patients [sudden cardiac death (SCD), acute coronary syndromes, heart failure, and atrial fibrillation]. RECENT FINDINGS: Current and ongoing research aims to quantify the rate and pattern of significant arrhythmia in dialysis patients and to determine the predominant mechanism of SCD. Preliminary findings from these studies suggest a high rate of atrial fibrillation and that bradycardia and asystole may be more frequent than ventricular arrhythmia as a cause of sudden death. A recently published matched cohort study in dialysis patients who received a defibrillator for primary prevention showed that there was no significant difference in mortality rates between defibrillator-treated patients and propensity-matched controls. Two randomized controlled trials are currently recruiting participants and will hopefully answer the question of whether implantable or wearable cardioverter defibrillators can prevent SCD. An observational study using United States Renal Data System data demonstrated how difficult it is to keep hemodialysis patients on warfarin, as more than two-thirds discontinued the drug during the first year. The ISCHEMIA-CKD trial may provide answers about the optimal strategy for the treatment of atherosclerotic coronary disease in patients with advanced chronic kidney disease. SUMMARY: The article reviews the diagnosis of acute coronary syndromes in dialysis patients, current literature on myocardial revascularization, and data on fatal and nonfatal cardiac arrhythmia. The new classification of heart failure in end-stage renal disease is reviewed. Finally, available cohort studies on warfarin for stroke prevention in dialysis patients with atrial fibrillation are reviewed.