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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.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Insuficiencia Renal Crónica , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Insuficiencia Renal Crónica/complicaciones , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/etiología , Prueba de Estudio Conceptual , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Angiopatías Diabéticas/prevención & control , Receptor del Péptido 1 Similar al Glucagón/agonistas , Antagonistas de Receptores de Angiotensina/uso terapéutico , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Biomarcadores/sangre , Péptido Natriurético Encefálico/sangreRESUMEN
Atrial fibrillation (AF) is highly prevalent in patients with chronic kidney disease (CKD). It is associated with an increased risk of stroke, which increases as kidney function declines. In the general population and in those with a moderate degree of CKD (creatinine clearance 30-50 mL/min), the use of oral anticoagulation to decrease the risk of stroke has been the standard of care based on a favorable risk-benefit profile that had been established in seminal randomized controlled trials. However, evidence regarding the use of oral anticoagulants for stroke prevention is less clear in patients with severe CKD (creatinine clearance <30 mL/min) and those receiving maintenance dialysis, as these individuals were excluded from such large randomized controlled trials. Nevertheless, the direct oral anticoagulants have invariably usurped vitamin K antagonists as the preferred choice for oral anticoagulation among patients with AF across all strata of CKD based on their well-defined safety and efficacy and multiple pharmacokinetic benefits (e.g., less drug-drug interactions). This review summarizes the current literature on the role of oral anticoagulation in the management of AF among patients with CKD and highlights current deficiencies in the evidence base and how to overcome them.
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Anticoagulantes , Fibrilación Atrial , Insuficiencia Renal Crónica , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/etiología , Administración OralRESUMEN
Rationale & Objective: Patients treated with dialysis are commonly prescribed multiple medications (polypharmacy), including some potentially inappropriate medications (PIMs). PIMs are associated with an increased risk of medication harm (eg, falls, fractures, hospitalization). Deprescribing is a solution that proposes to stop, reduce, or switch medications to a safer alternative. Although deprescribing pairs well with routine medication reviews, it can be complex and time-consuming. Whether clinical decision support improves the process and increases deprescribing for patients treated with dialysis is unknown. This study aimed to test the efficacy of the clinical decision support software MedSafer at increasing deprescribing for patients treated with dialysis. Study Design: Prospective controlled quality improvement study with a contemporaneous control. Setting & Participants: Patients prescribed ≥5 medications in 2 outpatient dialysis units in Montréal, Canada. Exposures: Patient health data from the electronic medical record were input into the MedSafer web-based portal to generate reports listing candidate PIMs for deprescribing. At the time of a planned biannual medication review (usual care), treating nephrologists in the intervention unit additionally received deprescribing reports, and patients received EMPOWER brochures containing safety information on PIMs they were prescribed. In the control unit, patients received usual care alone. Analytical Approach: The proportion of patients with ≥1 PIMs deprescribed was compared between the intervention and control units following a planned medication review to determine the effect of using MedSafer. The absolute risk difference with 95% CI and number needed to treat were calculated. Outcomes: The primary outcome was the proportion of patients with one or more PIMs deprescribed. Secondary outcomes include the reduction in the mean number of prescribed drugs and PIMs from baseline. Results: In total, 195 patients were included (127, control unit; 68, intervention unit); the mean age was 64.8 ± 15.9 (SD), and 36.9% were women. The proportion of patients with ≥1 PIMs deprescribed in the control unit was 3.1% (4/127) vs 39.7% (27/68) in the intervention unit (absolute risk difference, 36.6%; 95% CI, 24.5%-48.6%; P < 0.0001; number needed to treat = 3). Limitations: This was a single-center nonrandomized study with a type 1 error risk. Deprescribing durability was not assessed, and the study was not powered to reduce adverse drug events. Conclusions: Deprescribing clinical decision support and patient EMPOWER brochures provided during medication reviews could be an effective and scalable intervention to address PIMs in the dialysis population. A confirmatory randomized controlled trial is needed.
Patients treated with dialysis are commonly prescribed multiple medications, some of which are potentially inappropriate medications (PIMs). PIMs can increase a patient's pill burden and are associated with an increased risk of harm (some examples include falls, fractures, and hospitalization). Deprescribing is a proposed solution that aims to highlight medications that can be stopped, reduced, or switched to a safer option, under supervision of a health care provider. We aimed to determine if a quality improvement intervention in the dialysis unit could increase deprescribing compared to usual care. The study took place in 2 outpatient hemodialysis units where usual care involves nurses and nephrologists performing medication reviews twice a year. The intervention was a deprescribing report that was generated with the help of a software tool called MedSafer, along with brochures for patients with information on PIMs they were taking. In the intervention unit, we increased the number of patients who had a medication safely deprescribed by 36.6% more than on the control unit. Although the study was small, a future larger study in dialysis patients might show that a computer software such as MedSafer can prevent harmful complications from taking too many medications.
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BACKGROUND: The cardiovascular and renal benefits of renin-angiotensin aldosterone system (RAAS) blockade are not well established in patients with advanced chronic kidney disease (CKD). We conducted a systematic review and meta-analysis to identify potential risks and benefits from RAAS blockade in patients with CKD stage 4-5. METHODS: A Medline search from inception to November 2022 was conducted to identify randomised controlled trials (RCTs) in patients with CKD stage 4-5 (estimated glomerular filtration rate ≤ 30 mL/min/1.73 m2) comparing RAAS blockade vs placebo or alternative antihypertensive therapy. Different intervention strategies were assessed (RAAS use vs nonuse, initiation vs placebo/alternative therapy, or discontinuation vs continuation). The primary outcome was progression to end-stage kidney disease (ESKD). Secondary outcomes were all-cause mortality and major adverse cardiovascular events (MACE). The risk ratio (RR) was estimated with the use of a random-effects model. RESULTS: Nine RCTs (1150 patients) were included. RAAS blockade was associated with a significant reduction in progression to ESKD: RR 0.84 (95% confidence interval [CI] 0.74-0.96; P = 0.01). There was no benefit from RAAS blockade on all-cause mortality or MACE: RR 1.02 (95% CI 0.63-1.65; P = 0.93) and RR 0.87 (95% CI 0.49-1.57; P = 0.65), respectively. CONCLUSIONS: RAAS blockade may be considered in selected patients with CKD stage 4-5 to delay progression to ESKD.
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OBJECTIVE: The study was undertaken because it was unknown whether the duration of type 2 diabetes modifies the effects of sodium-glucose cotransporter 2 inhibitor canagliflozin on cardiovascular (CV) and kidney outcomes. RESEARCH DESIGN AND METHODS: This post hoc analysis of the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program (N = 10,142) and Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (CREDENCE) trial (N = 4,401) evaluated hazard ratios and 95% CIs using Cox proportional hazards for the effects of canagliflozin on CV and kidney outcomes, including progression and regression of albuminuria over 5-year intervals of disease duration. RESULTS: Canagliflozin had ranges of benefit across intervals of diabetes duration, with no heterogeneity for major adverse CV events, CV death or heart failure hospitalization, and kidney failure requiring therapy or doubling serum creatinine. Furthermore, canagliflozin reduced albuminuria progression and increased albuminuria regression with no interaction across all diabetes duration subgroups. CONCLUSIONS: Our findings suggest that earlier treatment with canagliflozin confers consistent cardiorenal benefits to individuals with type 2 diabetes.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Canagliflozina/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Albuminuria/tratamiento farmacológico , RiñónRESUMEN
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.
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Fibrilación Atrial , Piridinas , Insuficiencia Renal Crónica , Accidente Cerebrovascular , Tiazoles , Tromboembolia Venosa , Humanos , Warfarina/efectos adversos , Rivaroxabán/efectos adversos , Dabigatrán/efectos adversos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control , Estudios Retrospectivos , Resultado del Tratamiento , Anticoagulantes/efectos adversos , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Vitamina K , Administración OralRESUMEN
Purpose of review: Lung ultrasound is a noninvasive bedside technique that can accurately assess pulmonary congestion by evaluating extravascular lung water. This technique is expanding and is easily available. Our primary outcome was to compare the efficacy of volume status assessment by lung ultrasound with clinical evaluation, echocardiography, bioimpedance, or biomarkers. The secondary outcomes were all-cause mortality and cardiovascular events. Sources of information: We conducted a MEDLINE literature search for observational and randomized studies with lung ultrasound in patients on maintenance dialysis. Methods: From a total of 2363 articles, we included 28 studies (25 observational and 3 randomized). The correlation coefficients were pooled for each variable of interest using the generic inverse variance method with a random effects model. Among the clinical parameters, New York Heart Association Functional Classification of Heart Failure status and lung auscultation showed the highest correlation with the number of B-lines on ultrasound, with a pooled r correlation coefficient of .57 and .36, respectively. Among echocardiographic parameters, left ventricular ejection fraction and inferior vena cava index had the strongest correlation with the number of B-lines, with a pooled r coefficient of .35 and .31, respectively. Three randomized studies compared a lung ultrasound-guided approach with standard of care on hard clinical endpoints. Although patients in the lung ultrasound group achieved better decongestion and blood pressure control, there was no difference between the 2 management strategies with respect to death from any cause or major adverse cardiovascular events. Key findings: Lung ultrasound may be considered for the identification of patients with subclinical volume overload. Trials did not show differences in clinically important outcomes. The number of studies was small and many were of suboptimal quality. Limitations: The included studies were heterogeneous and of relatively limited quality.
Motif de la revue: L'échographie pulmonaire est une technique non-invasive réalisée au chevet du patient qui permet d'évaluer avec précision la congestion pulmonaire en mesurant l'eau pulmonaire extravasculaire. Cette technique facilement accessible est de plus en plus utilisée. Notre principal critère de jugement était de comparer l'efficacité de l'évaluation de la volémie par échographie pulmonaire avec l'évaluation clinique, l'échocardiographie, la bio-impédance ou les biomarqueurs. Les critères d'évaluation secondaires étaient la mortalité toutes causes confondues et les événements cardiovasculaires. Sources: Nous avons recherché sur MEDLINE les études observationnelles et les essais randomisés où une échographie pulmonaire avait été réalisée chez des patients sous dialyse d'entretien. Méthodologie: Sur un total de 2 363 articles, nous avons retenu 28 études (25 observationnelles et 3 randomisées). Les coefficients de corrélation ont été regroupés pour chaque variable d'intérêt en utilisant la méthode générique de variance inverse avec un modèle à effets aléatoires. Les paramètres cliniques qui avaient montré les corrélations les plus élevées avec le nombre de lignes B à l'échographie étaient le statut de l'insuffisance cardiaque selon la classification de la New York Heart Association et l'auscultation pulmonaire, avec des coefficients de corrélation r regroupés respectifs de 0,57 et de 0,36. Les paramètres de l'échocardiographie qui avaient montré les plus fortes corrélations avec le nombre de lignes B étaient la fraction d'éjection du ventricule gauche et l'indice de la veine cave inférieure, avec des coefficients r regroupés respectifs de 0,35 et de 0,31. Trois essais randomisés avaient comparé une approche guidée par échographie pulmonaire aux normes de soins selon des critères cliniques stricts. Bien que les patients du groupe avec échographie pulmonaire aient montré une décongestion plus efficace et un meilleur contrôle de la pression artérielle, aucune différence n'a été observée entre les deux stratégies de prise en charge en ce qui concerne les décès de toutes causes confondues ou les événements cardiovasculaires indésirables majeurs. Principales observations: L'échographie pulmonaire pourrait être envisagée pour identifier les patients qui présentent une surcharge volumique subclinique. Les essais inclus n'ont pas montré de différences dans les résultats cliniquement pertinents. Le nombre d'études incluses était faible et plusieurs étaient de qualité sous-optimale. Limites: Les études incluses étaient hétérogènes et de qualité relativement limitée.
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Introduction: Chronic kidney disease (CKD) and left ventricular (LV) dysfunction are risk factors for cardiovascular events. We explore whether the association of LV ejection fraction (LVEF) with cardiac arrest, heart failure hospitalization, and all-cause mortality differs across stages of kidney impairment. Methods: We performed an observational cohort study of 19,032 patients from 2004 to 2014 with estimated glomerular filtration rate (eGFR) ≤90 ml/min per 1.73 m2 and without end-stage kidney disease (ESKD). Cox regression models, incorporating an interaction term for eGFR and LVEF, were fit and adjusted for relevant covariates. Results: Mean age of the patients was 67 ± 14 years, and 51% were male. The mean eGFR was 64 ± 19 ml/min per 1.73 m2 and LVEF was 54 ± 13%. Over a median follow-up of 3.0 (0.7-6.0) years there were 504 cardiac arrests, 4181 heart failure hospitalizations, and 6989 deaths. The association of LVEF with cardiac arrest and heart failure hospitalization differed according to continuous eGFR (P-interaction <0.01 for both outcomes). The association of LVEF with cardiac arrest in the lowest quartile was attenuated (adjusted hazard ration [aHR] per 5% higher LVEF 0.92; 95% confidence interval [CI] 0.88-0.96) compared to the highest eGFR quartile (aHR per 5% higher LVEF 0.85; 95% CI 0.78-0.91). The association of LVEF with heart failure hospitalization was similarly attenuated in the lowest eGFR quartile. There was no effect modification of LVEF by continuous eGFR for all-cause mortality (P-interaction 0.26). Conclusion: Among non-ESKD patients with eGFR ≤90 ml/min per 1.73 m2, the association of LVEF with cardiac arrest and heart failure hospitalization is attenuated at lower levels of kidney function. Further research is required to elucidate what factors beyond LVEF drive these observations.
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The effect of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on cardiovascular and renal outcomes has not been systematically reviewed across baseline kidney function groups. We conducted a systematic review and meta-analysis of randomized control trials (RCTs) with SGLT-2 inhibitors in patients with and without CKD. We performed a PubMed/Medline search of randomized, placebo-controlled, event-driven outcome trials of SGLT-2 inhibitors versus active or placebo control in patients with and without diabetes from inception to November 2022. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 (PROSPERO registration CRD4202016054). The primary outcome was cardiovascular death. Secondary outcomes included hospitalization for heart failure, major adverse cardiovascular events, CKD progression, all-cause mortality, treatment discontinuation, and acute kidney injury (AKI). The relative risk (RR) was estimated using a random-effects model. Twelve RCTs were included in this meta-analysis (89,191 patients, including 38,949 with eGFR < 60 ml/min/1.73m2). Use of an SGLT-2 inhibitor in patients with CKD was associated with a lower incidence of cardiovascular death (RR 0.87; 95% CI 0.79-0.95) and of heart failure (RR 0.67; 95% CI 0.61-0.75), compared with placebo. Heart failure risk reduction with SGLT-2 inhibitors was larger among patients with CKD compared with patients without CKD (RR for the interaction 0.87, 95% CI 0.75-1.02, and p-value for interaction 0.08). SGLT-2 inhibitors were associated with a lower incidence of CKD progression among patients with pre-existing CKD: RR 0.77 (95% CI 0.68-0.88), compared with placebo. Among patients with CKD, a lower risk of AKI (RR 0.82; 95% CI 0.72-0.93) and treatment discontinuation was seen with SGLT-2 inhibitors compared with placebo. SGLT-2 inhibitors offer substantial protection against cardiovascular and renal outcomes in patients with CKD. These results strongly advocate in favor of using them in patients with CKD and keeping them as kidney function declines.
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Lesión Renal Aguda , Insuficiencia Cardíaca , Insuficiencia Renal Crónica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/tratamiento farmacológico , Riñón , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológicoRESUMEN
AIMS: Intravenous (IV) iron increases haemoglobin/haematocrit and improves outcomes in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) also increase haemoglobin/haematocrit and improve outcomes in heart failure by mechanisms linked to nutrient deprivation signalling and reduction of inflammation and oxidative stress. The effect of IV iron among patients using SGLT2i has not yet been studied. The aim of this study was to evaluate the changes in haemoglobin, haematocrit, and iron biomarkers in HFrEF patients treated with IV iron with and without background SGLT2i treatment. Secondary outcomes included changes in natriuretic peptides, kidney function and heart failure-associated outcomes. METHODS AND RESULTS: Retrospective, single-centre analysis of HFrEF patients with iron deficiency treated with IV iron using (n = 60) and not using (n = 60) SGLT2i, matched for age and sex. Mean age was 73 ± 12 years, 48% were men, with more than 65% of patients having chronic kidney disease and anaemia. After adjustment for all baseline differences, SGLT2i users experienced a greater increase in haemoglobin and haematocrit compared to SGLT2i non-users: haemoglobin +0.57 g/dl (95% confidence interval [CI] 0.04-1.10, p = 0.036) and haematocrit +1.64% (95% CI 0.18-3.11, p = 0.029). No significant differences were noted for iron biomarkers or any of the secondary outcomes. CONCLUSION: Combined treatment with IV iron and background SGLT2i was associated with a greater increase in haemoglobin and haematocrit than IV iron without background SGLT2i. These results suggest that in HFrEF patients treated with IV iron, SGLT2i may increase the erythropoietic response. Further studies are needed to ascertain the potential benefit or harm of combining these two treatments in heart failure patients.
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Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Deficiencias de Hierro , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Hierro , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/tratamiento farmacológico , Estudios Retrospectivos , Volumen Sistólico , Biomarcadores , Hemoglobinas , Glucosa , Sodio , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológicoAsunto(s)
Fibrilación Atrial , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Warfarina , Anticoagulantes/efectos adversos , Piridonas/efectos adversos , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Administración OralRESUMEN
Diabetes drives an increasing burden of cardiovascular and renal disease worldwide, motivating the search for new hypoglycemic agents that confer cardiac and renal protective effects. Although initially developed as hypoglycemic agents, sodium-glucose co-transporter 2 (SGLT-2) inhibitors have since been studied in patients with and without diabetes for the management of heart failure and chronic kidney disease. A growing body of evidence supports the efficacy and safety of SGLT-2 inhibitors in patients with chronic kidney disease (CKD), based on complex mechanisms of action that extend far beyond glucosuria and that confer beneficial effects on cardiovascular and renal hemodynamics, fibrosis, inflammation, and end-organ protection. This review focuses on the pharmacology and pathophysiology of SGLT-2 inhibitors in patients with CKD, as well as their cardiovascular and renal effects in this population. We are focusing on the five agents that have been tested in cardiovascular outcome trials and that have been approved either in Europe or in North America: empagliflozin, dapagliflozin, canagliflozin, ertugliglozin, and sotagliflozin.
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Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Simportadores , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/efectos adversos , Insuficiencia Renal Crónica/tratamiento farmacológico , Glucosa , SodioRESUMEN
Patients with end-stage kidney disease (ESKD) experience a high thrombotic risk but are also at increased risk of bleeding. There is an unmet need for safer antithrombotic therapy in patients with ESKD on hemodialysis. Factor XI (FXI) represents an attractive therapeutic target for anticoagulation because of the potential to mitigate the bleeding risks associated with currently approved anticoagulants, especially in patients at high risk of bleeding. FXI inhibition is also an attractive option in settings where coagulation is activated by exposure of the blood to artificial surfaces, including the extracorporeal circuit during hemodialysis. Therapies targeting FXI that are in the most advanced stages of clinical development include antisense oligonucleotides, monoclonal antibodies, and synthetic small molecules, which serve either to lower FXI levels or block its physiological effects. This review article presents the most recent pharmacological data with FXI inhibitors, briefly describes phase 2 and 3 clinical trials with these agents, and critically examines the potential future use of FXI inhibitors for extracorporeal circuit anticoagulation in patients with ESKD. In addition, laboratory monitoring and reversal of FXI inhibitors are briefly discussed.
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Anticoagulantes , Factor XI , Fallo Renal Crónico , Diálisis Renal , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Factor XI/antagonistas & inhibidores , Anticoagulantes/uso terapéutico , Hemorragia/inducido químicamente , Oligonucleótidos Antisentido/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Trombosis/prevención & control , Trombosis/etiologíaRESUMEN
In patients with atrial fibrillation on dialysis, the incidence of stroke was similar with apixaban or no anticoagulation, regardless of P2Y12 prescription.In patients with atrial fibrillation on dialysis who were on a P2Y12 inhibitor, apixaban increased the risk of bleeding, compared with no anticoagulation.The incidence of myocardial infarction or ischemic stroke was similar with apixaban or no anticoagulation, regardless of P2Y12 prescription status.
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Fibrilación Atrial , Humanos , Fibrilación Atrial/complicaciones , Diálisis Renal/efectos adversos , Piridonas/efectos adversos , PrescripcionesRESUMEN
Introduction: The combination of hydralazine-isosorbide dinitrate (H-ISDN) has potential as a heart failure (HF) therapy in the setting of maintenance dialysis. Methods: In this retrospective study, we analyzed the efficacy of H-ISDN using United States Renal Data System (USRDS) data. We identified all adult patients with a history of HF on maintenance dialysis between January 1, 2011, and December 31, 2016, with at least 1 prescription for H-ISDN. Baseline characteristics, prescriptions, and outcomes were retrieved from institutional and physician claims. The primary outcome was death from any cause. Additional outcomes included cardiovascular death, sudden cardiac death, hospitalization for HF, an inpatient diagnosis of myocardial infarction (MI), or new-onset atrial fibrillation. Stabilized inverse probability weights were estimated using relevant baseline characteristics and were used in Cox proportional hazards regression. Results: We identified 6306 patients who were treated with H-ISDN and 75,509 patients who did not receive H-ISDN. The crude all-cause mortality rate was lower in patients treated with H-ISDN (16.0 events/100 patient years [PYs]) than in nonusers (27.9/100-PY). H-ISDN use was independently associated with lower mortality: hazard ratio (HR) 0.48 (95% CI 0.43-0.54). Cardiovascular death and sudden cardiac death were less common among H-ISDN users than nonusers, Weighted HR was 0.62 (95% CI 0.53-0.71) and 0.62 (95% CI 0.52-0.73), respectively. In contrast, HF admission and MI were more frequent in patients treated with H-ISDN (195.5 and 18.0 events/100-PY) compared with nonusers (73.4 and 10.2 events/100-PY). Conclusion: H-ISDN therapy may improve cardiovascular outcomes in maintenance dialysis patients with HF.
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Peer review aims to select articles for publication and to improve articles before publication. We believe that this process can be infused by kindness without losing rigor. In 2014, the founding editorial team of the Canadian Journal of Kidney Health and Disease (CJKHD) made an explicit commitment to treat authors as we would wish to be treated ourselves. This broader group of authors reaffirms this principle, for which we suggest the terminology "supportive review."
L'évaluation par les pairs vise à sélectionner les articles à publier et à en améliorer le contenu avant publication. Nous sommes d'avis que ce processus peut être fait avec bienveillance sans perdre en rigueur. En 2014, l'équipe de rédaction fondatrice du Canadian Journal of Kidney Health and Disease (CJKHD) a pris l'engagement ferme de traiter les auteurs comme ses membres souhaiteraient eux-mêmes être traités. Aujourd'hui, notre groupe élargi d'auteur(e)s réaffirme ce principe pour lequel nous proposons la terminologie « évaluation constructive ¼.
RESUMEN
Background Clinical prediction models have been developed for hospitalization for heart failure in type 2 diabetes. However, a systematic evaluation of these models' performance, applicability, and clinical impact is absent. Methods and Results We searched Embase, MEDLINE, Web of Science, Google Scholar, and Tufts' clinical prediction registry through February 2021. Studies needed to report the development, validation, clinical impact, or update of a prediction model for hospitalization for heart failure in type 2 diabetes with measures of model performance and sufficient information for clinical use. Model assessment was done with the Prediction Model Risk of Bias Assessment Tool, and meta-analyses of model discrimination were performed. We included 15 model development and 3 external validation studies with data from 999 167 people with type 2 diabetes. Of the 15 models, 6 had undergone external validation and only 1 had low concern for risk of bias and applicability (Risk Equations for Complications of Type 2 Diabetes). Seven models were presented in a clinically useful manner (eg, risk score, online calculator) and 2 models were classified as the most suitable for clinical use based on study design, external validity, and point-of-care usability. These were Risk Equations for Complications of Type 2 Diabetes (meta-analyzed c-statistic, 0.76) and the Thrombolysis in Myocardial Infarction Risk Score for Heart Failure in Diabetes (meta-analyzed c-statistic, 0.78), which was the simplest model with only 5 variables. No studies reported clinical impact. Conclusions Most prediction models for hospitalization for heart failure in patients with type 2 diabetes have potential concerns with risk of bias or applicability, and uncertain external validity and clinical impact. Future research is needed to address these knowledge gaps.