Jenny I. Shen

Outcomes After Warfarin Initiation in a Cohort of Hemodialysis Patients With Newly Diagnosed Atrial Fibrillation

BACKGROUND Although warfarin is indicated to prevent ischemic strokes in most patients with atrial fibrillation (AF), evidence supporting its use in hemodialysis patients is limited. Our aim was to examine outcomes after warfarin therapy initiation, relative to no warfarin use, following incident AF in a large cohort of hemodialysis patients who had comprehensive prescription drug coverage through Medicare Part D. STUDY DESIGN Retrospective observational cohort study. SETTING & PARTICIPANTS Patients in the US Renal Data System undergoing maintenance hemodialysis who had AF newly diagnosed in 2007 to 2011, with Medicare Part D coverage, who had no recorded history of warfarin use. PREDICTOR Warfarin therapy initiation, identified by a filled prescription within 30 days of the AF event. OUTCOMES Death, ischemic stroke, hemorrhagic stroke, severe gastrointestinal bleeding, and composite outcomes. MEASUREMENTS HRs estimated by applying Cox regression to an inverse probability of treatment and censoring-weighted cohort. RESULTS Of 12,284 patients with newly diagnosed AF, 1,838 (15%) initiated warfarin therapy within 30 days; however, ∼70% discontinued its use within 1 year. In intention-to-treat analyses, warfarin use was marginally associated with a reduced risk of ischemic stroke (HR, 0.68; 95% CI, 0.47-0.99), but not with the other outcomes. In as-treated analyses, warfarin use was associated with reduced mortality (HR, 0.84; 95% CI, 0.73-0.97). LIMITATIONS Short observation period, limited number of nonfatal events, limited generalizability of results to more affluent patients. CONCLUSIONS In hemodialysis patients with incident AF, warfarin use was marginally associated with reduced risk of ischemic stroke, and there was a signal toward reduced mortality in as-treated analyses. These results support clinical equipoise regarding the use of warfarin in hemodialysis patients and underscore the need for randomized trials to fill this evidence gap.

Use and safety of unfractionated heparin for anticoagulation during maintenance hemodialysis.

Anticoagulation is essential to hemodialysis, and unfractionated heparin (UFH) is the most commonly used anticoagulant in the United States. However, there is no universally accepted standard for its administration in long-term hemodialysis. Dosage schedules vary and include weight-based protocols and low-dose protocols for those at high risk of bleeding, as well as regional anticoagulation with heparin and heparin-coated dialyzers. Adjustments are based largely on clinical signs of under- and overanticoagulation. Risks of UFH use include bleeding, heparin-induced thrombocytopenia, hypertriglyceridemia, anaphylaxis, and possibly bone mineral disease, hyperkalemia, and catheter-associated sepsis. Alternative anticoagulants include low-molecular-weight heparin, direct thrombin inhibitors, heparinoids, and citrate. Anticoagulant-free hemodialysis and peritoneal dialysis also are potential substitutes. However, some of these alternative treatments are not as available as or are more costly than UFH, are dependent on country and health care system, and present dosing challenges. When properly monitored, UFH is a relatively safe and economical choice for anticoagulation in long-term hemodialysis for most patients.

Establishing Core Outcome Domains in Hemodialysis: Report of the Standardized Outcomes in Nephrology–Hemodialysis (SONG-HD) Consensus Workshop

Evidence-informed decision making in clinical care and policy in nephrology is undermined by trials that selectively report a large number of heterogeneous outcomes, many of which are not patient centered. The Standardized Outcomes in Nephrology-Hemodialysis (SONG-HD) Initiative convened an international consensus workshop on November 7, 2015, to discuss the identification and implementation of a potential core outcome set for all trials in hemodialysis. The purpose of this article is to report qualitative analyses of the workshop discussions, describing the key aspects to consider when establishing core outcomes in trials involving patients on hemodialysis therapy. Key stakeholders including 8 patients/caregivers and 47 health professionals (nephrologists, policymakers, industry, and researchers) attended the workshop. Attendees suggested that identifying core outcomes required equitable stakeholder engagement to ensure relevance across patient populations, flexibility to consider evolving priorities over time, deconstruction of language and meaning for conceptual consistency and clarity, understanding of potential overlap and associations between outcomes, and an assessment of applicability to the range of interventions in hemodialysis. For implementation, they proposed that core outcomes must have simple, inexpensive, and validated outcome measures that could be used in clinical care (quality indicators) and trials (including pragmatic trials) and endorsement by regulatory agencies. Integrating these recommendations may foster acceptance and optimize the uptake and translation of core outcomes in hemodialysis, leading to more informative research, for better treatment and improved patient outcomes.

Anticoagulation for atrial fibrillation in patients on dialysis: are the benefits worth the risks?

Purpose of reviewAtrial fibrillation is common among patients with end-stage renal disease undergoing hemodialysis. Although oral anticoagulation is recommended for stroke prevention in most patients with atrial fibrillation, limited evidence is available to guide treatment in hemodialysis patients with this arrhythmia. We summarize the available evidence on the epidemiology of atrial fibrillation in dialysis patients and review the data on the effectiveness of oral anticoagulation in this population. Recent findingsAtrial fibrillation is increasingly common in patients undergoing chronic hemodialysis, especially among older patients wherein one in six patients is diagnosed with this arrhythmia. Patients with atrial fibrillation experience double the mortality of otherwise similar patients without it. Few hemodialysis patients with atrial fibrillation receive oral anticoagulation, which is consistently associated with excess risks of hemorrhagic stroke. Observational studies did not detect a beneficial association of oral anticoagulation with the risk of ischemic stroke, with some studies describing higher risks of ischemic stroke among warfarin users. New therapeutic options including one oral direct thrombin inhibitor and two oral factor Xa inhibitors have become available, but were not tested in patients with advanced kidney disease. SummaryAtrial fibrillation is increasingly common in patients undergoing hemodialysis, yet little is known about the optimal management of these patients. The current evidence does not support net benefits from oral anticoagulation in the dialysis population.

Determinants of Peritoneal Dialysis Technique Failure in Incident US Patients

♦ Objectives: Switching from peritoneal dialysis (PD) to hemodialysis (HD) is undesirable, because of complications from temporary vascular access, disruption of daily routine, and higher costs. Little is known about the role that social factors play in technique failure. ♦ Design, Setting, Participants, Measurements: We followed for 3 years a nationally representative cohort of US patients who initiated PD in 1996 - 1997. Technique failure was defined as any switch from PD to HD for 30 days or more. We used Cox regression to examine associations between technique failure and demographic, medical, social, and pre-dialysis factors. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs). ♦ Results: We identified an inception cohort of 1587 patients undergoing PD. In multivariate analysis, female sex (HR: 0.78; 95% CI: 0.64 to 0.95) was associated with lower rates of technique failure, and black race [compared with white race (HR: 1.48; 95% CI: 1.20 to 1.82)] and receiving Medicaid (HR: 1.48; 95% CI: 1.17 to 1.86) were associated with higher rates. Compared with patients who worked full-time, those who were retired (HR: 1.49; 95% CI: 1.07 to 2.08) or disabled (HR: 1.38; 95% CI: 1.01 to 1.88) had higher rates of failure. Patients with a systolic blood pressure of 140 - 160 mmHg had a higher rate of failure than did those with a pressure of 120 - 140 mmHg (HR: 1.24; 95% CI: 1.00 to 1.52). Earlier referral to a nephrologist (>3 months before dialysis initiation) and the primary decision-maker for the dialysis modality (physician vs patient vs shared) were not associated with technique failure. ♦ Conclusions: This study confirms that several socio-demographic factors are associated with technique failure, emphasizing the potential importance of social and financial support in maintaining PD.

Outcomes of renal transplantation in recipients with Wegener’s granulomatosis

Shen J, Gill J, Shangguan M, Sampaio MS., Bunnapradist S. Outcomes of renal transplantation in recipients with Wegener’s granulomatosis.
Clin Transplant 2011: 25: 380–387.

Use and safety of heparin-free maintenance hemodialysis in the USA

BACKGROUND Although heparin is used to anticoagulate the extracorporeal circuit for most patients on maintenance hemodialysis (HD), some patients undergo heparin-free HD. We describe the determinants of heparin-free HD and its association with adverse outcomes using data from a national dialysis provider merged with Medicare claims. METHODS We identified patients aged ≥67 years with no recent history of warfarin use who initiated maintenance HD from 2007 to 2008. We applied the Cox regression to a propensity score-matched cohort to estimate the hazards of all-cause mortality, bleeding (gastrointestinal hemorrhage, hemorrhagic stroke, other hemorrhage), atherothrombosis (ischemic stroke, myocardial infarction) and venous thromboembolism (VTE) (deep vein thrombosis, pulmonary embolism). RESULTS Among 12 468 patients, 836 (6.7%) were dialyzed heparin-free. In multivariable-adjusted analyses, a history of gastrointestinal bleeding, hemorrhagic stroke and lower hemoglobin and platelet counts were associated with higher odds of heparin-free HD. Heparin-free HD use also varied as much as 4-fold by facility region. We found no significant association of heparin-free HD with all-cause mortality [hazard ratio (HR) 1.08; 95% confidence interval (CI): 0.94-1.26], bleeding (HR 1.15; 95% CI: 0.83-1.60), atherothrombosis (HR 1.09, 95% CI: 0.90-1.31) or VTE (HR 1.23, 95% CI: 0.93-1.64) compared with HD with heparin. CONCLUSIONS Patient markers of increased risk of bleeding and facility region associated with heparin-free HD use. Despite the potential benefits of avoiding heparin use, heparin-free HD was not significantly associated with decreased hazards of death, bleeding or thrombosis, suggesting that it may be no safer than HD with heparin.

Chronic kidney disease and arrhythmias: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Patients with chronic kidney disease (CKD) are predisposed to heart rhythm disorders, including atrial fibrillation (AF)/atrial flutter, supraventricular tachycardias, ventricular arrhythmias, and sudden cardiac death (SCD). While treatment options, including drug, device, and procedural therapies, are available, their use in the setting of CKD is complex and limited. Patients with CKD and end-stage kidney disease (ESKD) have historically been under-represented or excluded from randomized trials of arrhythmia treatment strategies,1 although this situation is changing.2 Cardiovascular society consensus documents have recently identified evidence gaps for treating patients with CKD and heart rhythm disorders.3–7 To identify key issues relevant to the optimal prevention, management, and treatment of arrhythmias and their complications in patients with kidney disease, Kidney Disease: Improving Global Outcomes (KDIGO) convened an international, multidisciplinary Controversies Conference in Berlin, Germany, titled CKD and Arrhythmias in October 2016. The conference agenda and discussion questions are available on the KDIGO website (http://kdigo.org/conferences/ckd-arrhythmias/; 13 February 2018).

Correlates and outcomes of warfarin initiation in kidney transplant recipients newly diagnosed with atrial fibrillation

In the kidney transplant population with atrial fibrillation (AF), evidence regarding the effectiveness and safety of warfarin treatment is lacking. We used fee-for-service Medicare claims to identify kidney transplant recipients with newly diagnosed AF from the United States Renal Data System. Warfarin use within 30 days of AF diagnosis was ascertained from Medicare Part D prescription claims (2007-11) or using a validated algorithm (1997-2011). The study end points were (i) the composite of death, stroke or gastrointestinal bleed, (ii) death and (iii) death-censored graft failure. Warfarin user and non-user groups were balanced using inverse probability of treatment weighting and hazard ratios were (HRs) estimated using Cox regression. Among 718 subjects with an indication for anticoagulation, 24% initiated warfarin treatment within 30 days of AF diagnosis. Age was the only independent correlate of warfarin use [odds ratio = 1.02 per year; 95% confidence interval (95% CI) 1.01-1.04]. In the larger cohort of 6492 patients with AF, warfarin use [(23.5%) versus non-use (76.5%)] was associated with small and non-significant reductions in the composite of death, stroke or gastrointestinal bleed (HR = 0.92; 95% CI 0.83-1.02), death (HR = 0.92; 95% CI 0.82-1.02) and death-censored graft failure (HR = 0.90; 95% CI 0.76-1.08). Our study suggests the need for clinical trials of warfarin use in the kidney transplant population with AF.

Toward Establishing Core Outcome Domains For Trials in Kidney Transplantation: Report of the Standardized Outcomes in Nephrology-Kidney Transplantation Consensus Workshops

Background Treatment decisions in kidney transplantation requires patients and clinicians to weigh the benefits and harms of a broad range of medical and surgical interventions, but the heterogeneity and lack of patient-relevant outcomes across trials in transplantation makes these trade-offs uncertain, thus, the need for a core outcome set that reflects stakeholder priorities. Methods We convened 2 international Standardized Outcomes in Nephrology-Kidney Transplantation stakeholder consensus workshops in Boston (17 patients/caregivers; 52 health professionals) and Hong Kong (10 patients/caregivers; 45 health professionals). In facilitated breakout groups, participants discussed the development and implementation of core outcome domains for trials in kidney transplantation. Results Seven themes were identified. Reinforcing the paramount importance of graft outcomes encompassed the prevailing dread of dialysis, distilling the meaning of graft function, and acknowledging the terrifying and ambiguous terminology of rejection. Reflecting critical trade-offs between graft health and medical comorbidities was fundamental. Contextualizing mortality explained discrepancies in the prioritization of death among stakeholders—inevitability of death (patients), preventing premature death (clinicians), and ensuring safety (regulators). Imperative to capture patient-reported outcomes was driven by making explicit patient priorities, fulfilling regulatory requirements, and addressing life participation. Specificity to transplant; feasibility and pragmatism (long-term impacts and responsiveness to interventions); and recognizing gradients of severity within outcome domains were raised as considerations. Conclusions Stakeholders support the inclusion of graft health, mortality, cardiovascular disease, infection, cancer, and patient-reported outcomes (ie, life participation) in a core outcomes set. Addressing ambiguous terminology and feasibility is needed in establishing these core outcome domains for trials in kidney transplantation.