Age- and Race-Specific Changes in ESKD Incidence over Four Decades.

SIGNIFICANCE STATEMENT: ESKD incidence has changed substantially in the past four decades, but differences by age and race have been unexplored. Using data from the United States Renal Data System, we found that ESKD incidence rose for Black and White teenagers, adults, and older adults for two decades beginning in 1980. Growth in incidence slowed for most groups by 1993, and by 2006, the annual percent change (APC) in ESKD incidence had declined for all groups, except White adults, for whom rates continued to rise. By 2019, ESKD incidence among Black and White adolescents nearly returned to 1980 levels, but no other group achieved that degree of improvement. Nonetheless, the ESKD incidence rate among Black American patients exceeds that of White patients in every age group. Distinct patterns in ESKD incidence among patients of different age, sex, and racial groups are shown. These findings could reflect changes in dialysis acceptance rates, access to preventive health care, incidence of diabetes mellitus, implementation of evidence-based guidelines for treatment of CKD, or other unrecognized factors. There may be population-specific opportunities to change the growth of the US ESKD population and address current racial disparities. BACKGROUND: Substantial changes in ESKD incidence over four decades among Black and White Americans of different ages have been incompletely explored. METHODS: We analyzed United States Renal Data System data from 1980 to 2019 to determine ESKD incidence trends among Black and White adolescent (13-17 years), adult (18-64 years), and older adult (≥65) populations. We used the National Cancer Institute Joinpoint Regression Program to estimate annual percent change (APC) in ESKD incidence and to define points in time where a statistically significant change in APC slope occurred for each group. RESULTS: ESKD incidence rose after 1980 for all groups, although the trends differed ( P < 0.001). Growth in incidence slowed for most by 1993, and by 2006, the APC in ESKD incidence had declined for all groups, except White adults, for whom rates continued to rise ( P < 0.05). By 2019, ESKD incidence among Black and White adolescents nearly returned to 1980 levels, but no other group achieved that degree of improvement. Nonetheless, the ESKD incidence among Black American patients exceeds that of White patients in every age group. CONCLUSIONS: Distinct patterns in ESKD incidence among patients of different age, sex, and racial groups are shown. These findings could reflect changes in dialysis acceptance rates, access to preventive health care, incidence of diabetes mellitus, implementation of evidence-based guidelines for treatment of CKD, or other unrecognized factors. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2024_03_13_ASN0000000000000310.mp3.

Opioid Prescriptions for US Patients Undergoing Long-Term Dialysis or with Kidney Transplant from 2011 to 2020.

BACKGROUND: Pain is important for patients with kidney failure, but opioid medication prescriptions are associated with morbidity and mortality. The Centers for Disease Control and Prevention issued opioid prescription guidelines in 2016 and 2022, associated with dramatically decreased prescription rates in the United States. It is critical to know if nationwide opioid prescription rates for patients with kidney failure have decreased. METHODS: We analyzed the USRDS database from 2011 to 2020 to describe trends in the proportion of ESKD patients who received one or more, or long-term opioid prescriptions, examined factors associated with long-term opioid prescriptions, and evaluated associations of all-cause death with short-term or long-term opioid prescriptions. RESULTS: From 2011-2022, the percentage of patients with kidney failure (dialysis and kidney transplant) who received at least one or more, or who had received long-term opioid medication prescriptions decreased steadily, from 60% to 42%, and from 23% to 13%, respectively (both P for trend <0.001). The largest reductions in prescription rates were for hydrocodone and oxycodone. Similar trends existed for dialysis and kidney transplant patients. Women, the poor and those in rural settings were more likely to receive long-term opioid prescriptions. Prescription rates were highest in White patients and those 45 to 64 years old. Short-term and long-term opioid medication prescriptions were associated with higher mortality in both dialysis and kidney transplant patients. CONCLUSIONS: ESKD patients' opioid prescription rates decreased between 2011 and 2020. Higher mortality risk was associated with both short-term and long-term opioid prescriptions. Mortality risk was monotonically associated with morphine milligram equivalents in patients with kidney failure who received long-term opioid prescriptions.

Transplantation Mediates Much of the Racial Disparity in Survival from Childhood-Onset Kidney Failure.

BACKGROUND: The role of kidney transplantation in differential survival in Black and White patients with childhood-onset kidney failure is unexplored. METHODS: We analyzed 30-year cohort data of children beginning RRT before 18 years of age between January 1980 and December 2017 (n=28,337) in the US Renal Data System. Cox regression identified transplant factors associated with survival by race. The survival mediational g-formula estimated the excess mortality among Black patients that could be eliminated if an intervention equalized their time with a transplant to that of White patients. RESULTS: Black children comprised 24% of the cohort and their crude 30-year survival was 39% compared with 57% for White children (log rank P<0.001). Black children had 45% higher risk of death (adjusted hazard ratio [aHR], 1.45; 95% confidence interval [95% CI], 1.36 to 1.54), 31% lower incidence of first transplant (aHR, 0.69; 95% CI, 0.67 to 0.72), and 39% lower incidence of second transplant (aHR, 0.61; 95% CI, 0.57 to 0.65). Children and young adults are likely to require multiple transplants, yet even after their first transplant, Black patients had 11% fewer total transplants (adjusted incidence rate ratio [aIRR], 0.89; 95% CI, 0.86 to 0.92). In Black patients, grafts failed earlier after first and second transplants. Overall, Black patients spent 24% less of their RRT time with a transplant than did White patients (aIRR, 0.76; 95% CI, 0.74 to 0.78). Transplantation compared with dialysis strongly protected against death (aHR, 0.28; 95% CI, 0.16 to 0.48) by time-varying analysis. Mediation analyses estimated that equalizing transplant duration could prevent 35% (P<0.001) of excess deaths in Black patients. CONCLUSIONS: Equalizing time with a functioning transplant for Black patients may equalize survival of childhood-onset ESKD with White patients.

Racial/Ethnic Disparities in Atrial Fibrillation Treatment and Outcomes among Dialysis Patients in the United States.

BACKGROUND: Because stroke prevention is a major goal in the management of ESKD hemodialysis patients with atrial fibrillation, investigating racial/ethnic disparities in stroke among such patients is important to those who could benefit from strategies to maximize preventive measures. METHODS: We used the United States Renal Data System to identify ESKD patients who initiated hemodialysis from 2006 to 2013 and then identified those with a subsequent atrial fibrillation diagnosis and Medicare Part A/B/D. Patients were followed for 1 year for all-cause stroke, mortality, prescription medications, and cardiovascular disease procedures. The survival mediational g-formula quantified the percentage of excess strokes attributable to lower use of atrial fibrillation treatments by race/ethnicity. RESULTS: The study included 56,587 ESKD hemodialysis patients with atrial fibrillation. Black, white, Hispanic, and Asian patients accounted for 19%, 69%, 8%, and 3% of the population, respectively. Compared with white patients, black, Hispanic, or Asian patients were more likely to experience stroke (13%, 15%, and 16%, respectively) but less likely to fill a warfarin prescription (10%, 17%, and 28%, respectively). Warfarin prescription was associated with decreased stroke rates. Analyses suggested that equalizing the warfarin distribution to that in the white population would prevent 7%, 10%, and 12% of excess strokes among black, Hispanic, and Asian patients, respectively. We found no racial/ethnic disparities in all-cause mortality or use of cardiovascular disease procedures. CONCLUSIONS: Racial/ethnic disparities in all-cause stroke among hemodialysis patients with atrial fibrillation are partially mediated by lower use of anticoagulants among black, Hispanic, and Asian patients. The reasons for these disparities are unknown, but strategies to maximize stroke prevention in minority hemodialysis populations should be further investigated.

Concomitant Use of Gabapentinoids with Opioids Is Associated with Increased Mortality and Morbidity among Dialysis Patients.

BACKGROUND: The opioid epidemic is a public health emergency and appropriate medication prescription for pain remains challenging. Physicians have increasingly prescribed gabapentinoids for pain despite limited evidence supporting their use. We determined the prevalence of concomitant gabapentinoid and opioid prescriptions and evaluated their associations with outcomes among dialysis patients. METHODS: We used the United States Renal Data System to identify patients treated with dialysis with Part A, B, and D coverage for all of 2010. Patients were grouped into 4 categories of drugs exposure status in 2010: (1) no prescriptions of either an opioid or gabapentinoid, (2) ≥1 prescription of an opioid and no prescriptions of gabapentinoids, (3) no prescriptions of an opioid and ≥1 prescription of gabapenbtinoids, (4) ≥1 prescription of both an opioid and gabapentinoid. Outcomes included 2-year all-cause death, dialysis discontinuation, and hospitalizations assessed in 2011 and 2012. RESULTS: The study population included 153,758 dialysis patients. Concomitant prescription of an opioid and gabapentin (15%) was more common than concomitant prescription of an opioid and pregabalin (4%). In adjusted analyses, concomitant prescription of an opioid and gabapentin compared to no prescription of either was associated with increased risk of death (hazard ratio [HR] 1.16, 95% CI 1.12-1.19), dialysis discontinuation (HR 1.14, 95% CI 1.03-1.27), and hospitalization (HR 1.33, 95% CI 1.31-1.36). Concomitant prescription of an opioid and pregabalin compared to no prescription of either was associated with increased mortality (HR 1.22, 95% CI 1.16-1.28) and hospitalization (HR 1.37, 95% CI 1.33-1.41), but not dialysis discontinuation (HR 1.13, 95% CI 0.95-1.35). Prescription of opioids and gabepentinoids compared to only being prescribed opioids was associated with higher risk of hospitalizations, but not mortality, or dialysis discontinuation. CONCLUSIONS: Concomitant prescription of opioids and gabapentinoids among US dialysis patients is common, and both drugs have independent effects on outcomes. Future research should prospectively investigate the potential harms of such drugs and identify safer alternatives for treatment of pain in end-stage renal disease patients.

Pulmonary Hypertension, Mortality, and Cardiovascular Disease in CKD and ESRD Patients: A Systematic Review and Meta-analysis.

BACKGROUND: Pulmonary hypertension is common in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) and may be associated with poor outcomes. The magnitude of the association between pulmonary hypertension and mortality is uncertain due to the small size and variable findings of observational studies. STUDY DESIGN: Systematic review and meta-analysis of observational studies using subgroup analyses and metaregression. SETTING & POPULATION: Patients with ESRD or earlier stages of CKD. SELECTION CRITERIA FOR STUDIES: Observational studies reporting clinical outcomes in patients with co-existing pulmonary hypertension and CKD or ESRD identified using a systematic search of PubMed and Embase. PREDICTOR: Pulmonary hypertension diagnosed by Doppler echocardiography. OUTCOMES: All-cause mortality, cardiovascular mortality, and cardiovascular events. RESULTS: 16 studies, with 7,112 patients with an overall pulmonary hypertension prevalence of 23%, were included. Pulmonary hypertension was associated with increased risk for all-cause mortality among patients with CKD (relative risk [RR], 1.44; 95% CI, 1.17-1.76), with ESRD receiving maintenance dialysis (RR, 2.32; 95% CI, 1.91-2.83), and with a functioning kidney transplant (RR, 2.08; 95% CI, 1.35-3.20). Pulmonary hypertension was associated with increased risk for cardiovascular events in patients with CKD (RR, 1.67; 95% CI, 1.07-2.60) and ESRD receiving dialysis (RR, 2.33; 95% CI, 1.76-3.08). There was an association between pulmonary hypertension and increased risk for cardiovascular mortality in patients with CKD or ESRD (RR, 2.20; 95% CI, 1.53-3.15). LIMITATIONS: Heterogeneity of included studies, possibility of residual confounding, unavailability of individual patient-level data, and possibility of outcome reporting bias. CONCLUSIONS: Pulmonary hypertension is associated with a substantially increased risk for death and cardiovascular events in patients with CKD and ESRD. Risk is higher in patients with ESRD receiving dialysis compared with patients with CKD stages 1 to 5. Understanding the effect of interventions to lower pulmonary artery pressure on the survival of these patents awaits their evaluation in randomized controlled trials.

A Nationally Representative Study of Calcific Uremic Arteriolopathy Risk Factors.

Accurate identification of risk factors for calcific uremic arteriolopathy (CUA) is necessary to develop preventive strategies for this morbid disease. We investigated whether baseline factors recorded at hemodialysis initiation would identify patients at risk for future CUA in a matched case-control study using data from a large dialysis organization. Hemodialysis patients with newly diagnosed CUA (n=1030) between January 1, 2010, and December 31, 2014, were matched by age, sex, and race in a 1:2 ratio to hemodialysis patients without CUA (n=2060). Mean ages for patients and controls were 54 and 55 years, respectively; 67% of participants were women and 49% were white. Median duration between hemodialysis initiation and subsequent CUA development was 925 days (interquartile range, 273-2185 days). In multivariable conditional logistic regression analyses, diabetes mellitus; higher body mass index; higher levels of serum calcium, phosphorous, and parathyroid hormone; and nutritional vitamin D, cinacalcet, and warfarin treatments were associated with increased odds of subsequent CUA development. Compared with patients with diabetes receiving no insulin injections, those receiving insulin injections had a dose-response increase in the odds of CUA involving lower abdomen and/or upper thigh areas (odds ratio, 1.49; 95% confidence interval, 1.03 to 2.51 for one or two injections per day; odds ratio, 1.88; 95% confidence interval, 1.30 to 3.43 for 3 injections per day; odds ratio, 3.74; 95% confidence interval, 2.28 to 6.25 for more than three injections per day), suggesting a dose-effect relationship between recurrent skin trauma and CUA risk. The presence of risk factors months to years before CUA development observed in this study will direct the design of preventive strategies and inform CUA pathobiology.

Dabigatran and rivaroxaban use in atrial fibrillation patients on hemodialysis.

BACKGROUND: Dabigatran and rivaroxaban are new oral anticoagulants that are eliminated through the kidneys. Their use in dialysis patients is discouraged because these drugs can bioaccumulate to precipitate inadvertent bleeding. We wanted to determine whether prescription of dabigatran or rivaroxaban was occurring in the dialysis population and whether these practices were safe. METHODS AND RESULTS: Prevalence plots were used to describe the point prevalence (monthly) of dabigatran and rivaroxaban use among 29977 hemodialysis patients with atrial fibrillation. Poisson regression compared the rate of bleeding, stroke, and arterial embolism in patients who started dabigatran, rivaroxaban, or warfarin. The first record of dabigatran prescription among hemodialysis patients occurred 45 days after the drug became available in the United States. Since then, dabigatran and rivaroxaban use in the atrial fibrillation-end-stage renal disease population has steadily risen where 5.9% of anticoagulated dialysis patients are started on dabigatrian or rivaroxaban. In covariate adjusted Poisson regression, dabigatran (rate ratio, 1.48; 95% confidence interval, 1.21-1.81; P=0.0001) and rivaroxaban (rate ratio, 1.38; 95% confidence interval, 1.03-1.83; P=0.04) associated with a higher risk of hospitalization or death from bleeding when compared with warfarin. The risk of hemorrhagic death was even larger with dabigatran (rate ratio, 1.78; 95% confidence interval, 1.18-2.68; P=0.006) and rivaroxaban (rate ratio, 1.71; 95% confidence interval, 0.94-3.12; P=0.07) relative to warfarin. There were too few events in the study to detect meaningful differences in stroke and arterial embolism between the drug groups. CONCLUSIONS: More dialysis patients are being started on dabigatran and rivaroxaban, even when their use is contraindicated and there are no studies to support that the benefits outweigh the risks of these drugs in end-stage renal disease.

Heritability of Risk for Sudden Cardiac Arrest in ESRD.

Patients on dialysis are 20 times more likely to have a cardiac arrest compared with the general population. We considered whether inherited factors associate with cardiac arrest among patients on dialysis. From a sample of 647,457 patients on chronic dialysis, we identified 5117 pairs of patients who came from the same family. These patients were each matched to a control subject from the same population. McNemar's tests were used to compare the risk of cardiac arrest between the familial related and unrelated pairs. Genetically related family members who did not cohabitate had an odds ratio of 1.88 (95% confidence interval [95% CI], 1.25 to 2.84) for cardiac arrest compared with their phenotypically matched unrelated controls. Genetically related family members who lived together in the same environment had an odds ratio of 1.66 (95% CI, 1.20 to 2.28). Spouses, who are genetically unrelated but live together in the same environment, had an odds ratio of 0.95 (95% CI, 0.60 to 1.59) for cardiac arrest. The risk of cardiac arrest in patients on dialysis may be attributable to inherited factors. Additional studies are needed to identify such candidate genes that modify cardiovascular risk in ESRD.

Adherence barriers to chronic dialysis in the United States.

Hemodialysis patients often do not attend their scheduled treatment session. We investigated factors associated with missed appointments and whether such nonadherence poses significant harm to patients and increases overall health care utilization in an observational analysis of 44 million hemodialysis treatments for 182,536 patients with ESRD in the United States. We assessed the risk of hospitalization, emergency room visit, or intensive-coronary care unit (ICU-CCU) admission in the 2 days after a missed treatment relative to the risk for patients who received hemodialysis. Over the 5-year study period, the average missed treatment rate was 7.1 days per patient-year. In covariate adjusted logistic regression, the risk of hospitalization (odds ratio [OR], 3.98; 95% confidence interval [95% CI], 3.93 to 4.04), emergency room visit (OR, 2.00; 95% CI, 1.87 to 2.14), or ICU-CCU admission (OR, 3.89; 95% CI, 3.81 to 3.96) increased significantly after a missed treatment. Overall, 0.9 missed treatment days per year associated with suboptimal transportation to dialysis, inclement weather, holidays, psychiatric illness, pain, and gastrointestinal upset. These barriers also associated with excess hospitalization (5.6 more events per patient-year), emergency room visits (1.1 more visits), and ICU-CCU admissions (0.8 more admissions). In conclusion, poor adherence to hemodialysis treatments may be a substantial roadblock to achieving better patient outcomes. Addressing systemic and patient barriers that impede access to hemodialysis care may decrease missed appointments and reduce patient morbidity.

No difference in bleeding risk between subcutaneous enoxaparin and heparin for thromboprophylaxis in end-stage renal disease.

Enoxaparin, a low-molecular-weight form of heparin, is not approved for use in dialysis patients in the United States, because it is eliminated through the kidneys and could therefore accumulate and cause inadvertent bleeding. Accordingly, it is unknown if enoxaparin is as safe to prescribe as subcutaneous heparin for thromboprophylaxis in patients with chronic renal failure. Here we conducted a retrospective comparative effectiveness study in a large population of chronic maintenance dialysis patients initiated with subcutaneous injections of enoxaparin or heparin for thromboprophylaxis. The primary study end point was hospitalization or death related to bleeding, with a secondary end point of venous thromboembolism. Among 7721 dialysis patients started on subcutaneous enoxaparin or heparin at doses for thromboprophylaxis, the crude rate for bleeding requiring hospitalization or resulting in death was 15.2 (95% confidence interval (CI) 12.7-18.2) events per 100 patient-years in the enoxaparin group, which did not differ from the heparin group in which the crude rate was 16.2 (95% CI 14.0-18.7) events per 100 patient-years. In risk factor-adjusted Poisson models, enoxaparin was not associated with more bleeding in comparison to heparin (risk ratio, 0.98; 95% CI 0.78-1.23). The risk of venous thromboembolism was not associatively worse with enoxaparin (risk ratio, 0.77; 95% CI 0.49-1.22). Thus, in dialysis patients, daily enoxaparin for thromboprophylaxis was not associated with increased serious bleeding or less effective compared to subcutaneous heparin.

Prevalence and outcomes of antimicrobial treatment for Staphylococcus aureus bacteremia in outpatients with ESRD.

Staphylococcus bacteremia is a common and life-threatening medical emergency, but it is treatable with appropriate antibiotic therapy. To identify opportunities that may reduce morbidity and mortality associated with S. aureus, we analyzed data from 293,094 chronic hemodialysis outpatients to characterize practices of antibiotic selection. In the study population, the overall rate of bacteremia was 15.4 per 100 outpatient-years; the incidence rate for methicillin-sensitive (MSSA) was 2.1 per 100 outpatient-years, and the incidence rate for methicillin-resistant (MRSA) S. aureus was 1.9 per 100 outpatient-years. One week after the collection of the index blood culture, 56.1% of outpatients with MSSA bacteremia were receiving vancomycin, and 16.7% of outpatients with MSSA were receiving cefazolin. Among MSSA-bacteremic patients who did not die or get hospitalized 1 week after blood culture collection, use of cefazolin was associated with a 38% lower risk for hospitalization or death compared with vancomycin (adjusted HR=0.62, 95% CI=0.46-0.84). In conclusion, vancomycin is commonly used to treat MSSA bacteremia in outpatients receiving chronic dialysis, but there may be more risk of treatment failure than observed among those individuals who receive a ß-lactam antibiotic such as cefazolin.

RightReturn. Partnering to reduce the high rate of hospital readmission for dialysis-dependent patients.

The rate of rehospitalization is at a critical level. Twenty percent of all Medicare patients are rehospitalized within 30 days of discharge, and this rate is even higher (36%) for end-stage renal disease patients. Dialysis-dependent patients are commonly discharged from the hospital with a decline in various health measures (such as hemoglobin, albumin, and estimated dry weight) when compared to pre-hospital values, making the common response to resume previous orders" in the outpatient setting inadequate. Both quality of care and financial penalties by the Centers for Medicare & Medicaid Services have set the stage for partnerships between dialysis providers and hospitals to develop strategies to reduce readmissions for ESRD patients, and provide for the "RightReturn" to the outpatient setting with resumption of their daily lives at home in optimal health.

Combined angiotensin-converting enzyme inhibition and receptor blockade associate with increased risk of cardiovascular death in hemodialysis patients.

To compare the relative effectiveness of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in reducing cardiovascular mortality in chronic hemodialysis patients, we conducted an observational analysis of all patients initiated on ACEI or ARB therapy undergoing chronic hemodialysis at a large dialysis provider. Survival curves with mortality hazard ratios (HRs) were generated using the Kaplan-Meier method and Cox regression. Outcomes were compared using inverse probability of treatment weighting and propensity score matching. Over 6 years, 22,800 patients were newly initiated on an ACEI and 5828 on an ARB after at least 60 days of chronic hemodialysis. After adjustment for baseline cardiovascular risk factors, there was no significant difference in the risk of cardiovascular, all-cause, or cerebrovascular mortality in patients initiated on an ARB compared with an ACEI (HR of 0.96). A third of 28,628 patients, newly started on an ACEI or ARB, went on to another antihypertensive medication in succession. After adjustment for risk factors, 701 patients initiated on combined ACEI and ARB therapy (HR of 1.45) or 6866 patients on ACEI and non-ARB antihypertensive agent (HR of 1.27) were at increased risk of cardiovascular death compared with 1758 patients initiated on an ARB and non-ACEI antihypertensive therapy. Thus, an ARB, in combination with another antihypertensive medication (but not an ACEI), may have a beneficial effect on cardiovascular mortality. As observational studies may be confounded by indication, even when adjusted, randomized clinical trials are needed to confirm these findings.

Digoxin associates with mortality in ESRD.

The safety of prescribing digoxin in ESRD is unknown. Hypokalemia, which frequently occurs among dialysis patients, may enhance the toxicity of digoxin. Here, we analyzed the association between digoxin prescription and survival in a retrospective cohort using covariate- and propensity score-adjusted Cox models to minimize the potential for confounding by indication. Among 120,864 incident hemodialysis patients, digoxin use associated with a 28% increased risk for death (hazard ratio [HR] 1.28; 95% confidence interval 1.25 to 1.31). Increasing serum digoxin level was also significantly associated with mortality (HR 1.19 per ng/ml increase; 95% confidence interval 1.05 to 1.35). This increased mortality risk with level was most pronounced in patients with lower predialysis serum potassium (K) levels (HR 2.53 [P = 0.01] for K <4.3 mEq/L versus HR 0.86 [P = 0.35] for K >4.6 mEq/L). In conclusion, digoxin use among patients who are on hemodialysis associates with increased mortality, especially among those with low predialysis K concentrations.

Anticoagulant and antiplatelet usage associates with mortality among hemodialysis patients.

Many prescribe anticoagulants and antiplatelet medications to prevent thromboembolic events and access thrombosis in dialysis patients despite limited evidence of their efficacy in this population. This retrospective cohort study examined whether use of warfarin, clopidogrel, and/or aspirin affected survival in 41,425 incident hemodialysis patients during 5 yr of follow-up. The prescription frequencies for warfarin, clopidogrel, and aspirin were 8.3, 10.0, and 30.4%, respectively, during the first 90 d of initiating chronic hemodialysis. Compared with the 24,740 patients receiving none of these medications, Cox proportional hazards analysis suggested that exposure to these medications was associated with increased risk for mortality (warfarin hazard ratio [HR] 1.27 [95% confidence interval (CI) 1.18 to 1.37]; clopidogrel HR 1.24 [95% CI 1.13 to 1.35]; and aspirin HR 1.06 [95% CI 1.01 to 1.11]). The increased mortality associated with warfarin or clopidogrel use remained in stratified analyses. A covariate- and propensity-adjusted time-varying analysis, which accounted for longitudinal changes in prescription, produced similar results. In addition, matching for treatment facility and attending physician revealed similar associations between prescription and mortality. We conclude that warfarin, aspirin, or clopidogrel prescription is associated with higher mortality among hemodialysis patients. Given the possibility of confounding by indication, randomized trials are needed to determine definitively the risk and benefit of these medications.

Warfarin use associates with increased risk for stroke in hemodialysis patients with atrial fibrillation.

Use of warfarin, clopidogrel, or aspirin associates with mortality among patients with ESRD, but the risk-benefit ratio may depend on underlying comorbidities. Here, we investigated the association between these medications and new stroke, mortality, and hospitalization in a retrospective cohort analysis of 1671 incident hemodialysis patients with preexisting atrial fibrillation. We followed patient outcomes from the time of initiation of dialysis for an average of 1.6 yr. Compared with nonuse, warfarin use associated with a significantly increased risk for new stroke (hazard ratio 1.93; 95% confidence interval 1.29 to 2.90); clopidogrel or aspirin use did not associate with increased risk for new stroke. Analysis using international normalized ratio (INR) suggested a dose-response relationship between the degree of anticoagulation and new stroke in patients on warfarin (P = 0.02 for trend). Warfarin users who received no INR monitoring in the first 90 d of dialysis had the highest risk for stroke compared with nonusers (hazard ratio 2.79; 95% confidence interval 1.65 to 4.70). Warfarin use did not associate with statistically significant increases in all-cause mortality or hospitalization. In conclusion, warfarin use among patients with both ESRD and atrial fibrillation associates with an increased risk for stroke. The risk is greatest in warfarin users who do not receive in-facility INR monitoring.