Strategies for secondary use of real-world clinical and administrative data for outcome ascertainment in pragmatic clinical trials.

BACKGROUND: Pragmatic trials are gaining popularity as a cost-effective way to examine treatment effectiveness and generate timely comparative evidence. Incorporating supplementary real-world data is recommended for robust outcome monitoring. However, detailed operational guidelines are needed to inform effective use and integration of heterogeneous databases. OBJECTIVE: Lessons learned from the Veterans Affairs (VA) Diuretic Comparison Project (DCP) are reviewed, providing adaptable recommendations to capture clinical outcomes from real-world data. METHODS: Non-cancer deaths and major cardiovascular (CV) outcomes were determined using VA, Medicare, and National Death Index (NDI) data. Multiple ascertainment strategies were applied, including claims-based algorithms, natural language processing, and systematic chart review. RESULTS: During a mean follow-up of 2.4 (SD = 1.4) years, 907 CV events were identified within the VA healthcare system. Slight delays (∼1 year) were expected in obtaining Medicare data. An additional 298 patients were found having a CV event outside of the VA in 2016 - 2021, increasing the CV event rate from 3.5 % to 5.7 % (770 of 13,523 randomized). NDI data required âˆ¼2 years waiting period. Such inclusion did not increase the number of deaths identified (all 894 deaths were captured by VA data) but enhanced the accuracy in determining cause of death. CONCLUSION: Our experience supports the recommendation of integrating multiple data sources to improve clinical outcome ascertainment. While this approach is promising, hierarchical data aggregation is required when facing different acquisition timelines, information availability/completeness, coding practice, and system configurations. It may not be feasible to implement comparable applications and solutions to studies conducted under different constraints and practice. The recommendations provide guidance and possible action plans for researchers who are interested in applying cross-source data to ascertain all study outcomes.

Pharmacist-driven outreach initiative to increase prescribing of sodium-glucose cotransporter-2 inhibitors in eligible VHA patients with chronic kidney disease: a study protocol.

BACKGROUND: Patients with chronic kidney disease (CKD) are at increased risk for multiple adverse events, several of which have been proven to be less likely with the use of sodium-glucose cotransporter-2 inhibitors (SGLT2i). As a result, guidelines now recommend SGLT2i be given to those with mild to moderate CKD and type 2 diabetes. The objective of this study is to evaluate if a pharmacist-driven SGLT2i prescribing initiative among eligible patients with CKD and diabetes within the VA could more rapidly improve the adoption of SGLT2i via a pragmatic approach aligned with learning health systems. METHODS: Eligible patients will be identified through an established VA diabetes dashboard. Veterans with an odd social security number (SSN), which is effectively a random number, will be the intervention group. Those with even SSNs will serve as the control while awaiting a second iteration of the same interventional program. The intervention will be implemented in a rolling fashion across one Veterans Integrated Service Network. Our primary outcome is initiation of an SGLT2i. Secondary outcomes will include medication adherence and safety-related outcomes. DISCUSSION: This project tests the impact of a pharmacist-driven medication outreach initiative as a strategy to accelerate initiation of SGLT2i. The results of this work will not only illustrate the effectiveness of this strategy for SGLT2is but may also have implications for increasing other guideline-concordant care. Furthermore, the utilization of SSNs to select Veterans for the first wave of this program has created a pseudo-randomized interventional trial supporting a pragmatic learning health system approach. TRIAL REGISTRATION: ISRCTN12374636.

The impact of COVID-19 on a large pragmatic clinical trial embedded in primary care.

INTRODUCTION: The COVID-19 pandemic had significant impact on clinical care and clinical trial operations, but the impact on decentralized pragmatic trials is unclear. The Diuretic Comparison Project (DCP) is a Point-of Care (POC) pragmatic trial testing whether chlorthalidone is superior to hydrochlorothiazide in preventing major cardiovascular (CV) events and non-cancer death. DCP utilized telephone consent, data collection from the electronic health record and Medicare, forwent study visits, and limited provider commitment beyond usual care. We assessed the impact of COVID-19 on recruitment, follow-up, data collection, and outcome ascertainment in DCP. METHODS: We compared data from two 8-month periods: Pre-Pandemic (July 2019-February 2020) and Mid-Pandemic (July 2020-February 2021). Consent and randomization rates, diuretic adherence, blood pressure (BP) and electrolyte follow-up rates, records of CV events, hospitalization, and death rates were compared. RESULTS: Providers participated at a lower rate mid-pandemic (65%) than pre-pandemic (71%), but more patients were contacted (7622 vs. 5363) and consented (3718 vs. 3048) mid-pandemic than pre-pandemic. Patients refilled medications and remained on their randomized diuretic equally (90%) in both periods. Overall, rates of BP, electrolyte measurements, and hospitalizations decreased mid-pandemic while deaths increased. CONCLUSIONS: While recruitment, enrollment, and adherence did not suffer during the pandemic, documented blood pressure checks and laboratory evaluations decreased, likely due to fewer in-person visits. VA hospitalizations decreased, despite a considerable number of COVID-related hospitalizations. This suggests changes in clinical care during the pandemic, but the limited impact on DCP's operations during a global pandemic is an important strength of POC trials. CLINICAL TRIAL REGISTRATION: NCT02185417.

Practical issues in pragmatic trials: the implementation of the Diuretic Comparison Project.

BACKGROUND/AIMS: The US Department of Veterans Affairs Point of Care Clinical Trial Program conducts studies that utilize informatics infrastructure to integrate clinical trial protocols into routine care delivery. The Diuretic Comparison Project compared hydrochlorothiazide to chlorthalidone in reduction of major cardiovascular events in subjects with hypertension. Here we describe the cultural, technical, regulatory, and logistical challenges and solutions that enabled successful implementation of this large pragmatic comparative effectiveness Point of Care clinical trial. METHODS: Patients were recruited from 72 Veterans Affairs Healthcare Systems using centralized processes for subject identification, obtaining informed consent, data collection, safety monitoring, site communication, and endpoint identification with minimal perturbation of the local clinical care ecosystem. Patients continued to be managed exclusively by their clinical care providers without protocol specified study visits, treatment recommendations, or data collection extraneous to routine care. Centralized study processes were operationalized through the application layer of the electronic health record via a data coordinating center staffed by clinical nurses, data scientists, and statisticians without site-based research coordinators. Study data was collected from the Veterans Affairs electronic health record supplemented by Medicare and National Death Index data. RESULTS: The study exceeded its enrolled goal (13,523 subjects) and followed subjects for the 5-year study duration. The key determinant of program success was collaboration between researchers, regulators, clinicians, and administrative staff at the site level to customize study procedures to align with local clinical practice. This flexibility was enabled by designation of the study as minimal risk and determination that clinical care providers were not engaged in research by the Veterans Affairs Central Institutional Review Board. Cultural, regulatory, technical, and logistical problems were identified and solved through iterative collaboration between clinical and research entities. Paramount among these problems was customization of the Veterans Affairs electronic health record and data systems to accommodate study procedures. CONCLUSIONS: Leveraging clinical care for large-scale clinical trials is feasible but requires a rethinking of traditional clinical trial design (and regulation) to better meet requirements of clinical care ecosystems. Study designs must accommodate site-specific practice variation to reduce the impact on clinical care. A tradeoff thus exists between designing trial processes tailored to expedite local study implementation versus those to produce a more refined response to the research question. The availability of a uniform and flexible electronic health record in the Department of Veterans Affairs played a major role in the success of the trial. Conducting Point of Care research in other healthcare systems without such research-friendly infrastructure presents a more formidable challenge.

Does experience matter? The relationship between nephrologist characteristics and end stage kidney disease patient outcomes.

BACKGROUND: Nephrology offers the unique opportunity to directly link patients to providers, allowing the study of patient outcomes at the provider level. The purpose of this analysis was to determine whether nephrologist experience, defined as years in nephrology practice, was associated with clinical outcomes. DESIGN: Physician data contained within the American Medical Association (AMA) Physician Masterfile was combined with patient and Medicare claims data from the United States Renal Data System (USRDS) for the calendar year 2012, with follow up extending through June 30, 2014. Associations with important healthcare outcomes including mortality in patients receiving maintenance renal replacement therapy (RRT), waitlisting for kidney transplantation, and receipt of a kidney transplant were determined with broad adjustment for both patient and provider level variables, with attention on tertile of provider time in practice. RESULTS: We identified 256,324 patients on maintenance RRT cared for by 6193 nephrologists. Nephrologists with the least experience were more likely to be female, reside in a region with ≥1,000,000 people, have a Doctor of Osteopathic Medicine degree, and have a listed maintenance of certification status as "yes." Overall, 30.2% of the cohort died at a mean follow up of 1.99 years. Compared to those with the 0-10 years of experience, receipt of care from nephrologists with more experience was associated with lower mortality (AHR 0.97 CI 0.94-0.99 for nephrologists with 11-20 years) and increased listing for kidney transplantation (AHR 1.10; CI 1.01-1.21 for nephrologists with >21 years experience). Experience level did not result in a difference in kidney transplantation rates. CONCLUSIONS: Receipt of maintenance RRT from nephrologists with greater experience was associated with decreased mortality and increased listing for kidney transplantation, an effect that remained significant after multiple adjustments for important patient and nephrologist variables.

Race, Ethnicity, and End-of-Life Care in Dialysis Patients in the United States.

BACKGROUND: End-of-life care is a prominent consideration in patients on maintenance dialysis, especially when death appears imminent and quality of life is poor. To date, examination of race- and ethnicity-associated disparities in end-of-life care for patients with ESRD has largely been restricted to comparisons of white and black patients. METHODS: We performed a retrospective national study using United States Renal Data System files to determine whether end-of-life care in United States patients on dialysis is subject to racial or ethnic disparity. The primary outcome was a composite of discontinuation of dialysis and death in a nonhospital or hospice setting. RESULTS: Among 1,098,384 patients on dialysis dying between 2000 and 2014, the primary outcome was less likely in patients from any minority group compared with the non-Hispanic white population (10.9% versus 22.6%, P<0.001, respectively). We also observed similar significant disparities between any minority group and non-Hispanic whites for dialysis discontinuation (16.7% versus 31.2%), as well as hospice (10.3% versus 18.1%) and nonhospital death (34.4% versus 46.4%). After extensive covariate adjustment, the primary outcome was less likely in the combined minority group than in the non-Hispanic white population (adjusted odds ratio, 0.55; 95% confidence interval, 0.55 to 0.56; P<0.001). Individual minority groups (non-Hispanic Asian, non-Hispanic black, non-Hispanic Native American, and Hispanic) were significantly less likely than non-Hispanic whites to experience the primary outcome. This disparity was especially pronounced for non-Hispanic Native American and Hispanic subgroups. CONCLUSIONS: There appear to be substantial race- and ethnicity-based disparities in end-of-life care practices for United States patients receiving dialysis.

Efficacy of Patient Activation Interventions With or Without Financial Incentives to Promote Prescribing of Thiazides and Hypertension Control: A Randomized Clinical Trial.

Importance: Evidence-based guidelines recommend thiazide diuretics as a first-line therapy for uncomplicated hypertension; however, thiazides are underused, and hypertension remains inadequately managed. Objective: To test the efficacy of a patient activation intervention with financial incentives to promote thiazide prescribing. Design, Setting, and Participants: The Veterans Affairs Project to Implement Diuretics, a randomized clinical trial, was conducted at 13 Veterans Affairs primary care clinics from August 1, 2006, to July 31, 2008, with 12 months of follow-up. A total of 61 019 patients were screened to identify 2853 eligible patients who were not taking a thiazide and not at their blood pressure (BP) goal; 598 consented to participate. Statistical analysis was conducted from December 1, 2017, to September 12, 2018. Interventions: Patients were randomized to a control group (n = 196) or 1 of 3 intervention groups designed to activate patients to talk with their primary care clinicians about thiazides and hypertension: group A (n = 143) received an activation letter, group B (n = 128) received a letter plus a financial incentive, and group C (n = 131) received a letter, financial incentive, and a telephone call encouraging patients to speak with their primary care clinicians. Main Outcomes and Measures: Primary outcomes were thiazide prescribing and BP control. A secondary process measure was discussion between patient and primary care clinician about thiazides. Results: Among 598 participants (588 men and 10 women), the mean (SD) age for the combined intervention groups (n = 402) was 62.9 (8.8) years, and the mean baseline BP was 148.1/83.8 mm Hg; the mean (SD) age for the control group (n = 196) was 64.1 (9.2) years, and the mean baseline BP was 151.0/83.4 mm Hg. At index visits, the unadjusted rate of thiazide prescribing was 9.7% for the control group (19 of 196) and 24.5% (35 of 143) for group A, 25.8% (33 of 128) for group B, and 32.8% (43 of 131) for group C (P < .001). Adjusted analyses demonstrated an intervention effect on thiazide prescribing at the index visit and 6-month visit, which diminished at the 12-month visit. For BP control, there was a significant intervention effect at the 12-month follow-up for group C (adjusted odds ratio, 1.73; 95% CI, 1.06-2.83; P = .04). Intervention groups exhibited improved thiazide discussion rates in a dose-response fashion: group A, 44.1% (63 of 143); group B, 56.3% (72 of 128); and group C, 68.7% (90 of 131) (P = .004). Conclusions and Relevance: This patient activation intervention about thiazides for hypertension resulted in two-thirds of patients having discussions and nearly one-third initiating a prescription of thiazide. Adding a financial incentive and telephone call to the letter resulted in incremental improvements in both outcomes. By 12 months, improved BP control was also evident. This low-cost, low-intensity intervention resulted in high rates of discussions between patients and clinicians and subsequent thiazide treatment and may be used to promote evidence-based guidelines and overcome clinical inertia. Trial Registration: ClinicalTrials.gov Identifier: NCT00265538.

Clinical outcomes after parathyroidectomy in a nationwide cohort of patients on hemodialysis.

BACKGROUND AND OBJECTIVES: Patients receiving dialysis undergo parathyroidectomy to improve laboratory parameters in resistant hyperparathyroidism with the assumption that clinical outcomes will also improve. However, no randomized clinical trial data demonstrate the benefits of parathyroidectomy. This study aimed to evaluate clinical outcomes up to 1 year after parathyroidectomy in a nationwide sample of patients receiving hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using data from the US Renal Data System, this study identified prevalent hemodialysis patients aged ≥18 years with Medicare as primary payers who underwent parathyroidectomy from 2007 to 2009. Baseline characteristics and comorbid conditions were assessed in the year preceding parathyroidectomy; clinical events were identified in the year preceding and the year after parathyroidectomy. After parathyroidectomy, patients were censored at death, loss of Medicare coverage, kidney transplant, change in dialysis modality, or 365 days. This study estimated cause-specific event rates for both periods and rate ratios comparing event rates in the postparathyroidectomy versus preparathyroidectomy periods. RESULTS: Of 4435 patients who underwent parathyroidectomy, 2.0% died during the parathyroidectomy hospitalization and the 30 days after discharge. During the 30 days after discharge, 23.8% of patients were rehospitalized; 29.3% of these patients required intensive care. In the year after parathyroidectomy, hospitalizations were higher by 39%, hospital days by 58%, intensive care unit admissions by 69%, and emergency room/observation visits requiring hypocalcemia treatment by 20-fold compared with the preceding year. Cause-specific hospitalizations were higher for acute myocardial infarction (rate ratio, 1.98; 95% confidence interval, 1.60 to 2.46) and dysrhythmia (rate ratio 1.4; 95% confidence interval1.16 to 1.78); fracture rates did not differ (rate ratio 0.82; 95% confidence interval 0.6 to 1.1). CONCLUSIONS: Parathyroidectomy is associated with significant morbidity in the 30 days after hospital discharge and in the year after the procedure. Awareness of clinical events will assist in developing evidence-based risk/benefit determinations for the indication for parathyroidectomy.

Predialysis care and dialysis outcomes in hemodialysis patients with a functioning fistula.

BACKGROUND/AIMS: Predialysis care has been associated with improved first-year outcomes. We investigated types of predialysis care associated with improved patient outcomes in patients initiating dialysis with a fistula and at least 2 years of predialysis care. METHODS: In this retrospective cohort of incident hemodialysis patients with ≥2 years of Medicare coverage before dialysis initiation, care patterns and patients were determined using Medicare claims. Fistula use at initiation was ascertained from the Medical Evidence Report. RESULTS: Patients aged ≥67 years who initiated hemodialysis with a fistula (n = 14,459) differed demographically and clinically from patients who initiated with other vascular access types; however, 55% had diabetes, 28% heart failure, and 40% ischemic heart disease. In the year preceding initiation, 88% of these patients visited a nephrologist, 66% a cardiologist, 9% an endocrinologist, and 3% a dietician; most underwent routine laboratory measurements. In the first year of dialysis, 50% were hospitalized and 1.3% underwent transplant; the mortality rate remained constant (∼20 per 100 patient-years). Of predialysis care factors evaluated, only fistula placement more than 1 month before dialysis initiation was associated with lower hospitalization and mortality risk and greater likelihood of transplant. Other potentially modifiable factors included more contact with cardiologists and endocrinologists. CONCLUSION: Patients initiating dialysis with a functioning fistula appear to receive substantial predialysis preparation. This selected population does not show the excess mortality risk often observed early in dialysis treatment. Earlier fistula placement and referral to cardiology and endocrinology appear to be important aspects of predialysis care.

Agreement of reported vascular access on the medical evidence report and on medicare claims at hemodialysis initiation.

BACKGROUND: The choice of vascular access type is an important aspect of care for incident hemodialysis patients. However, data from the Centers for Medicare & Medicaid Services (CMS) Medical Evidence Report (form CMS-2728) identifying the first access for incident patients have not previously been validated. Medicare began requiring that vascular access type be reported on claims in July 2010. We aimed to determine the agreement between the reported vascular access at initiation from form CMS-2728 and from Medicare claims. METHODS: This retrospective study used a cohort of 9777 patients who initiated dialysis in the latter half of 2010 and were eligible for Medicare at the start of renal replacement therapy to compare the vascular access type reported on form CMS-2728 with the type reported on Medicare outpatient dialysis claims for the same patients. For each patient, the reported access from each data source was compiled; the percent agreement represented the percent of patients for whom the access was the same. Multivariate logistic analysis was performed to identify characteristics associated with the agreement of reported access. RESULTS: The two data sources agreed for 94% of patients, with a Kappa statistic of 0.83, indicating an excellent level of agreement. Further, we found no evidence to suggest that agreement was associated with the patient characteristics of age, sex, race, or primary cause of renal failure. CONCLUSION: These results suggest that vascular access data as reported on form CMS-2728 are valid and reliable for use in research studies.

Association of provider-patient visit frequency and patient outcomes on hemodialysis.

In January of 2004, the Centers for Medicare & Medicaid Services tied provider reimbursement for outpatient hemodialysis services to the number of provider-patient visits per month. We aimed to determine whether greater visit frequency associated with lower mortality and hospitalization rates among incident hemodialysis patients in a large, nationally representative contemporary cohort. Using US Renal Data System data for 130,892 patients who initiated in-center hemodialysis between October 1, 2003 and September 30, 2006, we determined associations between the frequency of provider visits and mortality, first hospitalization, multiple hospitalizations, and cause-specific hospitalizations. Our primary analysis used Cox proportional hazards models, but we also performed time-varying Cox proportional hazards and instrumental variable analyses. In the primary analysis, we did not detect a significance difference in mortality among patients with four provider visits per month compared with those patients with fewer provider visits (adjusted HR=0.98; 95% CI=0.96-1.01), but the risk for first hospitalization was 4% lower among those patients with more frequent visits (adjusted HR=0.96; 95% CI=0.95-0.97). The time-varying Cox analysis produced similar results. The fully adjusted instrumental variable analysis showed a 0.07% higher risk for death that was not statistically significant (P=0.88) but a significant 2.3% lower risk for first hospitalization (P=0.001) for patients with four provider visits per month. In summary, greater frequency of provider visits to hemodialysis patients associates with a small but significant reduction in hospitalizations, but it does not consistently associate with lower risk for death.

Prehemodialysis care by dietitians and first-year mortality after initiation of hemodialysis.

BACKGROUND: Since January 2002, Medicare has provided payment for medical nutrition therapy for patients with chronic kidney disease. Few patients receive dietary counseling before end-stage renal disease onset; whether such counseling is associated with improved outcomes is unknown. STUDY DESIGN: Retrospective cohort analysis. SETTING & PARTICIPANTS: Patients who initiated hemodialysis therapy on June 1, 2005, to May 31, 2007, in the United States for whom predialysis dietitian care was reported on the Centers for Medicare & Medicaid Services Medical Evidence Report. PREDICTOR: Dietitian care before end-stage renal disease onset. OUTCOME: Time to death. MEASUREMENTS: Propensity score for dietitian care calculated using logistic regression; Cox regression analysis used to compare time to death by predialysis dietitian care overall and stratified by tertiles of propensity score, adjusting for baseline characteristics. RESULTS: Most patients (88%) received no dietitian care; 9% received dietitian care for 12 months or less, and 3% received dietitian care for more than 12 months before dialysis therapy initiation (total N = 156,440). Predialysis dietitian care was associated independently with higher albumin and lower total cholesterol levels at dialysis therapy initiation. There was evidence of an independent association between predialysis dietitian care for longer than 12 months and decreased mortality during the first year on dialysis therapy for the second tertile of propensity score. Adjusted mortality HRs were 1.16 (95% CI, 0.44-3.09; P = 0.8), 0.81 (95% CI, 0.71-0.93; P = 0.002), and 0.93 (95% CI, 0.86-1.01; P = 0.1) in the first, second, and third tertiles of propensity score, respectively. LIMITATIONS: Information for dietitian care was missing for 18.6% of Medical Evidence Reports and has low sensitivity; including only incident dialysis patients precluded evaluation of an association between dietitian care and chronic kidney disease progression; the observational design allowed the possibility of residual confounding. CONCLUSIONS: Our study suggests an independent association between predialysis dietitian care for more than 12 months and lower mortality during the first year on dialysis therapy.

Trends in patient characteristics and first-year medical costs of older incident hemodialysis patients, 1995-2005.

BACKGROUND: Characteristics of patients with chronic kidney disease who survive to end-stage renal disease may change over time, affecting subsequent outcomes and costs. We examined trends in older incident hemodialysis patient characteristics and analyzed first-year post-dialysis therapy initiation medical costs. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: All US incident hemodialysis patients aged > or =67 years at dialysis therapy initiation from January 1, 1995, to December 31, 2005, with Medicare Part A and Part B in the prior 2 years. PREDICTOR: Year of dialysis therapy initiation. OUTCOMES: Changes in patient characteristics and first-year costs. MEASUREMENTS: Mean and median values for continuous variables and percentages of categorical variables; first-year total medical costs measured per person per year. Observed costs were adjusted using Medicare Price Indices and patient case-mix. RESULTS: Median age at dialysis therapy initiation increased from 74.9 to 77.0 years from 1995 (n = 19,044) to 2005 (n = 31,796; P < 0.001). Diabetes prevalence increased from 54.2% to 64.1% (P < 0.001). Median estimated glomerular filtration rate increased from 8.0 to 11.2 mL/min/1.73 m(2), and median hemoglobin level increased from 9.4 to 10.2 g/dL. Obesity increased from 8.9% to 22.9% (P < 0.001). First-year observed costs increased by 37.9%; however, inflation-adjusted and case-mix-inflation-adjusted costs were stable. Important adjusters for costs are inability to ambulate/transfer, baseline serum albumin level, primary end-stage renal disease cause, comorbid peripheral vascular disease, and baseline hospital days. LIMITATIONS: Population aged > or =67 years at dialysis therapy initiation and results may not generalize to the overall hemodialysis population. CONCLUSIONS: From 1995 to 2005, incident hemodialysis patients aged > or =67 years became older, sicker, and more obese with significantly increased estimated glomerular filtration rates and hemoglobin levels at dialysis therapy initiation. Increased first-year post-dialysis therapy initiation costs became stable over time after adjustment for price inflation; case-mix-inflation-adjusted costs remained constant, possibly because of mixed changes in patient characteristics.

Atherosclerotic renovascular disease in the United States.

Atherosclerotic renovascular disease (ARVD) is an increasingly recognized clinical condition that is diagnosed predominantly in older patients. Here we used annual United States Medicare 5% Denominator Files and studied 16,036,904 patients, 66 years of age and older, to quantify trends in diagnostic rates, associations, treatment, and outcomes of ARVD over a 13-year period. Overall, there was an ARVD rate of 3.09 per 1000 patient-years, which rose progressively with an adjusted hazard ratio of 3.35, comparing data from 1992 to 2004. Within 6 months of disease diagnosis, 13.4% of patients had undergone revascularization. A biphasic pattern of revascularization was found where the adjusted hazard ratios significantly increased in a progressive manner until 1999, following which there was a decline through 2004, which was not significant. The method of revascularization changed markedly over time with endovascular intervention steadily replacing direct surgical revascularization. As a time-dependent variable, ARVD was associated with excess mortality in each calendar year, albeit with declining hazard ratio estimates in more recent years. Among patients with this disease, revascularization was associated with mortality adjusted hazard ratios <1 in each year. Our study shows the diagnosis of ARVD has substantially risen in the United States but the survival implications were not fully explained by other comorbid vascular diseases.