The Association Between Beta-blocker and Renin-Angiotensin System Inhibitor Use After Heart Failure With Reduced Ejection Fraction Hospitalization and Outcomes in Older Patients.

INTRODUCTION: Beta-blockers (BB) and renin-angiotensin system inhibitors (RASi) are foundational for the treatment of heart failure with reduced ejection fraction (HFrEF). However, given the increased risk of side effects in older patients, uncertainty remains as to whether, on net, older patients benefit as much as the younger patients studied in trials. METHODS AND RESULTS: Using the Get With The Guidelines-Heart Failure registry linked with Medicare data, overlap propensity weighted Cox proportional hazard models were used to examine the association between BB and RASi use at hospital discharge and 30-day and 1-year outcomes among patients with HFrEF. Among the 48,711 patients (aged ≥65 years) hospitalized with HFrEF, there were significant associations between BB and/or RASi use at discharge and lower rates of 30-day and 1-year mortality, including those over age 85 (30-day hazard ratio 0.56, 95% confidence interval 0.45-0.70; 1-year hazard ratio 0.69, 95% confidence interval 0.61-0.78). In addition, the magnitude of benefit associated with BB and/or RASi use after discharge did not decrease with advancing age. Even among the oldest patients, those over age 85, with hypotension, renal insufficiency or frailty, BB and/or RASi use at discharge was still associated with lower 1-year mortality or readmission. CONCLUSIONS: Among older patients hospitalized with HFrEF, BB and/or RASi use at discharge is associated with lower rates of 30-day and 1-year mortality across all age groups and the magnitude of this benefit does not seem to decrease with advancing age. These data suggest that, absent a clinical contraindication, BB and RASi should be considered in all patients hospitalized with HFrEF before or at hospital discharge, regardless of age.

Sacubitril/valsartan vs ACEi/ARB at hospital discharge and 5-year survival in older patients with heart failure with reduced ejection fraction: A decision analysis approach.

BACKGROUND: In clinical trials, sacubitril/valsartan has demonstrated significant survival benefits compared to angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEi/ARB). Whether older patients with heart failure with reduced ejection fraction (HFrEF) benefit as much, due to higher rates of comorbidities, frailty and drug discontinuation, is unknown. METHODS AND RESULTS: Using a cohort of Medicare beneficiaries hospitalized with HFrEF between 2016 and 2018, we determined all-cause mortality and HF-readmission rates among patients not given ACEi/ARB or sacubitril/valsartan at hospital discharge, by age. We then used risk reductions from the SOLVD, PARADIGM-HF and PIONEER-HF trials to estimate the benefits of ACEi/ARB and sacubitril/valsartan. We then incorporated age-specific estimates of drug discontinuation from Medicare. A Markov decision process model was used to simulate 5-year survival and estimate number needed to treat, comparing discharge on ACEi/ARB vs sacubitril/valsartan by age. After accounting for drug discontinuation rates, which were surprisingly slightly higher among those discharged on ACEi/ARB (2.3%/month vs 1.9%/month), there was a small but significant survival advantage to discharge on sacubitril/valsartan over 5 years (+0.81 months [95% CI 0.80, 0.81]). The benefit of sacubitril/valsartan over ACEi/ARB did not decrease with increasing age - the number needed to treat among 66 to 74-year-old patients was 84 and among 85+ year-old patients was 67. CONCLUSIONS: Even after accounting for "real world" rates of drug discontinuation, discharge on sacubitril/valsartan after conferred a small, but significant, survival advantage which does not appear to wane with increasing age.

Comparative effectiveness of cardiac resynchronization therapy in older patients with heart failure: Systematic review and meta-analysis.

BACKGROUND: Pivotal CRT trials enrolled patients with HFrEF significantly younger than the typical contemporary patient with HFrEF. Thus, the risks and benefits in this older population with HFrEF are largely unknown. We sought to perform meta-analyses comparing safety and effectiveness of cardiac resynchronization therapy (CRT) in older vs younger patients with heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: PubMed, The Cochrane Library, Scopus, and Web of Science were queried for comparative effectiveness studies of CRT in older patients with HFrEF. Title, abstract, and full-text screening was performed to identify studies comparing at least 1 prespecified end point between older and younger adult patients with at least 50 participants. Random effects meta-analysis in the left ventricular ejection fraction (LVEF) mean difference (older minus younger) and the relative risk (RR) of death, improvement in New York Heart Association (NYHA) functional class, and complications are reported along with estimates of heterogeneity. In 7 studies, there was similar LVEF improvement between groups (mean difference 1.14, 95% confidence interval [CI] -0.04 to 2.32, P = .06, I2 = 53%). Older patients were equally likely as younger patients to see an improvement in NYHA functional class of at least 1 in 6 studies (RR 0.99, 95% CI 0.93-1.06, P = .76, I2 = 25%). No significant differences in the incidence of hematoma, pneumothorax, lead dislodgment, cardiac perforation, or infection requiring explant was observed. The RR of mortality in 11 studies demonstrated higher risk of all-cause mortality in older patients (RR 1.05, 95% CI 1.03-1.08, P < .01, I2 = 0%). CONCLUSIONS: Compared with younger patients, older patients receiving CRT were equally likely to experience improvement in LVEF, left ventricular end-diastolic diameter, and NYHA functional class. There was no difference in procedural complications. The higher rate of all-cause mortality in older patients likely reflects a greater underlying risk of death from competing causes.

Evaluation of Hospital Performance Using the Excess Days in Acute Care Measure in the Hospital Readmissions Reduction Program.

The Hospital Readmissions Reduction Program (HRRP) has penalized hospitals with higher 30-day readmission rates more than $3 billion to date. Clinicians and policy experts have raised concerns that the 30-day readmission measure used in this program provides an incomplete picture of performance because it does not capture all hospital encounters that may occur after discharge. In contrast, the excess days in acute care (EDAC) measure, which currently is not used in the HRRP, captures the full spectrum of hospital encounters (emergency department, observation stay, inpatient readmission) and their associated lengths of stay within 30 days of discharge. This study of 3173 hospitals that participated in the HRRP in fiscal year 2019 compared performance on the readmission and EDAC measures and evaluated whether using the EDAC measure would change hospitals' penalty status for 3 conditions targeted by the HRRP. Overall, only moderate agreement was found on hospital performance rankings by using the readmission and EDAC measures (weighted κ statistic: heart failure, 0.45 [95% CI, 0.42 to 0.47]; acute myocardial infarction [AMI], 0.37 [CI, 0.35 to 0.40]; and pneumonia, 0.50 [CI, 0.47 to 0.52]). Under the HRRP, the penalty status of 769 (27.0%) of 2845 hospitals for heart failure, 581 (28.3%) of 2055 for AMI, and 724 (24.9%) of 2911 for pneumonia would change if the EDAC measure were used instead of the readmission measure to evaluate performance. Fewer small and rural hospitals would receive penalties. The Centers for Medicare & Medicaid Services should consider using the EDAC measure, which provides a more comprehensive picture of postdischarge hospital use, rather than the 30-day readmission measure to evaluate health care system performance under federal quality, reporting, and value-based programs.

Inclusion of Performance Parameters and Patient Context in the Clinical Practice Guidelines for Heart Failure.

BACKGROUND: To facilitate evidence-based medicine (EBM) on an individual level, it may be important for clinical practice guidelines (CPGs) to incorporate the performance parameters of diagnostic studies and therapeutic interventions (such as likelihood ratio and absolute benefit or harm), and to incorporate relevant patient contexts that may influence decision-making. We sought to determine the extent to which heart failure CPGs currently incorporate this information. METHODS: We reviewed the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) 2013 Heart Failure CPG, the 2017 ACCF/AHA/HFSA update, and European Society of Cardiology (ESC) 2016 Heart Failure CPG. We abstracted variables for each CPG recommendation from the following domains: quality of evidence, strength of recommendation, diagnostic and therapeutic performance parameters, and patient context. RESULTS: We examined 169 recommendations from the ACCF/AHA 2013 CPGs and 2017 update and 187 recommendations from the 2016 ESC CPGs. Performance parameters for diagnostic studies (2013 ACCF/AHA: 13%; 2017 ACCF/AHA/HFSA update: 0%; 2016 ESC: 0%) and therapeutic interventions (2013 ACCF/AHA: 65%; 2017 ACCF/AHA/HFSA update: 64%; 2016 ESC: 16%) were not commonly included in CPGs. Patient context was included in about half of ACCF/AHA recommendations and a quarter of ESC recommendations. CONCLUSIONS: The majority of recommendations from heart failure CPGs lack information on diagnostic and therapeutic performance parameters and patient context. Given the importance of these components to effectively implement EBM, particularly for a heterogeneous heart failure population, innovative strategies are needed to optimize CPGs so they provide comprehensive yet succinct recommendations that can improve population-level outcomes and ensure optimal patient-centered care.

Association Between Beta-Blockers and Mortality and Readmission in Older Patients with Heart Failure: an Instrumental Variable Analysis.

BACKGROUND: The demographics of heart failure are changing. The rate of growth of the "older" heart failure population, specifically those ≥ 75, has outpaced that of any other age group. These older patients were underrepresented in the early beta-blocker trials. There are several reasons, including a decreased potential for mortality benefit and increased risk of side effects, why the risk/benefit tradeoff may be different in this population. OBJECTIVE: We aimed to determine the association between receipt of a beta-blocker after heart failure discharge and early mortality and readmission rates among patients with heart failure and reduced ejection fraction (HFrEF), specifically patients aged 75+. DESIGN AND PARTICIPANTS: We used 100% Medicare Parts A and B and a random 40% sample of Part D to create a cohort of beneficiaries with ≥ 1 hospitalization for HFrEF between 2008 and 2016 to run an instrumental variable analysis. MAIN MEASURE: The primary measure was 90-day, all-cause mortality; the secondary measure was 90-day, all-cause readmission. KEY RESULTS: Using the two-stage least squared methodology, among all HFrEF patients, receipt of a beta-blocker within 30-day of discharge was associated with a - 4.35% (95% CI - 6.27 to - 2.42%, p < 0.001) decrease in 90-day mortality and a - 4.66% (95% CI - 7.40 to - 1.91%, p = 0.001) decrease in 90-day readmission rates. Even among patients ≥ 75 years old, receipt of a beta-blocker at discharge was also associated with a significant decrease in 90-day mortality, - 4.78% (95% CI - 7.19 to - 2.40%, p < 0.001) and 90-day readmissions, - 4.67% (95% CI - 7.89 to - 1.45%, p < 0.001). CONCLUSION: Patients aged ≥ 75 years who receive a beta-blocker after HFrEF hospitalization have significantly lower 90-day mortality and readmission rates. The magnitude of benefit does not appear to wane with age. Absent a strong contraindication, all patients with HFrEF should attempt beta-blocker therapy at/after hospital discharge, regardless of age.

Unanswered Questions in Contemporary Heart Failure.

OBJECTIVE: The epidemiology of heart failure (HF) is changing. This study aimed to describe questions that arise during the routine care of HF patients that are unanswered by the current literature and describe how the type and focus of these questions has changed over time. METHODS: Investigators from the National Heart, Lung, and Blood Institute-sponsored Heart Failure Apprentice Network collected and categorized questions from 5 academic hospitals over 12 months. A total of 174 unanswered questions were collected and analyzed. RESULTS: Compared with 2004, there were more unanswered questions about "whether" to use therapies and fewer about "how" to use therapies. There were fewer questions about what therapeutic targets, therapy adjustment, and combination therapies. There were more questions about whether or how to stop therapies and how to add therapies back. Newly prominent topics, not observed in 2004, including novel therapeutics, refractory ventricular tachycardia, right heart failure, and nutrition/frailty, accounted for 24% of questions. CONCLUSIONS: Compared with 2004, there are fewer unanswered questions about how to use, adjust, and combine therapies. There were more unanswered questions about whether and how to stop therapies. Almost 25% of unanswered questions dealt with topics indicative of more advanced disease which were not observed in 2004.

Understanding the relationship between readmission and quality of hospital care in heart failure.

Hospital readmission rates for heart failure (HF) are increasingly seen as a quality metric and are being used to define reimbursement rates and penalize underperforming hospitals. As disease patterns shift from single acute episodes of illness to more chronic and degenerative diseases, healthcare systems across the country are grappling with the challenge of providing quality care while simultaneously controlling both readmission rates and spending. Using HF as a prototypical example of chronic illness, this review begins by describing the historical underpinnings of readmission rates and how they have become a mainstream metric of healthcare quality. It then examines the controversial relationship between hospital quality and readmission rates. The paper examines several strategies to decrease readmission rates, including discharge planning and readmission reduction programs, as well as the relationship between readmission rates and mortality rates. The principal drivers of readmissions are discussed and the impact of new readmission-based financial policy is explored as well.

The association between beta-blockers and outcomes in patients with heart failure and concurrent Alzheimer's disease and related dementias.

BACKGROUND: Contemporary patients with heart failure with reduced ejection fraction (HFrEF) are older and have a higher prevalence of cognitive impairment than those studied in trials. The risk/benefit trade-off of routine beta-blocker (BB) use in patients with HFrEF and Alzheimer's disease and related dementias (ADRD) has not been explored. This study aimed to determine the association between BB use and outcomes among patients with HFrEF and ADRD. METHODS: Using a random 40% sample of Medicare Parts A, B, and D data we identified patients with ≥1 hospitalization for HFrEF between 2008 and 2018. Each patient was classified based on BB use prior to admission and after discharge. Outcomes include 90-day and 1-year mortality and readmission. RESULTS: Between 2008 and 2018, we identified 357,030 patients hospitalized with HFrEF; 12.7% had ADRD. Patients with HFrEF and ADRD had higher 90-day and 1-year mortality compared to patients with HFrEF-only. Among patients admitted on a BB, 60.5% of patients with HFrEF-only were continued on therapy after discharge, compared to 56.8% of patients with HFrEF and ADRD. Discontinuing BB was associated with a 2.2-fold higher risk of 90-day mortality (p < 0.001) among patients with HF-only and a 2.- fold higher risk of 90-day mortality (p < 0.001) among patients with HFrEF + ADRD. Not starting a BB was associated with a 1.8-fold higher risk of 90-day mortality (p < 0.001) among patients with HFrEF-only and a 1.7-fold higher risk of 90-day mortality (p < 0.001) among patients with HFrEF + ADRD. Similar risks were seen at 1 year. CONCLUSIONS: BB therapy is associated with significantly lower short and long-term mortality rates among all patients with HFrEF; the magnitude of these associated benefits appear at least as large in patients with HFrEF and ADRD compared to patients with HFrEF-only.

Real-World Characteristics of Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy: An Analysis of Electronic Healthcare Records in the United States.

BACKGROUND: Tafamidis was approved for the treatment of hereditary and wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) in May 2019, based on findings from the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). METHODS: This retrospective cohort study evaluated the factors associated with tafamidis prescription after diagnosis of ATTRwt-CM in the real world. Between May 2019 and December 2020, 430 patients with 6 months' database activity were indexed from the de-identified US Optum electronic healthcare records at first diagnosis of ATTRwt-CM or prescription of tafamidis, then followed until last activity or death. Of these, 209 patients were prescribed tafamidis during follow-up, 167 (80%) within 1 month, 98% by 6 months, and 100% by 9 months. Median time from index to tafamidis prescription, calculated using the Kaplan-Meier method, was 5.8 months (95% confidence interval [CI] 2.4-not evaluable). RESULTS: Factors associated with tafamidis prescription in a multivariable Cox proportional hazards regression (hazard ratio [95% CI]) included age ≥ 65 years (2.1 [1.07-4.05]), male sex (1.6 [1.07-2.28]), having heart failure/cardiomyopathy (2.4 [1.54-3.82]), and having had technetium-99m pyrophosphate myocardial scintigraphy (1.7 [1.28-2.28]). CONCLUSIONS: The clinical characteristics of patients with ATTRwt-CM who were prescribed tafamidis in the real world were broadly comparable with those who took part in ATTR-ACT. Further studies are needed to evaluate hereditary and ATTRwt-CM patient populations in the real world and assess the long-term outcomes associated with disease management pathways. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT01994889.

Outpatient intravenous diuresis in a rural setting: safety, efficacy, and outcomes.

Purpose: To evaluate the safety, efficacy, and outcomes of outpatient intravenous diuresis in a rural setting and compare it to urban outcomes. Methods: A single-center study was conducted on 60 patients (131 visits) at the Dartmouth-Hitchcock Medical Center (DHMC) from 1/2021-12/2022. Demographics, visit data, and outcomes were collected and compared to urban outpatient IV centers, and inpatient HF hospitalizations from DHMC FY21 and national means. Descriptive statistics, T-tests and chi-squares were used. Results: The mean age was 70 ± 13 years, 58% were male, and 83% were NYHA III-IV. Post-diuresis, 5% had mild-moderate hypokalemia, 16% had mild worsening of renal function, and 3% had severe worsening of renal function. No hospitalizations occurred due to adverse events. The mean infusion-visit urine output was 761 ± 521 ml, and post-visit weight loss was -3.9 ± 5.0 kg. No significant differences were observed between HFpEF and HFrEF groups. 30-day readmissions were similar to urban outpatient IV centers, DHMC FY21, and the national mean (23.3% vs. 23.5% vs. 22.2% vs. 22.6%, respectively; p = 0.949). 30-day mortality was similar to urban outpatient IV centers but lower than DHMC FY21 and the national means (1.7% vs. 2.5% vs. 12.3% vs. 10.7%, respectively; p < 0.001). At 60 days, 42% of patients had ≥1 clinic revisit, 41% had ≥1 infusion revisit, 33% were readmitted to the hospital, and two deaths occurred. The clinic avoided 21 hospitalizations, resulting in estimated cost savings of $426,111. Conclusion: OP IV diuresis appears safe and effective for rural HF patients, potentially decreasing mortality rates and healthcare expenses while mitigating rural-urban disparities.

Real-world safety of neurohormonal antagonist initiation among older adults following a heart failure hospitalization.

AIMS: To optimize guideline-directed medical therapy for heart failure, patients may require the initiation of multiple neurohormonal antagonists (NHAs) during and following hospitalization. The safety of this approach for older adults is not well established. METHODS AND RESULTS: We conducted an observational cohort study of 207 223 Medicare beneficiaries discharged home following a hospitalization for heart failure with reduced ejection fraction (HFrEF) (2008-2015). We performed Cox proportional hazards regression to examine the association between the count of NHAs initiated within 90 days of hospital discharge (as a time-varying exposure) and all-cause mortality, all-cause rehospitalization, and fall-related adverse events over the 90 day period following hospitalization. We calculated inverse probability-weighted hazard ratios (IPW-HRs) with 95% confidence intervals (CIs) comparing initiation of 1, 2, or 3 NHAs vs. 0. The IPW-HRs for mortality were 0.80 [95% CI (0.78-0.83)] for 1 NHA, 0.70 [95% CI (0.66-0.75)] for 2, and 0.94 [95% CI (0.83-1.06)] for 3. The IPW-HRs for readmission were 0.95 [95% CI (0.93-0.96)] for 1 NHA, 0.89 [95% CI (0.86-0.91)] for 2, and 0.96 [95% CI (0.90-1.02)] for 3. The IPW-HRs for fall-related adverse events were 1.13 [95% CI (1.10-1.15)] for 1 NHA, 1.25 [95% CI (1.21-1.30)] for 2, and 1.64 [95% CI (1.54-1.76)] for 3. CONCLUSIONS: Initiating 1-2 NHAs among older adults within 90 days of HFrEF hospitalization was associated with lower mortality and lower readmission. However, initiating 3 NHAs was not associated with reduced mortality or readmission and was associated with a significant risk for fall-related adverse events.

Variation in Risk-Standardized Acute Admission Rates Among Patients With Heart Failure in Accountable Care Organizations: Implications for Quality Measurement.

Background Accountable care organizations (ACOs) aim to improve health care quality and reduce costs, including among patients with heart failure (HF). However, variation across ACOs in admission rates for patients with HF and associated factors are not well described. Methods and Results We identified Medicare fee-for-service beneficiaries with HF who were assigned to a Medicare Shared Savings Program ACO in 2017 and survived ≥30 days into 2018. We calculated risk-standardized acute admission rates across ACOs, assigned ACOs to 1 of 3 performance categories, and examined associations between ACO characteristics and performance categories. Among 1 232 222 beneficiaries with HF, 283 795 (mean age, 81 years; 54% women; 86% White; 78% urban) were assigned to 1 of 467 Medicare Shared Savings Program ACOs. Across ACOs, the median risk-standardized acute admission rate was 87 admissions per 100 people, ranging from 61 (minimum) to 109 (maximum) admissions per 100 beneficiaries. Compared to the overall average, 13% of ACOs performed better on risk-standardized acute admission rates, 72% were no different, and 14% performed worse. Most ACOs with better performance had fewer Black beneficiaries and were not hospital affiliated. Most ACOs that performed worse than average were large, located in the Northeast, had a hospital affiliation, and had a lower proportion of primary care providers. Conclusions Admissions are common among beneficiaries with HF in ACOs, and there is variation in risk-standardized acute admission rates across ACOs. ACO performance was associated with certain ACO characteristics. Future studies should attempt to elucidate the relationship between ACO structure and characteristics and admission risk.

Biomarkers and cardiovascular risk assessment for primary prevention: an update.

BACKGROUND: Interest in cardiovascular biomarkers in primary prevention has increased dramatically in the past decade. This increase has been fueled by an improved understanding of cardiovascular pathophysiology, as well as novel technologies for biomarker identification. CONTENT: In this review we provide a brief overview of recent concepts in the evaluation of screening biomarkers, because biomarkers may behave differently when used for screening as opposed to diagnosis or disease staging. The following specific biomarker examples are then discussed, with a focus on data from primary prevention studies: high-sensitivity C-reactive protein, B-type natriuretic peptide, lipoprotein-associated phospholipase A2, and high-sensitivity troponin T. The article concludes by addressing novel platforms for biomarker discovery, reviewing recent examples from the field of metabolomics. SUMMARY: An ongoing challenge is to develop screening strategies that can identify individuals at risk for cardiovascular events well before symptoms appear. For this purpose, the measurement of soluble biomarkers could be an important adjunct to traditional cardiovascular risk assessment. Recent studies highlight both the strengths and limitations of "novel" circulating biomarkers, and suggest that substantial work is still needed to identify biomarkers that are sufficiently accurate and cost-effective for routine use in primary prevention.

How Do I Optimize Heart Failure Medications for Patients with Hypotension or Chronic Kidney Disease?

HF Medications for Hypotension or CKDThe cornerstone of treatment for HF with reduced ejection fraction is GDMT; however, safely delivering maximal therapy is often hampered by low blood pressure, labile renal function, or both. Reviewing the physiologic basis of GDMT and exploring each drug's mechanism of action and unique properties can enable careful initiation and titration of therapy, even in patients with hypotension or CKD.

Opposing forces of cardiogenic shock: left ventricular outflow obstruction, severe mitral regurgitation, and left ventricular dysfunction in Takotsubo cardiomyopathy.

Rates of stress (Takotsubo) cardiomyopathy have increased during the coronavirus pandemic due to social stressors, even in patients who are not infected with the virus. At times, Takotsubo cardiomyopathy (TC) may present as cardiogenic shock. Herein, we present a case during the pandemic of shock from TC secondary to left ventricular outflow tract obstruction (LVOTO), mitral regurgitation (MR), and left ventricular (LV) dysfunction. The contrasting management strategy of LVOTO, MR, and LV failure was cause for clinical challenge, and we highlight the balance of treating these opposing forces.

Trends in Mortality Rates Among Medicare Enrollees With Alzheimer Disease and Related Dementias Before and During the Early Phase of the COVID-19 Pandemic.

IMPORTANCE: The COVID-19 pandemic fundamentally altered the delivery of health care in the United States. The associations between these COVID-19-related changes and outcomes in vulnerable patients, such as among persons with Alzheimer disease and related dementias (ADRD), are not yet well understood. OBJECTIVE: To determine the association between regional rates of COVID-19 infection and excess mortality among individuals with ADRD. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study used data from beneficiaries of 100% fee-for-service Medicare Parts A and B between January 1, 2019, and December 31, 2020, to assess age- and sex-adjusted mortality rates. Participants were 53 640 888 Medicare enrollees 65 years of age or older categorized into 4 prespecified cohorts: enrollees with or without ADRD and enrollees with or without ADRD residing in nursing homes. EXPOSURES: Monthly COVID-19 infection rates by hospital referral region between January and December 2020. MAIN OUTCOMES AND MEASURES: Mortality rates from March through December 2020 were compared with those from March through December 2019. Excess mortality was calculated by comparing mortality rates in 2020 with rates in 2019 for specific, predetermined groups. Means were compared using t tests, and 95% CIs were estimated using the delta method. RESULTS: This cross-sectional study included 26 952 752 Medicare enrollees in 2019 and 26 688 136 enrollees in 2020. In 2019, the mean (SD) age of community-dwelling beneficiaries without ADRD was 74.1 (8.8) years and with ADRD was 82.6 (8.4) years. The mean (SD) age of nursing home residents with ADRD (83.6 [8.4] years) was similar to that for patients without ADRD (79.7 [8.8] years). Among patients diagnosed as having ADRD in 2019, 63.5% were women, 2.7% were Asian, 9.2% were Black, 5.7% were Hispanic, 80.7% were White, and 1.7% were identified as other (included all races or ethnicities other than those given); the composition did not change appreciably in 2020. Compared with 2019, adjusted mortality in 2020 was 12.4% (95% CI, 12.1%-12.6%) higher among enrollees without ADRD and 25.7% (95% CI, 25.3%-26.2%) higher among all enrollees with ADRD, with even higher percentages for Asian (36.0%; 95% CI, 32.6%-39.3%), Black (36.7%; 95% CI, 35.2%-38.2%), and Hispanic (40.1%; 95% CI, 37.9%-42.3%) populations with ADRD. The hospital referral region in the lowest quintile for COVID-19 infections in 2020 had no excess mortality among enrollees without ADRD but 8.8% (95% CI, 7.5%-10.2%) higher mortality among community-dwelling enrollees with ADRD and 14.2% (95% CI, 12.2%-16.2%) higher mortality among enrollees with ADRD living in nursing homes. CONCLUSIONS AND RELEVANCE: The results of this cross-sectional study suggest that the COVID-19 pandemic may be associated with excess mortality among older adults with ADRD, especially for Asian, Black, and Hispanic populations and people living in nursing homes, even in areas with low COVID-19 prevalence.