Contemporary American and European Guidelines for Heart Failure Management: JACC: Heart Failure Guideline Comparison.

This review serves to compare contemporary clinical practice recommendations for the management of heart failure (HF), as codified in the 2021 European Society of Cardiology (ESC) guideline, the 2022 American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Failure Society of America (HFSA) guideline, and the 2023 focused update of the 2021 ESC document. Overall, these guidelines aim to solidify significant advances throughout the HF continuum since the publication of previous full guideline iterations (2013 and 2016 for the ACC/AHA and ESC, respectively). All guidelines provide new recommendations for an increasingly complex landscape of HF care, with focus on primary HF prevention, HF stages, rapid initiation and optimization of evidence-based pharmacotherapies, overlapping cardiac and noncardiac comorbidities, device-based therapies, and management pathways for special groups of patients, including those with cardiac amyloidosis. Importantly, the ACC/AHA/HFSA document features special emphasis on HF risk prediction and screening, cost/value, social determinants of health, and health care disparities. The review discusses major similarities and differences between these recent guidelines and guideline updates, as well as their potential downstream implications for clinical care.

Clinical Trial Inclusion and Impact on Early Adoption of Medical Innovation in Diverse Populations.

BACKGROUND: Inadequate inclusion in clinical trial enrollment may contribute to health inequities by evaluating interventions in cohorts that do not fully represent target populations. OBJECTIVES: The aim of this study was to determine if characteristics of patients with heart failure (HF) enrolled in a pivotal trial are associated with who receives an intervention after approval. METHODS: Demographics from 2,017,107 Medicare patients hospitalized for HF were compared with those of the first 10,631 Medicare beneficiaries who received implantable pulmonary artery pressure sensors. Characteristics of the population studied in the pivotal CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) clinical trial (n = 550) were compared with those of both groups. All demographic data were analyzed nationally and in 4 U.S. regions. RESULTS: The Medicare HF cohort included 80.9% White, 13.3% African American, 1.9% Hispanic, 1.3% Asian, and 51.5% female patients. Medicare patients <65 years of age were more likely to be African American (33%) and male (58%), whereas older patients were mostly White (84%) and female (53%). Forty-one percent of U.S. HF hospitalizations occurred in the South; demographic characteristics varied significantly across all U.S. regions. The CHAMPION trial adequately represented African Americans (23% overall, 35% <65 years of age), Hispanic Americans (2%), and Asian Americans (1%) but underrepresented women (27%). The trial's population characteristics were similar to those of the first patients who received pulmonary artery sensors (82% White, 13% African American, 1% Asian, 1% Hispanic, and 29% female). CONCLUSIONS: Demographics of Centers for Medicare and Medicaid Services beneficiaries hospitalized with HF vary regionally and by age, which should be considered when defining "adequate" representation in clinical studies. Enrollment diversity in clinical trials may affect who receives early application of recently approved innovations.

Cost Effectiveness of Dapagliflozin for Heart Failure Across the Spectrum of Ejection Fraction: An Economic Evaluation Based on Pooled, Individual Participant Data From the DELIVER and DAPA-HF Trials.

BACKGROUND: The sodium glucose cotransporter-2 inhibitors are guideline-recommended to treat heart failure across the spectrum of left ventricular ejection fraction; however, economic evaluations of adding sodium glucose cotransporter-2 inhibitors to standard of care in chronic heart failure across a broad left ventricular ejection fraction range are lacking. METHODS AND RESULTS: We conducted a US-based cost-effectiveness analysis of dapagliflozin added to standard of care in a chronic heart failure population using pooled, participant data from the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trials. The 3-state Markov model used estimates of transitional probabilities, effectiveness of dapagliflozin, and utilities from the pooled trials. Costs estimates were obtained from published sources, including published rebates in dapagliflozin cost. Adding dapagliflozin to standard of care was estimated to produce an additional 0.53 quality-adjusted life years (QALYs) compared with standard of care alone. Incremental cost effectiveness ratios were $85 554/QALY when using the publicly reported full (undiscounted) Medicare cost ($515/month) and $40 081/QALY, at a published nearly 50% rebate ($263/month). The addition of dapagliflozin to standard of care would be of at least intermediate value (<$150 000/QALY) at a cost of <$872.58/month, of high value (<$50 000/QALY) at <$317.66/month, and cost saving at <$40.25/month. Dapagliflozin was of at least intermediate value in 92% of simulations when using the full (undiscounted) Medicare list cost in probabilistic sensitivity analyses. Cost effectiveness was most sensitive to the dapagliflozin cost and the effect on cardiovascular death. CONCLUSIONS: The addition of dapagliflozin to standard of care in patients with heart failure across the spectrum of ejection fraction was at least of intermediate value at the undiscounted Medicare cost and may be potentially of higher value on the basis of the level of discount, rebates, and price negotiations offered. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01035255 & NCT01920711.

Medical Therapy Before, During and After Hospitalization in Medicare Beneficiaries With Heart Failure and Diabetes: Get With The Guidelines - Heart Failure Registry.

BACKGROUND: Patients hospitalized with heart failure (HF) and diabetes mellitus (DM) are at risk for worsening clinical status. Little is known about the frequency of therapeutic changes during hospitalization. We characterized the use of medical therapies before, during and after hospitalization in patients with HF and DM. METHODS: We identified Medicare beneficiaries in Get With The Guidelines-Heart Failure (GWTG-HF) hospitalized between July 2014 and September 2019 with Part D prescription coverage. We evaluated trends in the use of 7 classes of antihyperglycemic therapies (metformin, sulfonylureas, GLP-1RA, SGLT2-inhibitors, DPP-4 inhibitors, thiazolidinediones, and insulins) and 4 classes of HF therapies (evidence-based ß-blockers, ACEi or ARB, MRA, and ARNI). Medication fills were assessed at 6 and 3 months before hospitalization, at hospital discharge and at 3 months post-discharge. RESULTS: Among 35,165 Medicare beneficiaries, the median age was 77 years, 54% were women, and 76% were white; 11,660 (33%) had HFrEF (LVEF ≤ 40%), 3700 (11%) had HFmrEF (LVEF 41%-49%), and 19,805 (56%) had HFpEF (LVEF ≥ 50%). Overall, insulin was the most commonly prescribed antihyperglycemic after HF hospitalization (n = 12,919, 37%), followed by metformin (n = 7460, 21%) and sulfonylureas (n = 7030, 20%). GLP-1RA (n = 700, 2.0%) and SGLT2i (n = 287, 1.0%) use was low and did not improve over time. In patients with HFrEF, evidence-based beta-blocker, RASi, MRA, and ARNI fills during the 6 months preceding HF hospitalization were 63%, 62%, 19%, and 4%, respectively. Fills initially declined prior to hospitalization, but then rose from 3 months before hospitalization to discharge (beta-blocker: 56%-82%; RASi: 51%-57%, MRA: 15%-28%, ARNI: 3%-6%, triple therapy: 8%-20%; P < 0.01 for all). Prescription rates 3 months after hospitalization were similar to those at hospital discharge. CONCLUSIONS: In-hospital optimization of medical therapy in patients with HF and DM is common in participating hospitals of a large US quality improvement registry.

Pharmacy and neighborhood-level variation in cash price of diabetes medications in the United States.

BACKGROUND: Diabetes medications place significant financial burden on patients but less is known about factors affecting cost variation. OBJECTIVE: To examine pharmacy and neighborhood factors associated with cost variation for diabetes drugs in the US. RESEARCH DESIGN, SUBJECTS AND MEASURES: We used all-payer US pharmacy data from 45,874 chain and independent pharmacies reflecting 7,073,909 deidentified claims. We divided diabetes drugs into insulins, non-insulin generic medications, and brand name medications. Generalized linear models, stratified by pharmacy type, identified pharmacy and neighborhood factors associated with higher or lower cash price-per-unit (PPU) for each set of drugs. RESULTS: Cash PPU was highest for brand name therapies ($149.4±203.2), followed by insulins ($42.4±25.0), and generic therapies ($1.3±4.4). Pharmacy-level price variation was greater for non-insulin generic therapies than insulins or brand name therapies. Chain pharmacies had both lower prices and lesser variation compared with independent pharmacies. CONCLUSIONS: Cash prices for diabetes medications in the US can vary considerably and that the greatest degree of price variation occurs in non-insulin generic therapies.

Health and Economic Evaluation of Sacubitril-Valsartan for Heart Failure Management.

Importance: The US Food and Drug Administration expanded labeling of sacubitril-valsartan from the treatment of patients with chronic heart failure (HF) with reduced ejection fraction (EF) to all patients with HF, noting the greatest benefits in those with below-normal EF. However, the upper bound of below normal is not clearly defined, and value determinations across a broader EF range are unknown. Objective: To estimate the cost-effectiveness of sacubitril-valsartan vs renin-angiotensin system inhibitors (RASis) across various upper-level cutoffs of EF. Design, Setting, and Participants: This economic evaluation included participant-level data from the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and the PARAGON-HF (Prospective Comparison of ARNi with ARB Global Outcomes in HF With Preserved Ejection Fraction) trials. PARADIGM-HF was conducted between 2009 and 2014, PARAGON-HF was conducted between 2014 and 2019, and this analysis was conducted between 2021 and 2023. Main Outcomes and Measures: A 5-state Markov model used risk reductions for all-cause mortality and HF hospitalization from PARADIGM-HF and PARAGON-HF. Quality-of-life differences were estimated from EuroQol-5D scores. Hospitalization and medication costs were obtained from published national sources; the wholesale acquisition cost of sacubitril-valsartan was $7092 per year. Risk estimates and treatment effects were generated in consecutive 5% EF increments up to 60% and applied to an EF distribution of US patients with HF from the Get With the Guidelines-Heart Failure registry. The base case included a lifetime horizon from a health care sector perspective. Incremental cost-effectiveness ratios (ICERs) were estimated at EFs of 60% or less (base case) and at various upper-level EF cutoffs. Results: Among 13 264 total patients whose data were analyzed, for those with EFs of 60% or less, sacubitril-valsartan was projected to add 0.53 quality-adjusted life-years (QALYs) at an incremental lifetime cost of $40 892 compared with RASi, yielding an ICER of $76 852 per QALY. In a probabilistic sensitivity analysis, 95% of the values of the ICER occurred between $71 516 and $82 970 per QALY. Among patients with chronic HF and an EF of 60% or less, treatment with sacubitril-valsartan vs RASis would be at least of economic intermediate value (ICER <$180 000 per QALY) at a sacubitril-valsartan cost of $10 242 or less per year, of high economic value (ICER <$60 000 per QALY) at a cost of $3673 or less per year, and cost-saving at a cost of $338 or less per year. The ICERs were $67 331 per QALY, $59 614 per QALY, and $56 786 per QALY at EFs of 55% or less, 50% or less, and 45% or less, respectively. Treatment with sacubitril-valsartan in only those with EFs of 45% or greater (up to ≤60%) yielded an ICER of $127 172 per QALY gained; treatment was more cost-effective in those at the lower end of this range (ICER of $100 388 per QALY gained for those with EFs of 45%-55%; ICER of $84 291 per QALY gained for those with EFs of 45%-50%). Conclusions and Relevance: Cost-effectiveness modeling provided an ICER for treatment with sacubitril-valsartan vs RASis consistent with high economic value for patients with reduced and mildly reduced EFs (≤50%) and at least intermediate value at the current undiscounted wholesale acquisition cost price at an EF of 60% or less. Treatment was more cost-effective at lower EF ranges. These findings may have implications for coverage decisions and value assessments in contemporary clinical practice guidelines.

Sodium-glucose cotransporter 2 inhibitors vs. sitagliptin in heart failure and type 2 diabetes: an observational cohort study.

AIMS: The effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with heart failure (HF) in routine clinical practice is not extensively studied. This study aimed to evaluate the comparative effectiveness of SGLT2i vs. sitagliptin in older adults with HF and type 2 diabetes and to investigate whether there were any differences between agents within the SGLT2i class or for reduced and preserved ejection fraction. METHODS AND RESULTS: Using Medicare claims data (April 2013 to December 2019), 16 253 SGLT2i initiators vs. 43 352 initiators of sitagliptin aged ≥65 years with type 2 diabetes and HF were included. The primary outcome was a composite of all-cause mortality, hospitalization for HF or urgent visit requiring intravenous diuretics; secondary outcomes included its individual components. Propensity score fine stratification weighted Cox regression was used to adjust for 100 pre-exposure characteristics. Mean age was 74 years; 49.8% were women. Initiation of SGLT2i vs. sitagliptin was associated with a lower risk of the primary composite outcome [adjusted hazard ratio (HR) 0.72; 95% confidence interval 0.67-0.77]. The adjusted HRs were 0.70 (0.63-0.78) for all-cause mortality, 0.64 (0.58-0.70) for hospitalization for HF, and 0.77 (0.69-0.86) for urgent visit requiring intravenous diuretics. Similar associations with the primary composite outcome were observed for all three agents within the SGLT2i class, for reduced and preserved ejection fraction, and subgroups based on demographics, comorbidities, and other HF treatments. Bias-calibrated HRs for the primary endpoint using negative and positive control outcomes ranged between 0.81 and 0.89, suggesting that the observed benefit could not be fully explained by residual confounding. CONCLUSION: In routine US clinical practice, SGLT2i demonstrated robust clinical effectiveness in older adults with HF and type 2 diabetes compared with sitagliptin, with no evidence of heterogeneity across the SGLT2i class or across ejection fraction.

Association of Prescription Co-payment With Adherence to Glucagon-Like Peptide-1 Receptor Agonist and Sodium-Glucose Cotransporter-2 Inhibitor Therapies in Patients With Heart Failure and Diabetes.

Importance: Type 2 diabetes (T2D) and heart failure (HF) prevalence are rising in the US. Although glucagon-like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve outcomes for these conditions, high out-of-pocket costs may be associated with reduced medication adherence. Objective: To compare 1-year adherence to GLP1-RA and SGLT2i therapies by prescription co-payment level in individuals with T2D and/or HF. Design, Setting, and Participants: This retrospective cohort study used deidentified data from Optum Insight's Clinformatics Data Mart Database of enrollees with commercial and Medicare health insurance plans. Individuals aged 18 years or older with T2D and/or HF who had a prescription claim for a GLP1-RA or SLGT2i from January 1, 2014, to September 30, 2020, were included. Exposures: Prescription co-payment, categorized as low (<$10), medium ($10 to<$50), and high (≥$50). Main Outcomes and Measures: The primary outcome was medication adherence, defined as a proportion of days covered (PDC) of 80% or greater at 1 year. Logistic regression models were used to examine the association between co-payment and adherence, adjusting for patient demographics, medical comorbidities, and socioeconomic factors. Results: A total of 94 610 individuals (mean [SD] age, 61.8 [11.4] years; 51 226 [54.1%] male) were prescribed GLP1-RA or SGLT2i therapy. Overall, 39 149 individuals had a claim for a GLP1-RA, of whom 25 557 (65.3%) had a PDC of 80% or greater at 1 year. In fully adjusted models, individuals with a medium (adjusted odds ratio [AOR], 0.62; 95% CI, 0.58-0.67) or high (AOR, 0.47; 95% CI, 0.44-0.51) co-payment were less likely to have a PDC of 80% or greater with a GLP1-RA compared with those with a low co-payment. Overall, 51 072 individuals had a claim for an SGLT2i, of whom 37 339 (73.1%) had a PDC of 80% or greater at 1 year. Individuals with a medium (AOR, 0.67; 95% CI, 0.63-0.72) or high (AOR, 0.68; 95% CI, 0.63-0.72) co-payment were less likely to have a PDC of 80% or greater with an SGLT2i compared with those with a low co-payment. Conclusions and Relevance: In this cohort study of individuals with T2D and/or HF, 1-year adherence to GLP1-RA or SGLT2i therapies was highest among individuals with a low co-payment. Improving adherence to guideline-based therapies may require interventions that reduce out-of-pocket prescription costs.

Functional assessment based on cardiopulmonary exercise testing in mild heart failure: A multicentre study.

AIMS: In this multicentre study, we compared cardio-pulmonary exercise test (CPET) parameters between heart failure (HF) patients classified as New York Heart Association (NYHA) class I and II to assess NYHA performance and prognostic role in mild HF. METHODS AND RESULTS: We included consecutive HF patients in NYHA class I or II who underwent CPET in three Brazilian centres. We analysed the overlap between kernel density estimations for the per cent-predicted peak oxygen consumption (VO2 ), minute ventilation/carbon dioxide production (VE/VCO2 ) slope, and oxygen uptake efficiency slope (OUES) by NYHA class. Area under the receiver-operating characteristic curve (AUC) was used to assess the capacity of per cent-predicted peak VO2 to discriminate between NYHA class I and II. For prognostication, time to all-cause death was used to produce Kaplan-Meier estimates. Of 688 patients included in this study, 42% were classified as NYHA I and 58% as NYHA II, 55% were men, and mean age was 56 years. Median global per cent-predicted peak VO2 was 66.8% (IQR 56-80), VE/VCO2 slope was 36.9 (31.6-43.3), and mean OUES was 1.51 (±0.59). Kernel density overlap between NYHA class I and II was 86% for per cent-predicted peak VO2 , 89% for VE/VCO2 slope, and 84% for OUES. Receiving-operating curve analysis showed a significant, albeit limited performance of per cent-predicted peak VO2 alone to discriminate between NYHA class I vs. II (AUC 0.55, 95% CI 0.51-0.59, P = 0.005). Model accuracy for probability of being classified as NYHA class I (vs. NYHA class II) across the spectrum of the per cent-predicted peak VO2 was limited, with an absolute probability increment of 13% when per cent-predicted peak VO2 increased from 50% to 100%. Overall mortality in NYHA class I and II was not significantly different (P = 0.41), whereas NYHA class III patients displayed a distinctively higher death rate (P < 0.001). CONCLUSIONS: Patients with chronic HF classified as NYHA I overlapped substantially with those classified as NYHA II in objective physiological measures and prognosis. NYHA classification may represent a poor discriminator of cardiopulmonary capacity in patients with mild HF.

Intersection of atrial fibrillation and heart failure with mildly reduced and preserved ejection fraction in >400 000 participants in the Get With The Guidelines-Heart Failure Registry.

AIMS: Although atrial fibrillation (AF) frequently coexists with heart failure with preserved ejection fraction (HFpEF), few data are available evaluating AF-specific care patterns and post-discharge outcomes in patients hospitalized for HFpEF. We evaluated AF-specific medical therapies and post-discharge outcomes among patients hospitalized for heart failure with mildly reduced ejection fraction (HFmrEF) or HFpEF by AF history. METHODS AND RESULTS: Trends in AF prevalence were evaluated among patients hospitalized for HFmrEF or HFpEF in the Get With The Guidelines-Heart Failure Registry from 2014 to 2020. Among those with linked Centers for Medicare & Medicaid Services post-discharge data, we assessed associations of AF with 12-month outcomes and determined trends in post-discharge prescriptions. Among 429 464 patients (median age 76 years [interquartile range 65-85], 57% women), 216 486 (50%) had a history of AF. Over time, the proportion of patients with AF increased slightly. Among the 79 895 patients with post-discharge data, AF was independently associated with higher risk of mortality and all-cause readmissions at 12 months, with stronger associations in HFpEF than in HFmrEF (mortality hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.09-1.16 vs. HR 1.03, 95% CI 0.97-1.10; pinteraction  = 0.009). Anti-arrhythmic drug use after heart failure hospitalization was low (18%) and increased modestly over time. Amiodarone accounted for 71% of total anti-arrhythmic drug prescriptions. Overall use of anticoagulants after heart failure hospitalization has significantly increased from 52% in 2014 to 61% in 2019, but remained modest. CONCLUSION: Prevalence of AF is rising among patients hospitalized with HFpEF. Those with comorbid AF face elevated post-discharge risks of death and rehospitalization. Current use of pharmacological rhythm control is low.

Risk of Acute Kidney Injury Among Older Adults With Heart Failure and With Reduced Ejection Fraction Treated With Angiotensin-Neprilysin Inhibitor vs Renin-Angiotensin System Inhibitor in Routine Clinical Care.

BACKGROUND: The acute hemodynamic effects of sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor (ARNI), may result in early changes in kidney function, raising concerns about acute kidney injury (AKI), particularly in those who are naïve to renin-angiotensin system inhibitors (RASis). METHODS: We conducted a cohort study using U.S. Medicare fee-for-service claims data (2014-2017). Patients with HFrEF ≥ 65 years newly initiating ARNI or RASi, with no prior use of either drug class, were included. The primary outcome was hospitalization due to AKI as the primary discharge diagnosis, and the secondary outcome included AKI as a primary or secondary discharge diagnosis. AKI risks were described under an as-treated follow-up approach, with censoring on treatment discontinuation, switch, insurance disenrollment, death, or administrative censoring as well as an intent-to-treat approach. Propensity-score-based fine-stratification weighting was used to account for potential confounding by 81 pre-exposure characteristics. Cumulative incidence functions were used to report absolute risks, and Cox proportional hazards models were used to provide hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: We included 27,166 patients with a mean (SD) age of 73 (7.3) years, and 4155 (15.3%) were initiating ARNI. After propensity score weighting, the 180-day cumulative incidence was 2.7% (2.4%-3.1%) among RASi initiators and 2.7% (2.2%-3.5%) among ARNI initiators for the primary outcome, and it was 6.5% (6.0%-7.1%) and 6.1% (5.2%-7.1%), respectively, for the secondary outcome under as-treated follow-up. HR (95% CI) comparing ARNI with RASi were 0.91 (95% CI: 0.72-1.16) for the primary outcome and 0.92 (95% CI: 0.79-1.08) for the secondary outcome. Similar results were observed in the intent-to-treat analysis. CONCLUSIONS: Among a large cohort of U.S. Medicare beneficiaries with HFrEF, ARNI treatment was not associated with higher rates of AKI than RASi treatment. These results provide reassurance for providers considering ARNI initiation in older patients who are RASi-naïve.

Diabetes Care Among Older Adults Enrolled in Medicare Advantage Versus Traditional Medicare Fee-For-Service Plans: The Diabetes Collaborative Registry.

OBJECTIVE: Medicare Advantage (MA), Medicare's managed care program, is quickly expanding, yet little is known about diabetes care quality delivered under MA compared with traditional fee-for-service (FFS) Medicare. RESEARCH DESIGN AND METHODS: This was a retrospective cohort study of Medicare beneficiaries ≥65 years old enrolled in the Diabetes Collaborative Registry from 2014 to 2019 with type 2 diabetes treated with one or more antihyperglycemic therapies. Quality measures, cardiometabolic risk factor control, and antihyperglycemic prescription patterns were compared between Medicare plan groups, adjusted for sociodemographic and clinical factors. RESULTS: Among 345,911 Medicare beneficiaries, 229,598 (66%) were enrolled in FFS and 116,313 (34%) in MA plans (for ≥1 month). MA beneficiaries were more likely to receive ACE inhibitors/angiotensin receptor blockers for coronary artery disease, tobacco cessation counseling, and screening for retinopathy, foot care, and kidney disease (adjusted P ≤ 0.001 for all). MA beneficiaries had modestly but significantly higher systolic blood pressure (+0.2 mmHg), LDL cholesterol (+2.6 mg/dL), and HbA1c (+0.1%) (adjusted P < 0.01 for all). MA beneficiaries were independently less likely to receive glucagon-like peptide 1 receptor agonists (6.9% vs. 9.0%; adjusted odds ratio 0.80, 95% CI 0.77-0.84) and sodium-glucose cotransporter 2 inhibitors (5.4% vs. 6.7%; adjusted odds ratio 0.91, 95% CI 0.87-0.95). When integrating Centers for Medicare and Medicaid Services-linked data from 2014 to 2017 and more recent unlinked data from the Diabetes Collaborative Registry through 2019 (total N = 411,465), these therapeutic differences persisted, including among subgroups with established cardiovascular and kidney disease. CONCLUSIONS: While MA plans enable greater access to preventive care, this may not translate to improved intermediate health outcomes. MA beneficiaries are also less likely to receive newer antihyperglycemic therapies with proven outcome benefits in high-risk individuals. Long-term health outcomes under various Medicare plans requires surveillance.

Sacubitril/valsartan use patterns among older adults with heart failure in clinical practice: a population-based cohort study of >25 000 Medicare beneficiaries.

AIMS: Sacubitril/valsartan is strongly supported in guidelines for the management of heart failure, but suboptimal adherence and treatment non-persistence may limit the population-level benefit that this therapy might otherwise offer. METHODS AND RESULTS: We identified a cohort of Medicare beneficiaries (2014-2017) initiating sacubitril/valsartan after ≥6 months of continuous enrolment. We assessed adherence as the proportion of days covered (PDC) and proportion of patients non-persistent (having no prescription available) at 180 days after initiation. We fit a multivariable negative binomial model with a count of adherent days to evaluate independent factors associated with of sacubitril/valsartan adherence. Among 27 063 new sacubitril/valsartan users, most (n = 17 663, 65%) were prescribed low-dose at 24 mg/26 mg and most (n = 19 984, 74%) were switched from prior angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB) rather than being RASi treatment naïve. Median 180-day PDC was 86% (25th-75th percentiles 58-98%). Black patients, those with high comorbid disease burden (≥8 comorbidities), and patients with recent hospitalization within 30 days had fewer adherent days, while those treated with preceding ACEi/ARB had more adherent days. Thirty-four percent of patients did not have an active sacubitril/valsartan prescription at day 180. Among these, few had preceding dose down-titrations (6% among patients on 49 mg/51 mg and 9% among patients on 97 mg/103 mg) and 68% did not have a subsequent ACEi/ARB prescription. Among patients who remained persistent, dose up-titrations occurred in 29% of patients who started on 24 mg/26 mg and 27% of patients on 49 mg/51 mg. CONCLUSIONS: Overall adherence to sacubitril/valsartan among Medicare beneficiaries is acceptable, but is lower in Black patients, those with higher comorbidities or those who started therapy after recent hospitalization. While broad implementation of guideline-directed medical therapy is a key priority, additional focused efforts to improve adherence early after hospitalization and among at-risk patients are needed in parallel.

Contemporary Trends in the Use of and Expenditures on Digoxin in the United States.

BACKGROUND: Digoxin is indicated for the management of heart failure with reduced ejection fraction and atrial fibrillation. Despite stronger guideline recommendations for other pharmacologic and device therapies, digoxin retains a role in select patients unable to tolerate or refractory to standard therapies. Contemporary utilization of and costs related to digoxin in the United States of America (USA) remain uncharacterized. The objective of this study was to estimate trends in digoxin use and expenditures across the USA from 2010 to 2017. METHODS: We utilized the Medical Expenditure Panel Survey to estimate trends in digoxin use and expenditures across the USA from 2010 to 2017. The Medical Expenditure Panel Survey is an overlapping panel survey that interviews households in the USA to ascertain their healthcare utilization and expenditures. Complex sampling procedures allow for nationally representative estimates of utilization and expenditures. We report the number of digoxin users and expenditures across key subgroups in 2-year increments from 2010 to 2017. RESULTS: The number of digoxin users in the USA declined by 47% from 766 users per 100,000 adults in 2010-11 to 402 users per 100,000 adults in 2016-17. While digoxin use declined among women and self-identified White adults, adults living at or below the federal poverty level and those who self-identified as Asian or Hispanic represent an increasing proportion of overall digoxin users. While nationwide digoxin expenditures declined by 26% from 2010-11 to 2012-13, they peaked at $260.3 million in 2014-15 and remained elevated at $188.7 million in 2016-17. CONCLUSIONS: Despite a nationwide trend towards declining use, digoxin remains prevalent amongst people of Asian and Hispanic descent in the USA. After a spike in cost in 2013, digoxin prices have yet to return to pre-spike levels. The role of digoxin in contemporary heart failure and arrhythmia management will continue to evolve as additional randomized and observational analyses become available.

Rates of Spironolactone Initiation and Subsequent Hyperkalemia Hospitalizations in Patients with Heart Failure with Preserved Ejection Fraction Following the TOPCAT trial: A Cohort Study of Medicare Beneficiaries.

BACKGROUND: The impact of the TOPCAT trial publication on spironolactone initiation and subsequent hospitalizations for hyperkalemia among patients with heart failure with preserved ejection fraction (HFpEF) has not been evaluated empirically. METHODS AND RESULTS: We designed a cohort study using US Medicare fee-for-service data. Annual cohorts of patients with HFpEF from 2013 to 2018 were identified based on a validated claims-based phenotyping model. We determined spironolactone initiation in each annual cohort overall and within subgroups with hyperkalemia risk factors of baseline renin-angiotensin system inhibitors use, chronic kidney disease, and diabetes. We reported incidence rates of hospitalization for hyperkalemia within 6 months of treatment initiation. A total of 621,171 patients with HFpEF (mean age 80 ± 8 years, 62.9% female) were included. We identified 40,241 initiations of spironolactone with initiation rate/100 person-years of 16.8 (95% confidence interval [CI] 16.4-17.1) in 2013 and increasing to 19.9 (95% CI 19.4-20.5) in 2018. Among initiators, we identified a total of 164 hyperkalemia hospitalization with stable incidence rates per 1000 person-years between 2013 (12.0, 95% CI 8.8-16.1) and 2018 (10.6, 95% CI 6.2-17.0). These results were consistent for all subgroups. CONCLUSIONS: After the dissemination of TOPCAT findings, we noted a steady increase in the initiation of spironolactone, but not in hyperkalemia hospitalizations.

Association of readmission penalty amount with subsequent 30-day risk standardized readmission and mortality rates among patients hospitalized with heart failure: An analysis of get with the guidelines - heart failure participating centers.

BACKGROUND: The Hospital Readmissions Reduction Program penalizes hospitals with excess 30-day risk-standardized readmission rates (RSRR) for heart failure (HF). The association of financial penalty amount with subsequent short-term clinical outcomes is unknown. METHODS: Patients admitted to American Heart Association Get With The Guidelines-HF registry participating centers from October 1, 2012 through December 1, 2015 who had Medicare-linked data were included. October 2012 hospital-specific penalty amounts were calculated based on diagnosis-related group payments and excess readmission ratios. Adjusted Cox models were created to evaluate the association of penalty amount categories (non-penalized: 0%; low-penalized: >0%-<0.50%; mid-penalized ≥0.50%-<0.99%; high-penalized ≥0.99%) with subsequent 30-day RSRR and risk-standardized mortality rates (RSMR). Trends in post-discharge 30-day RSRR and RSMR from 2012 to 2015 were analyzed across hospitals stratified by penalty amount categories. RESULTS: The present study included 61,329 patients who were admitted across 262 hospitals. Compared with patients admitted to non-penalized hospitals (36.3%), those admitted to increasingly penalized hospitals were more likely to have higher 30-day RSRR (low-penalized [43.9%]: HR, 1.10 [95% CI, 1.04-1.16]; mid-penalized [12.0%]: HR, 1.07 [95% CI, 0.99-1.16]; high-penalized [7.9%]: HR, 1.23 [95% CI, 1.12-1.35]) but not 30-day RSMR. Over time, 30-day RSRR and RSMR did not meaningfully change across penalized versus non-penalized hospitals. CONCLUSIONS: Financial penalties based on 30-day RSRR are not associated with declines in 30-day RSRR or RSMR from 2012 to 2015 among patients hospitalized with HF. Financially penalizing hospitals based on current Hospital Readmissions Reduction Program metrics may not incentivize improvements in short-term clinical outcomes for HF.

Projected Clinical Benefits of Implementation of SGLT-2 Inhibitors Among Medicare Beneficiaries Hospitalized for Heart Failure.

BACKGROUND: The sodium-glucose cotransporter-2 (SGLT-2) inhibitors form the latest pillar in the management of heart failure with reduced ejection fraction (HFrEF) and appear to be effective across a range of patient profiles. There is increasing interest in initiating SGLT-2 inhibitors during hospitalization, yet little is known about the putative benefits of this implementation strategy. METHODS: We evaluated Medicare beneficiaries with HFrEF (≤ 40%) hospitalized at 228 sites in the Get With The Guidelines-Heart Failure (GWTG-HF) registry in 2016 who had linked claims data for ≥ 1 year postdischarge. We identified those eligible for dapagliflozin under the latest U.S. Food and Drug Administration label (excluding estimated glomerular filtration rates < 25 mL/min per 1.73 m2, dialysis and type 1 diabetes). We evaluated 1-year outcomes overall and among key subgroups (age ≥ 75 years, gender, race, hospital region, kidney function, diabetes status, triple therapy). We then projected the potential benefits of implementation of dapagliflozin based on the risk reductions observed in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial. RESULTS: Among 7523 patients hospitalized for HFrEF, 6576 (87%) would be candidates for dapagliflozin (mean age 79 ± 8 years, 39% women, 11% Black). Among eligible candidates, discharge use of ß-blockers, ACEi/ARB, MRA, ARNI, and triple therapy (ACEi/ARB/ARNI+ß-blocker+MRA) was recorded in 88%, 64%, 29%, 3%, and 20%, respectively. Among treatment-eligible patients, the 1-year incidence (95% CI) of mortality was 37% (36-38%) and of HF readmission was 33% (32-34%), and each exceeded 25% across all key subgroups. Among 1333 beneficiaries eligible for dapagliflozin who were already on triple therapy, the 1-year incidence of mortality was 26% (24%-29%) and the 1-year readmission due to HF was 30% (27%-32%). Applying the relative risk reductions observed in DAPA-HF, absolute risk reductions with complete implementation of dapagliflozin among treatment-eligible Medicare beneficiaries are projected to be 5% (1%-9%) for mortality and 9% (5%-12%) for HF readmission by 1 year. The projected number of Medicare beneficiaries who would need to be treated for 1 year to prevent 1 death is 19 (11-114), and 12 (8-21) would need to be treated to prevent 1 readmission due to HF. CONCLUSIONS: Medicare beneficiaries with HFrEF who are eligible for dapagliflozin after hospitalization due to HF, including those well-treated with other disease-modifying therapies, face high risks of mortality and HF readmission by 1 year. If the benefits of reductions in death and hospitalizations due to HF observed in clinical trials can be fully realized, the absolute benefits of implementation of SGLT-2 inhibitors among treatment-eligible candidates are anticipated to be substantial in this high-risk postdischarge setting.

Cost and Value in Contemporary Heart Failure Clinical Guidance Documents.

OBJECTIVES: This study sought to evaluate the frequency and nature of cost/value statements in contemporary heart failure (HF) clinical guidance documents (CGDs). BACKGROUND: In an era of rising health care costs and expanding therapeutic options, there is an increasing need for formal consideration of cost and value in the development of HF CGDs. METHODS: HF CGDs published by major professional cardiovascular organizations between January 2010 and February 2021 were reviewed for the inclusion of cost/value statements. RESULTS: Overall, 33 documents were identified, including 5 (15%) appropriate use criteria, 7 (21%) clinical practice guidelines, and 21 (64%) expert consensus documents. Most CGDs (27 of 33; 82%) included at least 1 cost/value statement, and 20 (61%) CGDs included at least 1 cost/value-related citation. Most of these statements were found in expert consensus documents (77.7%). Three (9%) documents reported estimated costs of recommended interventions, but only 1 estimated out-of-pocket cost. Of 179 cost/value-related statements observed, 116 (64.8%) highlighted the economic impact of HF or HF-related care, 6 (3.4%) advocated for cost/value issues, 15 (8.4%) reported gaps in cost/value evidence, and 42 (23.5%) supported clinical guidance recommendations. Over time, patterns of inclusion of statements and citations of cost/value have been largely stable. CONCLUSIONS: Although most contemporary HF CGDs contain at least 1 cost/value statement, most CGDs focus on the high economic impact of HF and its related care; explicit inclusion of cost/value to support clinical guidance recommendations remains infrequent. These results highlight key opportunities for the integration of formalized cost/value considerations in future HF-focused CGDs.