Background Heart failure presents a growing clinical and economic burden in the USA. Robust cost data on the burden of illness are critical to inform economic evaluations of new therapeutic interventions. Objectives This systematic literature review of heart failure-related costs in the USA aimed to assess the quality of the published evidence and provide a narrative synthesis of current data. Methods Four electronic databases (MEDLINE, EMBASE, EconLit, and the Centre for Reviews and Dissemination York Database, including the NHS Economic Evaluation Database and Health Technology Assessment Database) were searched for journal articles published between January 2014 and March 2020. The review, registered with PROSPERO (CRD42019134201), was restricted to cost-of-illness studies in adults with heart failure events in the USA. Results Eighty-seven studies were included, 41 of which allowed a comparison of cost estimates across studies. The annual median total medical costs for heart failure care were estimated at $24,383 per patient, with heart failure-specific hospitalizations driving costs (median $15,879 per patient). Analyses of subgroups revealed that heart failure-related costs are highly sensitive to individual patient characteristics (such as the presence of comorbidities and age) with large variations even within a subgroup. Additionally, differences in study design and a lack of standardized reporting limited the ability to compare cost estimates. The finding that costs are higher for patients with heart failure with reduced ejection fraction compared with patients with preserved ejection fraction highlights the need for differentiating among different heart failure types. Conclusions The review underpins the conclusion drawn in earlier reviews, namely that hospitalization costs are the key driver of heart failure-related costs. Analyses of subgroups provide a clearer understanding of sources of heterogeneity in cost data. While current cost estimates provide useful indications of economic burden, understanding the nuances of the data is critical to support its application.

Discrete choice experiments (DCEs) are economic tools that elicit the stated preferences of respondents. Because of their increasing importance in informing the design of health products and services, it is critical to understand the extent to which DCEs give reliable predictions outside of the experimental context. We systematically reviewed the literature of published DCE studies comparing predictions to choices made in reality; we extracted individual-level data to estimate a bivariate mixed-effects model of pooled sensitivity and specificity. Eight studies met the inclusion criteria, and six of these gave sufficient data for inclusion in a meta-analysis. Pooled sensitivity and specificity estimates were 88% (95% CI 81, 92%) and 34% (95% CI 23, 46%), respectively, and the area under the SROC curve (AUC) was 0.60 (95% CI 0.55, 0.64). Results indicate that DCEs can produce reasonable predictions of health-related behaviors. There is a great need for future research on the external validity of DCEs, particularly empirical studies assessing predicted and revealed preferences of a representative sample of participants.

Summary. Background: Anticoagulation management of patients with atrial fibrillation (AF) should be tailored individually on the basis of ischemic stroke risk. The objective of this study was to compare the predictive ability of 15 published stratification schemes for stroke risk in actual clinical practice in the UK. Methods: AF patients aged ≥ 18 years in the General Practice Research Database, which contains computerized medical records, were included. The c‐statistic was estimated to determine the predictive ability for stroke for each scheme. Outcomes included stroke, hospitalizations for stroke, and death resulting from stroke (as recorded on death certificates). Results: The study cohort included 79 844 AF patients followed for an average of 4 years (average of 2.4 years up to the start of warfarin therapy). All risk schemes had modest discriminatory ability in AF patients, with c‐statistics for predicting events ranging from 0.55 to 0.69 for strokes recorded by the general practitioner or in hospital, from 0.56 to 0.69 for stroke hospitalizations, and from 0.56 to 0.78 for death resulting from stroke as reported on death certificates. The proportion of patients assigned to individual risk categories varied widely across the schemes, with the proportion categorized as moderate risk ranging from 12.7% (CHA₂DS₂‐VASc) to 61.5% (modified CHADS₂). Low‐risk subjects were truly low risk (with annual stroke events < 0.5%) with the modified CHADS₂, National Institute for Health and Clinical Excellence and CHA₂DS₂‐VASc schemes. Conclusion: Current published risk schemes have modest predictive value for stroke. A new scheme (CHA₂DS₂‐VASc) may discriminate those at truly low risk and minimize classification of subjects as intermediate/moderate risk. This approach would simplify our approach to stroke risk stratification and improve decision‐making for thromboprophylaxis in patients with AF.

Significance Statement: The CREDENCE randomized trial demonstrated that canagliflozin reduces risk of cardiovascular and renal events in people with type 2 diabetes and substantial albuminuria. The authors analyzed CREDENCE data to assess whether canagliflozin’s benefits are safely preserved in people with reduced eGFR, finding that the relative benefits for renal and cardiovascular outcomes appeared consistent among subgroups with initial eGFR ranging from 30 to <90 ml/min per 1.73 m². Absolute benefit for renal outcomes was greater in subgroups with an initial eGFR of <60 ml/min per 1.73 m². Safety outcomes were generally consistent among eGFR subgroups. Canagliflozin led to an acute eGFR drop, followed by relative stabilization of eGFR loss across subgroups. Canagliflozin’s benefits and safety are apparent across the eGFR range, including among those initiating treatment with eGFR as low as 30 ml/min per 1.73 m². Background: Canagliflozin reduced renal and cardiovascular events in people with type 2 diabetes in the CREDENCE trial. We assessed efficacy and safety of canagliflozin by initial estimated glomerular filtration rate (eGFR). Methods: CREDENCE randomly assigned 4401 participants with an eGFR of 30 to <90 ml/min per 1.73 m² and substantial albuminuria to canagliflozin 100 mg or placebo. We used Cox proportional hazards regression to analyze effects on renal and cardiovascular efficacy and safety outcomes within screening eGFR subgroups (30 to <45, 45 to <60, and 60 to <90 ml/min per 1.73 m²) and linear mixed effects models to analyze the effects on eGFR slope. Results: At screening, 1313 (30%), 1279 (29%), and 1809 (41%) participants had an eGFR of 30 to <45, 45 to <60, and 60 to 0.11). Subgroups with lower eGFRs, who were at greater risk, exhibited larger absolute benefits for renal outcomes. Canagliflozin’s lack of effect on serious adverse events, amputations, and fractures appeared consistent among eGFR subgroups. In all subgroups, canagliflozin use led to an acute eGFR drop followed by relative stabilization of eGFR loss. Among those with an eGFR of 30 to <45 ml/min per 1.73 m², canagliflozin led to an initial drop of 2.03 ml/min per 1.73 m². Thereafter, decline in eGFR was slower in the canagliflozin versus placebo group (–1.72 versus –4.33 ml/min per 1.73 m²; between-group difference 2.61 ml/min per 1.73 m²). Conclusions: Canagliflozin safely reduced the risk of renal and cardiovascular events, with consistent results across eGFR subgroups, including the subgroup initiating treatment with an eGFR of 30 to <45 ml/min per 1.73 m². Absolute benefits for renal outcomes were greatest in subgroups with lower eGFR. Clinical Trial registry name and registration number: Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (CREDENCE), NCT02065791.