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

Cardio-Renal-Metabolic Overlap, Outcomes, and Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction

Background: Cardio-renal-metabolic (CRM) conditions are individually common among patients with heart failure (HF), but the prevalence and influence of overlapping CRM conditions in this population have not been well-studied. Objectives: This study aims to evaluate the impact of overlapping CRM conditions on clinical outcomes and treatment effects of dapagliflozin in HF. Methods: In this post hoc analysis of DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure), we evaluated the prevalence of comorbid CRM conditions (atherosclerotic cardiovascular disease, chronic kidney disease, and type 2 diabetes), their impact on the primary outcome (cardiovascular death or worsening HF), and treatment effects of dapagliflozin by CRM status. Results: Among 6,263 participants, 1,952 (31%), 2,245 (36%), and 1,236 (20%) had 1, 2, and 3 additional CRM conditions, respectively. HF alone was uncommon (13%). Greater CRM multimorbidity was associated with older age, higher body mass index, longer-duration HF, worse health status, and lower left ventricular ejection fraction. Risk of the primary outcome increased with higher CRM overlap, with 3 CRM conditions independently associated with highest risk of primary events (adjusted HR: 2.16 [95% CI: 1.72-2.72]; P &lt; 0.001) compared with HF alone. Relative benefits of dapagliflozin on the primary outcome were consistent irrespective of the type of CRM overlap (Pinteraction = 0.773) and by the number of CRM conditions (Pinteraction = 0.734), with greatest absolute benefits among those with highest CRM multimorbidity. Estimated 2-year numbers needed to treat with dapagliflozin to prevent 1 primary event were approximately 52, 39, 33, and 24 for participants with 0, 1, 2, and 3 additional CRM conditions at baseline, respectively. Adverse events between treatment arms were similar across the CRM spectrum. Conclusions: CRM multimorbidity was common and associated with adverse outcomes among patients with HF and left ventricular ejection fraction &gt;40% in DELIVER. Dapagliflozin was safe and effective across the CRM spectrum, with greater absolute benefits among those with highest CRM overlap (Dapagliflozin Evaluation to Improve the LIVEs of Patients With Preserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213).</p

Cardiovascular-kidney-metabolic overlap in heart failure with mildly reduced or preserved ejection fraction a trial-level analysis

No abstract available

Effect of dapagliflozin in patients with diabetes and heart failure with mildly reduced or preserved ejection fraction according to background glucose‐lowering therapy: a pre‐specified analysis of the DELIVER trial

Aims: Type 2 diabetes (T2D) and heart failure (HF) frequently coexist, but whether clinical outcomes and treatment effects of sodium–glucose cotransporter 2 inhibitors (SGLT2i) vary in relation to background glucose-lowering therapy (GLT) in this population is uncertain. Methods and results: DELIVER randomized patients with HF and left ventricular ejection fraction (LVEF) &gt;40% to dapagliflozin or placebo. The primary outcome was a composite of worsening HF (HF hospitalization or urgent HF visit) or cardiovascular death. In this pre-specified analysis of participants with T2D, treatment effects were assessed by number and class of background GLT(s). Of 3150 participants with T2D at baseline, 22.9% were on no GLT, 36.5% were treated with 1 GLT, and 40.6% with ≥2 GLTs. During follow-up (median: 2.3 years), treatment benefits of dapagliflozin (vs. placebo) on the primary outcome were consistent irrespective of the number of background GLTs (0 GLTs: hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.50–1.00; 1 GLT: HR 1.04, 95% CI 0.80–1.34; ≥2 GLTs: HR 0.71, 95% CI 0.56–0.90; pinteraction = 0.59). Similar findings were observed among participants with (HR 0.73, 95% CI 0.59–0.92) and without background metformin use (HR 0.89, 95% CI 0.72–1.11; pinteraction = 0.22) and in participants with (HR 0.89, 95% CI 0.69–1.16) and without background insulin use (HR 0.78, 95% CI 0.65–0.95; pinteraction = 0.45). Dapagliflozin was well-tolerated irrespective of the number of background GLTs. Conclusions: Dapagliflozin safely and consistently improved clinical outcomes among individuals with T2D and HF with LVEF &gt;40% irrespective of the number and class of background GLTs, and the benefits were not influenced by concomitant metformin or insulin use. These data bolster contemporary guidelines supporting first-line SGLT2i among individuals with T2D and HF, irrespective of background GLT

Duration of heart failure with preserved ejection fraction and outcomes with sacubitril/valsartan: insights from the PARAGON-HF trial

Objective: In this post hoc analysis of the PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF) trial, we evaluated clinical outcomes and responses to sacubitril/valsartan by duration of heart failure (HF) with left ventricular ejection fraction ≥ 45% at initial diagnosis. Methods and Results: The primary outcome was a composite of total hospitalizations due to HF and cardiovascular deaths, analyzed by using a semiparametric proportional rates method, stratified by geographic region. Among 4784 (99.7%) randomized participants in the PARAGON-HF trial for whom baseline HF duration was captured, 1359 (28%) had durations of HF of &lt; 6 months, 1295 (27%) of 6 months–2 years, and 2130 (45%) of &gt; 2 years. Longer HF duration was associated with higher comorbidity burdens, worse health status and lower rates of prior hospitalization due to HF. Over a median follow-up of 35 months, longer HF duration was associated with a higher risk of first and recurrent primary events (per 100 patient-years): &lt; 6 months, 12.0 (95% CI, 10.4–14.0); 6 months–2 years, 12.2 (10.6–14.2); &gt; 2 years, 15.8 (14.2–17.5). Relative treatment effects of sacubitril/valsartan vs valsartan were consistent, irrespective of baseline HF duration on the primary endpoint (Pinteraction = 0.112). Clinically meaningful (≥ 5 point) improvements in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Scores were also similarly observed, irrespective of HF duration; (Pinteraction = 0.112). Adverse events were similar between treatment arms across HF duration categories. Conclusions: In PARAGON-HF, longer HF duration was independently predictive of adverse HF outcomes. Treatment effects of sacubitril/valsartan were consistent, irrespective of baseline HF duration, suggesting that even ambulatory patients with longstanding HFpEF and predominantly mild symptoms stand to benefit from treatment optimization

Cardiovascular‐kidney‐metabolic overlap in heart failure with preserved ejection fraction: Cardiac structure and function, clinical outcomes, and response to sacubitril/valsartan in PARAGON‐HF

Aims: Cardiovascular-kidney-metabolic (CKM) multimorbidity is prevalent among individuals with heart failure (HF), but whether cardiac structure and function, clinical outcomes, and treatment response to sacubitril/valsartan vary in relation to CKM status is unknown. Methods and results: In this PARAGON-HF post-hoc analysis, we evaluated the impact of CKM multimorbidity (atherosclerotic cardiovascular [CV] disease, chronic kidney disease, and type 2 diabetes) on cardiac structure and function, clinical outcomes, and treatment effects of sacubitril/valsartan versus valsartan. The primary outcome was a composite of total HF hospitalizations and CV death. Secondary outcomes included the individual components of the primary outcome and a composite kidney outcome (sustained estimated glomerular filtration rate reduction of ≥50%, end-stage kidney disease, or kidney-related death). At baseline, 35.2% had one CKM condition, 33.3% had two, 15.9% had three, and only 15.6% had HF alone. CKM multimorbidity was associated with higher septal and posterior wall thickness, lower global longitudinal strain, higher E/e', and worse right ventricular function. Total HF hospitalizations or CV death increased with greater CKM multimorbidity, with the highest relative risk observed with three CKM conditions (rate ratio 3.06, 95% confidence interval 2.33–4.03), compared with HF alone. Treatment effects of sacubitril/valsartan were consistent irrespective of the number of CKM conditions for the primary endpoint (pinteraction = 0.75), CV death (pinteraction = 0.82), total HF hospitalizations (pinteraction = 0.67), and the composite kidney endpoint (pinteraction = 0.99). Conclusions: Cardiovascular-kidney-metabolic multimorbidity was common in PARAGON-HF and associated with adverse changes in cardiac structure and function and with a stepwise increase in risk of clinical outcomes. Treatment effects of sacubitril/valsartan were consistent irrespective of CKM burden. Clinical Trial Registration: ClinicalTrials.gov NCT01920711

Dapagliflozin and Apparent Treatment-Resistant Hypertension in Heart Failure With Mildly Reduced or Preserved Ejection Fraction:The DELIVER Trial

BACKGROUND: Apparent treatment-resistant hypertension (aTRH) is prevalent and associated with adverse outcomes in heart failure with mildly reduced or preserved ejection fraction. Less is known about the potential role of sodium-glucose cotransporter 2 inhibition in this high-risk population. In this post hoc analysis of the DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure), we evaluated clinical profiles and treatment effects of dapagliflozin among participants with aTRH. METHODS: DELIVER participants were categorized on the basis of baseline blood pressure (BP), with aTRH defined as BP ≥140/90 mm Hg (≥130/80 mm Hg if diabetes) despite treatment with 3 antihypertensive drugs including a diuretic. Nonresistant hypertension was defined as BP above threshold but not meeting aTRH criteria. Controlled BP was defined as BP under threshold. Incidence of the primary outcome (cardiovascular death or worsening heart failure event), key secondary outcomes, and safety events was assessed by baseline BP category. RESULTS: Among 6263 DELIVER participants, 3766 (60.1%) had controlled BP, 1779 (28.4%) had nonresistant hypertension, and 718 (11.5%) had aTRH at baseline. Participants with aTRH had more cardiometabolic comorbidities and tended to have higher left ventricular ejection fraction and worse kidney function. Rates of the primary outcome were 8.7 per 100 patientyears in those with controlled BP, 8.5 per 100 patient-years in the nonresistant hypertension group, and 9.5 per 100 patientyears in the aTRH group. Relative treatment benefits of dapagliflozin versus placebo on the primary outcome were consistent across BP categories (Pinteraction=0.114). Participants with aTRH exhibited the greatest absolute reduction in the rate of primary events with dapagliflozin (4.1 per 100 patient-years) compared with nonresistant hypertension (2.7 per 100 patient-years) and controlled BP (0.8 per 100 patient-years). Irrespective of assigned treatment, participants with aTRH experienced a higher rate of reported vascular events, including myocardial infarction and stroke, over study follow-up. Dapagliflozin modestly reduced systolic BP (by ≈1 to 3 mm Hg) without increasing risk of hypotension, hypovolemia, or other serious adverse events, irrespective of BP category, but did not improve the proportion of participants with aTRH attaining goal BP over time. CONCLUSIONS: aTRH was identified in &gt;1 in 10 patients with heart failure and left ventricular ejection fraction &gt;40% in DELIVER. Dapagliflozin consistently improved clinical outcomes and was well-tolerated, including among those with aTRH.</p