Eligibility and Cost-Utility Analysis of Dapagliflozin in Patients with Heart Failure Across the Whole Spectrum of Ejection Fraction in South Korea.

BACKGROUND: The DAPA-HF and DELIVER trials demonstrated the clinical benefits of dapagliflozin in heart failure (HF) patients across the entire ejection fraction (EF) spectrum. However, further investigation is needed for the real-world application of dapagliflozin in HF patients. This study examines the proportion of real-world HF patients eligible for dapagliflozin and evaluates the cost-effectiveness of adding dapagliflozin to current HF therapy. METHODS: Data from the nationwide prospective registry, the Korean Acute Heart Failure (KorAHF) registry, were used to determine dapagliflozin eligibility based on the enrollment criteria of the DAPA-HF/DELIVER trials. A cost-utility analysis was conducted using a Markov model to assess the cost-effectiveness of dapagliflozin by comparing it to the standard of care. RESULTS: Out of 5178 KorAHF patients, 48.7% met the enrollment criteria of the DAPA-HF/DELIVER trials, while 89.5% met the label criteria (US Food and Drug Administration, European Medicines Agency, and Korean Ministry of Food and Drug Safety). Eligibility was highest among HF patients with preserved EF (55.3% vs. HF with mildly reduced EF and HF with reduced EF 46.4%). Dapagliflozin proved to be cost-effective, with an incremental cost-effectiveness ratio (ICER) of 4557 US dollar (US$) per quality-adjusted life year, which falls below the US$18,182 willingness-to-pay threshold. The cost-effectiveness benefit was more pronounced in patients with a left ventricular EF (LVEF) ≤ 40% (ICER US$3279 for LVEF ≤ 40% vs. US$8383 for LVEF > 40%). CONCLUSIONS: Discrepancies in dapagliflozin eligibility were observed between real-world data and clinical trial results. The addition of dapagliflozin to HF therapy proved to be highly cost-effective across the entire EF spectrum.

Real-World Eligibility and Cost-Effectiveness Analysis of Empagliflozin for Heart Failure in Korea.

BACKGROUND: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. METHODS: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). RESULTS: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). CONCLUSION: There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01389843.

Economic Burden of Heart Failure in Asian Countries with Different Healthcare Systems.

BACKGROUND AND OBJECTIVES: Heart failure (HF) poses substantial economic burden, primarily driven by high hospitalization and mortality rates. This study aimed to understand the economic burden of HF in 4 Asian countries under varying healthcare systems. METHODS: This was a non-interventional, retrospective study conducted in South Korea, Taiwan, Thailand and Malaysia through medical chart review. Eligible patients included those who had either ≥1 hospitalization or ≥2 outpatient visits from January 1st to December 31st, 2014, and at least one year of follow-up. Resource use and direct healthcare costs (adjusted to 2015 USD) of HF were assessed. HF costs for subgroups stratified by age and sex were assessed. RESULTS: A total of 568 patients were recruited from South Korea (n=200), Taiwan (n=200), Thailand (n=100) and Malaysia (n=68). The proportion of patients hospitalized ranged from 20.0% to 93.5% (South Korea 20.0%, Thailand 49.0%, Malaysia 70.6%, and Taiwan 93.5%). The overall annual HF cost per patient was $2,357, $4,513, $3,513 and $1,443 in South Korea, Taiwan, Thailand, and Malaysia, respectively; hospitalized HF care costs were $10,714, $4,790, $7,181 and $1,776, respectively. The length of stay was more than 12.2 days except in Malaysia. No specific trend was observed in subgroup analysis. CONCLUSIONS: In Asia, HF poses significant economic burden and hospitalization has emerged as the major cost driver among healthcare costs. A streamlined treatment strategy reducing hospitalization rate can minimize the economic burden.

Heart failure awareness in the Korean general population: Results from the nationwide survey.

BACKGROUND: For a better heart failure outcome, it is fundamental to improve the awareness of heart failure at the general population level. We conducted this study to identify the current status of awareness of heart failure in the Korean general population. METHODS: This cross-sectional nationwide survey recruited a total of 1,032 participants aged 30 years or older, based on a stratification systematic sampling method. A 23-item questionnaire was surveyed through telephone interviews. RESULTS: Although 80% of the participants had heard of heart failure, 47% exactly defined what heart failure is. A minority of participants correctly recognized the lifetime risk of developing heart failure (21%) as well as the mortality (16%) and readmission risk (18%) of heart failure and the cost burden of heart failure admission (28%). Regarding preferred treatment options, 71% of the participants chose a treatment option that could improve the quality of life. Approximately two-thirds of the participants agreed that current medical treatment could reduce mortality and improve the quality of life. More than half of the participants (59%) thought that heart failure patients should live quietly and reduce all physical activities. Across survey items, we found a lower awareness state in the elderly groups and people at lower income and educational levels. CONCLUSIONS: The current awareness status of heart failure in the Korean general population is still low. Proactive educational efforts should be made to improve public awareness with special attention to individuals with lower disease awareness.

KSHF Guidelines for the Management of Acute Heart Failure: Part I. Definition, Epidemiology and Diagnosis of Acute Heart Failure.

The prevalence of heart failure (HF) is on the rise due to the aging of society. Furthermore, the continuous progress and widespread adoption of screening and diagnostic strategies have led to an increase in the detection rate of HF, effectively increasing the number of patients requiring monitoring and treatment. Because HF is associated with substantial rates of mortality and morbidity, as well as high socioeconomic burden, there is an increasing need for developing specific guidelines for HF management. The Korean guidelines for the diagnosis and management of chronic HF were introduced in March 2016. However, chronic and acute heart failure (AHF) represent distinct disease entities. Here, we introduce the Korean guidelines for the management of AHF with reduced or preserved ejection fraction. Part I of this guideline covers the definition, epidemiology, and diagnosis of AHF.

KSHF Guidelines for the Management of Acute Heart Failure: Part III. Specific Management of Acute Heart Failure According to the Etiology and Co-morbidity.

The prevalence of heart failure (HF) is on the rise due to the aging of society. Furthermore, the continuous progress and widespread adoption of screening and diagnostic strategies have led to an increase in the detection rate of HF, effectively increasing the number of patients requiring monitoring and treatment. Because HF is associated with substantial rates of mortality and morbidity, as well as high socioeconomic burden, there is an increasing need for developing specific guidelines for HF management. The Korean guidelines for the diagnosis and management of chronic heart failure (CHF) were introduced in March 2016. However, CHF and acute heart failure (AHF) represent distinct disease entities. Here, we introduce the Korean guidelines for the management of AHF with reduced or preserved ejection fraction. Part III of this guideline covers management strategies optimized according to the etiology of AHF and the presence of co-morbidities.

Assessment of clinical effect and treatment quality of immediate-release carvedilol-IR versus SLOW release carvedilol-SR in Heart Failure patients (SLOW-HF): study protocol for a randomized controlled trial.

BACKGROUND: Carvedilol is a non-selective, third-generation beta-blocker and is one of the cornerstones for treatment for patients with heart failure and reduced ejection fraction (HFrEF). However, due to its short half-life, immediate-release carvedilol (IR) needs to be prescribed twice a day. Recently, slow-release carvedilol (SR) has been developed. The aim of this study is to evaluate whether carvedilol-SR is non-inferior to standard carvedilol-IR in terms of its clinical efficacy in patients with HFrEF. METHODS/DESIGN: Patients with stable HFrEF will be randomly assigned in a 1:1 ratio to the carvedilol-SR group (160 patients) and the carvedilol-IR group (160 patients). Patients aged ≥ 20 years, with a left ventricular ejection fraction ≤ 40%, N-terminal pro B-natriuretic peptide (NT-proBNP) ≥ 125 pg/ml or BNP ≥ 35 pg/ml, who are clinically stable and have no evidence of congestion or volume retention, will be eligible. After randomization, patients will be followed up for 6 months. The primary endpoint is the change in NT-proBNP level from baseline to the study end. The secondary endpoints include the proportion of patients with NT-proBNP increment > 10% from baseline, composite of all-cause mortality and readmission, mortality rate, readmission rate, changes in blood pressure, quality of life, and drug compliance. DISCUSSIONS: The SLOW-HF trial is a prospective, randomized, open-label, phase-IV, multicenter study to evaluate the therapeutic efficacy of carvedilol-SR compared to carvedilol-IR in HFrEF patients. If carvedilol-SR proves to be non-inferior to carvedilol-IR, a once-daily prescription of carvedilol may be recommended for patients with HFrEF. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03209180 . Registered on 6 July 2017.

Coronary vasospastic angina: assessment by multidetector CT coronary angiography.

OBJECTIVE: We aimed to describe the imaging findings of multidetector CT coronary angiography (MDCTA) in cases of vasospastic angina (VA) and to determine the accuracy of MDCTA in the identification of VA as compared with invasive coronary angiography with an ergonovine provocation test (CAG with an EG test). MATERIALS AND METHODS: Fifty-three patients with clinically suspected VA were enrolled in this study. Two radiologists analyzed the stenosis degree, presence or absence of plaque, plaque composition, and a remodeling index of the related-segment in CAG with an EG test, which were used as a gold standard. We evaluated the diagnostic performances of MDCTA by comparing the MDCTA findings with those of CAG with an EG test. RESULTS: Among the 25 patients with positive CAG with an EG test, all 12 patients with significant stenosis showed no definite plaque with the negative arterial remodeling. Of the six patients with insignificant stenosis, three (50%) had non-calcified plaque (NCP), two (33%) had mixed plaque, and one (17%) had calcified plaque. When the criteria for significant stenosis with negative remodeling but no definite evidence of plaque as a characteristic finding of MDCTA were used, results showed sensitivities, specificities, positive predictive values (PPV), and negative predictive values (NPV) of 48%, 100%, 100%, and 68%, respectively. CONCLUSION: Significant stenosis with negative remodeling, but no definite evidence of plaque, is the characteristic finding on MDCTA of VA. Cardiac MDCTA shows good diagnostic performance with high specificity and PPV as compared with CAG with an EG test.

Significance of noncalcified coronary plaque in asymptomatic subjects with low coronary artery calcium score: assessment with coronary computed tomography angiography.

We aimed to investigate the prevalence and severity of noncalcified coronary plaques (NCP) using coronary CT angiography (CCTA) and analyze predictors of significant coronary stenosis by NCP in asymptomatic subjects with low coronary artery calcium score (CACS). The institutional review board approved this retrospective study and all patients gave written, informed consent. The presence of plaque, severity of stenosis, plaque characteristics, and CACS were assessed in 7,515 asymptomatic subjects. We evaluated the prevalence and severity of NCP in subjects having low CACS (707 subjects; men with CACS from 1 to 50 and women from 1 to 10) in comparison to those having 0 CACS (6,040 subjects) as the reference standard. Conventional risk factors were assessed for predictors of NCP and significant stenosis by NCP. We also investigated the cardiac events of the patients through medical records. Compared to subjects with 0 CACS, those with low CACS showed higher prevalence of NCP (6.9% vs. 31.5%, P < 0.001) and significant stenosis caused by NCP (0.8% vs. 7.5%, P < 0.001). In the low CACS group, independent predictors for significant NCP included diabetes mellitus (DM), hypertension, and elevated low-density lipoprotein (LDL)-cholesterol (all P < 0.05). However, 47.2% of subjects with significant NCP were classified into the low to intermediate risk according to Framingham Risk Score. At the median follow up of 42 months (range: 3-60 months), cardiac events were significantly higher in the low CACS group compared to the 0 CACS group (2.6% vs. 0.27%, P < 0.001). In asymptomatic subjects having low CACS, the prevalence and severity of NCP were higher as compared to subjects having zero CACS and predictors of significant stenosis by NCP were DM, hypertension and LDL-Cholesterol. Therefore, CCTA may be useful for risk stratification of coronary artery disease as added value over CACS in selected populations with low CACS who have predictors of significant NCP.

Detection of masked hypertension and the 'mask effect' in patients with well-controlled office blood pressure.

BACKGROUND: Masked hypertension (MH) is characterized by its hidden nature and poor prognosis. However, it is not practical to routinely recommend home or ambulatory blood pressure monitoring (HBP or AMBP) to all patients with apparently well-controlled BP. The purpose of this study is to present, within the group of patients with well-controlled office BP (OBP), the clinical predictors of MH and to evaluate the gap (ie, the `mask effect' (ME)) between OBP and HBP. METHODS AND RESULTS: BP was measured at the outpatient clinic and at home in 1,019 treated hypertensive patients. Candidate predictors for MH were analyzed within 511 patients with well-controlled OBP (45.6% men, 57.1±9.0 years). Among them, the prevalence of MH was 20.9% (n=107). In the multivariate-adjusted analysis, the risk of MH increased with high serum fasting blood glucose level (odds ratio (OR) 1.009, 95% confidence interval (CI): 1.001-1.018, P=0.020), higher systolic OBP (OR 1.075, 95%CI 1.045-1.106, P<0.001), higher diastolic OBP (OR 1.045, 95%CI 1.007-1.084, P=0.019) and the number of antihypertensive medications (OR 1.320, 95%CI 1.113-1.804, P=0.021). Furthermore, systolic HBP correlated well with systolic OBP (r=0.351, P<0.001) and with the degree of systolic ME (r=-0.672, P<0.001). CONCLUSIONS: To recognize MH, it is practical to investigate those patients who are taking multiple antihypertensive drugs and have a high OBP with a high FBG level. The term "ME" identifies MH more appropriately than the term "negative white-coat effect".

Are metabolic risk factors and target organ damage more frequent in masked hypertension than in white coat hypertension?

Patients with masked hypertension (MH) tend to have a higher risk than those with white-coat hypertension (WCH). Therefore, we evaluated the characteristics of MH and WCH in Korean patients receiving medical treatment for hypertension. We enrolled 1019 outpatients (56 ± 10 y, 488 males) with diagnosed hypertension who had not changed oral anti-hypertensive medication for 6 months. Clinic blood pressure (CBP) was checked by a nurse and doctor twice per visit. Home BP (HBP) was checked every morning and evening for 1 week. In the MH patients, mean CBP was 130/80 mmHg, whereas HBP was 137/86 mmHg. In the WCH patients, mean CBP was 149/86 mmHg by physician and 143/85 mmHg by nurse and mean HBP was 124/75 mmHg. Age and gender did not differ between the groups. Waist and hip circumferences and the level of fasting glucose were higher in patients with MH than in patients with WCH (p = 0.008, 0.016, 0.009, respectively). Metabolic risk factors were more frequent in patients with WCH, MH, and uncontrolled hypertension than in patients with controlled hypertension. The incidence of metabolic risk factors, however, did not differ between patients with WCH and MH. Heart damage was more frequent in MH than in WCH (p = 0.03). The incidence of metabolic risk factors did not differ between patients with WCH and those with MH. Target organ damage was more closely related to MH than to WCH. Home BP measurement was a useful tool for discriminating WCH and MH in patients with hypertension.