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.

2018 Korean Society of Hypertension guidelines for the management of hypertension: part I-epidemiology of hypertension.

The Korean Society of Hypertension guideline defines hypertension as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg, where the effectiveness of pharmacological treatment has been established. It is confirmed that higher blood pressure levels are associated with increased risk of cardiovascular disease and mortality also in the Korean population. About one third of Korean adults aged 30 years or older are estimated to have hypertension, and the prevalence of hypertension gradually increases as the age increases. The awareness, treatment, and control rates of hypertension are generally improving in Korea, but more efforts are required to increase awareness and treatment among younger patients with hypertension and to improve lifestyle modification compliance at all ages. More studies are required to determine the magnitude and impact of white coat hypertension and masked hypertension in the Korean population.

2013 Korean Society of Hypertension guidelines for the management of hypertension: part I-epidemiology and diagnosis of hypertension.

The standardized techniques of blood pressure measurement in the clinic are emphasized and the indications for ambulatory and/or home blood pressure monitoring are specified more broadly. The epidemiologic findings specific to Korean population related to blood pressure are reviewed. Cardiovascular risk of hypertensive patients are stratified based upon the data of a Korean population cohort study.

Comparative assessment of angiotensin II type 1 receptor blockers in the treatment of acute myocardial infarction: surmountable vs. insurmountable antagonist.

BACKGROUND: The mechanisms of antagonism vary between the angiotensin II type 1 receptor blockers (ARBs): insurmountable antagonism and surmountable antagonism. Recent retrospective observational studies suggest that ARBs may not have equivalent benefits in various clinical situations. The aim of this study was to compare the effect of two categories of ARBs on the long-term clinical outcomes of patients with acute myocardial infarction (AMI). METHODS: We analyzed the large-scale, prospective, observational Korea Acute Myocardial Infarction Registry study, which enrolled 2740 AMI patients. They divided by the prescription of surmountable ARBs or insurmountable ARBs at discharge. Primary outcome was major adverse cardiac events (MACEs), defined as a composite of cardiac death, nonfatal MI, and re-percutaneous coronary intervention, coronary artery bypass graft surgery. RESULTS: In the overall population, the MACEs rate in 1 year was significantly higher in the surmountable ARB group (14.3% vs. 11.2%, p=0.025), which was mainly due to increased cardiac death (3.3% vs. 1.9%, p=0.031). Matching by propensity-score showed consistent results (MACEs rate: 14.9% vs. 11.4%, p=0.037). In subgroup analysis, the insurmountable ARB treatment significantly reduced the incidence of MACEs in patients with left ventricular ejection fraction greater than 40%, with a low killip class, with ST segment elevation MI, and with normal renal function. CONCLUSIONS: In our study, insurmountable ARBs were more effective on long-term clinical outcomes than surmountable ARBs in patients with AMI.

Hospital discharge risk score system for the assessment of clinical outcomes in patients with acute myocardial infarction (Korea Acute Myocardial Infarction Registry [KAMIR] score).

Assessment of risk at time of discharge could be a useful tool for guiding postdischarge management. The aim of this study was to develop a novel and simple assessment tool for better hospital discharge risk stratification. The study included 3,997 hospital-discharged patients with acute myocardial infarction who were enrolled in the nationwide prospective Korea Acute Myocardial Infarction Registry-1 (KAMIR-1) from November 2005 through December 2006. The new risk score system was tested in 1,461 hospital-discharged patients who were admitted from January 2007 through January 2008 (KAMIR-2). The new risk score system was compared to the Global Registry of Acute Coronary Events (GRACE) postdischarge risk model during a 12-month clinical follow-up. During 1-year follow-up, all-cause death occurred in 228 patients (5.7%) and 81 patients (5.5%) in the development and validation cohorts, respectively. The new risk score (KAMIR score) was constructed using 6 independent variables related to the primary end point using a multivariable Cox regression analysis: age, Killip class, serum creatinine, no in-hospital percutaneous coronary intervention, left ventricular ejection fraction, and admission glucose based on multivariate-adjusted risk relation. The KAMIR score demonstrated significant differences in its predictive accuracy for 1-year mortality compared to the GRACE score for the developmental and validation cohorts. In conclusion, the KAMIR score for patients with acute myocardial infarction is a simpler and better risk scoring system than the GRACE hospital discharge risk model in prediction of 1-year mortality.

Gender differences in clinical features and in-hospital outcomes in ST-segment elevation acute myocardial infarction: from the Korean Acute Myocardial Infarction Registry (KAMIR) study.

BACKGROUND: Studies have suggested that women are biologically different and that female gender itself is independently associated with poor clinical outcome after an acute myocardial infarction (AMI). HYPOTHESIS: We analyzed data from the Korean Acute Myocardial Infarction Registry (KAMIR) to assess gender differences in in-hospital outcomes post ST-segment elevation myocardial infarction (STEMI). METHODS: Between November 2005 and July 2007, 4037 patients who were admitted with STEMI to 41 facilities were registered into the KAMIR database; patients admitted within 72 hours of symptom onset were selected and included in this study. RESULTS: The proportion of patients who had reperfusion therapy within 12 hours from chest pain onset was lower in women. Women had higher rates of in-hospital mortality (8.6% vs 3.2%, P < .01), noncardiac death (1.5% vs 0.4%, P < .01), cardiac death (7.1% vs 2.8%, P < .01), and stroke (1.2% vs 0.5%, P < .05) than men. Multivariate logistic regression analysis identified age, previous angina, hypertension, a Killip class > or = II, a left ventricular ejection fraction (LVEF) < 40%, and a thrombolysis in myocardial infarction flow (TIMI) grade < or = 3 after angioplasty as independent risk factors for in-hospital death for all patients; however, female gender itself was not an independent risk factor. CONCLUSIONS: The results of this study show that although women have a higher in-hospital mortality than men, female gender itself is not an independent risk factor for in-hospital mortality.

A new risk score system for the assessment of clinical outcomes in patients with non-ST-segment elevation myocardial infarction.

BACKGROUND AND OBJECTIVES: Prediction for long-term clinical outcomes in patients with non-ST elevation acute coronary syndrome is important as well as early risk stratification. The aim of this study is to develop a simple assessment tool for better early bedside risk stratification for both short- and long-term clinical outcomes. SUBJECTS AND METHODS: 2148 patients with non-ST-segment elevation myocardial infarction (NSTEMI) (64.9±12.2 years, 35.0% females) were enrolled in a nationwide prospective Korea Acute Myocardial Infarction Registry (KAMIR). A new risk score was constructed using the variables related to one year mortality: TIMI risk index (17.5-30: 1 point, >30: 2 points), Killip class (II: 1 point, >II: 2 points) and serum creatinine (≥1.5 mg/dL: 1 point), based on the multivariate-adjusted risk relationship. The new risk score system was compared with the Global Registry of Acute Coronary Events (GRACE) and TIMI risk scores during a 12-month clinical follow-up. RESULTS: During a one year follow-up, all causes of death occurred in 362 patients (14.3%), and 184 (8.6%) patients died in the hospital. The new risk score showed good predictive value for one year mortality. The accuracy for in-hospital and one year post-discharge mortality rates, the new risk score demonstrated significant differences in predictive accuracy when compared with TIMI and GRACE risk scores. CONCLUSION: A new risk score in the present study provides simplicity with accuracy simultaneously for early risk stratification, and also could be a powerful predictive tool for long-term prognosis in NSTEMI.

Flow cytometric assessment of platelet aspirin resistance using light scattering.

BACKGROUND: A simple and reliable assay is needed for the prediction of the clinical efficacy of antiplatelet aspirin therapy. We have devised another method for the evaluation of platelet function and aspirin resistance (AR), via conventional flow cytometry (FCM). METHODS: To devise an optimized protocol for the assessment of platelet AR, various analytic variables of FCM were investigated. Using this devised protocol, AR was assessed in healthy subjects as an example. RESULTS: The protocol utilized herein is as follows: citrate-anticoagulated platelet-rich plasma was mixed 1:1 with HEPES-buffered saline in two tubes, one of which is treated with aspirin. During the acquisition of FCM, arachidonate is added to the tube. The response of the aspirin-treated platelets is then compared with those of nontreated ones on a time/forward scatter plot. In the 61 total subjects, none was identified as aspirin resistant by this assay. CONCLUSIONS: Using light scattering, platelet aggregation and aspirin's antiplatelet effects can be readily and cost-effectively detected. According to this assay, biochemical AR appears to be rare. This new protocol may prove useful in a clinical setting or as a research tool.