Effectiveness and safety of empagliflozin: final results from the EMPRISE study.

AIMS/HYPOTHESIS: Limited evidence exists on the comparative safety and effectiveness of empagliflozin against alternative glucose-lowering medications in individuals with type 2 diabetes with the broad spectrum of cardiovascular risk. The EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) cohort study was designed to monitor the safety and effectiveness of empagliflozin periodically for a period of 5 years with data collection from electronic healthcare databases. METHODS: We identified individuals ≥18 years old with type 2 diabetes who initiated empagliflozin or dipeptidyl peptidase-4 inhibitors (DPP-4i) from 2014 to 2019 using US Medicare and commercial claims databases. After 1:1 propensity score matching using 143 baseline characteristics, we identified four a priori-defined effectiveness outcomes: (1) myocardial infarction (MI) or stroke; (2) hospitalisation for heart failure (HHF); (3) major adverse cardiovascular events (MACE); and (4) cardiovascular mortality or HHF. Safety outcomes included lower-limb amputations, non-vertebral fractures, diabetic ketoacidosis (DKA), acute kidney injury (AKI), severe hypoglycaemia, retinopathy progression, and short-term kidney and bladder cancers. We estimated HRs and rate differences (RDs) per 1000 person-years, overall and stratified by age, sex, baseline atherosclerotic cardiovascular disease (ASCVD) and heart failure. RESULTS: We identified 115,116 matched pairs. Compared with DPP-4i, empagliflozin was associated with lower risks of MI/stroke (HR 0.88 [95% CI 0.81, 0.96]; RD -2.08 [95% CI (-3.26, -0.90]), HHF (HR 0.50 [0.44, 0.56]; RD -5.35 [-6.22, -4.49]), MACE (HR 0.73 [0.62, 0.86]; RD -6.37 [-8.98, -3.77]) and cardiovascular mortality/HHF (HR 0.57 [0.47, 0.69]; RD -10.36 [-12.63, -8.12]). Absolute benefits were larger in older individuals and in those with ASCVD/heart failure. Empagliflozin was associated with an increased risk of DKA (HR 1.78 [1.44, 2.19]; RD 1.59 [1.08, 2.09]); decreased risks of AKI (HR 0.62 [0.54, 0.72]; RD -2.39 [-3.08, -1.71]), hypoglycaemia (HR 0.75 [0.67, 0.84]; RD -2.46 [-3.32, -1.60]) and retinopathy progression (HR 0.78 [0.63, 0.96)]; RD -9.49 [-16.97, -2.10]); and similar risks of other safety events. CONCLUSIONS/INTERPRETATION: Empagliflozin relative to DPP-4i was associated with risk reductions of MI or stroke, HHF, MACE and the composite of cardiovascular mortality or HHF. Absolute risk reductions were larger in older individuals and in those who had history of ASCVD or heart failure. Regarding the safety outcomes, empagliflozin was associated with an increased risk of DKA and lower risks of AKI, hypoglycaemia and progression to proliferative retinopathy, with no difference in the short-term risks of lower-extremity amputation, non-vertebral fractures, kidney and renal pelvis cancer, and bladder cancer.

Poor adherence to and persistence with biologics in generalized pustular psoriasis: A claim-based study using real-world data from two large US databases.

Background: Generalized pustular psoriasis (GPP) is a rare skin disease characterized by episodes of widespread sterile pustules. Methods: A retrospective cohort study using data from the US IBM MarketScan Commercial and Optum Clinformatics Data Mart databases between October 1, 2015 and March 31, 2020 was performed to describe adherence and persistence to biologics in patients with GPP. Patients were aged ≥18 years with newly diagnosed GPP (International Classification of Diseases code L40.1) and had ≥1 inpatient or ≥2 outpatient claims. Results: Biologics were dispensed to 110 of 502 (22%) and 73 of 528 (14%) patients from MarketScan and Optum databases, respectively. The mean proportion of days covered (PDC) (range) was similar in both databases (MarketScan, 65% [8%-100%]; Optum, 59% [8%-99%]), and good adherence (≥80% PDC) was uncommon (MarketScan, 36%; Optum, 24%). Mean (standard deviation) persistence was similar in both databases (MarketScan, 287 [122] days; Optum, 261 [134] days). In Optum, the mean PDC was similar between age categories; good adherence was more common in patients aged 18 to 64 years (28%) versus ≥65 years (13%). Mean persistence was longer in patients aged 18 to 64 years (267 days) versus ≥65 years (242 days). Conclusions: Overall, adherence and persistence were generally poor and varied according to the biologic class, database, and age. Improving adherence may help improve GPP treatment outcomes.

Cardiorenal effectiveness of empagliflozin vs. glucagon-like peptide-1 receptor agonists: final-year results from the EMPRISE study.

BACKGROUND: No randomized clinical trials have directly compared the cardiorenal effectiveness of empagliflozin and GLP-1RA agents with demonstrated cardioprotective effects in patients with a broad spectrum of cardiovascular risk. We reported the final-year results of the EMPRISE study, a monitoring program designed to evaluate the cardiorenal effectiveness of empagliflozin across broad patient subgroups. METHODS: We identified patients ≥ 18 years old with type 2 diabetes who initiated empagliflozin or GLP-1RA from 2014 to 2019 using US Medicare and commercial claims databases. After 1:1 propensity score matching using 143 baseline characteristics, we evaluated risks of outcomes including myocardial infarction (MI) or stroke, hospitalization for heart failure (HHF), major adverse cardiovascular events (MACE - MI, stroke, or cardiovascular mortality), a composite of HHF or cardiovascular mortality, and progression to end-stage kidney disease (ESKD) (in patients with chronic kidney disease stages 3-4). We estimated hazard ratios (HR) and rate differences (RD) per 1,000 person-years, overall and within subgroups of age, sex, baseline atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF). RESULTS: We identified 141,541 matched pairs. Compared with GLP-1RA, empagliflozin was associated with similar risks of MI or stroke [HR: 0.99 (0.92, 1.07); RD: -0.23 (-1.25, 0.79)], and lower risks of HHF [HR: 0.50 (0.44, 0.56); RD: -2.28 (-2.98, -1.59)], MACE [HR: 0.90 (0.82, 0.99); RD: -2.54 (-4.76, -0.32)], cardiovascular mortality or HHF [HR: 0.77 (0.69, 0.86); RD: -4.11 (-5.95, -2.29)], and ESKD [0.75 (0.60, 0.94); RD: -6.77 (-11.97, -1.61)]. Absolute risk reductions were larger in older patients and in those with baseline ASCVD/HF. They did not differ by sex. CONCLUSIONS: The cardiovascular benefits of empagliflozin vs. cardioprotective GLP-1RA agents were larger in older patients and in patients with history of ASCVD or HF, while they did not differ by sex. In patients with advanced CKD, empagliflozin was associated with risk reductions of progression to ESKD.

The clinical burden of newly diagnosed Heart failure among patients with Reduced, mildly Reduced, and preserved ejection fraction.

Background: Contemporary analyses of the distribution of heart failure (HF) patients by groups of ejection fraction are not available or are limited to hospitalized patients. Our objective was to quantify the per-person and system level clinical burden of a broad population of HF patients. Methods: We studied 16,516 patients with a new HF diagnosis recorded in the electronic medical record of a U.S. integrated delivery system between 2005 and 2017. We used the diagnosis date as the index date and the nearest echocardiogram result to classify patients as HFrEF (n = 2,430), HFmrEF (n = 1,646), HFpEF (n = 12,440) and followed them through 2019 for major clinical outcomes (all-cause mortality, HF hospitalizations [HHF], all-cause hospitalizations, incident chronic kidney disease [CKD], progression of eGFR category, progression of CKD, incident type 2 diabetes [T2D], and progression to insulin use). We compared age and sex adjusted incidence rates and rate ratios of the outcomes between the HF types. Results: Incidence rates for most outcomes were significantly higher among patients with HFrEF compared with HFpEF. HHF was 59 % greater, mortality 31 % greater, and CKD incidence 55 % greater, (p < 0.001 for all comparisons). However, the larger size of the HFpEF group generated 4.7-6.7 times as many total outcomes. Conclusions: Regardless of subtype, the presence of HF was associated with poor clinical outcomes. Incidence rates were higher for HFrEF than HFpEF, but as the latter represented 75% of the study population, HFpEF caused a greater overall burden on the health care system, reflecting the high unmet need of target therapies for HFpEF.

Prognostic Factors of COVID-19: An Umbrella Review Endorsed by the International Society for Pharmacoepidemiology.

During the coronavirus disease 2019 (COVID-19) pandemic, the urgency for updated evidence to inform public health and clinical care placed systematic literature reviews (SLRs) at the cornerstone of research. We aimed to summarize evidence on prognostic factors for COVID-19 outcomes through published SLRs and to critically assess quality elements in the findings' interpretation. An umbrella review was conducted via electronic databases from January 2020 to April 2022. All SLRs (and meta-analyses) in English were considered. Data screening and extraction were conducted by two independent reviewers. AMSTAR 2 tool was used to assess SLR quality. The study was registered with PROSPERO (CRD4202232576). Out of 4,564 publications, 171 SLRs were included of which 3 were umbrella reviews. Our primary analysis included 35 SLRs published in 2022, which incorporated studies since the beginning of the pandemic. Consistent findings showed that, for adults, older age, obesity, heart disease, diabetes, and cancer were more strongly predictive of risk of hospitalization, intensive care unit admission, and mortality due to COVID-19. Male sex was associated with higher risk of short-term adverse outcomes, but female sex was associated with higher risk of long COVID. For children, socioeconomic determinants that may unravel COVID-19 disparities were rarely reported. This review highlights key prognostic factors of COVID-19, which can help clinicians and health officers identify high-risk groups for optimal care. Findings can also help optimize confounding adjustment and patient phenotyping in comparative effectiveness research. A living SLR approach may facilitate dissemination of new findings. This paper is endorsed by the International Society for Pharmacoepidemiology.

Empagliflozin cardiovascular and renal effectiveness and safety compared to dipeptidyl peptidase-4 inhibitors across 11 countries in Europe and Asia: Results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study.

BACKGROUND: Continued expansion of indications for sodium-glucose cotransporter-2 inhibitors increases importance of evaluating cardiovascular and kidney efficacy and safety of empagliflozin in patients with type 2 diabetes compared to similar therapies. METHODS: The EMPRISE Europe and Asia study is a non-interventional cohort study using data from 2014-2019 in seven European (Denmark, Finland, Germany, Norway, Spain, Sweden, United Kingdom) and four Asian (Israel, Japan, South Korea, Taiwan) countries. Patients with type 2 diabetes initiating empagliflozin were 1:1 propensity score matched to patients initiating dipeptidyl peptidase-4 inhibitors. Primary endpoints included hospitalization for heart failure, all-cause mortality, myocardial infarction and stroke. Other cardiovascular, renal, and safety outcomes were examined. FINDINGS: Among 83,946 matched patient pairs, (0·7 years overall mean follow-up time), initiation of empagliflozin was associated with lower risk of hospitalization for heart failure compared to dipeptidyl peptidase-4 inhibitors (Hazard Ratio 0·70; 95% CI 0.60 to 0.83). Risks of all-cause mortality (0·55; 0·48 to 0·63), stroke (0·82; 0·71 to 0·96), and end-stage renal disease (0·43; 0·30 to 0·63) were lower and risk for myocardial infarction, bone fracture, severe hypoglycemia, and lower-limb amputation were similar between initiators of empagliflozin and dipeptidyl peptidase-4 inhibitors. Initiation of empagliflozin was associated with higher risk for diabetic ketoacidosis (1·97; 1·28 to 3·03) compared to dipeptidyl peptidase-4 inhibitors. Results were consistent across continents and regions. INTERPRETATION: Results from this EMPRISE Europe and Asia study complements previous clinical trials and real-world studies by providing further evidence of the beneficial cardiorenal effects and overall safety of empagliflozin compared to dipeptidyl peptidase-4 inhibitors.

Empagliflozin is associated with lower risk of cardiovascular events and all-cause mortality in routine care in East Asia: Results from the EMPRISE study.

AIMS/INTRODUCTION: The EMPA-REG OUTCOME® trial demonstrated benefits of empagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT2i), on cardiovascular, renal outcomes and all-cause mortality in patients with type 2 diabetes and established cardiovascular disease. The EMPRISE study program evaluates how these effects translate in a broad population of patients with type 2 diabetes in routine clinical care across countries. MATERIALS AND METHODS: The study included patients ≥18 years with type 2 diabetes initiating empagliflozin or any dipeptidyl peptidase-4 inhibitors (DPP-4i) from large administrative databases in Japan, South Korea, and Taiwan. Propensity score-matched (1:1) 'as-treated' analyses comparing the risk of cardiovascular outcomes and all-cause mortality between empagliflozin and DPP-4i use were performed in each country. Pooled hazard ratios (pHR) with 95% confidence intervals (CI) were computed using random effects meta-analysis models comparing both empagliflozin and SGLT2i with DPP-4i use, respectively. Intention-to-treat and subgroup analyses in patients with/without cardiovascular disease and in patients receiving 10 mg empagliflozin were performed. RESULTS: The study included 28,712 and 70,233 matched patient pairs for empagliflozin/DPP-4i and SGLT2i/DPP-4i analyses, respectively. The risk of composite outcomes including (i) hospitalization for heart failure (HHF) and all-cause mortality was lower with empagliflozin (pHR 0.76, 95% CI 0.67-0.86) and SGLT2i (0.71, 0.65-0.77); (ii) combined myocardial infarction, stroke, and all-cause mortality was also lower with empagliflozin (0.74, 0.61-0.88) and SGLT2i (0.69, 0.60-0.78) compared to DPP-4i. The intention-to-treat and three subgroup analyses were consistent with results of the main analyses. CONCLUSIONS: The results suggest that both empagliflozin and SGLT2i compared with DPP-4i are associated with a lower risk of cardiovascular events and all-cause mortality in routine clinical care in East Asia.

Comparative Effectiveness of Empagliflozin vs Liraglutide or Sitagliptin in Older Adults With Diverse Patient Characteristics.

Importance: Limited evidence is available on the comparative effectiveness of empagliflozin vs alternative second-line glucose-lowering agents in patients with type 2 diabetes (T2D) receiving routine care who have a broad spectrum of cardiorenal risk. Objective: To evaluate the association of empagliflozin with cardiovascular outcomes relative to liraglutide and sitagliptin, stratified by age, sex, baseline atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD). Design, Setting, and Participants: This retrospective comparative effectiveness cohort study used deidentified Medicare claims data from August 1, 2014, to September 30, 2018, with follow-up from drug initiation until treatment changes, death, or gap in Medicare enrollment (>30 days). Data analysis was performed from October 1, 2021, to April 30, 2022. Medicare fee-for-service beneficiaries older than 65 years with T2D were included. A total of 45 788 patients (22 894 propensity score-matched pairs initiating treatment with either empagliflozin or liraglutide) were included in cohort 1, and 45 624 patients (22 812 propensity score-matched pairs initiating treatment with either empagliflozin or sitagliptin) were included in cohort 2. Exposures: Empagliflozin vs liraglutide (cohort 1) or empagliflozin vs sitagliptin (cohort 2). Main Outcomes and Measures: Primary outcomes were (1) modified major adverse cardiovascular events (MACEs), including a composite of myocardial infarction, stroke, and all-cause mortality, and (2) hospitalization for heart failure (HHF). Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years were estimated, adjusting for 143 baseline covariates using 1:1 propensity score matching. Results: Among 45 788 patients in cohort 1, the mean (SD) age was 71.9 (5.1) years; 23 396 patients (51.1%) were female, 22 392 (48.9%) were male, and 38 049 (83.1%) were White. Among 45 624 patients in cohort 2, the mean (SD) age was 72.1 (5.1) years; 21 418 patients (46.9%) were female, 24 206 (53.1%) were male, and 37 814 (82.9%) were White. Relative to patients initiating liraglutide, those initiating empagliflozin had a similar risk of the modified MACE outcome (HR, 0.90; 95% CI, 0.79-1.03) and a reduced risk of HHF (HR, 0.66; 95% CI, 0.52-0.82). Across subgroups, empagliflozin was associated with a lower risk of the modified MACE outcome in patients with a history of ASCVD (HR, 0.83; 95% CI, 0.71-0.98) and HF (HR, 0.77; 95% CI, 0.60-1.00) compared with liraglutide, and potential heterogeneity in estimates was observed by sex (male: HR, 0.85 [95% CI, 0.71-1.01]; female: HR, 1.16 [95% CI, 0.94-1.42]; P = .02 for homogeneity). However, reductions in the risk of HHF were observed across most subgroups (eg, ASCVD: HR, 0.66 [95% CI, 0.51-0.85]; HF: HR, 0.66 [95% CI, 0.49-0.88]). Compared with sitagliptin, empagliflozin was associated with reduced risks of the modified MACE outcome (HR, 0.68; 95% CI, 0.60-0.77) and HHF (HR, 0.45; 95% CI, 0.36-0.56), which were consistent across all subgroups. Absolute benefits of empagliflozin vs sitagliptin were larger in patients with a history of ASCVD (modified MACE: RD, -17.6 [95% CI, -24.9 to -10.4]; HHF: RD, -16.7 [95% CI, -21.7 to -11.9]), HF (modified MACE: RD, -41.1 [95% CI, -59.9 to -22.6]; HHF: RD, -50.4 [95% CI, -67.5 to -33.9]), or CKD (modified MACE: RD, -26.7 [95% CI, -41.3 to -12.3]; HHF: RD, -31.9 [95% CI, -43.5 to -20.8]). Conclusions and Relevance: In this comparative effectiveness study of older adults, empagliflozin was associated with a lower risk of HHF (relative to both liraglutide and sitagliptin) and the modified MACE outcome (relative to sitagliptin), with larger absolute benefits in patients with established cardiorenal diseases. These findings suggest that older adults with T2D might benefit more from empagliflozin vs liraglutide or sitagliptin with respect to the risk of HHF; with respect to the risk of MACEs, empagliflozin might be preferable to liraglutide only in patients with cardiovascular disease history and to sitagliptin across all patient subgroups.

Comparative effectiveness of Empagliflozin in reducing the burden of recurrent cardiovascular hospitalizations among older adults with diabetes in routine clinical care.

BACKGROUND: The effect of sodium glucose cotransporter 2 inhibitors (SGLT2i) on the total (first and recurrent) burden of cardiovascular (CV) hospitalizations, including hospitalization for heart failure, myocardial infarction, and stroke, is poorly understood. OBJECTIVE: To assess the effect of empagliflozin, an SGLT2i, on total CV hospitalizations among older adults with T2D. METHODS: Using data from Medicare fee-for-service (08/2014-09/2017), we identified 1:1 propensity score-matched cohorts of patients with T2D initiating empagliflozin versus sitagliptin or empagliflozin versus glucagon-like peptide-1 receptor agonists (GLP-1RA), balancing >140 baseline covariates. We compared the risk of first and recurrent hospitalizations with any CV condition as the primary discharge diagnosis (ICD-9: 390-459; ICD-10: I00-I99), hospitalizations for heart failure (HHF), and myocardial infarctions (MI) or stroke. We estimated treatment effects based on the Ghosh-Lin semiparametric model for recurrent events as primary and joint frailty model as secondary analysis. RESULTS: We included 11,429 matched-pairs of empagliflozin and sitagliptin initiators and 17,502 matched-pairs of empagliflozin and GLP1-RA initiators with an average age of 72 years. Empagliflozin was associated with a reduced risk of total CV hospitalizations (0.80 [0.69-0.93] vs sitagliptin; 0.88 [0.77-1.00] vs GLP-1RA) and total HHF (0.70 [0.51-0.98] vs sitagliptin; 0.76 [0.56-1.03] vs GLP1-RA) over a mean follow up of 6.3 months. No differences between treatments were observed for MI or stroke. Results were consistent for joint frailty models. CONCLUSION: Empagliflozin, compared to sitagliptin or to a lesser extent GLP1-RA, was associated with a reduction in the burden of total CV hospitalizations and HHF in older patients with T2D.

ISPE-Endorsed Guidance in Using Electronic Health Records for Comparative Effectiveness Research in COVID-19: Opportunities and Trade-Offs.

As the scientific research community along with healthcare professionals and decision makers around the world fight tirelessly against the coronavirus disease 2019 (COVID-19) pandemic, the need for comparative effectiveness research (CER) on preventive and therapeutic interventions for COVID-19 is immense. Randomized controlled trials markedly under-represent the frail and complex patients seen in routine care, and they do not typically have data on long-term treatment effects. The increasing availability of electronic health records (EHRs) for clinical research offers the opportunity to generate timely real-world evidence reflective of routine care for optimal management of COVID-19. However, there are many potential threats to the validity of CER based on EHR data that are not originally generated for research purposes. To ensure unbiased and robust results, we need high-quality healthcare databases, rigorous study designs, and proper implementation of appropriate statistical methods. We aimed to describe opportunities and challenges in EHR-based CER for COVID-19-related questions and to introduce best practices in pharmacoepidemiology to minimize potential biases. We structured our discussion into the following topics: (1) study population identification based on exposure status; (2) ascertainment of outcomes; (3) common biases and potential solutions; and (iv) data operational challenges specific to COVID-19 CER using EHRs. We provide structured guidance for the proper conduct and appraisal of drug and vaccine effectiveness and safety research using EHR data for the pandemic. This paper is endorsed by the International Society for Pharmacoepidemiology (ISPE).

Effectiveness and safety of empagliflozin in routine care patients: Results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study.

AIM: To investigate effectiveness and safety outcomes among patients with type 2 diabetes (T2D) initiating empagliflozin versus dipeptidyl peptidase-4 (DPP-4) inhibitor treatment across the broad spectrum of cardiovascular risk. METHODS: In a population-based cohort study we identified 39 072 pairs of 1:1 propensity score-matched adult patients with T2D initiating empagliflozin or DPP-4 inhibitors, using data from 2 US commercial insurance databases and Medicare between August 2014 and September 2017. The primary outcomes were a composite of myocardial infarction (MI)/stroke, and hospitalization for heart failure (HHF). Safety outcomes were bone fractures, lower-limb amputations (LLAs), diabetic ketoacidosis (DKA), and acute kidney injury (AKI). We estimated pooled hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for more than 140 baseline covariates. RESULTS: Study participants had a mean age of 60 years and only 28% had established cardiovascular disease. Compared to DPP-4 inhibitors, empagliflozin was associated with similar risk of MI/stroke (HR 0.99 [95% CI 0.81-1.21]), and lower risk of HHF (HR 0.48 [95% CI 0.35-0.67] and 0.63 [95% CI 0.54-0.74], based on a primary and any heart failure discharge diagnosis, respectively). The HR was 0.52 (95% CI 0.38-0.72) for all-cause mortality (ACM) and 0.83 (95% CI 0.70-0.98) for a composite of MI/stroke/ACM. Empagliflozin was associated with a similar risk of LLA and fractures, an increased risk of DKA (HR 1.71 [95% CI 1.08-2.71]) and a decreased risk of AKI (HR 0.60 [95% CI 0.43-0.85]). CONCLUSIONS: In clinical practice, the initiation of empagliflozin versus a DPP-4 inhibitor was associated with a lower risk of HHF, ACM and MI/stroke/ACM, a similar risk of MI/stroke, and a safety profile consistent with documented information.

Healthcare resource utilization in patients treated with empagliflozin in East Asia.

AIMS/INTRODUCTION: We investigated the utilization of healthcare resources in patients with type 2 diabetes treated with empagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, versus dipeptidyl peptidase-4 (DPP-4) inhibitors in clinical practice in Japan, South Korea, and Taiwan. MATERIALS AND METHODS: We analyzed the Japanese Medical Data Vision database (December 2014-April 2018), the South Korean National Health Information Database, and the Taiwanese National Health Insurance claims database (both May 2016-December 2017). Patients with type 2 diabetes starting empagliflozin, 10 or 25 mg, or a DPP-4 inhibitor were matched 1:1 via propensity scores (PS). We compared inpatient care needs, emergency room (ER) visits, and outpatient visits between the treatment groups using Poisson regression and Cox proportional hazards models, pooled across countries by random-effects meta-analysis. RESULTS: We identified 28,712 pairs of PS-matched patients; the mean follow-up was 5.7-6.8 months. Empagliflozin-treated patients had a 27% lower risk of all-cause hospitalization compared with DPP-4 inhibitor-treated patients (rate ratio [RR] 0.73, 95% CI 0.67-0.79), and 23% reduced risk for first hospitalization (hazard ratio 0.77, 95% CI 0.73-0.81). The risk for an ER visit was 12% lower with empagliflozin than with DPP-4 inhibitors (RR 0.88, 95% CI 0.83-0.94) while the risk for outpatient visit was 4% lower (RR 0.96, 95% CI 0.96-0.97). These findings were generally consistent across countries, regardless of baseline cardiovascular disease, and in the subgroup starting empagliflozin with the 10 mg dose. CONCLUSIONS: Empagliflozin treatment was associated with lower inpatient care needs and other healthcare resource utilization than DPP-4 inhibitors in routine clinical practice in East Asia in this study.

Cardiovascular and renal effectiveness of empagliflozin in routine care in East Asia: Results from the EMPRISE East Asia study.

Aim: To evaluate the effectiveness of empagliflozin in clinical practice in East Asia in the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) East Asia study. Materials and methods: Data were obtained from the Medical Data Vision database (Japan), National Health Insurance Service database (South Korea) and National Health Insurance database (Taiwan). Patients aged ≥ 18 years with type 2 diabetes initiating empagliflozin or a dipeptidyl peptidase-4 (DPP-4) inhibitor were 1:1 propensity score (PS) matched into sequentially built cohorts of new users naïve to both drug classes. This design reduces confounding due to switching treatments, time lag and immortal time biases. Outcomes included hospitalization for heart failure (HHF), end-stage renal disease (ESRD) and all-cause mortality. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional models, controlling for > 130 baseline characteristics in each data source and pooled by random-effects meta-analysis. Results: Overall, 28 712 pairs of PS-matched patients were identified with mean follow-up of 5.7-6.8 months. Compared with DPP-4 inhibitors, the risk of HHF was reduced by 18% and all-cause mortality was reduced by 36% with empagliflozin (HR 0.82; 95% CI 0.71-0.94, and HR 0.64; 95% CI 0.50-0.81, respectively). Reductions were consistent across countries, and in patients with and without baseline cardiovascular disease. ESRD was also significantly reduced with empagliflozin versus DPP-4 inhibitors (HR 0.37; 95% CI 0.24-0.58). Conclusions: Empagliflozin treatment was associated with reduced risk for HHF, all-cause mortality and ESRD compared with DPP-4 inhibitors in routine clinical practice in Japan, South Korea and Taiwan.

Confirming diagnoses of acute pancreatitis with commonly available electronic data.

BACKGROUND: Recorded diagnoses of acute pancreatitis (AP) are often inaccurate resulting in limited utility for case identification in large data sources, especially where electronic medical records (EMR) are not available. Our objectives were to validate diagnoses of AP and to identify an algorithm using additional data to enhance the identification of AP cases in different data sources. METHODS: We randomly sampled 550 persons with an AP diagnosis from inpatient data or outpatient or emergency department diagnoses immediately preceding a hospitalization and 150 negative controls with a differential diagnosis (cholangitis or cholecystitis). We conducted an EMR review to confirm cases of AP and used logistic regression to develop EMR-based and claims-based algorithms to identify confirmed AP cases with variables typically available in electronic data sources. Algorithm performance was assessed using the C statistic, sensitivity, specificity, and positive and negative predictive value. RESULTS: Of the 550 patients with an AP diagnosis, 467 (84.9%) were confirmed cases. An AP diagnosis alone had high sensitivity (98.9%), modest specificity (63.6%), and a C statistic of 0.813. An EMR-based model using an AP diagnosis, body mass index ≥30 kg/m2 , a serum lipase >3 times upper limit of normal and diabetes attained a C-statistic of 0.914. A claims-based model attained a C-statistic of 0.892 using an AP diagnosis and dichotomous variables for whether a serum lipase test and/or an abdominal ultrasound was performed. CONCLUSIONS: Our simple algorithms increased the accuracy of identification of AP cases providing widespread applicability to epidemiological and drug safety studies.

Health Care Costs by Type of Expenditure across eGFR Stages among Patients with and without Diabetes, Cardiovascular Disease, and Heart Failure.

BACKGROUND: CKD is associated with higher health care costs that increase with disease progression. However, research is lacking on the type of health care costs associated with CKD across all stages in a general population with a substantial comorbidity burden. METHODS: Using electronic medical records of an integrated delivery system, we evaluated health care costs by expenditure type in general and in patients with CKD by eGFR and presence of comorbidities. We categorized 146,132 patients with eGFR data in 2016 or 2017 and examined nonmutually exclusive groups according to presence of diabetes mellitus, cardiovascular disease, or heart failure. We used 1 year of follow-up data to calculate outpatient, inpatient, emergency, pharmaceutical, dialysis, and total health care costs by eGFR (Kidney Disease Improving Global Outcomes-defined eGFR categories), adjusted for age, sex, and nonwhite race. RESULTS: Mean total health care costs among patients with CKD without comorbidities were 31% higher than among patients without CKD ($7374 versus $5631, respectively). Hospitalizations accounted for 35% of total costs among those with CKD and no comorbidities but up to 55% among patients with CKD and heart failure. The proportion of costs attributable to hospitalizations accelerated with declining kidney function, reaching as high as 66%. CONCLUSIONS: Poorer kidney function and the presence of diabetes mellitus, cardiovascular disease, or heart failure drive substantial health care costs and increase the proportion of costs attributable to inpatient care. The large contribution of inpatient costs begins in earlier stages of CKD and escalates as kidney function declines. Additional therapies to reduce CKD incidence, slow CKD progression, and lower hospitalization risk are needed to benefit patients and reduce CKD's economic burden.

Correction to: Kidney disease progression and all-cause mortality across estimated glomerular filtration rate and albuminuria categories among patients with vs. without type 2 diabetes.

An amendment to this paper has been published and can be accessed via the original article.

Kidney disease progression and all-cause mortality across estimated glomerular filtration rate and albuminuria categories among patients with vs. without type 2 diabetes.

BACKGROUND: Studies of progression of kidney dysfunction typically focus on renal replacement therapy or percentage decline in estimated glomerular filtration rate (eGFR) as outcomes. Our aim was to compare real-world patients with and without T2D to estimate progression from and to clinically defined categories of kidney disease and all-cause mortality. METHODS: This was an observational cohort study of 31,931 patients with and 33,201 age/sex matched patients without type 2 diabetes (T2D) who had a serum creatinine and urine albumin-to-creatinine ratio (UACR) or dipstick proteinuria (DP) values. We used the first available serum creatinine value between 2006 and 2012 to calculate baseline eGFR and categorized them and the corresponding UACR/DP values using the Kidney Disease Improving Global Outcomes (KDIGO) categories. To assess our primary outcomes, we extracted probabilities of eGFR progression or mortality from life-table analyses and conducted multivariable Cox regression analyses of relative risk adjusted for age, sex, race/ethnicity, smoking, ischemic heart disease, heart failure, and use of renal-angiotensin-aldosterone system inhibitors. RESULTS: Patterns of eGFR decline were comparable among patients with vs. without T2D with larger percentage declines at higher albuminuria levels across all eGFR categories. eGFR decline was generally larger among T2D patients, particularly in those with severely increased albuminuria. Across all CKD categories, risk of progression to the next higher category of eGFR was substantially increased with increasing albuminuria. For example, the risk was 23.5, 36.2, and 65.1% among T2D patients with eGFR 30-59 ml/min/1.73m2 and UACR < 30, 30-299, and > 300 mg/dL, respectively (p < 0.001). Other comparisons were similarly significant. Among patients with low eGFR and normal to mildly increased albuminuria, the relative risk was up to 8-fold greater for all-cause mortality compared with the non-CKD subgroup (eGFR> 60 ml/min/1.73m2 with normal to mildly increased albuminuria). CONCLUSIONS: Presence of albuminuria was associated with accelerated eGFR decline independent of T2D. Risk for adverse outcomes was remarkably high among patients with CKD and normal to mildly increased albuminuria levels. Independent of T2D or albuminuria, a substantial risk for adverse outcomes exists for CKD patients in a routine care setting.