Medicines Company Research Articles

Inter-individual variability in LDL-C reductions with inclisiran – data from ORION-10 and ORION-11

Abstract Introduction Inclisiran, an investigational siRNA, has been shown to effectively and durably lower LDL-C in Phase 3 trials. Inter-individual variability in LDL-C reductions has been documented for statin therapy and ezetimibe. Purpose To evaluate the inter-individual variability in LDL-C lowering with inclisiran. Methods The Phase 3 ORION-10 and ORION-11 trials randomized patients with established ASCVD (or risk-equivalents) who had LDL-C >70 mg/dl despite maximally tolerated statins to inclisiran or placebo (1:1). Inclisiran sodium 300 mg was administered s.c. at baseline, three months later, then every six months. Co-primary endpoints were the LDL-C reduction from baseline to Day 510 and the time adjusted average % change in LDL-C reduction after Day 90 and up to Day 540. Measures of response variability were pre-specified secondary endpoints. This analysis examines the inter-individual variability of LDL-C reductions at day 510 using pooled data from both trials. Results The analysis included 3178 individuals (92% on statins). At Day 90, 97% of inclisiran-treated patients had an LDL-C reduction. At Day 510, the median percent reduction in LDL-C levels from baseline was 57.3% in the inclisiran group (interquartile range, 44%-70%). An LDL-C reduction ≥50% was reached by 1359 (86.6%) inclisiran-treated patients versus 97 (6.2%) placebo patients at any visit (odds ratio [OR] 97.6, 95% confidence interval [CI] 76–126). An LDL-C reduction ≥30% was reached by 1523 (97.0%) inclisiran-treated patients versus 371 (23.7%) placebo patients (OR 104.5, 95% CI 76–143). At Day 510, 921 patients (65.1%) in the inclisiran group had a reduction ≥50% in LDL-C compared to 34 patients (2.4%) in the placebo group, and 1228 (86.8%) had a reduction ≥30% compared to 148 (10.5%), respectively. Among placebo-treated patients, there was a substantial proportion with notable increases in LDL-C at Day 510 (figure). Conclusion In Phase 3 trials, inclisiran on top of maximally tolerated statins provided reliable, consistent and durable reductions in LDL-C. A large percentage of subjects randomized to inclisiran achieved substantial reductions (>50%) in LDL-C and nearly all achieved at least a 30% reduction suggesting inclisiran is potentially a promising novel therapy for patients needing sustained LDL-C reductions. Waterfall plot of pooled trials Funding Acknowledgement Type of funding source: Private company. Main funding source(s): The Medicines Company

Pooled safety and efficacy of inclisiran in patients with statin intolerance (ORION-10 and ORION-11)

Abstract Introduction Statin-associated side effects prevent a substantial proportion of patients from being adequately treated with statin therapy and achieving adequate LDL-C reductions. Phase 3 trials showed that inclisiran, a new siRNA, durably lowers LDL-C by ≥50% on top of maximally tolerated statin therapy. Purpose To evaluate inclisiran's tolerability and LDL-C lowering effects among individuals who were not receiving statin therapy mainly because of statin intolerance. Methods The Phase 3 ORION-10 and ORION-11 trials randomized patients with established ASCVD (or risk-equivalents) with LDL-C >70 mg/dl despite maximally tolerated statins to inclisiran or placebo (1:1). Inclisiran sodium 300 mg was administered s.c. at baseline, three months later, then every six months. The primary efficacy endpoints were % change in LDL-C from baseline to Day 510 and time adjusted % change in LDL-C from baseline after Day 90 and up to Day 540. Absolute LDL-C reductions were secondary endpoints. This analysis included individuals who were not on statin therapy at baseline. Results The trials included 252 (7.9% of the pooled trial populations; mean age 68; male 62%; lipid-lowering therapy 28%). AE rates and LDL-C reductions are shown in the Table. Overall, 12 (4.7%) patients had myalgia (4.8% in the inclisiran groups, 4.7% in the placebo groups). There were 8 discontinuations in the inclisiran groups (6.5%) and 3 in the placebo groups (2.3%). The placebo-adjusted mean reduction in LDL-C at Day 510 was 45.8%, an absolute reduction of 68.0 mg/dL (p<0.0001). Conclusion Among statin intolerant individuals in ORION-10 and 11, inclisiran potently and durably lowered LDL-C with an adverse event profile comparable to placebo. Inclisiran may represent a new and potent therapeutic option for patients with elevated LDL-C unable to tolerate statins. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): The Medicines Company

Baseline triglycerides and non-HDL-C and apoB goal attainment in the ORION-10 and ORION-11 trials

Abstract Introduction Elevated triglyceride (TG) levels contribute to the total burden of circulating atherogenic lipoprotein levels and are associated with increased cardiovascular (CV) risk. LDL-C underestimates risk in patients with elevated TG. Therefore, 2019 ESC/EAS guidelines recommend apoB or non-HDL-C as secondary lipid goals for patients with TG >150mg/dL. Purpose To assess the impact of inclisiran on apoB and non-HDL-C goal attainment across a range of TG levels among patients with atherosclerotic CV disease (ASCVD). Methods The ORION-10 and ORION-11 trials included 3178 patients with ASCVD and LDL-C >70mg/dl despite maximally tolerated statins randomized to inclisiran or placebo (1:1). Pre-specified secondary endpoints were placebo-corrected changes in lipids at Day 510. For this analysis patients were stratified by TG quartiles at baseline within each trial. The proportion of individuals attaining apoB <55 mg/dL or non-HDL-C <70mg/dl within each trial were assessed across TG strata and the likelihood of goal attainment within TG strata assessed using logistic regression. Results In ORION-10, TG quartiles were ≤94, 94 to ≤128, 128 to ≤181 and >181mg/dl respectively and in ORION-11 corresponding values were ≤101, 101 to ≤135, 135 to ≤183 and >183mg/dl. As compared to placebo a significantly greater proportion of patients randomised to inclisiran attained apoB goals within each TG strata (Table). Similar results were observed for non-HDL-C. Conclusion Among patients with ASCVD on maximally tolerated statin and high TG levels, attainment of apoB and non-HDL-C secondary lipid targets was more likely with inclisiran than placebo. Inclisiran may be a useful therapeutic option for patients with atherogenic dyslipidaemia. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): The Medicines Company

Green Marketing to Customer Need and Customer Satisfaction in Herbal City Community: Case of the North of Thailand

Herbal medicine companies have essential role among the community. It has unique role in the medicine companies to fulfill the health-related needs of people. However, herbal city community was neglected by the literature. Especially, the role of green marketing was not examined in relation to the customer needs and customer satisfaction. Hence, the current study filled this literature gap by examining the role of green marketing in customer needs and customer satisfaction. This objective was achieved by examining the relationship between green marketing, green environment, customer needs and customer satisfaction. The survey questionnaire was effective tool for data collection which was used in this study and 210 valid responses were used in data analysis. Data were collected from North of Thailand. Results of the study shows that green marketing has positive effect on customer needs. Green marketing also has positive effect on customer satisfaction. Moreover, green marketing promotes green environment which further shows positive influence on customer needs and customer satisfaction.

Green Marketing to Customer Need and Customer Satisfaction in Herbal City Community: Case of the North of Thailand

Herbal medicine companies have essential role among the community. It has unique role in the medicine companies to fulfill the health-related needs of people. However, herbal city community was neglected by the literature. Especially, the role of green marketing was not examined in relation to the customer needs and customer satisfaction. Hence, the current study filled this literature gap by examining the role of green marketing in customer needs and customer satisfaction. This objective was achieved by examining the relationship between green marketing, green environment, customer needs and customer satisfaction. The survey questionnaire was effective tool for data collection which was used in this study and 210 valid responses were used in data analysis. Data were collected from North of Thailand. Results of the study shows that green marketing has positive effect on customer needs. Green marketing also has positive effect on customer satisfaction. Moreover, green marketing promotes green environment which further shows positive influence on customer needs and customer satisfaction.

The Efficacy and Safety of Evinacumab in Homozygous Familial Hypercholesterolemia Patients with Little to No Low-Density Lipoprotein Receptor Activity

Robert Rosenson has received honoraria from Amgen, Kowa, Pfizer, and Regeneron; consultancy/advisory board fees from Amgen, C5, Corvidia, CVS Caremark, Medicines Company, and Regeneron; and research funding from Akcea, Amgen, AstraZeneca, Medicines Compan.

303-OR: Effect of Dapagliflozin on Risk for Fast Decline in EGFR: Analyses from the DECLARE-TIMI 58 Trial

SGLT2 inhibitors may lead to short term decrease in eGFR, with later stabilization and long-term reduction in the risk for end stage kidney disease. Fast decline (FD) in eGFR can be defined as a reduction of ≥3 ml/min/1.73m2/year and is associated with poor long-term renal prognosis. In this post-hoc analysis we studied the effect of dapagliflozin (dapa) on the risk for FD in the DECLARE-TIMI 58 trial. In DECLARE-TIMI 58, 17,160 patients with T2D and established or increased risk for CVD, with mean baseline eGFR of 85.2 ml/min/1.73m2, were randomized to dapa vs. placebo and followed for a median of 4.2 years. The risk for FD was compared between treatment arms. In the time frame of 0.5 years (after stabilization) to 4 years, the proportion of patients with FD was reduced with dapa vs. placebo (26.8% vs. 37.1% respectively, p<0.0001). This observation was persistent in all subgroups assessed (Table). The mean (SD) reduction in eGFR per year was 6.3 (3.7) vs. 0.0 (2.5) ml/min/1.73m2/year in the FD (N=4,788) vs. non-FD (N=10,224) patients. The proportion of patients with FD during the entire study period (i.e., 0-4 years) was reduced with dapa vs. placebo as well (33.6% vs. 37.0% respectively, p<0.0001). Dapagliflozin reduced the risk for FD in eGFR in a broad population of patients with T2D and either established or increased risk for CVD, but relatively preserved renal function, irrespective of patients’ baseline characteristics.

185-OR: Efficacy and Safety of Bempedoic Acid in Patients with Diabetes, Prediabetes, and Normoglycemia: Analysis of Pooled Patient-Level Data from Four Phase 3 Clinical Trials

Background: Current guidelines support aggressive LDL-C lowering in patients with diabetes. We assessed the efficacy and safety of BA, a first-in-class ATP-citrate lyase inhibitor, by baseline glycemic status (diabetes, prediabetes, or normoglycemia) in patients with hypercholesterolemia. Methods: Four phase 3 trials randomized 3623 patients on stable lipid-lowering therapy to receive BA 180 mg or placebo (PBO) once daily for 12 to 52 weeks. Studies were grouped into 2 pools by enrollment criteria (52-weeks in patients with atherosclerotic cardiovascular disease and/or heterozygous familial hypercholesterolemia vs. 12- or 24- weeks in patients with statin intolerance). Primary efficacy endpoint was percent change from baseline to week 12 in LDL-C. Results: In both pools, BA significantly lowered LDL-C compared with PBO, regardless of baseline glycemic status (all P&amp;lt;.001; Table). Significant reductions with BA vs. PBO were seen in total cholesterol, non-HDL-C, apolipoprotein B, and hsCRP (all P&amp;lt;.01). The safety profile of BA was similar to PBO and did not vary by glycemic status. BA did not worsen measures of glycemic control or increase occurrence of new-onset diabetes mellitus compared with PBO. Conclusion: BA significantly lowered LDL-C and had a safety profile comparable to PBO, regardless of baseline glycemic status. Disclosure L.A. Leiter: Advisory Panel; Self; Abbott, Amgen, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Boehringer Ingelheim International GmbH, Eli Lilly and Company, HLS Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi, Servier. Research Support; Self; Amgen, AstraZeneca, Kowa Pharmaceuticals America, Inc., Medicines Company. Speaker’s Bureau; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, HLS Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Medscape, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi, Servier. M. Banach: Advisory Panel; Self; Esperion Therapeutics, Inc., Novo Nordisk Inc. Research Support; Self; Resverlogix Corp. Speaker’s Bureau; Self; Amgen, Sanofi. A.L. Catapano: Other Relationship; Self; Akcea Therapeutics, Amgen, Daiichi Sankyo, Esperion Therapeutics, Inc., Kowa Company, Ltd., Menarini Group, Mylan, Novartis, Ionis Pharmaceuticals, Medco, MSD, Recordati, Astrazeneca, Aegerion, Amryt, Eli Lilly, Genzyme, Regeneron Pharmaceuticals, Sanofi. P. Duell: Consultant; Self; Akcea Therapeutics, AstraZeneca, Esperion Therapeutics, Inc. Other Relationship; Self; Regeneron Pharmaceuticals, REGENXBIO Inc., Retrophin, Inc. A. Gotto: Board Member; Self; Esperion Therapeutics, Inc. Consultant; Self; Amarin Corporation, Kowa Company, Ltd. Other Relationship; Self; Ionis Pharmaceuticals, Inc. U. Laufs: Advisory Panel; Self; Esperion Therapeutics, Inc. G. Mancini: Advisory Panel; Self; Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Boehringer Ingelheim (Canada) Ltd., Esperion Therapeutics, Inc., HLS Therapeutics, Inc., Sanofi. K.K. Ray: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Esperion Therapeutics, Inc., Novo Nordisk Inc., Sanofi. J.C. Hanselman: Employee; Self; Esperion Therapeutics, Inc. Stock/Shareholder; Self; Esperion Therapeutics, Inc. A. Feng: Employee; Self; Esperion Therapeutics, Inc. H. Bays: Advisory Panel; Self; Esperion Therapeutics, Inc. Consultant; Self; Kowa Company, Ltd. Research Support; Self; Abbott, Acasti, Akcea, Amarin Corporation, Amgen, AstraZeneca, Dr. Reddy’s Laboratories, Esperion Therapeutics, Inc., Gan &amp; Lee Pharmaceuticals, Ionis Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Johnson &amp; Johnson, LIB, Lilly Diabetes, Matinas BioPharma, Medicines Company, MedImmune, Merck &amp; Co., Inc., Novo Nordisk A/S, Pfizer Inc., Regeneron Pharmaceuticals, Sanofi.

271-OR: ADA Presidents’ Select Abstract: Effect of Dapagliflozin on the Incidence of Diabetes: A Prespecified Exploratory Analysis from DAPA-HF

In DAPA-HF, the SGLT2 inhibitor (i) dapagliflozin (dapa) reduced worsening heart failure (HF) and cardiovascular death in 4744 patients (pts) with HF and reduced ejection fraction (HFrEF.) Only 45% had type 2 diabetes (T2D) at baseline. We evaluated whether dapa reduced the incidence of diabetes in the 55% of pts without T2D. Pts were randomized to dapa 10 mg or placebo and followed for a median of 18.2 months. New-onset T2D was defined as A1c ≥6.5% measured at 2 consecutive study visits post-randomization or investigator-reported new T2D (with the initiation of a glucose-lowering agent.) The effect of dapa on incident T2D was assessed using a Cox proportional hazards model and confirmed with a Fine and Gray competing risk model to account for mortality. Of the 2605 non-T2D pts at baseline, 157 developed T2D on trial, 150 (95.5%) of whom had prediabetes (A1c 5.7-6.4%) (136 [86.6%] using the more restrictive 6.0-6.4% criterion.) Those with incident T2D had a higher mean baseline A1c (6.2 ±0.3 vs. 5.7 ±0.4%; p&amp;lt;0.001), greater BMI (28.5 ±5.9 vs. 27.1 ±5.7 kg/m2; p=0.003), and lower eGFR (61.5 ±17.4 vs. 68.2 ±19.3 ml/min/1.73 m2; p&amp;lt;0.001) than those who remained nondiabetic. Dapa reduced new-onset diabetes by 32%: placebo 93/1307 (7.1%) vs. dapa 64/1298 (4.9%); HR 0.68 (95% CI, 0.50-0.94; p=0.019) (Cox.) Results were virtually identical using the Fine and Gray model. Diabetes prevention may be another benefit of dapagliflozin. Disclosure S.E. Inzucchi: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; Abbott, Merck &amp; Co., Inc., vTv Therapeutics. K. Docherty: Speaker’s Bureau; Self; Eli Lilly and Company. Other Relationship; Self; AstraZeneca. L. Kober: Speaker’s Bureau; Self; AstraZeneca, Novartis AG. Other Relationship; Self; AstraZeneca. M.N. Kosiborod: Consultant; Self; Amarin Corporation, Amgen, Applied Therapeutics, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., Eli Lilly and Company, GlaxoSmithKline plc., Glytec, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck &amp; Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi US, Vifor Pharma Group. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. F. Martinez: Board Member; Self; AstraZeneca, Novartis Pharmaceuticals Corporation. P. Ponikowski: None. M.S. Sabatine: Consultant; Self; Amgen, AstraZeneca, Bristol-Myers Squibb, CVS Caremark, DalCor Pharmaceuticals, Dyrnamix Inc., Esperion Therapeutics, Inc., IFM Therapeutics, Intarcia Therapeutics, Ionis Pharmaceuticals, Inc., Medicines Company, MedImmune, Merck &amp; Co., Inc. Research Support; Self; Amgen, AstraZeneca, Bayer U.S., Daiichi Sankyo, Eisai Inc., Intarcia Therapeutics, Janssen Research and Development, Medicines Company, MedImmune, Merck &amp; Co., Inc., Novartis AG, Pfizer Inc., Quark Pharmaceuticals. S. Solomon: Consultant; Self; AstraZeneca, Theracos, Inc. Research Support; Self; AstraZeneca, Theracos, Inc. J. Belohlavek: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH. M. Böhm: Speaker’s Bureau; Self; Abbott, Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb, Medtronic, Novartis Pharmaceuticals Corporation, Servier, Vifor Pharma Group. C. Chiang: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Merck Sharp &amp; Dohme Corp., Novartis AG, Pfizer Inc., Sanofi. R.A. de Boer: Speaker’s Bureau; Self; Abbott, AstraZeneca, Novartis AG, Roche Diagnostics France. M. Diez: Other Relationship; Self; AstraZeneca. A. Dukat: None. C.E.A. Ljungman: Advisory Panel; Self; AstraZeneca, Novartis AG, Pfizer Foundation. Stock/Shareholder; Self; AstraZeneca. Other Relationship; Self; AstraZeneca, Novartis AG. S. Verma: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim (Canada) Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc. Other Relationship; Self; AstraZeneca, AstraZeneca, Bayer AG, Boehringer Ingelheim (Canada) Ltd., Boehringer Ingelheim International GmbH, Eli Lilly and Company, Eli Lilly and Company, EOCI Pharmacomm, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novartis Pharmaceuticals Canada Inc., Novo Nordisk A/S, Novo Nordisk A/S, Sanofi, Sanofi, Sun Pharmaceuticals, Toronto Knowledge Translation Working Group. D.L. DeMets: Consultant; Self; Actelion Pharmaceuticals US, Inc., AstraZeneca, Boston Scientific, Bristol-Myers Squibb, DalCor Pharmaceuticals, Intercept Pharmaceuticals, Inc., Medtronic. O. Bengtsson: Employee; Self; AstraZeneca. A. Langkilde: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. M. Sjöstrand: Employee; Self; AstraZeneca. P. Jhund: Advisory Panel; Self; Cytokinetics Inc. Research Support; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Novartis AG. Other Relationship; Self; AstraZeneca. J.J. McMurray: Other Relationship; Self; AbbVie Inc., Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Bristol-Myers Squibb, Cardurion, GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Theracos, Inc. Funding AstraZeneca

1112-P: Does Background T2D Therapy Modify the Benefits of Dapagliflozin in Heart Failure? Analysis of the DAPA-HF Trial

Background: At present, dapagliflozin (dapa) is typically used as a 2nd-line glucose-lowering medication (GLM) in T2D, often added to metformin. In DAPA-HF, dapa improved clinical outcomes vs. placebo in patients (pts) with HF and reduced ejection fraction (HFrEF), with or without T2D. We examined whether these benefits varied by background GLM in the T2D cohort, including in drug naïve pts and in pts not on metformin. Methods: The primary outcome was a composite of worsening HF (hospitalization or urgent visit requiring IV therapy) or cardiovascular death. The effect of dapa vs. placebo was examined using Cox proportional hazards models. Results: Of the 2139 T2D pts, 1596 (75%) were treated with GLM: metformin (48%), insulin (25%), sulfonylurea (21%), DPP-4 inhibitor (14%) and GLP-1 agonist (1%). Drug-naïve pts had a lower A1c (6.9%±1.2 vs. 7.5%±1.6; P&amp;lt;0.001) and shorter T2D duration (median 5.5 vs. 103 months; P&amp;lt;0.001). Those not using metformin had a lower eGFR (61 vs. 66; P&amp;lt;0.001). The effect of dapa on the primary outcome was consistent in the drug-naïve vs. pts receiving GLM (HR 0.86 [95%CI 0.60-1.23] vs. 0.72 [0.58-0.88]; P-interaction=0.39) and across GLM classes, including those using vs. not using metformin (HR 0.67 [0.51-0.88] vs. 0.81 [0.64-1.03]; P-interaction=0.30). Conclusion: In DAPA-HF, dapa improved outcomes irrespective of use/no use of GLM or by type of GLM used in pts with T2D and HFrEF. Disclosure K. Docherty: Speaker’s Bureau; Self; Eli Lilly and Company. Other Relationship; Self; AstraZeneca. S.E. Inzucchi: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; Abbott, Merck &amp; Co., Inc., vTv Therapeutics. M.N. Kosiborod: Consultant; Self; Amarin Corporation, Amgen, Applied Therapeutics, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., Eli Lilly and Company, GlaxoSmithKline plc., Glytec, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck &amp; Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi US, Vifor Pharma Group. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. L. Kober: Speaker’s Bureau; Self; AstraZeneca, Novartis AG. Other Relationship; Self; AstraZeneca. A. Langkilde: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. F. Martinez: Board Member; Self; AstraZeneca, Novartis Pharmaceuticals Corporation. O. Bengtsson: Employee; Self; AstraZeneca. D.L. DeMets: Consultant; Self; Actelion Pharmaceuticals US, Inc., AstraZeneca, Boston Scientific, Bristol-Myers Squibb, DalCor Pharmaceuticals, Intercept Pharmaceuticals, Inc., Medtronic. M. Sjöstrand: Employee; Self; AstraZeneca. M.S. Sabatine: Consultant; Self; Amgen, AstraZeneca, Bristol-Myers Squibb, CVS Caremark, DalCor Pharmaceuticals, Dyrnamix Inc., Esperion Therapeutics, Inc., IFM Therapeutics, Intarcia Therapeutics, Ionis Pharmaceuticals, Inc., Medicines Company, MedImmune, Merck &amp; Co., Inc. Research Support; Self; Amgen, AstraZeneca, Bayer U.S., Daiichi Sankyo, Eisai Inc., Intarcia Therapeutics, Janssen Research and Development, Medicines Company, MedImmune, Merck &amp; Co., Inc., Novartis AG, Pfizer Inc., Quark Pharmaceuticals. S. Solomon: Consultant; Self; AstraZeneca, Theracos, Inc. Research Support; Self; AstraZeneca, Theracos, Inc. P. Jhund: Advisory Panel; Self; Cytokinetics Inc. Research Support; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Novartis AG. Other Relationship; Self; AstraZeneca. J.J. McMurray: Other Relationship; Self; AbbVie Inc., Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Bristol-Myers Squibb, Cardurion, GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Theracos, Inc.

1429-P: Use of Guideline-Recommended Risk-Reduction Strategies among Patients with Type 2 Diabetes and Established ASCVD: A 1-Year Update from Getting to an Improved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management (GOULD)

Due to emerging evidence, recent practice guidelines are emphasizing more aggressive use of effective prevention strategies in high-risk patients with diabetes (DM). We assessed changes in the use of evidence-based therapies among pts with DM from a registry of 5006 U.S. participants (pts) with ASCVD and LDL-C ≥70mg/dL across 120 U.S. centers taking lipid-lowering therapy (LLT). Among 1,622 DM pts with 12-month follow-up, 14% had intensification of LLT since baseline, 7% de-escalated. Median LDL-C at 12 months was 81 mg/dL, an 11% decrease from baseline. Among pts in the LDL-C cohorts, the percentage with LDL-C &amp;lt;70mg/dL increased from baseline through 12 months (Table). Use of statins and high-intensity statins was stable, while ezetimibe increased, and PCSK9i’s were initiated in 3% of pts not on a PCSK9i at enrollment. Use of SGLT2i, GLP-1RA’s, and fish oil did not change. At 12 months, 8% were on all guideline-recommended therapies for optimal risk reduction, similar to 7% at baseline (p for trend=0.1). Although some modest improvements in the use of secondary cardiovascular prevention therapies were observed, the proportion of patients with DM and ASCVD that receive optimal guideline-recommended risk reduction strategies remains very low. Disclosure M.N. Kosiborod: Consultant; Self; Amarin Corporation, Amgen, Applied Therapeutics, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., Eli Lilly and Company, GlaxoSmithKline plc., Glytec, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck &amp; Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi US, Vifor Pharma Group. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. S.V. Arnold: None. J. Delemos: Consultant; Self; Amgen, Novo Nordisk A/S, Regeneron Pharmaceuticals. R.S. Rosenson: Advisory Panel; Self; Amgen, Medicines Company. Consultant; Self; CVS Caremark. Research Support; Self; Amgen, Medicines Company, Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals. Other Relationship; Self; Amgen, Kowa Pharmaceuticals America, Inc., UpToDate. C.M. Ballantyne: Consultant; Self; Abbott, Akcea Therapeutics, Amarin Corporation, Amgen, Arrowhead Pharmaceuticals, Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Corvidia, Denka-Seiken Co., Ltd., Esperion Therapeutics, Inc., Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Matinas BioPharma, Merck &amp; Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Regeneron Pharmaceuticals, Roche Diagnostic USA, Sanofi. Research Support; Self; Abbott, Akcea Therapeutics, Amgen, Esperion Therapeutics, Inc., Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Roche Diagnostic USA. Y. Liu: None. K.E. Mues: Employee; Self; Amgen. Stock/Shareholder; Self; Amgen. S. Alam: Employee; Self; Amgen. D.L. Bhatt: Research Support; Self; Abbott, Afimmune, Amarin Corporation, Amgen, AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Cardax, Chiesi USA, Inc., CSL Behring, Ferring Pharmaceuticals, Fractyl Laboratories, Inc., Idorsia, Ironwood Pharmaceuticals, Ischemix, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Pfizer Inc., PhaseBio Pharmaceuticals, Inc., PLx Pharma Inc., Regeneron Pharmaceuticals, Roche Pharma, Sanofi-Aventis, Synaptic. C. Cannon: None. Funding Amgen Inc.

403-P: Impact of Diabetes-Related Factors and Background Antihyperglycemic Therapy on the Efficacy and Safety of Ticagrelor Added to Aspirin: Insights from the THEMIS Trial

In the THEMIS trial of 19,220 patients with stable CAD and T2DM without prior MI or stroke followed for a median of 39.9 months, ticagrelor plus aspirin (ASA) lowered ischemic CV events but increased major bleeding events compared with placebo plus ASA, with a more favorable net clinical benefit in those with prior PCI. We now report the efficacy and safety by diabetes-related factors and background antihyperglycemic therapy. While the incidence of the primary efficacy outcome (CV death, MI, stroke; MACE) event rates (overall 8.1%) was higher with increasing diabetes duration (11.1% &amp;gt;20 years vs. 6.7% ≤5 years) and A1c (11.8% &amp;gt;10% vs. 6.4% ≤6%), the relative benefits of ticagrelor on MACE reduction (overall HR 0.90; p=0.04) did not differ across these various subgroups (p-values for interaction=0.83 and 0.16, respectively). In contrast, the primary safety outcome (TIMI major bleeding) event rate (overall 1.6%) did not vary by diabetes duration or A1c and was similarly increased by ticagrelor in all of these subgroups (overall HR=2.32 [1.82,2.94]; p&amp;lt;0.01). The impact of diabetes duration and A1c were similar in the prior PCI subgroup. Regardless of treatment assignment, patients treated with insulin vs. not had a higher risk for MACE (HR=1.65 [1.49, 1.83]; p&amp;lt;0.01) with no difference in major bleeding (HR=0.92 [0.71, 1.19]; p=0.52), while those treated with sulfonylurea vs. not had no difference in risk for MACE (HR=1.00 [0.91,1.11]; p=0.93) or major bleeding (HR=1.12 [0.89,1.41]; p=0.34) endpoints. The efficacy and safety of ticagrelor did not differ based on background antihyperglycemic therapy. These data suggest that, in general, the relative benefits and risks of ticagrelor added to aspirin are consistent regardless of T2DM duration, A1c, or background antihyperglycemic therapy. NCT01991795. Disclosure L.A. Leiter: Advisory Panel; Self; Abbott, Amgen, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Boehringer Ingelheim International GmbH, Eli Lilly and Company, HLS Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi, Servier. Research Support; Self; Amgen, AstraZeneca, Kowa Pharmaceuticals America, Inc., Medicines Company. Speaker’s Bureau; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, HLS Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Medscape, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi, Servier. D.L. Bhatt: Research Support; Self; Abbott, Afimmune, Amarin Corporation, Amgen, AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Cardax, Chiesi USA, Inc., CSL Behring, Ferring Pharmaceuticals, Fractyl Laboratories, Inc., Idorsia, Ironwood Pharmaceuticals, Ischemix, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Pfizer Inc., PhaseBio Pharmaceuticals, Inc., PLx Pharma Inc., Regeneron Pharmaceuticals, Roche Pharma, Sanofi-Aventis, Synaptic. D.K. McGuire: Consultant; Self; Afimmune, Applied Therapeutics, Merck Sharp &amp; Dohme Corp., Metavant. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Co., Ltd., Eli Lilly and Company, Esperion Therapeutics, Inc., GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis. K. Fox: Other Relationship; Self; AstraZeneca, Servier. T. Simon: Advisory Panel; Self; Novartis Pharmaceuticals Corporation, Servier. Board Member; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc. Consultant; Self; Air Liquide, Sanofi. S. Mehta: Research Support; Self; AstraZeneca. E. Lev: None. R.G. Kiss: Speaker’s Bureau; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Boehringer Ingelheim International GmbH, Merck Sharp &amp; Dohme Corp., Pfizer Inc. A.J. Dalby: None. H. Bueno: Advisory Panel; Self; AstraZeneca, Bayer AG, Novartis AG. Consultant; Self; Amgen, Bristol-Myers Squibb, Pfizer Inc. Research Support; Self; AstraZeneca, Novartis AG. W. Ridderstråle: Employee; Self; AstraZeneca. A. Himmelmann: Employee; Self; AstraZeneca. J. Prats: Other Relationship; Self; AstraZeneca. Y. Liu: None. J.J. Lee: None. J. Amerena: None. M.N. Kosiborod: Consultant; Self; Amarin Corporation, Amgen, Applied Therapeutics, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., Eli Lilly and Company, GlaxoSmithKline plc., Glytec, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck &amp; Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi US, Vifor Pharma Group. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. P.G. Steg: Consultant; Self; Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Idorsia, Mylan, Novartis AG, Pfizer Inc., Sanofi, Servier. Research Support; Self; Amarin Corporation. Speaker’s Bureau; Self; Novo Nordisk A/S.

28-OR: How Early after Treatment Initiation Are the CV Benefits of Empagliflozin Apparent? A Post Hoc Analysis of EMPA-REG OUTCOME

In the EMPA-REG OUTCOME trial, in patients with type 2 diabetes (T2D) with established atherosclerotic cardiovascular disease (ASCVD), empagliflozin reduced the risk of hospitalization for HF (HHF) by 35% (HR [95%CI] 0.65 [0.50-0.85]), CV death/HHF by 34% (0.66 [0.55-0.79]), and CV death by 38% (0.62 [0.49-0.77]) with an early separation of the cumulative incidence curves. We aimed to explore at what time point after randomization the benefits became apparent. Overall, 7020 patients were treated with empagliflozin 10, 25 mg or placebo. We expressed time trajectories for the effect of pooled empagliflozin doses vs. placebo on HHF, CV death/HHF and CV death based on Hazard Ratios (HRs) (95% CI), and calculated the HR on the day the effect reached significance using Cox proportional hazards models. The reduction in risk with empagliflozin vs. placebo reached significance at day 17 for HHF [0.10 [0.01, 0.87), p=0.0372], and day 27 for CV death/HHF [HR 0.28 (0.08, 0.97), p=0.0445], and sustained significant throughout follow-up (Figure). The benefit on CV death reached significance for the first time at day 59 [HR 0.28 (0.08, 0.96)]. HRs stabilized as the number of patients with events increased over time. The benefit of empagliflozin in reducing the risk of HHF, CV death/HHF and CV death emerged within weeks after treatment initiation in EMPA-REG OUTCOME. The earliest effect appears to be on HHF. Disclosure S. Verma: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim (Canada) Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc. Other Relationship; Self; AstraZeneca, AstraZeneca, Bayer AG, Boehringer Ingelheim (Canada) Ltd., Boehringer Ingelheim International GmbH, Eli Lilly and Company, Eli Lilly and Company, EOCI Pharmacomm, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novartis Pharmaceuticals Canada Inc., Novo Nordisk A/S, Novo Nordisk A/S, Sanofi, Sanofi, Sun Pharmaceuticals, Toronto Knowledge Translation Working Group. L.A. Leiter: Advisory Panel; Self; Abbott, Amgen, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Boehringer Ingelheim International GmbH, Eli Lilly and Company, HLS Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi, Servier. Research Support; Self; Amgen, AstraZeneca, Kowa Pharmaceuticals America, Inc., Medicines Company. Speaker’s Bureau; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, HLS Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Medscape, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi, Servier. A. Sharma: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Roche Pharma. Research Support; Self; Bristol-Myers Squibb, Merck &amp; Co., Inc. Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation. B. Zinman: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. M. Mattheus: None. D.H. Fitchett: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Lilly Diabetes. Other Relationship; Self; Novo Nordisk Inc. J.T. George: Employee; Self; Boehringer Ingelheim International GmbH. A. Ofstad: Employee; Self; Boehringer Ingelheim International GmbH. C. Wanner: Advisory Panel; Self; Eli Lilly and Company, Merck &amp; Co., Inc., Mundipharma International. Consultant; Self; Boehringer Ingelheim (Canada) Ltd., Sanofi Genzyme. Speaker’s Bureau; Self; AstraZeneca. Other Relationship; Self; Boehringer Ingelheim International GmbH. S.E. Inzucchi: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; Abbott, Merck &amp; Co., Inc., vTv Therapeutics. Funding Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance

1021-P: HbA1c Levels and Rates of Hypoglycemia with Insulin Degludec U200 and Insulin Glargine U300 Stratified by Renal Function Subgroups: Post Hoc Analysis from the CONCLUDE Trial

CONCLUDE was a randomized, open-label, treat-to-target trial in participants with T2D, who received basal insulin ± oral antihyperglycemic drugs (OADs) and had ≥1 baseline hypoglycemia risk factors, including moderate renal impairment. Participants were randomized to degludec U200 or glargine U300 (± OADs). CONCLUDE demonstrated no significant difference in the overall symptomatic hypoglycemia rate with degludec U200 vs. glargine U300 in the maintenance period (primary endpoint, tested for superiority). However, lower rates of nocturnal symptomatic and severe hypoglycemia in the maintenance period (exploratory secondary endpoints) were observed with degludec U200 vs. glargine U300. The current post-hoc analysis investigated these hypoglycemia endpoints and HbA1c stratified by baseline estimated glomerular filtration rate (eGFR) subgroups (&amp;lt;60, 60-&amp;lt;90, ≥90 mL/min/1.73 m2). Change in HbA1c from baseline to end of treatment and rates and rate ratios for all hypoglycemia endpoints were comparable across eGFR subgroups and to the primary analyses. No statistically significant interactions were found between the subgroups for the endpoints assessed (Table). Irrespective of renal function, degludec U200 and glargine U300 resulted in similar HbA1c, and hypoglycemia rates were consistent with the primary analyses. Disclosure T.R. Pieber: Advisory Panel; Self; ADOCIA, Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; Novo Nordisk A/S, Roche Diagnostics K.K. H.S. Bajaj: Research Support; Self; Amgen, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Kowa Pharmaceuticals America, Inc., Novartis Pharmaceuticals Canada Inc., Novo Nordisk Inc., Sanofi. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., mdBriefCase, Medscape, Merck Sharp &amp; Dohme Corp., Novo Nordisk Inc. S.R. Heller: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S, Zealand Pharma A/S. Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk A/S. Other Relationship; Self; MannKind Corporation. T. Jia: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. K. Khunti: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp &amp; Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Board Member; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp &amp; Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier. Speaker’s Bureau; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp &amp; Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. D.C. Klonoff: Consultant; Self; Abbott, Ascensia Diabetes Care, Dexcom, Inc., EOFlow, Fractyl Laboratories, Inc., Know Labs, LifeCare, Inc., Novo Nordisk Inc., Roche Diabetes Care. S. Ladelund: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. L.A. Leiter: Advisory Panel; Self; Abbott, Amgen, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Boehringer Ingelheim International GmbH, Eli Lilly and Company, HLS Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi, Servier. Research Support; Self; Amgen, AstraZeneca, Kowa Pharmaceuticals America, Inc., Medicines Company. Speaker’s Bureau; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, HLS Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Medscape, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi, Servier. M.V. Hansen: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. A. Philis-Tsimikas: Advisory Panel; Self; Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi. Funding Novo Nordisk A/S

526-P: Urine Tricarboxylic Acid Cycle Organic Anions and Progression of Diabetic Kidney Disease

Background: Urine tricarboxylic acid (TCA) cycle organic anions (OAs) are elevated in diabetes and may be biomarkers for diabetic kidney disease (DKD) progression. Methods: We conducted an ancillary study to the Simultaneous Risk Factor Control Using Telehealth to Slow Progression of Diabetic Kidney Disease (STOP-DKD) Trial - a randomized trial of pharmacist-led medication and behavior management in 281 patients with early to moderate DKD at Duke from 2014-2015. In this study, we used linear mixed models to assess associations of 10 urine TCA cycle OAs with estimated glomerular filtration rate (eGFR) and eGFR decline. TCA cycle OAs were measured in 24h urine samples by targeted MS and modeled as: (1) the average of z-scores for each OAs; and (2) factor scores derived by principal component analysis (PCA). We extended follow-up for eGFR to mid-2019 using electronic health records. Results: Among 132 participants (50% men; 58% Black; mean age 64 years [SD 9]; median eGFR 72 ml/min/1.73m2 [IQR 59-89] and urine albumin-to-creatinine [UACR] 25 mg/g [IQR 9-81]), PCA identified 3 OA metabolite factors (F). Fumarate, malate, α-ketoglutarate, citrate, lactate, and pyruvate loaded positively on F1; succinate, pyruvate, and lactate loaded negatively on F2; and methylsuccinate, ethylmalonate, and methylmalonate loaded positively on F3. Over a median follow-up of 1 year [IQR 1.3], higher average OA z score, F1, and F3 were each strongly associated with higher baseline eGFR after adjustment for age, sex, race, and log(UACR) at baseline (all p&amp;lt;0.01). Higher F2, but not other scores, was associated with faster eGFR decline (p=0.05). Conclusion: Lower urine TCA cycle OAs, most notably a factor comprising lower succinate, pyruvate and lactate, are potential biomarkers for faster DKD progression. Disclosure J. Lunyera: None. M. Nguyen: None. C.J. Diamantidis: None. H.B. Bosworth: Board Member; Self; Preventric Diagnostic. Consultant; Self; Abbott, Medicines Company, Novartis Pharmaceuticals Corporation. Research Support; Self; improved patient outcomes, Novo Nordisk Foundation, Otsuka Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Pharma foundation, Proteus Digital Health, Proteus Digital Health, Sanofi. U.D. Patel: Board Member; Self; Goldfinch Bio. Employee; Self; Gilead Sciences, Inc. C.A. Davenport: None. J.R. Bain: None. M. Muehlbauer: None. O. Ilkayeva: None. S.H. Shah: Research Support; Self; AstraZeneca, Verily Life Sciences LLC. J. Scialla: Advisory Panel; Self; Tricida. Other Relationship; Self; GlaxoSmithKline plc., Sanofi. Funding National Institute of Diabetes and Digestive and Kidney Diseases (DK076169)

21-OR: Implementation of an Intensive Telehealth Intervention for Rural Patients with Uncontrolled Diabetes

Background: In rural areas, lack of access to specialty care and intensive self-management programs may perpetuate poor diabetes outcomes. Telehealth presents an opportunity to extend specialized diabetes care to rural areas, but may be difficult to implement in routine practice. We examined rural implementation of an intensive telehealth intervention designed to leverage existing Veterans Health Administration (VHA) Home Telehealth (HT) infrastructure for patients with uncontrolled type 2 diabetes despite receiving routine care. Methods: Advanced Comprehensive Diabetes Care (ACDC) is a 6-month telehealth intervention for patients with poor glycemic control (varies by site, typically ≥8.5%), established as effective in a prior randomized trial. ACDC combines telemonitoring, self-management support, and clinician-guided medication management, and is delivered by clinical HT nurses using standard HT equipment. During 2017-2019, we implemented and evaluated ACDC at 5 rural VHA sites with guidance from the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Results: From 2017-2019, 30-100% of eligible patients at each site were enrolled in ACDC, for a total of 125 patients (94% male, 89% white, 71% classified as rural/highly rural). Across sites, mean HbA1c improved from 9.25% at baseline to 7.89% at 6 months (-1.36%, 95% CI: -1.61,-1.11; p&amp;lt;0.001), a benefit that persisted at 12 (-1.22%, 95% CI: -1.48,-0.97; p&amp;lt;0.001) and 18 months (-1.07%, 95% CI -1.40,-0.73; p&amp;lt;0.001). Implementation at each site was acceptable, with an average of 8-10 of 12 scheduled ACDC calls completed. Qualitatively, ACDC enhanced patient engagement and awareness of glycemic control, while moderately increasing workload for providers. Conclusions: When strategically designed to use existing infrastructure, intensive telehealth interventions are conducive to implementation and produce sustained improvements in glycemic control among rural patients. Disclosure E.A. Kobe: None. A. Lewinski: None. S. Danus: None. E.L. Sidoli: None. B. Greck: None. L.C. Horne: None. D. Saxon: None. S.D. Shook: None. L.E. Aguirre: None. C. Evenson: None. C.S. Elizagaray: None. G.L. Jackson: None. H.B. Bosworth: Board Member; Self; Preventric Diagnostic. Consultant; Self; Abbott, Medicines Company, Novartis Pharmaceuticals Corporation. Research Support; Self; improved patient outcomes, Novo Nordisk Foundation, Otsuka Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Pharma foundation, Proteus Digital Health, Proteus Digital Health, Sanofi. D. Edelman: None. M. Crowley: None. Funding VA Office of Rural Health; Veterans Rural Health Resource Center-Iowa City (13366); National Center for Advancing Translation Sciences (TL1TR002555); VA Health Services Research and Development Service (IIR 16-213, 08-027); U.S. Department of Veterans Affairs (TPH 21-000); Durham Center of Innovation to Accelerate Discovery and Practice Transformation (CIN 13-410)

4-LB: Substantial Cardiovascular Benefit from Icosapent Ethyl in Patients with Diabetes: REDUCE-IT DIABETES

Background: Statin-treated patients with diabetes mellitus (DM) are at high cardiovascular (CV) risk. Methods: In REDUCE-IT, icosapent ethyl (IPE; 4 g/day) reduced CV risk vs. placebo in statin-treated patients with either DM plus risk factors or established CV disease. The primary endpoint was CV death, myocardial infarction (MI), stroke, coronary revascularization, or unstable angina. The key secondary endpoint was CV death, MI, or stroke. Key DM analyses were prespecified. Results: 58.5% of patients had DM; 91.0% on ≥1 DM medication, 49.5% on ≥2. IPE reduced primary (Figure) and key secondary first and total (first plus recurrent) events. Patients with and without DM both showed substantial benefits, but patients with DM had 1.5-fold greater rates of the primary endpoint in the placebo group, and a 7% absolute risk reduction in first and a 12.7% reduction in total events (both p&amp;lt;0.001) with IPE. Efficacy and safety were generally consistent with the full study, including reductions in secondary and tertiary endpoints and subgroups, and increases in atrial fibrillation/flutter (3.5% vs. 2.2%; p=0.13) and bleeding (13.1% vs. 10.9%; p=0.02); serious bleeding was not significant (3.2% vs. 2.5%). Fasting glucose and HbA1c were stable. Conclusion: IPE 4 g/day provides robust CV benefits in statin-treated patients with DM, with large relative and absolute risk reductions in both first and total CV events. Disclosure D.L. Bhatt: Research Support; Self; Abbott, Afimmune, Amarin Corporation, Amgen, AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Cardax, Chiesi USA, Inc., CSL Behring, Ferring Pharmaceuticals, Fractyl Laboratories, Inc., Idorsia, Ironwood Pharmaceuticals, Ischemix, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Pfizer Inc., PhaseBio Pharmaceuticals, Inc., PLx Pharma Inc., Regeneron Pharmaceuticals, Roche Pharma, Sanofi-Aventis, Synaptic. E.A. Brinton: Consultant; Self; Esperion Therapeutics, Inc., Medicines Company, Regeneron Pharmaceuticals. Speaker’s Bureau; Self; Amarin Corporation, Amgen, Esperion Therapeutics, Inc. Other Relationship; Self; Amarin Corporation, Kowa Pharmaceuticals America, Inc. M. Miller: Consultant; Self; Amarin Corporation. P.G. Steg: Consultant; Self; Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Idorsia, Mylan, Novartis AG, Pfizer Inc., Sanofi, Servier. Research Support; Self; Amarin Corporation. Speaker’s Bureau; Self; Novo Nordisk A/S. T.A. Jacobson: Consultant; Self; Esperion Therapeutics, Inc., Regeneron Pharmaceuticals, Sanofi US. Other Relationship; Self; Amarin Corporation. S.B. Ketchum: Other Relationship; Self; Amarin Corporation. R.T. Doyle: Other Relationship; Self; Amarin Corporation. R.A. Juliano: Other Relationship; Self; Amarin Corporation. L. Jiao: Other Relationship; Self; Amarin Corporation. C. Granowitz: Other Relationship; Self; Amarin Corporation. O. Ganda: Consultant; Self; Amarin Corporation. Other Relationship; Self; Novo Nordisk A/S. F.K. Welty: Other Relationship; Self; Boehringer Ingelheim International GmbH. R.S. Busch: Research Support; Self; Amarin Corporation, Bayer AG, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc. Speaker’s Bureau; Self; Amarin Corporation, Amgen, Esperion Therapeutics, Inc., Novo Nordisk Inc., Sanofi US. A.C. Goldberg: Advisory Panel; Self; Akcea Therapeutics, Esperion Therapeutics, Inc., Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Sanofi-Aventis. Research Support; Self; Akcea Therapeutics, Amarin Corporation, Amgen, Ionis Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., Regeneron Pharmaceuticals, Sanofi-Aventis. Other Relationship; Self; Merck &amp; Co., Inc. D.M. Herrington: None. M. Budoff: Research Support; Self; Amarin Corporation, General Electric. Speaker’s Bureau; Self; Amarin Corporation. J. Tardif: Research Support; Self; Esperion Therapeutics, Inc., Ionis Pharmaceuticals, Inc., REGENXBIO Inc., Sanofi, Servier. Other Relationship; Self; Amarin Corporation, AstraZeneca, DalCor Pharmaceuticals. C.M. Ballantyne: Consultant; Self; Abbott, Akcea Therapeutics, Amarin Corporation, Amgen, Arrowhead Pharmaceuticals, Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Corvidia, Denka-Seiken Co., Ltd., Esperion Therapeutics, Inc., Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Matinas BioPharma, Merck &amp; Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Regeneron Pharmaceuticals, Roche Diagnostic USA, Sanofi. Research Support; Self; Abbott, Akcea Therapeutics, Amgen, Esperion Therapeutics, Inc., Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Roche Diagnostic USA. Funding Amarin Pharma Inc

EFFICIENCY OF MARKETING IN SELECTION AND EVALUATION OF THE COMPETENCE OF PERSONNEL OF VETERINARY ENTERPRISES

Not only animal welfare but also the state of the environment and human health depend on the quality and harmlessness of the products produced by the veterinary medicine enterprises. Practice, foreign and domestic experience confirm that the competence of the personnel of the enterprise, the ability to organize production and qualified, professional decision making are the leading in ensuring the quality of products produced for veterinary medicine. The point is that every employee, regardless of their position, should see the results of their professional contribution to the quality of veterinary medicine products, their competitiveness in the market. This is undoubtedly justified in the use of marketing opportunities, which will help the managers of enterprises to find those decisions in the selection of personnel, evaluation of their professional competence, which will be the most favorable for the enterprise and will guarantee the stability of the personnel, which will ensure the qualitative and effective execution of the production program of the enterprise, regardless of forms of his property.&#x0D; The study of the objective necessity of using marketing in the selection and evaluation of the personnel of the enterprise shows that marketing in solving this problem will be effective under the conditions: understanding of marketing by all employees in the enterprise, its necessity in solving specific tasks, providing management and specialists of the enterprise with the tasks defined by marketing . In such circumstances, marketing studies of the personnel problem will help to obtain objective information about the compliance of the company staff with the positions held, the attitude of the employees to fulfill their duties, the ability of the staff to find priorities in improving the activity of the company as a whole and its authority in the market of veterinary medicine and consumers respectively.&#x0D; The winners are those businesses that use marketing research results in their work. Although, it should be noted that not all domestic veterinary medicine companies use the principles of marketing, while in developed countries, marketing research is a priority, they are catalysts for achieving the desired economic results. Analysis of the activity of veterinary medicine enterprises shows the need to intensify the organizational work on the introduction of marketing at domestic enterprises and provide the necessary methodological assistance as a whole.

Significance and operation mode of moxibustion intervention for the group under quarantine after close contact with COVID-19

On the base of the idea of traditional Chinese medicine as "disease prevention", the mode and the protocol of the moxibustion intervention for the group under quarantine after close contact with coronavirus disease 2019 (COVID-19) were explored. The group under quarantine after close contact with COVID-19 was taken as the subjects. By the non-contact physician-patient communication network platform co-developed by China Association of Acupuncture-Moxibustion, Hunan Provincial Association of Acupuncture-Moxibustion, Data Center of China Academy of Chinese Medical Sciences and Yuge Medicine Company, an exploratory randomized controlled trial was designed. A total of 100 cases were included and randomized into a moxibustion group and a conventional intervention group, 50 cases in each one. In the moxibustion group, moxibustion intervention was used. In the conventional intervention group, the conventional observation was adopted without moxibusiton intervention applied. The outcomes included the symptoms changes, e.g. anxiety, emotional disturbance, fatigue, headache and diarrhea, as well as whether quarantine release and the case confirmed or not, etc. The results were evaluated before intervention, in 14 days of intervention and 2 weeks after intervention separately. In this research, on the base of internet plus technology and with the internet communication platform adopted, through mobile phone WeChat App, it was to implement the subject screen, the random allocation and the instruction of moxibustion intervention as well as the quality control of patient's diary and data collection. It is anticipated that the significance and the implementation mode of moxibustion intervention can be assessed preliminarily for the group under quarantine after close contact with COVID-19.

COVID-19 in solid organ transplant recipients: Initial report from the US epicenter.

Solid organ transplant recipients may be at a high risk for SARS‐CoV‐2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with SARS‐CoV‐2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and immunosuppressive management were compared between patients with mild/moderate and severe disease (defined as ICU admission, intubation or death). Ninety patients were analyzed with a median age of 57 years. Forty‐six were kidney recipients, 17 lung, 13 liver, 9 heart, and 5 dual‐organ transplants. The most common presenting symptoms were fever (70%), cough (59%), and dyspnea (43%). Twenty‐two (24%) had mild, 41 (46%) moderate, and 27 (30%) severe disease. Among the 68 hospitalized patients, 12% required non‐rebreather and 35% required intubation. 91% received hydroxychloroquine, 66% azithromycin, 3% remdesivir, 21% tocilizumab, and 24% bolus steroids. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU) and 37 (54%) were discharged. In this initial cohort, transplant recipients with COVID‐19 appear to have more severe outcomes, although testing limitations likely led to undercounting of mild/asymptomatic cases. As this outbreak unfolds, COVID‐19 has the potential to severely impact solid organ transplant recipients.