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Background: Among people with ASCVD, those with T2D have excess CVD risk and derive greater absolute benefit from CVD risk reduction therapies. We describe the use of evidence-based therapies for secondary prevention in participants (pts) with T2D. Methods: We report a registry to longitudinally describe LDL-C treatment patterns among U.S. pts with ASCVD and LDL-C ≥70mg/dL taking lipid-lowering therapy. Pts (n=5006) were enrolled in 1 of 3 cohorts: taking PCSK9i (11%); LDL-C 70-99mg/dL (53%); and LDL-C ≥100mg/dL (36%). Results: Overall, 1655 (33%) had diabetes (96% with T2D): 146 in the PCSK9i cohort, 874 in the LDL-C 70-99mg/dL cohort, and 635 in the LDL-C ≥100mg/dL cohort. Mean age among pts with diabetes was 68 y, 60% were male, 81% had CAD (including 33% with prior MI), 17% with PAD, and 17% had HF. Mean LDL-C was 100mg/dL. Although overall statin use was at 87%, high-intensity statins were used in only 45% and ezetimibe in only 9.5% of pts. Aspirin and ACE-I/ARB were each used in 72% and beta blockers in 71% of pts. The most commonly used glucose-lowering medications among patients with T2D were metformin (56%), insulin (34%), and sulfonylurea (22%). Only 10% and 8% of pts with T2D were treated with SGLT2i or GLP-1RA, respectively. The proportion of pts with T2D that were receiving all guideline-recommended therapies for optimal risk reduction (high-intensity statins, aspirin, ACE-I/ARB, and either SGLT2i or GLP-1RA) was just 3%. Conclusion: In GOULD, among pts with T2D, ASCVD, and LDL-C ≥70mg/dL, most are not receiving high intensity statin therapy at baseline and few receive ezetimibe. Furthermore, less than 20% are treated with glucose-lowering therapies that have a proven CVD benefit, and a strikingly low proportion receive all guideline-recommended risk reduction strategies. These results highlight an opportunity to improve care and outcomes. Disclosure M.N. Kosiborod: Consultant; Self; Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eisai Co., Ltd., GlaxoSmithKline plc., Glytec, LLC, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novartis AG, Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. J. De Lemos: Other Relationship; Self; Amgen Inc., Novo Nordisk A/S, Regeneron Pharmaceuticals. R.S. Rosenson: Consultant; Self; CVS/Caremark, Regeneron Pharmaceuticals. Research Support; Self; Akcea Therapeutics, Amgen Inc., Medicines Company, Regeneron Pharmaceuticals. Other Relationship; Self; Amgen Inc., Kowa Pharmaceutical Europe Co. Ltd. C.M. Ballantyne: Consultant; Self; Abbott, Akcea Therapeutics, Amarin Corporation, Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Esperion, Gilead Sciences, Inc., Matinas BioPharma, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Regeneron Pharmaceuticals, Roche Diagnostic USA, Sanofi. Research Support; Self; Abbott, Akcea Therapeutics, Amarin Corporation, Amgen Inc., Esperion, Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Roche Diagnostic USA, Sanofi. Other Relationship; Self; Roche Diagnostic USA. K. Philip: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc. Y. Liu: None. K.E. Mues: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc. S. Alam: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc. M. Elliott: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc. D.L. Bhatt: Research Support; Self; Abbott, Amarin Corporation, Amgen Inc., AstraZeneca, Bayer Vital GmbH, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Chiesi USA, Inc., Eisai Inc., Eli Lilly and Company, Ethicon, Inc., FlowCo, Forest Laboratories, Inc., Idorsia, Ironwood Pharmaceuticals, Inc., Ischemix, Medicines Company, Medtronic, Merck & Co., Inc., Novo Nordisk Inc., Pfizer Inc., PhaseBio Pharmaceuticals, Inc., PLx Pharma, Regeneron Pharmaceuticals, Roche Pharma, Sanofi, Synaptic, Takeda Pharmaceutical Company Limited. C.P. Cannon: Consultant; Self; Alnylam, Amarin Corporation, Amgen Inc., Corvia Medical, Inc., Eisai Inc., Kowa Pharmaceutical Europe Co. Ltd., Pfizer Inc., Regeneron Pharmaceuticals, Sanofi. Research Support; Self; Daiichi Sankyo Company, Limited. Other Relationship; Self; Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Funding Amgen Inc.

Aim: To examine the efficacy of 12 weeks of monthly evolocumab (EvoMab) 420 mg vs. placebo (Pbo) in lowering LDL-C in those with type 2 diabetes mellitus (T2DM) and hypercholesterolemia or mixed dyslipidemia and on statin therapy. Methods: Patients ≥18 years with T2DM, HbA1c Results: Mean participant age (SD) was 62 (8) years; 44% women; 77% Caucasian. In modified, intent to treat analyses (all randomized and dosed patients) EvoMab significantly reduced LDL-C and non-HDL-C vs. Pbo, and did not impact glycemic control. The incidence of AEs was comparable between EvoMab and Pbo, with no clinically meaningful differences in serious AEs. See Table.Table.Placebo(N=141)Evolocumab(N=280)Baseline LDL-C (mg/dL), mean (SD)110.4 (33.0)108.6 (31.0)Baseline non-HDL-C (mg/dL), mean (SD)145.5 (33.9)144.6 (34.9)Any adverse event (AE), n (%)52 (36.9)110 (39.3)Serious AE, n (%)2 (1.4)14 (5.0) 14 (5.0)14 (5.0)aMean of Weeks 10 and 12LipidsPercent change from baseline in LDL-C, mean (SE)–0.8 (1.8)–65.0 (1.3)bPercent change from baseline in non-HDL-C, mean (SE)–0.(1.6)–56.6 (1.2)bAchievement of LDL-C < 70 mg/dL, n, %20 (14.8)253 (92.7)bAchievement of ≥50% reduction in LDL-C, n, %1 (0.7)230 (84.2)bWeek 12Glycemic ControlChange from baseline in FSG in mg/dL, median (Q1, Q3)4.0(–15.0, 29.0)5.0(–13.5, 29.5)Change from baseline in HbA1c in percent, median (Q1, Q3)0.1(–0.2, 0.5)0.1(–0.2, 0.5)aNo pattern in differences in serious AEs was observed. Chronic obstructive pulmonary disease was the only serious AE reported by ≥ 1% of patients in the evolocumab treatment group.bP < 0.0001 for evolocumab versus placebo comparisonFSG, fasting serum glucose; HbA1c, glycated hemoglobin; LDL-C, low-density lipoprotein cholesterol; non-HDL-C, non-high-density lipoprotein cholesterol; SE, standard errorFunding: Amgen Inc. Conclusion: In statin-treated patients with T2DM and hypercholesterolemia or mixed dyslipidemia, evolocumab safely and effectively lowered LDL-C. Disclosure R.S. Rosenson: Other Relationship; Self; Akcea Therapeutics, Amgen Inc., AstraZeneca, Eli Lilly and Company, The Medicines Company, Regeneron Pharmaceuticals, Inc., Sanofi US, Kowa Pharmaceuticals America, Inc., UpToDate. M.L. Daviglus: Advisory Panel; Self; Amgen Inc. P. Reaven: Research Support; Self; AstraZeneca, Amgen Inc., Bristol-Myers Squibb Company. P. Pozzilli: Research Support; Self; Sanofi. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; Merck Sharp & Dohme Corp. H. Bays: Research Support; Self; Amgen Inc. M. Monsalvo: Employee; Self; Amgen Inc.. Stock/Shareholder; Self; Amgen Inc. M. Elliott: Employee; Self; Amgen Inc.. Stock/Shareholder; Self; Amgen Inc. R. Somaratne: Employee; Self; NGM Biopharmaceuticals. Stock/Shareholder; Self; NGM Biopharmaceuticals. Y. Handelsman: Consultant; Self; Amarin Corporation. Speaker's Bureau; Self; Amarin Corporation. Board Member; Self; American Association of Clinical Endocrinologists. Consultant; Self; Amgen Inc.. Research Support; Self; Amgen Inc.. Speaker's Bureau; Self; Amgen Inc.. Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Gan & Lee Pharmaceuticals. Consultant; Self; Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; Lexicon Pharmaceuticals, Inc.. Consultant; Self; Merck & Co., Inc.. Research Support; Self; Merck & Co., Inc.. Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc., Regeneron Pharmaceuticals, Inc.. Consultant; Self; Sanofi. Research Support; Self; Sanofi. Speaker's Bureau; Self; Sanofi.

OBJECTIVE—Plasmacytoid precursor dendritic cell facilitating cells (p-preDC FCs) play a critical role in facilitation of syngeneic and allogeneic hematopoietic stem cell (HSC) engraftment. Here, we evaluated the phenotype and function of CD8+/TCR− FCs from NOD mice.RESEARCH DESIGN AND METHODS—The phenotype of CD8+/TCR− FCs was analyzed by flow cytometry using sorted FCs from NOD, NOR, or B6 mice. The function of NOD FCs was evaluated by colony-forming cell (CFC) assay in vitro and syngeneic or allogeneic HSC transplantation in vivo.RESULTS—We report for the first time that NOD FCs are functionally impaired. They fail to facilitate engraftment of syngeneic and allogeneic HSCs in vivo and do not enhance HSC clonogenicity in vitro. NOD FCs contain subpopulations similar to those previously described in B6 FCs, including p-preDC, CD19+, NK1.1+DX5+, and myeloid cells. However, the CD19+ and NK1.1+DX5+ subpopulations are significantly decreased in number in NOD FCs compared with disease-resistant controls. Removal of the CD19+ or NK1.1+DX5+ subpopulations from FCs did not significantly affect facilitation. Notably, Flt3 ligand (FL) treatment of NOD donors expanded FC total in peripheral blood and restored facilitating function in vivo.CONCLUSIONS—These data demonstrate that NOD FCs exhibit significantly impaired function that is reversible, since FL restored production of functional FCs in NOD mice and suggest that FL plays an important role in the regulation and development of FC function. FCs may therefore be linked to diabetes pathogenesis and prevention.