Effect of Liraglutide on Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Polyvascular Disease
2018; Lippincott Williams & Wilkins; Volume: 137; Issue: 20 Linguagem: Inglês
10.1161/circulationaha.118.033898
ISSN1524-4539
AutoresSubodh Verma, Deepak L. Bhatt, Stephen C. Bain, John B. Buse, Johannes F.E. Mann, Steven P. Marso, Michael A. Nauck, Neil R Poulter, Richard E. Pratley, Bernard Zinman, Marie Mide Michelsen, Tea Monk Fries, Søren Rasmussen, Lawrence A. Leiter,
Tópico(s)Cardiovascular Function and Risk Factors
ResumoHomeCirculationVol. 137, No. 20Effect of Liraglutide on Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Polyvascular Disease Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBEffect of Liraglutide on Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Polyvascular DiseaseResults of the LEADER Trial Subodh Verma, MD, PhD, Deepak L. Bhatt, MD, MPH, Stephen C. Bain, MD, John B. Buse, MD, PhD, Johannes F.E. Mann, MD, Steven P. Marso, MD, Michael A. Nauck, MD, Neil R. Poulter, FMedSci, Richard E. Pratley, MD, Bernard Zinman, MD, Marie M. Michelsen, MD, Tea Monk Fries, MD, PhD, Søren Rasmussen, MSc, PhD and Lawrence A. Leiter, MDthe LEADER Publication Committee on behalf of the LEADER Trial Investigators Subodh VermaSubodh Verma Division of Cardiac Surgery (S.V.) St. Michael's Hospital, and Departments of Surgery and Pharmacology and Toxicology (S.V.) , Deepak L. BhattDeepak L. Bhatt Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, MA (D.L.B.) , Stephen C. BainStephen C. Bain Institute of Life Science, Swansea University, United Kingdom (S.C.B.) , John B. BuseJohn B. Buse University of North Carolina School of Medicine, Chapel Hill (J.B.B.) , Johannes F.E. MannJohannes F.E. Mann Friedrich Alexander University of Erlangen, Germany (J.F.E.M.) , Steven P. MarsoSteven P. Marso HCA Midwest Health Heart and Vascular Institute, Kansas City, MO (S.P.M.) , Michael A. NauckMichael A. Nauck Diabetes Center Bochum-Hattingen, St. Josef-Hospital, Ruhr-University Bochum, Germany (M.A.N.) , Neil R. PoulterNeil R. Poulter Faculty of Medicine, National Heart & Lung Institute, Imperial College London, United Kingdom (N.R.P.) , Richard E. PratleyRichard E. Pratley Florida Hospital Translational Research Institute for Metabolism and Diabetes, Orlando, FL (R.E.P.) , Bernard ZinmanBernard Zinman Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Canada (B.Z.) , Marie M. MichelsenMarie M. Michelsen Novo Nordisk A/S, Søborg, Denmark (M.M.M., T.M.F., S.R.). , Tea Monk FriesTea Monk Fries Novo Nordisk A/S, Søborg, Denmark (M.M.M., T.M.F., S.R.). , Søren RasmussenSøren Rasmussen Novo Nordisk A/S, Søborg, Denmark (M.M.M., T.M.F., S.R.). and Lawrence A. LeiterLawrence A. Leiter Li Ka Shing Knowledge Institute (L.A.L.) University of Toronto (L.A.L.), Canada and the LEADER Publication Committee on behalf of the LEADER Trial Investigators Originally published18 Jun 2018https://doi.org/10.1161/CIRCULATIONAHA.118.033898Circulation. 2018;137:2179–2183The presence of polyvascular disease, defined as atherosclerosis involving >1 distinct vascular territory, is a strong, independent predictor of cardiovascular events.1–4 In the LEADER trial (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results),5 the human glucagon-like peptide 1 analog liraglutide reduced cardiovascular events in patients with type 2 diabetes mellitus at high cardiovascular risk. In this post hoc analysis of LEADER, we evaluated the effects of liraglutide stratified by a number of atherosclerotic vascular territories (coronary, cerebrovascular, and peripheral).LEADER (ClinicalTrials.gov, NCT01179048) was a randomized trial of liraglutide (1.8 mg or maximum tolerated dose) versus placebo in 9340 patients with type 2 diabetes mellitus and high cardiovascular risk (median follow-up, 3.8 years).5 The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (major adverse cardiovascular events [MACE]). The key secondary expanded outcome (expanded MACE) also included hospitalization for unstable angina, coronary revascularization, or hospitalization for heart failure.The ethics committee or institutional review board at each participating center approved the trial protocol. Patients provided informed consent. Cardiovascular outcomes were prospectively adjudicated by an independent, blinded event adjudication committee. Atherosclerotic vascular territories included coronary (myocardial infarction, ≥50% coronary artery stenosis, percutaneous coronary intervention or coronary artery bypass graft surgery, angina pectoris, or asymptomatic ischemia), cerebrovascular (stroke, transient ischemic attack, ≥50% intracranial or carotid artery stenosis), and peripheral (≥50% peripheral artery stenosis) arteries. Information was extracted from patients' baseline medical history. Risk groups were determined by number of vascular territories involved: polyvascular disease as ≥2, single vascular disease as 1, and a group with no documented atherosclerotic cardiovascular disease (ASCVD).The hazard ratios (HRs) comparing risk groups were calculated using a Cox proportional hazards model with treatment and risk group as factors. The treatment effect of liraglutide versus placebo within risk groups was estimated by using the Cox proportional hazards regression model with treatment, risk group, and the interaction of both as factors.In LEADER, 6775 patients (72.5%) had documented ASCVD. In patients with ASCVD, 1536 (23%) had a baseline history of polyvascular disease, and 5239 (77%) had single vascular disease. For the total population, the distribution of vascular territory involvement is shown in the Figure (A). In brief, 5364 patients (57.4%) had a history of coronary artery disease, 1968 (21.1%) had cerebrovascular disease, 1184 (12.7%) had peripheral artery disease, and 2565 (27.5%) had no documented ASCVD. At baseline, in patients with polyvascular disease versus single vascular disease, mean age±SD was higher (65.1±7.7 versus 63.5±7.3 years), and more patients were male (68.8% versus 67.9%), were current or previous smokers (67.1% versus 60.1%), had an estimated glomerular filtration rate <60 mL·min–1·1.73m–2 (27.1% versus 19.0%), had history of heart failure (26.4% versus 16.5%), had history of myocardial infarction (47.2% versus 39.7%), had history of stroke (33.5% versus 10.0%), or had history of peripheral artery disease (47.1% versus 8.5%), and there was a higher frequency of cardiovascular medication use (95.6% versus 92.7% for antihypertensive therapy, 83.8% versus 79.2% for lipid-lowering therapy, and 79.7% versus 75.7% for antiplatelet therapy). Baseline hemoglobin A1c was similar between groups.Download figureDownload PowerPointFigure. Analysis of LEADER data stratified by the number of atherosclerotic vascular territories (no ASCVD: no documented evidence of atherosclerotic disease in any of 3 vascular territories [coronary artery, cerebrovascular, or peripheral artery]; single vascular disease: atherosclerotic disease in 1 of the 3 vascular territories; polyvascular disease: atherosclerotic disease in ≥2 of the specified vascular territories).A, Venn diagram of number (%) of patients according to number of vascular territories involved at baseline. B, Kaplan-Meier estimates (based on number of vascular territories involved at baseline) of time to first: primary MACE (composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) (i), and expanded MACE (composite of the primary, with hospitalization for unstable angina, coronary revascularization, or hospitalization for heart failure also included) (ii). C, Cardiovascular outcomes by number of vascular territories involved. Hazard ratios and 95% CIs are based on Cox regression analyses. Interaction P value is for test of homogeneity of treatment group difference among all 3 subgroups (no ASCVD, single vascular disease, and, polyvascular disease) with no adjustment for multiple tests. ASCVD indicates atherosclerotic cardiovascular disease; CAD, coronary artery disease; CD, cerebrovascular disease; CI, confidence interval; LEADER, Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; MACE, major adverse cardiovascular event; and PAD, peripheral artery disease.Patients with polyvascular disease had a higher risk of cardiovascular outcomes than those with single vascular disease (MACE: HR, 1.52; 95% confidence interval [CI], 1.33–1.73; expanded MACE: HR, 1.45; 95% CI, 1.31–1.62; cardiovascular death: HR, 1.41; 95% CI, 1.13–1.75) (Figure [B and C]).Liraglutide reduced MACE consistently in patients with polyvascular disease (HR, 0.82; 95% CI, 0.66–1.02) and with single vascular disease (HR, 0.82; 95% CI, 0.71–0.95). Results were similar for expanded MACE and cardiovascular death (Figure [C]). The risk reduction in MACE and expanded MACE was similar to that of the total trial population in LEADER (Figure [C]).5 The corresponding data for nonfatal myocardial infarction and stroke are displayed in the Figure (C).In patients without ASCVD at baseline, the HR for liraglutide versus placebo for MACE was 1.08 (95% CI, 0.84–1.38), with similar results for expanded MACE and cardiovascular death (Figure [C]). However, no significant interaction was found among risk groups, with the exception of expanded MACE (Pinteraction=0.03), which could be a chance finding, because no adjustment for multiple testing was performed, or may suggest a difference in treatment effects across risk groups, driven by the group without ASCVD (Figure [C]). The reason for a neutral response in patients without ASCVD could be that the baseline risk was lower, and to establish any potential effect might require a longer treatment period or larger sample size. Nevertheless, patients with type 2 diabetes mellitus benefit from liraglutide treatment regarding glycemic control, potential weight reductions, and better blood pressure control.5In patients with type 2 diabetes mellitus and documented ASCVD, the presence of polyvascular disease was associated with greater cardiovascular risk versus those with single vascular disease. Liraglutide consistently appeared to reduce major cardiovascular outcomes in both patients with polyvascular and single vascular disease.AcknowledgmentsEditorial assistance, limited to formatting and collation of coauthor comments, was supported financially by Novo Nordisk and provided by Gillian Groeger and Izabel James, of Watermeadow Medical, an Ashfield Company, part of UDG Healthcare plc, during preparation of this article. Dr Verma wrote the first draft. The authors were fully responsible for all content and editorial decisions, were involved at all stages of manuscript development, and have approved the final version.Sources of FundingThe LEADER trial was funded by Novo Nordisk.DisclosuresDr Verma reported research grants and/or speaking honoraria from Boehringer Ingelheim/Eli Lilly, AstraZeneca, Janssen, Merck, Novartis, Novo Nordisk, Sanofi, Valeant and Amgen (all significant). Dr Bhatt was on the advisory board for Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; was on the board of directors for Boston VA Research Institute and Society of Cardiovascular Patient Care; was the chair for the American Heart Association Quality Oversight Committee; was on data monitoring committees for the Cleveland Clinic, Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine, and Population Health Research Institute; received honoraria from the American College of Cardiology (senior associate editor, clinical trials and news, ACC.org; vice-chair, American College of Cardiology Accreditation Committee), Belvoir Publications (editor in chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor; associate editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (chief medical editor, Cardiology Today's Intervention), Society of Cardiovascular Patient Care (secretary/treasurer), WebMD (continuing medical education [CME] steering committees); held other positions for Clinical Cardiology (deputy editor), National Cardiovascular Data Registry (NCDR)-ACTION Registry Steering Committee (chair), and Veterans Affairs Clinical Assessment Reporting and Tracking (VA CART) Research and Publications Committee (chair); received research funding from Abbott, Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Ironwood, Ischemix, Lilly, Medtronic, Pfizer, Regeneron, Roche, Sanofi Aventis, and The Medicines Company; received royalties from Elsevier (editor, Cardiovascular Intervention: A Companion to Braunwald's Heart Disease); was site coinvestigator for Biotronik, Boston Scientific, and St. Jude Medical (now Abbott); was a trustee for the American College of Cardiology; and conducted unfunded research for FlowCo, Merck, PLx Pharma, and Takeda. Dr Bain reported research grants (includes principal investigator, collaborator, or consultant and pending grants as well as grants already received) from Healthcare and Research Wales (Welsh Government) (significant) and Novo Nordisk (significant); received other research and infrastructure support from Healthcare and Research Wales (Welsh Government) (significant); received honoraria from Novo Nordisk (significant), Sanofi (significant), Lilly (significant), Boehringer Ingelheim (significant), and Merck (significant); and has an ownership interest in Gycosmedia (diabetes online news service) (significant). Dr Buse reported consulting fees paid to his institution and travel support (all modest) from Novo Nordisk, Eli Lilly, Bristol-Myers Squibb, GI Dynamics, Elcelyx, Merck, Metavention, vTv Therapeutics, PhaseBio, AstraZeneca, Dance Biopharm, Quest Diagnostics, Sanofi-Aventis, Lexicon Pharmaceuticals, Orexigen Therapeutics, Takeda Pharmaceuticals, Adocia, and Roche; received grant support from Eli Lilly, Bristol-Myers Squibb, GI Dynamics, Merck, PhaseBio, AstraZeneca, Medtronic, Sanofi, Tolerex, Osiris Therapeutics, Halozyme Therapeutics, Johnson & Johnson, Andromeda, Boehringer Ingelheim, GlaxoSmithKline, Astellas Pharma, MacroGenics, Intarcia Therapeutics, Lexicon, Scion NeuroStim, Orexigen Therapeutics, Takeda Pharmaceuticals, Theracos, Roche, and the National Institutes of Health (UL1TR001111) (all modest); received fees and stock options from PhaseBio (modest); and served on the boards of the AstraZeneca Healthcare Foundation and Bristol-Myers Squibb Together on Diabetes Foundation (both modest). Dr Mann reported research grants from Celgene, Europ Union, McMaster University Canada, AbbVie, Novo Nordisk, Roche, and Sandoz; and received personal fees (includes committee member and/or speaker fees) from Boehringer Ingelheim, Astra, Amgen, ACI Pharma, Fresenius, Celgene, Gambro, AbbVie, Medice, Novo Nordisk, Roche, Sandoz, Lanthio, Sanifit, Relypsa, and ZS Pharma (all significant). Dr Marso reported consulting fees from Novo Nordisk and St. Jude Medical; and received research support from Novo Nordisk, Terumo, The Medicines Company, AstraZeneca, and Bristol Myers-Squibb (all significant). Dr Michelsen was a Novo Nordisk employee (significant). Dr Monk Fries was a Novo Nordisk employee (significant) and shareholder (modest). Dr Nauck reported advisory board membership or consultancy for AstraZeneca (modest), Boehringer Ingelheim (modest), Eli Lilly (significant), Fractyl (modest), GlaxoSmithKline (modest), Menarini/Berlin Chemie (modest), Merck, Sharp & Dohme (significant), and Novo Nordisk (significant); and was on the speakers' bureau for AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Menarini/Berlin Chemie (all modest), and Merck, Sharp & Dohme and Novo Nordisk A/S (both significant). His institution has received grant support from AstraZeneca, Eli Lilly, Menarini/Berlin-Chemie, Merck, Sharp & Dohme, Novartis Pharma, and Novo Nordisk A/S. Dr Poulter is president of the International Society of Hypertension; received personal speaker fees from Servier (modest), Takeda (modest) and Novo Nordisk (significant); was on advisory boards for AstraZeneca (modest) and Novo Nordisk (significant); and received research grants for his research group relating to type 2 diabetes mellitus from Diabetes UK, Efficacy and Mechanism Evaluation (EME) National Institute for Health Research (NIHR), Julius Clinical, and the British Heart Foundation, with a pending grant from Novo Nordisk (significant). Dr Pratley reported research grants from Gilead Sciences, Lexicon Pharmaceuticals, Ligand Pharmaceuticals Inc, Lilly, Merck, Novo Nordisk, Sanofi-Aventis US LLC, and Takeda; was a speaker for AstraZeneca, Novo Nordisk, and Takeda; and was a consultant for AstraZeneca, Boehringer Ingelheim, Eisai, Inc, GlaxoSmithKline, Janssen Scientific Affairs LLC, Ligand Pharmaceuticals Inc, Lilly, Merck, Novo Nordisk, Pfizer, and Takeda. All payments are made directly to his employer (Florida Hospital). Dr Rasmussen was a Novo Nordisk employee and shareholder (both significant). Dr Zinman received consulting fees from Merck (modest), Novo Nordisk (significant), Sanofi-Aventis (modest), Eli Lilly (modest), AstraZeneca (modest), Janssen (modest), and Boehringer Ingelheim (significant). Dr Leiter reported consultant and speaker fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi, and Servier (all modest); received consultant fees from Regeneron (modest); and received research grants or support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Esperion, GlaxoSmithKline, Janssen, Kowa, Merck, Novartis, Novo Nordisk, Resverlogix, Sanofi, and The Medicines Company (all modest).Footnoteshttp://circ.ahajournals.orgData sharing: Data and analytic methods supporting this study's findings are available from the corresponding author on reasonable request.Subodh Verma, MD, PhD, FRCSC, University of Toronto, St. Michael's Hospital, 30 Bond St, 8th Floor, Bond Wing, Toronto, ON, M5B 1W8, Canada. E-mail [email protected].References1. Bhatt DL, Eagle KA, Ohman EM, Hirsch AT, Goto S, Mahoney EM, Wilson PW, Alberts MJ, D'Agostino R, Liau CS, Mas JL, Röther J, Smith SC, Salette G, Contant CF, Massaro JM, Steg PG; REACH Registry Investigators. Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis.JAMA. 2010; 304:1350–1357. doi: 10.1001/jama.2010.1322.CrossrefMedlineGoogle Scholar2. Kaasenbrood L, Boekholdt SM, van der Graaf Y, Ray KK, Peters RJ, Kastelein JJ, Amarenco P, LaRosa JC, Cramer MJ, Westerink J, Kappelle LJ, de Borst GJ, Visseren FL. Distribution of estimated 10-year risk of recurrent vascular events and residual risk in a secondary prevention population.Circulation. 2016; 134:1419–1429. doi: 10.1161/CIRCULATIONAHA.116.021314.LinkGoogle Scholar3. Verma S, Mazer CD, Al-Omran M, Inzucchi SE, Fitchett D, Hehnke U, George JT, Zinman B. Cardiovascular outcomes and safety of empagliflozin in patients with type 2 diabetes mellitus and peripheral artery disease: a subanalysis of EMPA-REG OUTCOME.Circulation. 2018; 137:405–407. doi: 10.1161/CIRCULATIONAHA.117.032031.LinkGoogle Scholar4. Cavender MA, Steg PG, Smith SC, Eagle K, Ohman EM, Goto S, Kuder J, Im K, Wilson PW, Bhatt DL; REACH Registry Investigators. Impact of diabetes mellitus on hospitalization for heart failure, cardiovascular events, and death: outcomes at 4 years from the Reduction of Atherothrombosis for Continued Health (REACH) Registry.Circulation. 2015; 132:923–931. doi: 10.1161/CIRCULATIONAHA.114.014796.LinkGoogle Scholar5. Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, Buse JB, LEADER Steering Committee, LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes.N Engl J Med. 2016; 375:311–322. doi: 10.1056/NEJMoa1603827.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited ByMarx N, Husain M, Lehrke M, Verma S and Sattar N (2022) GLP-1 Receptor Agonists for the Reduction of Atherosclerotic Cardiovascular Risk in Patients With Type 2 Diabetes, Circulation, 146:24, (1882-1894), Online publication date: 13-Dec-2022. Jensen D, Skovsted G, Bonde M, Bentzon J, Rolin B, Franck G, Ougaard M, Voetmann L, Bachmann J, Uryga A, Pyke C, Kirk R, Hvid H, Knudsen L, Lykkesfeldt J and Nyberg M (2022) Semaglutide treatment attenuates vessel remodelling in ApoE−/− mice following vascular injury and blood flow perturbation, Atherosclerosis Plus, 10.1016/j.athplu.2022.05.004, 49, (32-41), Online publication date: 1-Aug-2022. Verma S, Al‐Omran M, Leiter L, Mazer C, Rasmussen S, Saevereid H, Sejersten Ripa M and Bonaca M (2022) Cardiovascular efficacy of liraglutide and semaglutide in individuals with diabetes and peripheral artery disease, Diabetes, Obesity and Metabolism, 10.1111/dom.14700, 24:7, (1288-1299), Online publication date: 1-Jul-2022. Landgraf R, Aberle J, Birkenfeld A, Gallwitz B, Kellerer M, Klein H, Müller-Wieland D, Nauck M, Wiesner T and Siegel E (2022) Therapie des Typ-2-DiabetesTreatment of type 2 diabetes, Die Diabetologie, 10.1007/s11428-022-00921-5, 18:5, (623-656), Online publication date: 1-Jul-2022. Linden F, Frey N and Erbel C (2022) Die polyvaskuläre Erkrankung – eine Übersicht über die Datenlage und Managementstrategien, Aktuelle Kardiologie, 10.1055/a-1693-2284, 11:02, (147-153), Online publication date: 1-Apr-2022. Hirose N, Tsujimoto N, Katayose T and Chin R (2021) Utilization of glucagon‐like peptide‐1 receptor agonists and changes in clinical characteristics in patients with type 2 diabetes by chronic kidney disease stage in Japan: A descriptive observational study using a nationwide electronic medical records database, Diabetes, Obesity and Metabolism, 10.1111/dom.14600, 24:3, (486-498), Online publication date: 1-Mar-2022. Kobo O, Saada M, Laanmets P, Karageorgiev D, Routledge H, Crowley J, Baello P, Requena J, Spanó F, Perez L, Jimenez Mazuecos J, Mamas M and Roguin A (2022) Impact of peripheral artery disease on prognosis after percutaneous coronary intervention: Outcomes from the multicenter prospective e-ULTIMASTER registry, Atherosclerosis, 10.1016/j.atherosclerosis.2022.01.007, 344, (71-77), Online publication date: 1-Mar-2022. Chunawala Z, Qamar A, Arora S, Pandey A, Fudim M, Vaduganathan M, Bhatt D, Mentz R and Caughey M (2022) Prevalence and Prognostic Significance of Polyvascular Disease in Patients Hospitalized With Acute Decompensated Heart Failure: The ARIC Study, Journal of Cardiac Failure, 10.1016/j.cardfail.2022.01.002, Online publication date: 1-Jan-2022. Gonzales K and Smith S (2021) Does HbA1c Remain the Most Important Therapeutic Target in Outpatient Management of Diabetes? Clinical Dilemmas in Diabetes, 10.1002/9781119603207.ch8, (101-114), Online publication date: 27-Dec-2022. Lin C, Armstrong D, Liu P, Lin C, Huang C and Huang Y (2021) Survival of Patients Following First Diagnosis of Diabetic Foot Complications: A Nationwide 15-Year Longitudinal Analysis, Frontiers in Endocrinology, 10.3389/fendo.2021.801324, 12 Arutyunov A, Batluk T, Bashkinov R and Trubnikova M (2021) Multifocal atherosclerosis: focus on the prevention of ischemic events, Russian Journal of Cardiology, 10.15829/1560-4071-2021-4808, 26:12, (4808) Myat A, Redwood S, Arri S, Gersh B, Bhatt D and Marber M (2021) Liraglutide to Improve corONary haemodynamics during Exercise streSS (LIONESS): a double-blind randomised placebo-controlled crossover trial, Diabetology & Metabolic Syndrome, 10.1186/s13098-021-00635-6, 13:1, Online publication date: 1-Dec-2021. Samsky M, Mentz R, Stebbins A, Lokhnygina Y, Aday A, Pagidipati N, Jones W, Katona B, Patel M, Holman R, Hernandez A and Gutierrez J (2021) Polyvascular disease and increased risk of cardiovascular events in patients with type 2 diabetes: Insights from the EXSCEL trial, Atherosclerosis, 10.1016/j.atherosclerosis.2021.10.011, 338, (1-6), Online publication date: 1-Dec-2021. Ma L, Wang A, Zhang Y, Wang Y, Wang Y and Meng X (2021) Associations Between Polyvascular Disease and Stroke Recurrence in Patients With Lacunar Stroke, Frontiers in Neurology, 10.3389/fneur.2021.706991, 12 Ajjan R, Kietsiriroje N, Badimon L, Vilahur G, Gorog D, Angiolillo D, Russell D, Rocca B and Storey R (2021) Antithrombotic therapy in diabetes: which, when, and for how long?, European Heart Journal, 10.1093/eurheartj/ehab128, 42:23, (2235-2259), Online publication date: 14-Jun-2021. Aday A and Matsushita K (2021) Epidemiology of Peripheral Artery Disease and Polyvascular Disease, Circulation Research, 128:12, (1818-1832), Online publication date: 11-Jun-2021.Bonaca M, Hamburg N and Creager M (2021) Contemporary Medical Management of Peripheral Artery Disease, Circulation Research, 128:12, (1868-1884), Online publication date: 11-Jun-2021. Wen S, Nguyen T, Gong M, Yuan X, Wang C, Jin J and Zhou L (2021) An Overview of Similarities and Differences in Metabolic Actions and Effects of Central Nervous System Between Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) and Sodium Glucose Co-Transporter-2 Inhibitors (SGLT-2is), Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 10.2147/DMSO.S312527, Volume 14, (2955-2972) Landgraf R, Aberle J, Birkenfeld A, Gallwitz B, Kellerer M, Klein H, Müller-Wieland D, Nauck M, Reuter H and Siegel E (2021) Therapie des Typ-2-DiabetesTherapy of type 2 diabetes, Der Diabetologe, 10.1007/s11428-021-00765-5, 17:4, (422-447), Online publication date: 1-Jun-2021. Grachev V, Vedenskaya S and Smolenskaya O (2021) Features of Risk Stratification, Diagnosis and Secondary Prevention in Patients with Multifocal Arterial Disease. Part 2: Treatment Options, Rational Pharmacotherapy in Cardiology, 10.20996/1819-6446-2021-03-02, 17:2, (239-248) Verma S, Mazer C, Inzucchi S, Wanner C, Ofstad A, Johansen O, Zwiener I, George J, Butler J and Zinman B (2021) Impact of polyvascular disease with and without co‐existent kidney dysfunction on cardiovascular outcomes in diabetes: A post hoc analysis of EMPA‐REG OUTCOME , Diabetes, Obesity and Metabolism, 10.1111/dom.14326, 23:5, (1173-1181), Online publication date: 1-May-2021. Fuentes B, Amaro S, Alonso de Leciñana M, Arenillas J, Ayo-Martín O, Castellanos M, Freijo M, García-Pastor , Gomis M, Gómez Choco M, López-Cancio E, Martínez Sánchez P, Morales A, Palacio-Portilla E, Rodríguez-Yáñez M, Roquer J, Segura T, Serena J and Vivancos-Mora J (2021) Stroke prevention in patients with type 2 diabetes mellitus or prediabetes: recommendations of the Spanish Society of Neurology's Stroke Study Group, Neurología (English Edition), 10.1016/j.nrleng.2020.04.022, 36:4, (305-323), Online publication date: 1-May-2021. Fuentes B, Amaro S, Alonso de Leciñana M, Arenillas J, Ayo-Martín O, Castellanos M, Freijo M, García-Pastor A, Gomis M, Gómez Choco M, López-Cancio E, Martínez Sánchez P, Morales A, Palacio-Portilla E, Rodríguez-Yáñez M, Roquer J, Segura T, Serena J and Vivancos-Mora J (2021) Prevención de ictus en pacientes con diabetes mellitus tipo 2 o prediabetes. Recomendaciones del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Española de Neurología, Neurología, 10.1016/j.nrl.2020.04.030, 36:4, (305-323), Online publication date: 1-May-2021. El Sanadi C, Pantalone K, Ji X and Kattan M (2021) Development and Internal Validation of A Prediction Tool To Assist Clinicians Selecting Second-Line Therapy Following Metformin Monotherapy For Type 2 Diabetes, Endocrine Practice, 10.1016/j.eprac.2020.10.015, 27:4, (334-341), Online publication date: 1-Apr-2021. Grachev V, Vedenskaya S and Smolenskaya O (2021) Features of Antithrombotic Therapy in Patients with Multifocal Arterial Disease, Kardiologiia, 10.18087/cardio.2021.3.n1498, 61:3, (87-95) Kosmopoulos A, Verma S, Meglis G, Bhatt D, Verma R, Mazer C and Voisine P (2020) Generalizability of Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial in patients with a history of coronary artery bypass graft surgery, Current Opinion in Cardiology, 10.1097/HCO.0000000000000800, 36:2, (172-178), Online publication date: 1-Mar-2021. H B (2021) Type 2 Diabetes Mellitus (T2DM) may have Four Subtypes Beneficial for Adequate Treatment, Asploro Journal of Biomedical and Clinical Case Reports, 10.36502/2021/ASJBCCR.6226, 4:1, (38-41) Aguilar-Ballester M, Hurtado-Genovés G, Taberner-Cortés A, Herrero-Cervera A, Martínez-Hervás S and González-Navarro H (2021) Therapies for the Treatment of Cardiovascular Disease Associated with Type 2 Diabetes and Dyslipidemia, International Journal of Molecular Sciences, 10.3390/ijms22020660, 22:2, (660) Salahuddin T, Richardson V, McNeal D, Henderson K, Hess P, Raghavan S, Saxon D, Valle J, Waldo S, Ho P and Schwartz G (2020) Potential unrealized mortality benefit of glucagon‐like peptide‐1 receptor agonists and sodium‐glucose co‐transport‐2 inhibitors: A report from the Veterans Health Administration Clinical Assessment, Reporting and Tracking program, Diabetes, Obesity and Metabolism, 10.1111/dom.14193, 23:1, (97-105), Online publication date: 1-Jan-2021. Landgraf R, Aberle J, Birkenfeld A, Gallwitz B, Kellerer M, Klein H, Müller-Wieland D, Nauck M, Reuter H and Siegel E (2020) Therapie des Typ-2-Diabetes, Diabetologie und Stoffwechsel, 10.1055/a-1193-3793, 15:S 01, (S65-S92), Online publication date: 1-Oct-2020. Bain S, Bakhai A, Evans M, Green A, Menown I and Strain W (2019) An update to: Pharmacological treatment for type 2 diabetes integrating findings from cardiovascular outcome trials: an expert consensus in the UK . Diabet Med 2019; 36: 1063–1071 , Diabetic Medicine, 10.1111/dme.14172, 37:8, (1405-1407), Online publication date: 1-Aug-2020. Bhatt D, Eikelboom J, Connolly S, Steg P, Anand S, Verma S, Branch K, Probstfield J, Bosch J, Shestakovska O, Szarek M, Maggioni A, Widimský P, Avezum A, Diaz R, Lewis B, Berkowitz S, Fox K, Ryden L, Yusuf S, Aboyans V, Alings M, Commerford P, Cook-Bruns N, Dagenais G, Dans A, Ertl G, Felix C, Guzik T, Hart R, Hori M, Kakkar A, Keltai K, Keltai M, Kim J, Lamy A, Lanas F, Liang Y, Liu L, Lonn E, Lopez-Jaramillo P, Metsarinne K, Moayyedi P, O'Donnell M, Parkhomenko A, Piegas L, Pogosova N, Sharma M, Stoerk S, Tonkin A, Torp-Pedersen C, Varigos J, Verhamme P, Vinereanu D, Yusoff K and Zhu J (2020) Role of Combination Antiplatelet and Anticoagulation Therapy in Diabetes Mellitus and Cardiovascular Disease, Circulation, 141:23, (1841-1854), Online publication date: 9-Jun-2020. Lingvay I, Beetz N, Sennewald R, Schuler-Metz A, Bertulis J, Loley C, Lang B, Lippert C, Lee J, Manning L and Terada D (2020) Triple fixed-dose combination empagliflozin, linagliptin, and metformin for patients with type 2 diabetes, Postgraduate Medicine, 10.1080/00325481.2020.1750228, 132:4, (337-345), Online publication date: 18-May-2020. Landgraf R, Aberle J, Birkenfeld A, Gallwitz B, Kellerer M, Klein H, Müller-Wieland D, Nauck M, Reuter H and Siegel E (2020) Therapie des Typ-2-DiabetesTherapy of type 2 diabetes, Der Diabetologe, 10.1007/s11428-020-00608-9, 16:3, (266-287), Online publication date: 1-May-2020. AlAsmari A, Ali N, AlAsmari F, AlAnazi W, AlShammari M, Al-Harbi N, Alhoshani A, As Sobeai H, AlSwayyed M, AlAnazi M and AlGhamdi N (2020) Liraglutide attenuates gefitinib-induced cardiotoxicity and promotes cardioprotection through the regulation of MAPK/NF-κB signaling pathways, Saudi Pharmaceutical Journal, 10.1016/j.jsps.2020.03.002, 28:4, (509-518), Online publication date: 1-Apr-2020. Husain M, Bain S, Jeppesen O, Lingvay I, Sørrig R, Treppendahl M and Vilsbøll T (2020) Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk, Diabetes, Obesity and Metabolism, 10.1111/dom.13955, 22:3, (442-451), Online publication date: 1-Mar-2020. Verma S, Leiter L, Latter D and Bhatt D (2020) A LEADER in the management of type 2 diabetes and cardiorenal disease, The Journal of Thoracic and Cardiovascular Surgery, 10.1016/j.jtcvs.2019.03.134, 159:3, (978-984), Online publication date: 1-Mar-2020. Gutierrez J, Aday A, Patel M and Jones W (2019) Polyvascular Disease, Circulation: Cardiovascular Interventions, 12:12, Online publication date: 1-Dec-2019. Verma S, Bain S, Buse J, Idorn T, Rasmussen S, Ørsted D and Nauck M (2019) Occurence of First and Recurrent Major Adverse Cardiovascular Events With Liraglutide Treatment Among Patients With Type 2 Diabetes and High Risk of Cardiovascular Events, JAMA Cardiology, 10.1001/jamacardio.2019.3080, 4:12, (1214), Online publication date: 1-Dec-2019. Liu B, Wang Y, Zhang Y and Yan B Mechanisms of Protective Effects of SGLT2 Inhibitors in Cardiovascular Disease and Renal Dysfunction, Current Topics in Medicinal Chemistry, 10.2174/1568026619666190828161409, 19:20, (1818-1849) Verma S, Bain S, Monk Fries T, Mazer C, Nauck M, Pratley R, Rasmussen S, Saevereid H, Zinman B and Buse J (2019) Duration of diabetes and cardiorenal efficacy of liraglutide and semaglutide: A post hoc analysis of the LEADER and SUSTAIN 6 clinical trials, Diabetes, Obesity and Metabolism, 10.1111/dom.13698, 21:7, (1745-1751), Online publication date: 1-Jul-2019. Gutierrez J, Bhatt D, Banerjee S, Glorioso T, Josey K, Swaminathan R, Maddox T, Armstrong E, Duvernoy C, Waldo S and Rao S (2019) Risk of obstructive coronary artery disease and major adverse cardiac events in patients with noncoronary atherosclerosis: Insights from the Veterans Affairs Clinical Assessment, Reporting, and Tracking (CART) Program, American Heart Journal, 10.1016/j.ahj.2019.04.004, 213, (47-56), Online publication date: 1-Jul-2019. Verma S, Mazer C and Perkovic V (2019) Is it time to REWIND the cardiorenal clock in diabetes?, The Lancet, 10.1016/S0140-6736(19)31267-X, 394:10193, (95-97), Online publication date: 1-Jul-2019. Madsbad S (2019) Liraglutide for the prevention of major adverse cardiovascular events in diabetic patients, Expert Review of Cardiovascular Therapy, 10.1080/14779072.2019.1615444, 17:5, (377-387), Online publication date: 4-May-2019. Knudsen L and Lau J (2019) The Discovery and Development of Liraglutide and Semaglutide, Frontiers in Endocrinology, 10.3389/fendo.2019.00155, 10 Landgraf R, Kellerer M, Aberle J, Fach E, Gallwitz B, Hamann A, Joost H, Klein H, Müller-Wieland D, Nauck M, Reuter H, Schreiber S and Siegel E (2019) Therapie des Typ-2-DiabetesTherapy of type 2 diabetes, Der Diabetologe, 10.1007/s11428-019-0459-7, 15:2, (146-167), Online publication date: 1-Mar-2019. Terenzi D, Al-Omran M, Quan A, Teoh H, Verma S and Hess D (2019) Circulating Pro-Vascular Progenitor Cell Depletion During Type 2 Diabetes, JACC: Basic to Translational Science, 10.1016/j.jacbts.2018.10.005, 4:1, (98-112), Online publication date: 1-Feb-2019. Verma S, Poulter N, Bhatt D, Bain S, Buse J, Leiter L, Nauck M, Pratley R, Zinman B, Ørsted D, Monk Fries T, Rasmussen S and Marso S (2018) Effects of Liraglutide on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus With or Without History of Myocardial Infarction or Stroke, Circulation, 138:25, (2884-2894), Online publication date: 18-Dec-2018. Verma S, Mazer C and Bhatt D (2018) The perils of polyvascular disease in type 2 diabetes, The Lancet Diabetes & Endocrinology, 10.1016/S2213-8587(18)30311-5, 6:12, (914-916), Online publication date: 1-Dec-2018. Bajaj H, Al-Jabri B and Verma S (2018) Glucagon-like peptide-1 receptor agonists and cardiovascular protection in type 2 diabetes, Current Opinion in Cardiology, 10.1097/HCO.0000000000000562, 33:6, (665-675), Online publication date: 1-Nov-2018. Sorensen C and Holst J (2018) Renoprotective effects of dulaglutide in patients with T2DM and CKD, Nature Reviews Nephrology, 10.1038/s41581-018-0055-x, 14:11, (659-660), Online publication date: 1-Nov-2018. Verma S and McMurray J (2018) SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review, Diabetologia, 10.1007/s00125-018-4670-7, 61:10, (2108-2117), Online publication date: 1-Oct-2018. Hussain M, Al-Omran M, Creager M, Anand S, Verma S and Bhatt D (2018) Antithrombotic Therapy for Peripheral Artery Disease, Journal of the American College of Cardiology, 10.1016/j.jacc.2018.03.483, 71:21, (2450-2467), Online publication date: 1-May-2018. Verma S, Mathew V and Farkouh M (2018) Targeting Inflammation in the Prevention and Treatment of Type 2 Diabetes, Journal of the American College of Cardiology, 10.1016/j.jacc.2018.03.480, 71:21, (2402-2404), Online publication date: 1-May-2018. May 15, 2018Vol 137, Issue 20 Advertisement Article InformationMetrics © 2018 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.118.033898PMID: 29760228 Originally publishedJune 18, 2018 Keywordsliraglutidemyocardial infarctiondiabetes mellitus, type 2glucagon-like peptide 1atherosclerosisPDF download Advertisement SubjectsCardiopulmonary Resuscitation and Emergency Cardiac CareCardiovascular DiseaseClinical StudiesCoronary CirculationDiabetes, Type 2
Referência(s)