Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus

被引：2717

作者：

Scirica, Benjamin M. ^{[2
,3
]}

Bhatt, Deepak L. ^{[1
,2
,3
,4
]}

Braunwald, Eugene ^{[2
,3
]}

Steg, P. Gabriel ^{[5
,6
]}

Davidson, Jaime ^{[7
]}

Hirshberg, Boaz ^{[9
]}

Ohman, Peter ^{[9
]}

Frederich, Robert ^{[10
]}

Wiviott, Stephen D. ^{[2
,3
]}

Hoffman, Elaine B. ^{[2
,3
]}

Cavender, Matthew A. ^{[2
,3
]}

Udell, Jacob A. ^{[2
,3
]}

Desai, Nihar R. ^{[2
,3
]}

Mosenzon, Ofri ^{[11
]}

McGuire, Darren K. ^{[8
]}

Ray, Kausik K. ^{[12
]}

Leiter, Lawrence A. ^{[13
]}

Raz, Itamar ^{[11
,252
]}

Braunwald, Eugene ^{[2
,3
]}

Bhatt, Deepak L. ^{[1
,2
,3
,4
]}

Scirica, Benjamin M. ^{[2
,3
]}

Udell, Jacob A. ^{[2
,3
]}

Cavender, Matthew A. ^{[2
,3
]}

Desai, Nihar

Abrahamsen, Timothy

Grossman, Michelle

Morin, Suzanne

Im, Kyungah

Hoffman, Elaine

Gabovitch, Daniel

Pricken, Alexandra

Mosenzon, Ofri ^{[11
]}

Buskila, Alona

Ohman, Peter ^{[9
]}

Hirshberg, Boaz ^{[9
]}

Stahre, Christina

Price, Deborah

Billing-Clason, Solveig

Sabel, Karin

Monyak, John

Sjostrand, Mikalea

Wei, Cheryl

Lu, Jane

Miller, Elinor

Raichlen, Joel

Fitt, Sandy

Frederich, Robert ^{[10
]}

Iqbal, Nayyar

Donovan, Mark

Davidson, Jaime A.

机构：

[1] VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA

[2] Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Boston, MA USA

[4] VA Boston Healthcare Syst, Boston, MA 02132 USA

[5] Univ Paris Diderot, Paris, France

[6] Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, F-75877 Paris, France

[7] Univ Texas SW Med Ctr Dallas, Div Endocrinol, Dept Internal Med, Dallas, TX 75390 USA

[8] Univ Texas SW Med Ctr Dallas, Div Cardiovasc Med, Dept Internal Med, Dallas, TX 75390 USA

[9] AstraZeneca Res & Dev, Wilmington, DE USA

[10] Bristol Myers Squibb, Princeton, NJ USA

[11] Hadassah Univ Hosp, Diabet Unit, Dept Internal Med, Jerusalem, Israel

[12] St Georges Univ London, Cardiovasc Sci Res Ctr, London, England

[13] Univ Toronto, Div Endocrinol & Metab, Keenan Res Ctr, Li Ka Shing Knowledge Inst,St Michaels Hosp, Toronto, ON, Canada

[14] Ctr Invest Med, Mar Del Plata, Buenos Aires, Argentina

[15] Framingham, La Plata, Buenos Aires, Argentina

[16] CEDyN Ctr Diabet & Nutr, Rosario, Santa Fe, Argentina

[17] CIAD Consultorio Integral Atenc Diabet, Moron, Buenos Aires, Argentina

[18] CIMeL, Lanus, Buenos Aires, Argentina

[19] Ctr Med Luquez Fdn Luquez, Cordoba, Argentina

[20] Inst Invest Clin Rosario, Rosario, Santa Fe, Argentina

[21] Consultorios Asociados Endocrionol, Buenos Aires, DF, Argentina

[22] Inst Invest Clin Cordoba, Cordoba, Argentina

[23] DIM Clin Privada, Ramos Mejia, Buenos Aires, Argentina

[24] Ctr Urol Ballester SRL, Villa Ballester, Buenos Aires, Argentina

[25] CEDIR Ctr Diagnost & Rehabil, San Martin, Santa Fe, Argentina

[26] Fdn Rusculleda, Cordoba, Argentina

[27] Hosp Sirio Libanes, Buenos Aires, DF, Argentina

[28] Hosp Churruca Visca, Buenos Aires, DF, Argentina

[29] St Deniss Med Grp, Buenos Aires, DF, Argentina

[30] MD Invest, Buenos Aires, DF, Argentina

[31] INSARES, Mendoza, Argentina

[32] Inst Cardiol Juana F Cabral, Corrientes, Argentina

[33] Sanat Guemes, Buenos Aires, DF, Argentina

[34] CEREHA Ctr Enfermedades Renales & Hipertens, Sarandi, Buenos Aires, Argentina

[35] Adelaide Med Res, Ashford, SA, Australia

[36] Geelong Hosp, Geelong, Vic, Australia

[37] Australian Clin Res Network, Maroubra, NSW, Australia

[38] Launceston Gen Hosp, Launceston, Tas, Australia

[39] Core Res Grp, Milton, Qld, Australia

[40] Gold Coast Hosp, Southport, Qld, Australia

[41] AusTrials, Auchenflower, Qld, Australia

[42] Ave Cardiovasc Ctr, Windsor, NSW, Australia

[43] AusTrials, Sherwood, Qld, Australia

[44] St Vincents Hosp Melbourne, Fitzroy, Vic, Australia

[45] Peninsula Heart Ctr, Frankston, Vic, Australia

[46] Canberra Hosp, Clin Trials Unit, Woden, ACT, Australia

[47] Ctr Pesquisa Clin Brasil, Brasilia, DF, Brazil

[48] CCBR BRASIL Ctr Pesquisas & Anal Clin, Rio De Janeiro, Brazil

[49] CPClin Ctr Pesquisas Clin, Sao Paulo, Brazil

[50] Hosp Univ Joao Barros Barreto, Belem, Para, Brazil

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2013年 / 369卷 / 14期

关键词：

GLUCOSE CONTROL; CLINICAL-USE; ALL-CAUSE; METAANALYSIS; EVENTS; DEATH; PREVENTION; DISEASE; RISK; MICROALBUMINURIA;

D O I：

10.1056/NEJMoa1307684

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BackgroundThe cardiovascular safety and efficacy of many current antihyperglycemic agents, including saxagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, are unclear. MethodsWe randomly assigned 16,492 patients with type 2 diabetes who had a history of, or were at risk for, cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years. Physicians were permitted to adjust other medications, including antihyperglycemic agents. The primary end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. ResultsA primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group (7.3% and 7.2%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio with saxagliptin, 1.00; 95% confidence interval [CI], 0.89 to 1.12; P=0.99 for superiority; P<0.001 for noninferiority); the results were similar in the on-treatment analysis (hazard ratio, 1.03; 95% CI, 0.91 to 1.17). The major secondary end point of a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group (12.8% and 12.4%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio, 1.02; 95% CI, 0.94 to 1.11; P=0.66). More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure (3.5% vs. 2.8%; hazard ratio, 1.27; 95% CI, 1.07 to 1.51; P=0.007). Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups (acute pancreatitis, 0.3% in the saxagliptin group and 0.2% in the placebo group; chronic pancreatitis, <0.1% and 0.1% in the two groups, respectively). ConclusionsDPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events, though the rate of hospitalization for heart failure was increased. Although saxagliptin improves glycemic control, other approaches are necessary to reduce cardiovascular risk in patients with diabetes.

引用

页码：1317 / 1326

页数：10

共 35 条

[1]

Amer Diabet Assoc, 2011, DIABETES CARE, V34, pS11, DOI [10.2337/dc10-S062, 10.2337/dc14-S081, 10.2337/dc11-S011, 10.2337/dc13-S011, 10.2337/dc13-S067, 10.2337/dc12-s064, 10.2337/dc11-S062, 10.2337/dc10-S011, 10.2337/dc12-s011]

[2]

Bhatt DL, 2007, AM HEART J, V154, P402

[3] Comparative Determinants of 4-Year Cardiovascular Event Rates in Stable Outpatients at Risk of or With Atherothrombosis [J].

Bhatt, Deepak L. ;

Eagle, Kim A. ;

Ohman, E. Magnus ;

Hirsch, Alan T. ;

Goto, Shinya ;

Mahoney, Elizabeth M. ;

Wilson, Peter W. F. ;

Alberts, Mark J. ;

D'Agostino, Ralph ;

Liau, Chiau-Suong ;

Mas, Jean-Louis ;

Roether, Joachim ;

Smith, Sidney C., Jr. ;

Salette, Genevieve ;

Contant, Charles F. ;

Massaro, Joseph M. ;

Steg, Ph. Gabriel .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2010, 304 (12) :1350-1357

[4] Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials [J].

Boussageon, Remy ;

Bejan-Angoulvant, Theodora ;

Saadatian-Elahi, Mitra ;

Lafont, Sandrine ;

Bergeonneau, Claire ;

Kassai, Behrouz ;

Erpeldinger, Sylvie ;

Wright, James M. ;

Gueyffier, Francois ;

Cornu, Catherine .

BMJ-BRITISH MEDICAL JOURNAL, 2011, 343

[5]

Butler PC, 2013, DIABETES CARE, V36, P2118, DOI 10.2337/dc12-2713

[6] Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events):: a randomised controlled trial [J].

Dormandy, JA ;

Charbonnel, B ;

Eckland, DJA ;

Erdmann, E ;

Massi-Benedetti, M ;

Kmoules, IK ;

Skene, AM ;

Tan, MH ;

Lefébvre, PJ ;

Murray, GD ;

Standl, E ;

Wilcox, RG ;

Wlhelmsen, L ;

Betteridge, J ;

Birkeland, K ;

Golay, A ;

Heine, RJ ;

Korányi, L ;

Laakso, M ;

Mokán, M ;

Norkus, A ;

Pirags, V ;

Podar, T ;

Scheen, A ;

Scherbaum, W ;

Schernthaner, G ;

Schmitz, O ;

Skrha, J ;

Smith, U ;

Taton, J .

LANCET, 2005, 366 (9493) :1279-1289

[7] Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes [J].

Duckworth, William ;

Abraira, Carlos ;

Moritz, Thomas ;

Reda, Domenic ;

Emanuele, Nicholas ;

Reaven, Peter D. ;

Zieve, Franklin J. ;

Marks, Jennifer ;

Davis, Stephen N. ;

Hayward, Rodney ;

Warren, Stuart R. ;

Goldman, Steven ;

McCarren, Madeline ;

Vitek, Mary Ellen ;

Henderson, William G. ;

Huang, Grant D. .

NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (02) :129-U62

[8]

Food and Drug Administration, 2008, GUID IND DIAB MELL E

[9]

Food and Drug Administration, 2010, STAND DEF END POINT

[10] A Systematic Assessment of Cardiovascular Outcomes in the Saxagliptin Drug Development Program for Type 2 Diabetes [J].

Frederich, Robert ;

Alexander, John H. ;

Fiedorek, Fred T. ;

Donovan, Mark ;

Berglind, Niklas ;

Harris, Susan ;

Chen, Roland ;

Wolf, Robert ;

Mahaffey, Kenneth W. .

POSTGRADUATE MEDICINE, 2010, 122 (03) :16-27

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