Effect of Valsartan on the Incidence of Diabetes and Cardiovascular Events

• Published in: New England Journal of Medicine
• Main Authors: McMurray, John J., Holman, Rury R., Haffner, Steven M., Bethel, M. Angelyn, Holzhauer, Bjoern, Hua, Tsushung A., Belenkov, Yuri, Boolell, Mitradev, Buse, John B., Buckley, Brendan M., Chacra, Antonio R., Chiang, Fu-Tien, Charbonnel, Bernard, Chow, Chun-Chung, Davies, Melanie J., Deedwania, Prakash, Diem, Peter, Einhorn, Daniel, Fonseca, Vivian, Fulcher, Gregory R., Gaciong, Zbigniew, Gaztambide, Sonia, Giles, Thomas, Horton, Edward, Ilkova, Hasan, Jenssen, Trond, Kahn, Steven E., Krum, Henry, Laakso, Markku, Leiter, Lawrence A., Levitt, Naomi S., Mareev, Viacheslav, Martinez, Felipe, Masson, Chantal, Mazzone, Theodore, Meaney, Eduardo, Nesto, Richard, Pan, Changyu, Prager, Rudolf, Raptis, Sotirios A., Rutten, Guy E. H. M., Sandstroem, Herbert, Schaper, Frank, Scheen, Andre, Schmitz, Ole, Sinay, Isaac, Soska, Vladimir, Stender, Steen, Tamas, Gyula, Tognoni, Gianni, Tuomilehto, Jaako, Villamil, Alberto S., Vozar, Juraj, Califf, Robert M., NAVIGATOR Study Grp
• Other Authors: Univ Glasgow, Univ Oxford, Univ Texas Hlth Sci Ctr San Antonio, Duke Univ, Novartis Pharmaceut, Moscow MV Lomonosov State Univ, Univ N Carolina, Natl Univ Ireland Univ Coll Cork, Universidade Federal de São Paulo (UNIFESP), Natl Taiwan Univ Hosp, Univ Hosp, Chinese Univ Hong Kong, Univ Leicester, Calif State Univ Fresno, VA Cent Calif Hlth Care Syst, Univ Hosp Bern, Univ Bern, Univ Calif San Diego, Scripps Whittier Diabet Inst, Tulane Univ, Univ Sydney, Warsaw Med Univ, Hosp Univ Cruces, Joslin Diabet Ctr, Istanbul Univ, Oslo Univ Hosp, Univ Tromso, VA Puget Sound Hlth Care Syst, Univ Washington, Monash Univ, Univ Kuopio, Kuopio Univ Hosp, Univ Toronto, Univ Cape Town, Natl Univ Cordoba, Univ Illinois, Hosp Primero Octubre, Lahey Clin Fdn, 301 Hosp, Krankenhaus Hietzing Neurol, Attikon Univ Hosp, Univ Med Ctr, Umea Univ, Tech Univ Dresden, Univ Liege, Aarhus Univ, Inst Cardiovasc Buenos Aires, Fac Hosp St Anna, Univ Copenhagen, Semmelweis Univ
• Format: Article in Journal/Newspaper
• Language: English
• Published: Massachusetts Medical Soc 2010
• Subjects: Argentina; Burlington; Canada; Chapel Hill; Leicester; Norway; Orleans; Scripps; Tromso
• Online Access: http://repositorio.unifesp.br/handle/11600/32479; https://doi.org/10.1056/NEJMoa1001121

BACKGROUNDIt is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance.METHODSIn this double-blind, randomized clinical trial with a 2-by-2 factorial design, we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan (up to 160 mg daily) or placebo (and nateglinide or placebo) in addition to lifestyle modification. We then followed the patients for a median of 5.0 years for the development of diabetes (6.5 years for vital status). We studied the effects of valsartan on the occurrence of three coprimary outcomes: the development of diabetes; an extended composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina; and a core composite outcome that excluded unstable angina and revascularization.RESULTSThe cumulative incidence of diabetes was 33.1% in the valsartan group, as compared with 36.8% in the placebo group (hazard ratio in the valsartan group, 0.86; 95% confidence interval [CI], 0.80 to 0.92; P<0.001). Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome (14.5% vs. 14.8%; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P = 0.43) or the core cardiovascular outcome (8.1% vs. 8.1%; hazard ratio, 0.99; 95% CI, 0.86 to 1.14; P = 0.85).CONCLUSIONSAmong patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events. (ClinicalTrials.gov number, NCT00097786.) Novartis Pharma Univ Glasgow, British Heart Fdn, Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland Univ Oxford, Diabet Trials Unit, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA Duke Univ, Duke Clin Res Inst, Durham, NC USA Novartis Pharmaceut, Basel, Switzerland Novartis Pharmaceut, E Hanover, NJ USA Moscow MV Lomonosov State Univ, Moscow 117234, Russia Univ N Carolina, Sch Med, Div Gen Med & Clin Epidemiol, Diabet Care Ctr, Chapel Hill, NC USA Natl Univ Ireland Univ Coll Cork, Cork, Ireland Universidade Federal de São Paulo, São Paulo, Brazil Natl Taiwan Univ Hosp, Dept Cardiol, Taipei, Taiwan Univ Hosp, Dept Endocrinol, Nantes, France Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England Calif State Univ Fresno, San Francisco Program Fresno, Div Cardiol, Fresno, CA 93740 USA VA Cent Calif Hlth Care Syst, Fresno, CA USA Univ Hosp Bern, Inselspital, Div Endocrinol Diabet & Clin Nutr, CH-3010 Bern, Switzerland Univ Bern, Bern, Switzerland Univ Calif San Diego, La Jolla, CA 92093 USA Scripps Whittier Diabet Inst, La Jolla, CA USA Tulane Univ, Dept Endocrinol, New Orleans, LA 70118 USA Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia Warsaw Med Univ, Dept Internal Med Hypertens & Vasc Dis, Warsaw, Poland Hosp Univ Cruces, CIBERDEM, Dept Endocrinol, Baracaldo, Spain Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA Joslin Diabet Ctr, Boston, MA 02215 USA Istanbul Univ, Dept Diabet Endocrinol & Metab, Istanbul, Turkey Oslo Univ Hosp, Rikshosp, Oslo, Norway Univ Tromso, Inst Clin Med, Tromso, Norway VA Puget Sound Hlth Care Syst, Seattle, WA USA Univ Washington, Seattle, WA 98195 USA Monash Univ, Alfred Hosp, Dept Epidemiol & Prevent Med, Clin Pharmacol Unit, Prahran, Vic, Australia Univ Kuopio, FIN-70211 Kuopio, Finland Kuopio Univ Hosp, SF-70210 Kuopio, Finland Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto, ON M5B 1W8, Canada Univ Cape Town, Dept Med, Groote Schuur Hosp, ZA-7925 Cape Town, South Africa Natl Univ Cordoba, Cordoba, Argentina Univ Illinois, Dept Diabet & Metab, Chicago, IL USA Hosp Primero Octubre, Mexico City, DF, Mexico Lahey Clin Fdn, Burlington, MA USA 301 Hosp, Dept Endocrinol, Beijing, Peoples R China Krankenhaus Hietzing Neurol, Zentrum Rosenhugel, Hietzig Hosp, Vienna, Austria Attikon Univ Hosp, Hellen Natl Diabet Ctr, Dept Internal Med Endocrinol & Diabetol 2, Athens, Greece Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden Tech Univ Dresden, Ctr Clin Studies Metab & Endocrinol Knowledge & T, D-8027 Dresden, Germany Univ Liege, Div Diabet, Liege, Belgium Univ Liege, Clin Pharmacol Unit, Ctr Hosp Univ Liege, Liege, Belgium Aarhus Univ, Med Dept Endocrinol & Diabet M, Aarhus, Denmark Aarhus Univ, Dept Clin Pharmacol, Aarhus, Denmark Inst Cardiovasc Buenos Aires, Buenos Aires, DF, Argentina Fac Hosp St Anna, Dept Clin Biochem, Brno, Czech Republic Fac Hosp St Anna, Clin Internal Med 2, Brno, Czech Republic Univ Copenhagen, Gentofte Hosp, Dept Clin Biochem, Copenhagen, Denmark Semmelweis Univ, Diabet Unit, Dept Med 1, H-1085 Budapest, Hungary Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, I-66030 Santa Maria Imbaro, Italy Univ Helsinki, Hjelt Inst, Helsinki, Finland Univ Helsinki, Dept Publ Hlth, Helsinki, Finland S Ostrobothnia Cent Hosp, Seinajoki, Finland Univ Buenos Aires, Div Cardiol, Hypertens Unit, Argerich Hosp, Buenos Aires, DF, Argentina Diabetol Outpatient Clin, Jesenius Samaria, Samorin, Slovakia Duke Univ, Duke Translat Med Inst, Durham, NC USA Universidade Federal de São Paulo, São Paulo, Brazil Web of Science