Article

Effect of Valsartan on the Incidence of Diabetes and Cardiovascular Events

John J McMurrayUniversity of Oxford, Oxford, United KingdomJohn J.V. McMurrayThe University of Texas Health Science Center at San Antonio, San Antonio, United StatesSteven M HaffnerUniversity of Oxford, Oxford, United KingdomM Angelyn BethelNovartis (Switzerland), Basel, SwitzerlandM. BethelNovartis (Switzerland), Basel, SwitzerlandTsushung A HuaLomonosov Moscow State University, Moscow, RussiaTsushung A. HuaNovartis (Switzerland), Basel, SwitzerlandYuri BelenkovUniversity of North Carolina at Chapel Hill, Chapel Hill, United StatesMitradev BoolellUniversity College Cork, Cork, IrelandJohn B. BuseUniversidade Federal de São Paulo, São Paulo, BrazilBrendan M. BuckleyNational Taiwan University, Taipei, TaiwanAntônio Roberto ChacraNational Taiwan UniversityFu‐Tien ChiangB CharbonnelUniversity of Leicester, Leicester, United KingdomMelanie J DaviesUniversity of California, Berkeley, Berkeley, United StatesMelanie J. DaviesUniversity of Bern, Bern, SwitzerlandPrakash DeedwaniaUniversity of California, Berkeley, Berkeley, United StatesPeter DiemTulane University, New Orleans, United StatesDaniel EinhornTulane UniversityVivian FonsecaGregory FulcherMedical University of WarsawZbigniew GaciongSonia GaztambideHarvard University, Cambridge, United StatesThomas D. GilesIstanbul University, Istanbul, TurkeyEdward S. HortonUiT The Arctic University of Norway, Tromsø, NorwayHasan İlkovaUniversity of Washington, Seattle, United StatesTrond JenssenUniversity of WashingtonSteven E. KahnHenry KrumMarkku LaaksoUniversity of Cape Town, Rondebosch, South AfricaLawrence A. LeiterUniversity of Cape TownNaomi LevittFelipe MartinezNovartis (Switzerland), Basel, SwitzerlandFelipe A. MartínezUniversity of Illinois at Chicago, Chicago, United StatesChantal MassonUniversity of Illinois ChicagoTheodore MazzoneEduardo MeaneyLahey Hospital and Medical CenterRichard W. NestoChangyu PanRudolf PragerS. RaptisGuy E.H.M. RuttenTU Dresden, Dresden, GermanyHerbert SandstroemUniversity of Liège, Liège, BelgiumFrank SchäperAarhus University, Aarhus, DenmarkAndré ScheenCardiovascular Institute of the South, Houma, United StatesOle SchmitzCardiovascular Institute of the SouthIsaac SinayVladimír SoškaSemmelweis University, Budapest, HungarySteen StenderTulane University, New Orleans, United StatesGyula TamásUniversity of Helsinki, Helsinki, FinlandGianni TognoniUniversity of HelsinkiAlberto S VillamilAlberto S. VillamilJ VozárDuke University

2010en

ABI

Abstract

BACKGROUND: It 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. METHODS: In 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. RESULTS: The 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). CONCLUSIONS: Among 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.)

Identifiers

DOI: 10.1056/nejmoa1001121

Citations and references

Cited by 20 references

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