Effect of valsartan on the incidence of diabetes and cardiovascular events.
NAVIGATOR Study Group None., McMurray JJ., Holman RR., Haffner SM., Bethel MA., Holzhauer B., Hua TA., Belenkov Y., Boolell M., Buse JB., Buckley BM., Chacra AR., Chiang FT., Charbonnel B., Chow CC., Davies MJ., Deedwania P., Diem P., Einhorn D., Fonseca V., Fulcher GR., Gaciong Z., Gaztambide S., Giles T., Horton E., Ilkova H., Jenssen T., Kahn SE., Krum H., Laakso M., Leiter LA., Levitt NS., Mareev V., Martinez F., Masson C., Mazzone T., Meaney E., Nesto R., Pan C., Prager R., Raptis SA., Rutten GE., Sandstroem H., Schaper F., Scheen A., Schmitz O., Sinay I., Soska V., Stender S., Tamás G., Tognoni G., Tuomilehto J., Villamil AS., Vozár J., Califf RM.
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.)