Effect of valsartan on the incidence of diabetes and cardiovascular events
NAVIGATOR Study Group, John J McMurray, Rury R Holman, Steven M Haffner, M Angelyn Bethel, Björn Holzhauer, Tsushung A Hua, Yuri Belenkov, Mitradev Boolell, John B Buse, Brendan M Buckley, Antonio R Chacra, Fu-Tien Chiang, Bernard Charbonnel, Chun-Chung Chow, Melanie J Davies, Prakash Deedwania, Peter Diem, Daniel Einhorn, Vivian Fonseca, Gregory R Fulcher, Zbigniew Gaciong, Sonia Gaztambide, Thomas Giles, Edward Horton, Hasan Ilkova, Trond Jenssen, Steven E Kahn, Henry Krum, Markku Laakso, Lawrence A Leiter, Naomi S Levitt, Viacheslav Mareev, Felipe Martinez, Chantal Masson, Theodore Mazzone, Eduardo Meaney, Richard Nesto, Changyu Pan, Rudolf Prager, Sotirios A Raptis, Guy E H M Rutten, Herbert Sandstroem, Frank Schaper, Andre Scheen, Ole Schmitz, Isaac Sinay, Vladimir Soska, Steen Stender, Gyula Tamás, Gianni Tognoni, Jaako Tuomilehto, Alberto S Villamil, Juraj Vozár, Robert M Califf, Robert M Califf, Rury R Holman, Mitradev Boolell, Steven M Haffner, John J McMurray, Anil Duggal, M Angelyn Bethel, Robert M Califf, Steven M Haffner, Rury R Holman, John J McMurray, Antonio Gotto, Aldo Maggioni, Eberhard Standl, Joel Verter, Bernard Zinman, Yuri Belenkov, John B Buse, Brendan M Buckley, Antonio R Chacra, Robert M Califf, Fu-Tien Chiang, Bernard Charbonnel, Chun-Chung Chow, Melanie J Davies, Prakash Deedwania, Peter Diem, Daniel Einhorn, Vivian Fonseca, Gregory R Fulcher, Zbigniew Gaciong, Sonia Gaztambide, Thomas Giles, Steven M Haffner, Rury R Holman, Edward Horton, Hasan Ilkova, Trond Jenssen, Steven E Kahn, Henry Krum, Markku Laakso, Lawrence A Leiter, Naomi S Levitt, John J McMurray, Viacheslav Mareev, Felipe Martinez, Theodore Mazzone, Eduardo Meaney, Richard Nesto, Changyu Pan, Rudolf Prager, Sotirios A Raptis, Guy E H M Rutten, Herbert Sandstroem, Frank Schaper, Andre Scheen, Ole Schmitz, Isaac Sinay, Vladimir Soska, Steen Stender, Gyula Tamás, Gianni Tognoni, Jaako Tuomilehto, Alberto S Villamil, Juraj Vozár, Robert J Heine, Markolf Hanefeld, Mustaffa Embong, Josef Drzewoski, J Eriksson, Clicerio González-Villalpando, Robert Ratner, Andrew Boulton, Nick J Wareham, Sorin Bresner, Arman Askari, Venugopal Menon, Michael Chen, Anjli Maroo, Oussama Wazni, Khaled Ziada, Matthews Chacko, Michael McWilliams, Vivek Rajagopal, Stephen Gimple, Mateen Akhtar, Matthew Casey Becker, John Galla, Deborah Kwon, Kellan Ashley, Cathy Sila, Irene Katza, Narcis Pasca, Lori Blashford, Kim J Brown, Mary Del Valle, Mary J Heckman, Andreea Mocanu, Kathleen K Sankovic, Wendy Sarver, Christine Shaffer, NAVIGATOR Study Group, John J McMurray, Rury R Holman, Steven M Haffner, M Angelyn Bethel, Björn Holzhauer, Tsushung A Hua, Yuri Belenkov, Mitradev Boolell, John B Buse, Brendan M Buckley, Antonio R Chacra, Fu-Tien Chiang, Bernard Charbonnel, Chun-Chung Chow, Melanie J Davies, Prakash Deedwania, Peter Diem, Daniel Einhorn, Vivian Fonseca, Gregory R Fulcher, Zbigniew Gaciong, Sonia Gaztambide, Thomas Giles, Edward Horton, Hasan Ilkova, Trond Jenssen, Steven E Kahn, Henry Krum, Markku Laakso, Lawrence A Leiter, Naomi S Levitt, Viacheslav Mareev, Felipe Martinez, Chantal Masson, Theodore Mazzone, Eduardo Meaney, Richard Nesto, Changyu Pan, Rudolf Prager, Sotirios A Raptis, Guy E H M Rutten, Herbert Sandstroem, Frank Schaper, Andre Scheen, Ole Schmitz, Isaac Sinay, Vladimir Soska, Steen Stender, Gyula Tamás, Gianni Tognoni, Jaako Tuomilehto, Alberto S Villamil, Juraj Vozár, Robert M Califf, Robert M Califf, Rury R Holman, Mitradev Boolell, Steven M Haffner, John J McMurray, Anil Duggal, M Angelyn Bethel, Robert M Califf, Steven M Haffner, Rury R Holman, John J McMurray, Antonio Gotto, Aldo Maggioni, Eberhard Standl, Joel Verter, Bernard Zinman, Yuri Belenkov, John B Buse, Brendan M Buckley, Antonio R Chacra, Robert M Califf, Fu-Tien Chiang, Bernard Charbonnel, Chun-Chung Chow, Melanie J Davies, Prakash Deedwania, Peter Diem, Daniel Einhorn, Vivian Fonseca, Gregory R Fulcher, Zbigniew Gaciong, Sonia Gaztambide, Thomas Giles, Steven M Haffner, Rury R Holman, Edward Horton, Hasan Ilkova, Trond Jenssen, Steven E Kahn, Henry Krum, Markku Laakso, Lawrence A Leiter, Naomi S Levitt, John J McMurray, Viacheslav Mareev, Felipe Martinez, Theodore Mazzone, Eduardo Meaney, Richard Nesto, Changyu Pan, Rudolf Prager, Sotirios A Raptis, Guy E H M Rutten, Herbert Sandstroem, Frank Schaper, Andre Scheen, Ole Schmitz, Isaac Sinay, Vladimir Soska, Steen Stender, Gyula Tamás, Gianni Tognoni, Jaako Tuomilehto, Alberto S Villamil, Juraj Vozár, Robert J Heine, Markolf Hanefeld, Mustaffa Embong, Josef Drzewoski, J Eriksson, Clicerio González-Villalpando, Robert Ratner, Andrew Boulton, Nick J Wareham, Sorin Bresner, Arman Askari, Venugopal Menon, Michael Chen, Anjli Maroo, Oussama Wazni, Khaled Ziada, Matthews Chacko, Michael McWilliams, Vivek Rajagopal, Stephen Gimple, Mateen Akhtar, Matthew Casey Becker, John Galla, Deborah Kwon, Kellan Ashley, Cathy Sila, Irene Katza, Narcis Pasca, Lori Blashford, Kim J Brown, Mary Del Valle, Mary J Heckman, Andreea Mocanu, Kathleen K Sankovic, Wendy Sarver, Christine Shaffer
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.)
2010 Massachusetts Medical Society
Source: PubMed