PMID- 18946890 OWN - NLM STAT- MEDLINE DCOM- 20081114 LR - 20220318 IS - 1097-6744 (Electronic) IS - 0002-8703 (Linking) VI - 156 IP - 4 DP - 2008 Oct TI - Prevention of diabetes and cardiovascular disease in patients with impaired glucose tolerance: rationale and design of the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial. PG - 623-32 AB - Patients with impaired glucose tolerance (IGT) have increased risk for developing type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Lifestyle modification and medication can prevent or delay progression to diabetes (PD), but whether such interventions also reduce the risk of CVD has not been rigorously tested. The Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial is a multinational, randomized, double-blind, 2 x 2 factorial trial in subjects with IGT (on a screening oral glucose tolerance test [OGTT]) aged > or = 50 years with known CVD or aged > or = 55 years with > or = 1 CVD risk factor. Enrollment began in January 2002 and was completed January 2004, with 9,518 patients randomized to receive 1 of 4 possible treatment combinations as follows: nateglinide with valsartan, nateglinide with valsartan-placebo, nateglinide-placebo with valsartan, or nateglinide-placebo with valsartan-placebo. All subjects are participating in a clinic-based and telephone-based lifestyle intervention aimed at reducing weight and dietary fat and increasing physical activity. The 3 coprimary end points are new onset of T2DM, a "core" composite of major cardiovascular events (death, myocardial infarction, stroke, or hospitalization for heart failure), and an "extended" composite including the components of the core composite plus coronary revascularization and hospitalization for unstable angina. The study was designed to evaluate whether reducing postprandial hyperglycemia, blockade of the renin-angiotensin-aldosterone system, or both interventions reduce the risk of T2DM or cardiovascular events in patients with IGT. FAU - Califf, Robert M AU - Califf RM AD - Duke Transitional Medicine Institute, Durham, NC 27715, USA. FAU - Boolell, Mitradev AU - Boolell M FAU - Haffner, Steven M AU - Haffner SM FAU - Bethel, M Angelyn AU - Bethel M FAU - McMurray, John AU - McMurray J FAU - Duggal, Anil AU - Duggal A FAU - Holman, Rury R AU - Holman RR CN - NAVIGATOR Study Group LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Am Heart J JT - American heart journal JID - 0370465 RN - 0 (Angiotensin II Type 1 Receptor Blockers) RN - 0 (Angiotensin-Converting Enzyme Inhibitors) RN - 0 (Cyclohexanes) RN - 0 (Hypoglycemic Agents) RN - 0 (Tetrazoles) RN - 41X3PWK4O2 (Nateglinide) RN - 47E5O17Y3R (Phenylalanine) RN - 80M03YXJ7I (Valsartan) RN - HG18B9YRS7 (Valine) SB - IM MH - Angiotensin II Type 1 Receptor Blockers/*therapeutic use MH - Angiotensin-Converting Enzyme Inhibitors/*therapeutic use MH - Cyclohexanes/*therapeutic use MH - Diabetic Angiopathies/drug therapy/physiopathology/*prevention & control MH - Disease Progression MH - Double-Blind Method MH - Glucose Intolerance/drug therapy/*prevention & control MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Life Style MH - Nateglinide MH - Outcome Assessment, Health Care MH - Phenylalanine/*analogs & derivatives/therapeutic use MH - Research Design MH - Tetrazoles/*therapeutic use MH - Valine/*analogs & derivatives/therapeutic use MH - Valsartan FIR - Califf, R IR - Califf R FIR - Holman, R IR - Holman R FIR - Boolell, M IR - Boolell M FIR - Haffner, S IR - Haffner S FIR - McMurray, J IR - McMurray J FIR - Duggal, A IR - Duggal A FIR - Martinez, F IR - Martinez F FIR - Sinay, I IR - Sinay I FIR - Villamil, A IR - Villamil A FIR - Fulcher, G IR - Fulcher G FIR - Krum, H IR - Krum H FIR - Prager, R IR - Prager R FIR - Scheen, A IR - Scheen A FIR - Chacra, A IR - Chacra A FIR - Leiter, L IR - Leiter L FIR - Pan, C IR - Pan C FIR - Stender, S IR - Stender S FIR - Laakso, M IR - Laakso M FIR - Tuomilehto, J IR - Tuomilehto J FIR - Charbonnel, B IR - Charbonnel B FIR - Schaper, F IR - Schaper F FIR - Raptis, S A IR - Raptis SA FIR - Chow, F IR - Chow F FIR - Tamas, G IR - Tamas G FIR - Buckley, B IR - Buckley B FIR - Tognoni, G IR - Tognoni G FIR - Meaney, E IR - Meaney E FIR - Rutten, G IR - Rutten G FIR - Jenssen, T IR - Jenssen T FIR - Gaciong, Z IR - Gaciong Z FIR - Belenkov, Y IR - Belenkov Y FIR - Mareev, V IR - Mareev V FIR - Vozar, J IR - Vozar J FIR - Levitt, N IR - Levitt N FIR - Gaztambide, S IR - Gaztambide S FIR - Sandstrom, H IR - Sandstrom H FIR - Diem, P IR - Diem P FIR - Chiang, F IR - Chiang F FIR - Ilkova, H IR - Ilkova H FIR - Davies, M IR - Davies M FIR - Buse, J IR - Buse J FIR - Deedwania, P IR - Deedwania P FIR - Einhorn, D IR - Einhorn D FIR - Fonseca, V IR - Fonseca V FIR - Giles, T IR - Giles T FIR - Horton, E IR - Horton E FIR - Kahn, S IR - Kahn S FIR - Mazzone, T IR - Mazzone T FIR - Nesto, R IR - Nesto R FIR - Heine, R IR - Heine R FIR - Hanefeld, M IR - Hanefeld M FIR - Embong, M IR - Embong M FIR - Drzewoski, J IR - Drzewoski J FIR - Eriksson, J IR - Eriksson J FIR - Gonzalez-Villalpando, C IR - Gonzalez-Villalpando C FIR - Gotto, A IR - Gotto A FIR - Maggioni, A IR - Maggioni A FIR - Standl, E IR - Standl E FIR - Zinman, B IR - Zinman B FIR - Verter, J IR - Verter J FIR - Ratner, R IR - Ratner R FIR - Wareham, N IR - Wareham N FIR - Boulton, A IR - Boulton A FIR - Askari, A IR - Askari A EDAT- 2008/10/24 09:00 MHDA- 2008/11/15 09:00 CRDT- 2008/10/24 09:00 PHST- 2008/10/24 09:00 [pubmed] PHST- 2008/11/15 09:00 [medline] PHST- 2008/10/24 09:00 [entrez] AID - S0002-8703(08)00389-X [pii] AID - 10.1016/j.ahj.2008.05.017 [doi] PST - ppublish SO - Am Heart J. 2008 Oct;156(4):623-32. doi: 10.1016/j.ahj.2008.05.017.