International variation in outcomes among people with cardiovascular disease or cardiovascular risk factors and impaired glucose tolerance: Insights from the NAVIGATOR trial

Background-regional differences in risk of diabetes mellitus and cardiovascular outcomes in people with impaired glucose tolerance are poorly characterized. our objective was to evaluate regional variation in risk of new-onset diabetes mellitus,cardiovascular outcomes,and treatment effects in participants from the navigator (nateglinide and valsartan in impaired glucose tolerance outcomes research) trial. methods and results-navigator randomized people with impaired glucose tolerance and cardiovascular risk factors or with established cardiovascular disease to valsartan (or placebo) and to nateglinide (or placebo) with a median 5-year follow-up. data from the 9306 participants were categorized by 5 regions: asia (n=552); europe (n=4909); latin america (n=1406); north america (n=2146); and australia,new zealand,and south africa (n=293). analyzed outcomes included new-onset diabetes mellitus; cardiovascular death; a composite cardiovascular outcome of cardiovascular death,nonfatal myocardial infarction,or nonfatal stroke; and treatment effects of valsartan and nateglinide. respective unadjusted 5-year risks for new-onset diabetes mellitus,cardiovascular death,and the composite cardiovascular outcome were 33%,0.4%,and 4% for asia; 34%,2%,and 6% for europe; 37%,4%,and 8% for latin america; 38%,2%,and 6% for north america; and 32%,4%,and 8% for australia,new zealand,and south africa. after adjustment,compared with north america,european participants had a lower risk of new-onset diabetes mellitus (hazard ratio 0.86,95% ci 0.78-0.94; p=0.001),whereas latin american participants had a higher risk of cardiovascular death (hazard ratio 2.68,95% ci 1.82-3.96; p < 0.0001) and the composite cardiovascular outcome (hazard ratio 1.48,95% ci 1.15-1.92; p=0.003). no differential interactions between treatment and geographic location were identified. conclusions-major regional differences regarding the risk of new-onset diabetes mellitus and cardiovascular outcomes in navigator participants were identified. these differences should be taken into account when planning global trials. © 2017 the authors.