International Variation in Outcomes Among People with Cardiovascular Disease or Cardiovascular Risk Factors and Impaired Glucose Tolerance: Insights from the NAVIGATOR Trial

Abstract

BackgroundRegional 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.ConclusionsMajor 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.Clinical Trial RegistrationURL: http://www.ClinicalTrials.gov. Unique identifier: NCT00097786.

First cardiovascular event in patients with type 2 diabetes mellitus of a cardiovascular risk management program of a poor Colombian population: a cohort study

“…In randomized clinical trials such as the NAVIGATOR study, Latin American participants with glucose intolerance had an increased risk of cardiovascular death (HR 2.68, 95% CI 1.82–3.96) and composite cardiovascular outcome (HR 1.48, 95% CI 1.15–1.92). When the data are recorded in the context of a clinical trial, they may not reflect the real characteristics of the population by the specified selection criteria [14]. In the PURE study identified that although risk-factor burden may be lower in LMIC, the risk of cardiovascular events was much higher [19].…”

“…The use of statins in the LMIC is low in comparison with the HIC [28]. In the NAVIGATOR study, was reported that patients in Latin America used fewer therapies for prevention of cardiovascular events, such as aspirin (32% versus 47% in North America and 35% in Europe), lipid-lowering therapies (28% versus 55% in North America and 35% in Europe), and ACEIs (4% versus 9% in North America and 8% in Europe) [14]. In the TECOS study, low use of statins and aspirin in Latin America compared to North America was reported [29].…”

“…In the INTERSTROKE study, a significant association between DM and stroke (Relative Risk (RR) 1.36, 95% CI 1.10–1.68) and a population risk attributable to DM of 5% was reported [13]. In randomized clinical trials such as the NAVIGATOR study, Latin American participants with glucose intolerance had an increased risk of cardiovascular death (Hazard Risk (HR) 2.68, 95% CI 1.82–3.96) and composite cardiovascular outcome (HR 1.48, 95% CI 1.15–1.92) [14]. Traditional multivariate risk adjustment models may be limited by residual biases and questioned the reliability and when the data are recorded in the context of a clinical trial, they may not reflect the real characteristics of the population by the specified selection criteria.…”

Development of Dual Drug Eluting Cardiovascular Stent with Ultrathin Flexible Poly(l-lactide-co-caprolactone) Coating

“…However, such expensive and complex strategies produced less satisfactory results in clinical trials. Further, epidemiological variations in the therapeutic outcomes have also been reported …”