nateglinide and Stroke

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.. 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.. 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.. URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00097786.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Asia; Australia; Cardiovascular Diseases; Cyclohexanes; Diabetes Mellitus, Type 2; Europe; Female; Glucose Intolerance; Humans; Hypoglycemic Agents; Incidence; Latin America; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Nateglinide; New Zealand; North America; Outcome Assessment, Health Care; Phenylalanine; Proportional Hazards Models; Randomized Controlled Trials as Topic; Risk Factors; South Africa; Stroke; Valsartan

Risk factors for stroke are well-established in general populations but sparsely studied in individuals with impaired glucose tolerance.. We identified predictors of stroke among participants with impaired glucose tolerance in the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. Cox proportional-hazard regression models were constructed using baseline variables, including the 2 medications studied, valsartan and nateglinide.. Among 9306 participants, 237 experienced a stroke over 6.4 years. Predictors of stroke included classical risk factors such as existing cerebrovascular and coronary heart disease, higher pulse pressure, higher low-density lipoprotein cholesterol, older age, and atrial fibrillation. Other factors, including previous venous thromboembolism, higher waist circumference, lower estimated glomerular filtration rate, lower heart rate, and lower body mass index, provided additional important predictive information, yielding a C-index of 0.72. Glycemic measures were not predictive of stroke. Variables associated with stroke were similar in participants with no prior history of cerebrovascular disease at baseline.. The most powerful predictors of stroke in patients with impaired glucose tolerance included a combination of established risk factors and novel variables, such as previous venous thromboembolism and elevated waist circumference, allowing moderately effective identification of high-risk individuals.

Topics: Aged; Antihypertensive Agents; Comorbidity; Controlled Clinical Trials as Topic; Cyclohexanes; Drug Therapy, Combination; Female; Glucose Intolerance; Humans; Hypoglycemic Agents; Male; Middle Aged; Nateglinide; Outcome Assessment, Health Care; Phenylalanine; Predictive Value of Tests; Risk Factors; Stroke; Tetrazoles; Valine; Valsartan