Dataset Information

Cardiovascular Outcomes According to Urinary Albumin and Kidney Disease in Patients With Type 2 Diabetes at High Cardiovascular Risk: Observations From the SAVOR-TIMI 53 Trial.

ABSTRACT: Importance:An elevated level of urinary albumin to creatinine ratio (UACR) is a marker of renal dysfunction and predictor of kidney failure/death in patients with type 2 diabetes. The prognostic use of UACR in established cardiac biomarkers is not well described. Objective:To evaluate whether UACR offers incremental prognostic benefit beyond risk factors and established plasma cardiovascular biomarkers. Design, Setting, and Participants:The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus-Thrombolysis in Myocardial Infarction (SAVOR-TIMI) 53 study was performed from May 2010 to May 2013 and evaluated the safety of saxagliptin vs placebo in patients with type 2 diabetes with overt cardiovascular disease or multiple risk factors. Median follow-up was 2.1 years (interquartile range, 1.8-2.3 years). Interventions:Patients were randomized to saxagliptin vs placebo plus standard care. Main Outcomes and Measures:Baseline UACR was measured in 15?760 patients (95.6% of the trial population) and categorized into thresholds. Results:Of 15?760 patients, 5205 were female (33.0%). The distribution of UARC categories were: 5805 patients (36.8%) less than 10 mg/g, 3891 patients (24.7%) at 10 to 30 mg/g, 4426 patients (28.1%) at 30 to 300 mg/g, and 1638 patients (10.4%) at more than 300 mg/g. When evaluated without cardiac biomarkers, there was a stepwise increase with each higher UACR category in the incidence of the primary composite end point (cardiovascular death, myocardial infarction, or ischemic stroke) (3.9%, 6.9%, 9.2%, and 14.3%); cardiovascular death (1.4%, 2.6%, 4.1%, and 6.9%); and hospitalization for heart failure (1.5%, 2.5%, 4.0%, and 8.3%) (adjusted P?

SUBMITTER: Scirica BM

PROVIDER: S-EPMC6594440 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Cardiovascular Outcomes According to Urinary Albumin and Kidney Disease in Patients With Type 2 Diabetes at High Cardiovascular Risk: Observations From the SAVOR-TIMI 53 Trial.

Scirica Benjamin M BM Mosenzon Ofri O Bhatt Deepak L DL Udell Jacob A JA Steg Ph Gabriel PG McGuire Darren K DK Im KyungAh K Kanevsky Estella E Stahre Christina C Sjöstrand Mikaela M Raz Itamar I Braunwald Eugene E

JAMA cardiology 20180201 2

<h4>Importance</h4>An elevated level of urinary albumin to creatinine ratio (UACR) is a marker of renal dysfunction and predictor of kidney failure/death in patients with type 2 diabetes. The prognostic use of UACR in established cardiac biomarkers is not well described.<h4>Objective</h4>To evaluate whether UACR offers incremental prognostic benefit beyond risk factors and established plasma cardiovascular biomarkers.<h4>Design, setting, and participants</h4>The Saxagliptin Assessment of Vascula ...[more]

PMID: 29214305

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Project description:BACKGROUND:Canagliflozin is approved for glucose lowering in type 2 diabetes and confers cardiovascular and renal benefits. We sought to assess whether it had benefits in people with chronic kidney disease, including those with an estimated glomerular filtration rate (eGFR) between 30 and 45 mL/min/1.73 m2 in whom the drug is not currently approved for use. METHODS:The CANVAS Program randomized 10 142 participants with type 2 diabetes and eGFR >30 mL/min/1.73 m2 to canagliflozin or placebo. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with other cardiovascular, renal, and safety outcomes. This secondary analysis describes outcomes in participants with and without chronic kidney disease, defined as eGFR <60 and ?60 mL/min/1.73 m2, and according to baseline kidney function (eGFR <45, 45 to <60, 60 to <90, and ?90 mL/min/1.73 m2). RESULTS:At baseline, 2039 (20.1%) participants had an eGFR <60 mL/min/1.73 m2, 71.6% of whom had a history of cardiovascular disease. The effect of canagliflozin on the primary outcome was similar in people with chronic kidney disease (hazard ratio, 0.70; 95% CI, 0.55-0.90) and those with preserved kidney function (hazard ratio, 0.92; 95% CI, 0.79-1.07; P heterogeneity = 0.08). Relative effects on most cardiovascular and renal outcomes were similar across eGFR subgroups, with possible heterogeneity suggested only for the outcome of fatal/nonfatal stroke ( P heterogeneity = 0.01), as were results for almost all safety outcomes. CONCLUSIONS:The effects of canagliflozin on cardiovascular and renal outcomes were not modified by baseline level of kidney function in people with type 2 diabetes and a history or high risk of cardiovascular disease down to eGFR levels of 30 mL/min/1.73 m2. Reassessing current limitations on the use of canagliflozin in chronic kidney disease may allow additional individuals to benefit from this therapy. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01032629, NCT01989754.

Project description:ObjectiveTo assess the reproducibility and clinical utility of clustering-based subtyping of patients with type 2 diabetes (T2D) and established cardiovascular (CV) disease.MethodsThe cardiovascular outcome trial SAVOR-TIMI 53 (n = 16,492) was used. Analyses focused on T2D patients with established CV disease. Unsupervised machine learning technique called "k-means clustering" was used to divide patients into subtypes. K-means clustering including HbA1c, age of diagnosis, BMI, HOMA2-IR and HOMA2-B was used to assign clusters to the following diabetes subtypes: severe insulin deficient diabetes (SIDD); severe insulin-resistant diabetes (SIRD); mild obesity-related diabetes (MOD); mild age-related diabetes (MARD). We refer these subtypes as "clustering-based diabetes subtypes". A simulation study using randomly generated data was conducted to understand how correlations between the above variables influence the formation of the cluster-based diabetes subtypes. The predictive utility of clustering-based diabetes subtypes for CV events (3-point MACE), renal function reduction (eGFR decrease >30%) and diabetic disease progression (introduction of additional anti-diabetic medication) were compared with conventional risk scores. Hazard ratios (HR) were estimated by Cox-proportional hazard models.ResultsIn the SAVOR-TIMI 53 trial based dataset, the percentage of the clustering-based T2D subtypes were; SIDD (18%), SIRD (17%), MOD (29%), MARD (37%). Using the simulated dataset, the diabetes subtypes could be largely reproduced from a log-normal distribution when including known correlations between variables. The predictive utility of clustering-based diabetic subtypes on CV events, renal function reduction, and diabetic disease progression did not show an advantage compared to conventional risk scores.ConclusionsThe consistent reproduction of four clustering-based T2D subtypes can be explained by the correlations between the variables used for clustering. Subtypes of T2D based on clustering had limited advantage compared to conventional risk scores to predict clinical outcome in patients with T2D and established CV disease.

Project description:Background and objectivesBlacks have high rates of cardiovascular disease and mortality. Diabetes and CKD, risk factors for cardiovascular mortality in the general population, are common among blacks. We sought to assess their contribution to cardiovascular disease and mortality in blacks.Design, setting, participants, & measurementsThis observational cohort study was of 3211 participants in the Jackson Heart Study (enrolled 2000-2004). Rates of incident stroke, incident coronary heart disease, and cardiovascular mortality were quantified in participants with diabetes, CKD (eGFR<60 ml/min per 1.73 m(2), urine albumin-to-creatinine ratio ≥30 mg/g, or both), or both through 2012, with a median follow-up of 6.99 years.ResultsFour hundred fifty-six (14.2%) participants had only diabetes, 257 (8.0%) had only CKD, 201 (6.3%) had both, and 2297 (71.5%) had neither. Diabetes without CKD was associated with excess risks of incident stroke, incident coronary heart disease, and cardiovascular mortality after adjustment for demographic and clinical covariates, including prevalent cardiovascular disease (excess incidence rates, 2.6; 95% confidence interval, 0.5 to 4.7; 2.6; 95% confidence interval, 0.3 to 4.8; and 2.4; 95% confidence interval, 0.4 to 4.3 per 1000 person-years, respectively). CKD without diabetes was associated with comparable nonsignificant excess risks for incident stroke and coronary heart disease (2.5; 95% confidence interval, -0.1 to 5.2 and 2.4; 95% confidence interval, -0.8 to 5.5 per 1000 person-years, respectively) but a larger excess risk for cardiovascular mortality (7.3; 95% confidence interval, 3.0 to 11.5 per 1000 person-years). Diabetes and CKD together were associated with greater excess risks for incident stroke (13.8; 95% confidence interval, 5.3 to 22.3 per 1000 person-years), coronary heart disease (12.8; 95% confidence interval, 4.9 to 20.8 per 1000 person-years), and cardiovascular mortality (14.8; 95% confidence interval, 7.2 to 22.3 per 1000 person-years). The excess risks associated with the combination of diabetes and CKD were larger than those associated with established risk factors, including prevalent cardiovascular disease.ConclusionsThe combination of diabetes and kidney disease is associated with substantial excess risks of cardiovascular events and mortality among blacks.

Project description:BackgroundThe FIDELIO-DKD trial (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) evaluated the effect of the nonsteroidal, selective mineralocorticoid receptor antagonist finerenone on kidney and cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes with optimized renin-angiotensin system blockade. Compared with placebo, finerenone reduced the composite kidney and cardiovascular outcomes. We report the effect of finerenone on individual cardiovascular outcomes and in patients with and without history of atherosclerotic cardiovascular disease (CVD).MethodsThis randomized, double-blind, placebo-controlled trial included patients with type 2 diabetes and urine albumin-to-creatinine ratio 30 to 5000 mg/g and an estimated glomerular filtration rate ≥25 to <75 mL per min per 1.73 m2, treated with optimized renin-angiotensin system blockade. Patients with a history of heart failure with reduced ejection fraction were excluded. Patients were randomized 1:1 to receive finerenone or placebo. The composite cardiovascular outcome included time to cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. Prespecified cardiovascular analyses included analyses of the components of this composite and outcomes according to CVD history at baseline.ResultsBetween September 2015 and June 2018, 13 911 patients were screened and 5674 were randomized; 45.9% of patients had CVD at baseline. Over a median follow-up of 2.6 years (interquartile range, 2.0-3.4 years), finerenone reduced the risk of the composite cardiovascular outcome compared with placebo (hazard ratio, 0.86 [95% CI, 0.75-0.99]; P=0.034), with no significant interaction between patients with and without CVD (hazard ratio, 0.85 [95% CI, 0.71-1.01] in patients with a history of CVD; hazard ratio, 0.86 [95% CI, 0.68-1.08] in patients without a history of CVD; P value for interaction, 0.85). The incidence of treatment-emergent adverse events was similar between treatment arms, with a low incidence of hyperkalemia-related permanent treatment discontinuation (2.3% with finerenone versus 0.8% with placebo in patients with CVD and 2.2% with finerenone versus 1.0% with placebo in patients without CVD).ConclusionsAmong patients with chronic kidney disease and type 2 diabetes, finerenone reduced incidence of the composite cardiovascular outcome, with no evidence of differences in treatment effect based on preexisting CVD status. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02540993.

Dataset Information

Cardiovascular Outcomes According to Urinary Albumin and Kidney Disease in Patients With Type 2 Diabetes at High Cardiovascular Risk: Observations From the SAVOR-TIMI 53 Trial.

Publications

Cardiovascular Outcomes According to Urinary Albumin and Kidney Disease in Patients With Type 2 Diabetes at High Cardiovascular Risk: Observations From the SAVOR-TIMI 53 Trial.

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