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Effect of intensive compared with standard glycemia treatment strategies on mortality by baseline subgroup characteristics: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

ABSTRACT: OBJECTIVE:To determine if baseline subgroups in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial can be identified for whom intensive compared with standard glycemia treatment had different effects on all-cause mortality. RESEARCH DESIGN AND METHODS:Exploratory post hoc intention-to-treat comparisons were made between intensive and standard glycemia groups on all-cause mortality by subgroups defined by baseline characteristics. RESULTS:There were few significant interactions between baseline characteristics and effects of intensive versus standard glycemia treatment on mortality: self-reported history of neuropathy (hazard ratio [HR] 1.95, 95% CI 1.41-2.69) versus no history of neuropathy (0.99, 0.79-1.26; P value for interaction 0.0008), higher A1C (A1C >8.5%: HR 1.64, 95% CI 1.22-2.22; A1C 7.5-8.4%: 1.00, 0.75-1.34; A1C <7.5%: 1.00, 0.67-1.50; P value for interaction 0.04), and aspirin use (HR 1.45, 95% CI 1.13-1.85, compared with 0.96, 0.72-1.27, in nonusers; P value for interaction 0.03). CONCLUSIONS:We found a remarkable similarity of effect from intensive compared with standard glycemia treatment on mortality across most baseline subgroups. No differential effect was found in subgroups defined by variables anticipated to have an interaction: age, duration of diabetes, and previous history of cardiovascular disease. The three baseline characteristics that defined subgroups for which there was a differential effect on mortality may help identify patients with type 2 diabetes at higher risk of mortality from intensive regimens for glycemic control. Further research is warranted.

SUBMITTER: Calles-Escandon J

PROVIDER: S-EPMC2845012 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Effect of intensive compared with standard glycemia treatment strategies on mortality by baseline subgroup characteristics: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

Calles-Escandón Jorge J Lovato Laura C LC Simons-Morton Denise G DG Kendall David M DM Pop-Busui Rodica R Cohen Robert M RM Bonds Denise E DE Fonseca Vivian A VA Ismail-Beigi Faramarz F Banerji Mary Ann MA Failor Alan A Hamilton Bruce B

Diabetes care 20100126 4

<h4>Objective</h4>To determine if baseline subgroups in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial can be identified for whom intensive compared with standard glycemia treatment had different effects on all-cause mortality.<h4>Research design and methods</h4>Exploratory post hoc intention-to-treat comparisons were made between intensive and standard glycemia groups on all-cause mortality by subgroups defined by baseline characteristics.<h4>Results</h4>There were few sig ...[more]

PMID: 20103550

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Project description:ObjectiveCurrent type 2 diabetes (T2D) management contraindicates intensive glycemia treatment in patients with high cardiovascular disease (CVD) risk and is partially motivated by evidence of harms in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Heterogeneity in response to intensive glycemia treatment has been observed, suggesting potential benefit for some individuals.Research design and methodsACCORD was a randomized controlled trial that investigated whether intensively treating glycemia in individuals with T2D would reduce CVD outcomes. Using a novel approach to cluster HbA1c trajectories, we identified groups in the intensive glycemia arm with modified CVD risk. Genome-wide analysis and polygenic score (PS) were developed to predict group membership. Mendelian randomization was performed to infer causality.ResultsWe identified four clinical groupings in the intensive glycemia arm, and clinical group 4 (C4) displayed fewer CVD (hazard ratio [HR] 0.34; P = 2.01 × 10-3) and microvascular outcomes (HR 0.86; P = 0.015) than those receiving standard treatment. A single-nucleotide polymorphism, rs220721, in MAS1 reached suggestive significance in C4 (P = 4.34 × 10-7). PS predicted C4 with high accuracy (area under the receiver operating characteristic curve 0.98), and this predicted C4 displayed reduced CVD risk with intensive versus standard glycemia treatment (HR 0.53; P = 4.02 × 10-6), but not reduced risk of microvascular outcomes (P < 0.05). Mendelian randomization indicated causality between PS, on-trial HbA1c, and reduction in CVD outcomes (P < 0.05).ConclusionsWe found evidence of a T2D clinical group in ACCORD that benefited from intensive glycemia treatment, and membership in this group could be predicted using genetic variants. This study generates new hypotheses with implications for precision medicine in T2D and represents an important development in this landmark clinical trial warranting further investigation.

Dataset Information

Effect of intensive compared with standard glycemia treatment strategies on mortality by baseline subgroup characteristics: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

Publications

Effect of intensive compared with standard glycemia treatment strategies on mortality by baseline subgroup characteristics: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

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