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Randomized Controlled Trial
. 2011 Mar 3;364(9):818-28.
doi: 10.1056/NEJMoa1006524.

Long-term Effects of Intensive Glucose Lowering on Cardiovascular Outcomes

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Free PMC article
Randomized Controlled Trial

Long-term Effects of Intensive Glucose Lowering on Cardiovascular Outcomes

ACCORD Study Group et al. N Engl J Med. .
Free PMC article

Abstract

Background: Intensive glucose lowering has previously been shown to increase mortality among persons with advanced type 2 diabetes and a high risk of cardiovascular disease. This report describes the 5-year outcomes of a mean of 3.7 years of intensive glucose lowering on mortality and key cardiovascular events.

Methods: We randomly assigned participants with type 2 diabetes and cardiovascular disease or additional cardiovascular risk factors to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level of 7 to 7.9%). After termination of the intensive therapy, due to higher mortality in the intensive-therapy group, the target glycated hemoglobin level was 7 to 7.9% for all participants, who were followed until the planned end of the trial.

Results: Before the intensive therapy was terminated, the intensive-therapy group did not differ significantly from the standard-therapy group in the rate of the primary outcome (a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) (P=0.13) but had more deaths from any cause (primarily cardiovascular) (hazard ratio, 1.21; 95% confidence interval [CI], 1.02 to 1.44) and fewer nonfatal myocardial infarctions (hazard ratio, 0.79; 95% CI, 0.66 to 0.95). These trends persisted during the entire follow-up period (hazard ratio for death, 1.19; 95% CI, 1.03 to 1.38; and hazard ratio for nonfatal myocardial infarction, 0.82; 95% CI, 0.70 to 0.96). After the intensive intervention was terminated, the median glycated hemoglobin level in the intensive-therapy group rose from 6.4% to 7.2%, and the use of glucose-lowering medications and rates of severe hypoglycemia and other adverse events were similar in the two groups.

Conclusions: As compared with standard therapy, the use of intensive therapy for 3.7 years to target a glycated hemoglobin level below 6% reduced 5-year nonfatal myocardial infarctions but increased 5-year mortality. Such a strategy cannot be recommended for high-risk patients with advanced type 2 diabetes. (Funded by the National Heart, Lung and Blood Institute; ClinicalTrials.gov number, NCT00000620.).

Conflict of interest statement

No other potential conflict of interest relevant to this article was reported.

Figures

Figure 1
Figure 1. Kaplan–Meier Curves for the Primary Outcome and Death from Any Cause
The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. Panels A and D show the incidence rates from randomization until the time of transition, Panels B and E show the rates from randomization until the end of the trial, and Panels C and F show the rates for the post-transition period. Plots for the post-transition period (Panels C and F) are included for descriptive purposes only; they cannot be used to infer any effect of the intensive therapy in this period.
Figure 2
Figure 2. Hazard Ratios for the Prespecified Primary and Secondary Outcomes
The effect of intensive glucose-lowering therapy is shown from randomization until the time of transition and from randomization until the end of the trial. Squares represent hazard ratios, and horizontal bars represent 95% confidence intervals. CHF denotes congestive heart failure.

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