Nine-Year Effects of 3.7 Years of Intensive Glycemic Control on Cardiovascular Outcomes

Abstract

Objective: In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, ∼4 years of intensive versus standard glycemic control in participants with type 2 diabetes and other cardiovascular risk factors had a neutral effect on the composite cardiovascular outcome, increased cardiovascular and total mortality, and reduced nonfatal myocardial infarction. Effects of the intervention during prolonged follow-up were analyzed.

Research design and methods: All surviving ACCORD participants were invited to participate in the ACCORD Follow-on (ACCORDION) study, during which participants were treated according to their health care provider's judgment. Cardiovascular and other health-related outcomes were prospectively collected and analyzed using an intention-to-treat approach according to the group to which participants were originally allocated.

Results: A total of 8,601 people, representing 98% of those who did not suffer a primary outcome or death during the ACCORD trial, were monitored for a median of 8.8 years and a mean of 7.7 years from randomization. Intensive glucose lowering for a mean of 3.7 years had a neutral long-term effect on the primary composite outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), death from any cause, and an expanded composite outcome that included all-cause death. Moreover, the risk of cardiovascular mortality noted during the active phase (hazard ratio 1.49; 95% CI 1.19, 1.87; P < 0.0001) decreased (HR 1.20; 95% CI 1.03, 1.39; P = 0.02).

Conclusions: In high-risk people with type 2 diabetes monitored for 9 years, a mean of 3.7 years of intensive glycemic control had a neutral effect on death and nonfatal cardiovascular events but increased cardiovascular-related death.

Trial registration: ClinicalTrials.gov NCT00000620.

Figure 1

Hazard of outcomes during ACCORD and ACCORD/ACCORDION. The event rates and hazard ratios (HRs, ●) with 95% CIs (horizontal lines) are shown for prespecified outcomes that occurred from randomization until the end of the ACCORD trial and until the end of prolonged follow-up comprising the ACCORD and ACCORDION phase. MI, myocardial infarction.

Figure 2

The Kaplan-Meier curves display the time to event for the primary outcome (A) and total mortality (B) during follow-up from randomization until the end of ACCORDION. The inset for each graph displays the same curve with a magnified y-axis. The numbers of individuals at risk are shown for each time point.

Figure 3

The Kaplan-Meier curves display the time to event for the three components of the primary outcome, including nonfatal myocardial infarction (MI) (A), nonfatal stroke (B), and cardiovascular (CV) death (C) during follow-up from randomization until the end of ACCORDION. The inset displays the same curve with a magnified y-axis. The numbers of individuals at risk are shown for each time point.