Diabetes Journal Club March 17, 2011 Margaux Añel-Tiangco, MD
Background ACCORD Cohort of 10,250 adults Mean age 62 Action to Control Cardiovascular Risk in Diabetes Cohort of 10,250 adults Mean age 62 Median DM duration of 10 years A1c ≥ 7.5% At high risk for CV disease Known CVD or two risk factors in addition to DM Assigned to: Intensive treatment: A1c <6% Standard treatment: A1c 7-7.9%
Background In 2008, the intensive treatment arm was stopped due to total and CV deaths (HR 1.22, 9% CI 1.01-1.46) On an average of 3.7 years, there was an excess of 3 deaths per 1000 subjects in the intensive tx arm No cause for excess mortality was found Not from increased hypoglycemia Not from a specific medication or combination of meds
Methods Intensive treatment arm was managed like the Standard treatment arm after year 3.7 Goal A1c 7-7.9% Pts were followed till year 5
Results By the final visit, both groups were similar in numbers of pts on oral agents, insulin, and their combinations Rates of severe hypoglycemia and other adverse events within the two groups were similar after the transition
Kaplan-Meier Curves Primary outcome: composite of nonfatal MI, nonfatal stroke, or death from CV causes
Hazard Ratios for the Prespecified Primary and Secondary Outcomes
Causes of Death
Incident Event Rates after the Transition Date
Conclusion Intensive DM therapy to A1c <6% did NOT decrease major CV events after 5 years and even led to more deaths than achieving an A1c 7-7.9%
Discussion Unclear reasons for mortality Equivalent rates of hypoglycemia in the post-transition period Degree of reduction in A1c cannot be implicated Those is intensive therapy were on multiple drug combos not used in standard therapy group 42% of pts were on ≥ 3 oral agents ± insulin Compared with only 19% of pts in the standard therapy
Discussion Results may not be applicable to those with newly diagnosed DM Holman et al. NEJM 2008; 359:1577-89 Newly dx DM Type 2 with normal goal A1c, median A1c 7% Neutral CV effect after 10 yrs MI and death after 20 years