More intensive glycemic control reduces nonfatal myocardial infarction but not all-cause mortality

Abstract

Design. A meta-analysis of randomized, controlled trials.Subjects. The meta-analysis included five trials with a total of 33,040 participants. Entry criteria differed among trials, but overall mean age was 62 years and 62% were male. Participants had an average of 8 years' duration of diabetes at entry.Methods. The goal of the meta-analysis was to compare the effect of more intensive versus conventional glycemic control on cardiovascular outcomes and mortality. Main outcomes of interest included coronary heart disease (CHD) events, including nonfatal myocardial infarction (MI) and CHD death and all-cause mortality. Secondary outcomes included stroke, heart failure, and hypoglycemia. Random effects models were used to combine outcome data across the five trials. Heterogeneity among trials was examined using X2 and I2 statistics.Results. Across the trials, intensive glycemic control was associated with a mean A1C 0.9% lower than for conventional glycemic control (6.6 vs. 7.5%). Intensive control was associated with a consistent, statistically significant reduction in nonfatal MIs (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.75-0.93) but had no clear effect on all-cause mortality (OR 1.02, 95% CI 0.87-1.19). For stroke, intensive control was associated with a small, non-statistically significant reduction in events (OR 0.93, 95% CI 0.81-1.06). Heart failure seemed to be increased for intensive regimens that involved the use of thiazolidinediones; intensive regimens were also associated with increased risk of hypoglycemia, including severe hypoglycemia. Available data were insufficient to assess the effects of patient characteristics (e.g., age, duration of diabetes, history of cardiovascular disease, and other concurrent therapies) on outcomes.Conclusion. More intensive glycemic control that achieves an A1C of 7.0% and a difference of approximately 1 percentage point compared to conventional therapy can produce a moderate reduction in nonfatal MIs.