Recently completed randomized controlled trials (RCTs) in patients with diabetes mellitus (DM) type 2 has shown conflicting results regarding the impact of concentrated glycemic control on macrovascular complications of the disease [1-4]. For this reason, the American Heart Association; the College of Cardiology and Diabetes Association was given only a Class IIb recommendation's level of evidence A for the effectiveness of tight control of glycemia on cardiovascular disease . Based on the assumption that the individual tests may not have sufficient statistical power, and the number of cardiovascular events was relatively small, British researchers conducted a meta-analysis of RCTs to assess the clinical effectiveness of intensive glycemic control compared with standard therapy diabetes.
Methods and progress in the study.
Search for RCTs published in English in January 2009, was held in the databases MEDLINE, Cochrane Central, and EMBASE. In a meta-analysis included only clinical trials that meet the following criteria: 1) with randomization in the intensive glucose control against the standard treatment (placebo, standard care, fewer intensive monitoring), 2) with the planned primary endpoint, consisting of a cardiovascular event, including nonfatal myocardial infarction (MI), the events of coronary heart disease (CHD) (nonfatal and fatal MI), stroke and overall mortality, 3) conducted in stable patient's diabetes.
The purpose of a meta-analysis was to evaluate the effectiveness of intensive glycemic control on major macrovascular events. Statistical heterogeneity between the different studies was evaluated according to criteria? χ2 and I2 statistics ..
It found only 5 RCTs, fully met the screening criteria. Data from two British studies United Kingdom Prospective Diabetes studies (UKPDS) were combined into one study. The other four trials were prospective pioglitazone Clinical Trial In macrovascular Events (Proactive), Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), Veterans Affairs Diabetes Trial (VADT) and Action to Control Cardiovascular Risk in Diabetes trial ( ACCORD).
All trials conducted mostly in developed countries, including 33 040 participants. The average age of patients ranged over from 53 to 66 years, the men - more than half of the participants, those with established cardiovascular disease - from 32 to 100%, average body mass index - 28 to 32 kg/m2, baseline HbA1c - 7, 1 to 9, 4%. Only in the UKPDS study, the duration of the diagnosis of diabetes was less than one year in other trials the average duration of disease was at least eight years.
During observation, 163 000 patient-years (average - 5 years) were recorded in 1497 nonfatal MI, 2318 CHD events, 1127 fatal and nonfatal strokes and 2892 deaths from any cause.
Intensive glycemic control was accompanied by a statistically significant reduction in risk of nonfatal MI by 17% (odd's ratio [OR] - 0.83, 95% confidence interval [CI], 0,75-0,93) and CBS by 15% (OR - 0.85, 95% CI 0,77-0,93) without the presence of heterogeneity between the studies (both I2 = 0%). In absolute terms, this means that intensive glycemic control, conducted in 200 patients over five years, will lead to a decrease in the number of nonfatal MI by 2.3 case, and CHD events - in the case of 2.9, compared with standard therapy.
However, intensive glycemic control has not led to significant reduction in the incidence of stroke (OR - 0.93, 95% CI 0,81-1,06; I2 = 0%), total mortality (OR - 1.02, 95% CI 0,87-1,19; in the presence of heterogeneity between the studies, I2 = 58%, p = 0.049) and heart failure (OR - 1.08, 95% CI 0,90-1,31; I2 = 62, 9%; p = 0.029).
In groups of intensive glycemic control were more common episodes of hypoglycemia (38.1% versus 28.6% in controls) and episodes of severe hypoglycemia (2.3% vs 1.2%, respectively), as well as a large weight gain (on average - to 2.5 kg more than in the control).
In a meta-analysis of RCTs showed that intensive glycemic control in patients with type two diabetes leads to a statistically significant reduction in the risk of coronary events (fatal and nonfatal MI) without increasing the risk of death. Nevertheless, the optimal methods of achieving glycemic control (the mechanism, the rate, the target level of HbA1c) in different populations of patients require further study.
Notice: Want to know when we update our site? Enter your email address below and be notified by mail every time we update our site