UPDATE ON MANAGING DYSGLYCEMIA IN ACUTE CORONARY SYNDROMES

According to Anna Norhammer, MD, PhD, Karolinska University Hospital, Stockholm, Sweden, managing dysglycemia in the coronary care unit has evolved with insight from trials of glycemic control in the intensive care unit setting. The first DIGAMI trial, published in 1995, showed a clear mortality reduction with glucose control during and after the acute phase of a myocardial infarction, aiming at blood glucose levels between 7 to 10 mmol/L (plasma 7.7 to 11 mmol/L) during the acute phase. Since then trials from the intensive ward have reported conflicting results when it comes to lowering glucose during hospitalization [Malmberg K, Ryden L. J Am Coll Cardiol 1995].

In 2001, van den Berghe et al. [N Engl J Med] found that intensive insulin therapy to maintain blood glucose at or below 110 mg/dL reduced both morbidity and mortality among critically ill patients in the surgical intensive care unit (ICU). In 2009, Finfer et al. [N Engl J Med] demonstrated that intensive glucose control increased mortality among adults in the ICU, with a more lenient blood glucose target of ≤180 mg/dL resulting in lower mortality compared with a more intense target of 81 to 108 mg/dL. These data demonstrate a consistent pattern across care settings of increased CV risk associated with both hyperglycemia as well as hypoglycema.

This year's European Society of Cardiology Guidelines on Diabetes, Pre-diabetes, and Cardiovascular Diseases (developed in collaboration with the European Association for the Study of Diabetes) recommend that insulin-based glycemic control should be considered in acute coronary syndrome (ACS) patients with significant hyperglycemia of >180 mg/dL (>10 mmol/L), with the target adapted in the presence of comorbidities [Rydén L et al. Eur Heart J 2013]. In addition, glycemic control that may be accomplished by different glucose-lowering agents should be considered in DM and ACS.

Remaining questions, said Prof. Norhammer, include the role and optimal level of glycemic control for the outcome in ACS patients; and whether it is possible to reduce final infarct size by means of very early glucose-insulin-potassium administration after symptoms of myocardial infarction. Prof. Norhammar concluded that we should keep measuring glucose in the cardiac care unit and suggested that aiming at glucose levels between 7.8 to <11 mmol/L should be safe while the risk for hypoglycemia probably will increase if targeting values lower than 7 mmol/L. She also pointed out that a large proportion of patients will have previously unknown diabetes and impaired glucose intolerance, about 60% of myocardial infarction patients. This is only determined by performing an oral glucose tolerance test before discharge [Norhammer A et al. Lancet 2002].

DIABETES AND HEART FAILURE: WHAT ARE THE MANAGEMENT OPTIONS?

Some 5.7 million people in the United States have heart failure (HF) [Roger VL et al. Circulation 2012]. HF causes >55,000 deaths each year [Kochanek KD et al. Natl Vital Stat Rep 2011], with significant associated costs related to healthcare services, medications, and lost productivity [Heidenriech PA et al. Circulation 2011]. David Aguilar, MD, Baylor College of Medicine, Houston, Texas, USA, discussed the management options for DM and HF.

According to Dr. Aguilar, management of diabetes in patients with HF is generally is similar to those without HF, but there are diabetes-specific issues. These include the appropriate glycemic targets in patients with HF, and the appropriate options for hyperglycemic therapy.

Recommendations for glycemic control from the American Diabetes Association [Diabetes Care 2013] call for:

• HbA1C goal below or around 7%, which is considered reasonable due to microvascular benefits and potential long-term macrovascular benefits if glucose lowering regimen implemented soon after DM diagnosis

• More stringent HbA1C goals (<6.5%) for selected patients (eg, those with short diabetes duration, less risk of hypoglycemia, long life expectancy, and no significant CVD)

• Less stringent HbA1C goals (<8%) for those with advanced microvascular or macrovascular complications, extensive comorbid conditions, or a history of hypoglycemia or difficult to treat, longstanding DM

According to Dr. Aguilar, optimal hyperglycemic therapy in HF patients is not clear. He noted that metformin can be used with caution, and that prospective outcome data are needed for other agents, including glucagon-like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors given unexpected results from the SAVOR-TIMI 53 trial in high-risk CV patients (see article on page 17).