Assessing and managing CV risk in patients with diabetes

Assessing and managing CV risk in patients with diabetes

Does intensive glycemic control decrease CVD events?
Does severe hypoglycemia impact CVD events?
UKPDS involved newly detected diabetes mellitus and included relatively low CVD risk patients. But BARI-2D trial had high risk patients with angiographically proven CAD.
ACCORD, ADVANCE and VADT compared intensive versus conventional control of diabetes.

ACCORD randomized 10,251 patients [1]. Had to be wound up after a mean 3.5 years of follow up because of excess risk in CAD death. But sub group analysis showed that intensive glycemic control reduces CV events in those with no previous CAD and baseline HbA1c less than 8 mg/dl. At least one severe episode of hypoglycemia increased the risk of death markedly in the intensive group with CAD. Hypoglycemia was associated with mortality beyond 90 days of the episode rather than the short term mortality. More of benefit was observed with intensive treatment in those with shorter duration of diabetes in risk reduction, while those with long duration of diabetes had worsened risk.

ADVANCE showed lesser deaths in intensive arm, which appeared only 4 to 5 years after onset of treatment, but failed to achieve statistical significance. There was lower new onset microalbuminuria in the intensive arm [2].

VADT also showed lower worsening of microalbuminuria in the intensive treatment group.

Statistical significance was not obtained in the initial report of UKPDS for macrovascular complications, but only for microvascular complications. In long term follow up, the gap between the two arms in HbA1C narrowed and disappeared. Still, there was a statistically significant 13% reduction in the risk of myocardial infarction at 10 years post trial follow up.

Risk of fractures was higher with rosiglitazone in the long term and this risk was more women. In high risk CAD patients, the risk of congestive heart failure was also higher.

BARI-2D had angiographically proven CAD was divided into potential PCI and potential CABG groups. They were further randomized into the proposed treatment versus intensive medical treatment. In the PCI intended group, insulin sensitizers did not make any difference. But in the intended CABG group those on insulin sensitizers had lower risk of MI and stroke, though all cause mortality was not lower.

References

1. Action to Control Cardiovascular Risk in Diabetes Study Group; Hertzel C Gerstein, Michael E Miller, Robert P Byington, David C Goff Jr, J Thomas Bigger, John B Buse, William C Cushman, Saul Genuth, Faramarz Ismail-Beigi, Richard H Grimm Jr, Jeffrey L Probstfield, Denise G Simons-Morton, William T Friedewald. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008 Jun 12;358(24):2545-59.
2. ADVANCE Collaborative Group; Anushka Patel, Stephen MacMahon, John Chalmers, Bruce Neal, Laurent Billot, Mark Woodward, Michel Marre, Mark Cooper, Paul Glasziou, Diederick Grobbee, Pavel Hamet, Stephen Harrap, Simon Heller, Lisheng Liu, Giuseppe Mancia, Carl Erik Mogensen, Changyu Pan, Neil Poulter, Anthony Rodgers, Bryan Williams, Severine Bompoint, Bastiaan E de Galan, Rohina Joshi, Florence Travert. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008 Jun 12;358(24):2560-72.