Stent Safety: Insulin vs Non-Insulin Treatment

Patients with diabetes often have an increased risk of cardiovascular disease. There is controversy regarding whether or not those patients treated with insulin experience increased adverse cardiovascular outcomes following revascularization. Some studies have shown worse outcomes compared to patients with diabetes not treated with insulin, while other studies indicate adverse outcomes are the same between insulin and non-insulin users after risk adjustment.

Even the choice of drug-eluting stent for patients taking insulin remains questionable. Investigators looked at the Taxus Element vs Xience Prime in a Diabetic Population (TUXEDO) trial¹ to compare results of insulin-treated vs non-insulin-treated patients undergoing percutaneous coronary intervention. They also investigated the safety and efficacy of everolimus-eluting stents vs paclitaxel-eluting stents.

In the Tuxedo trial, from June 23, 2011 to March 12, 2014, 1830 patients were randomized 1:1 to receive a paclitaxel-eluting stent or an everolimus-eluting stent. For this study,² patients were divided into an insulin-treated group or a non-insulin-treated group. The primary endpoint of the study was target vessel failure at 1 year. This was defined as the composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target vessel revascularization.

Patients treated with insulin (n=747) were more likely to be female, have a higher BMI, have a longer duration of diabetes and a higher hemoglobin A1c, were more likely to have undergone a previous percutaneous coronary intervention, were more likely to have kidney disease, and were more likely to be assymptomatic. This group was less likely to have a prior myocardial infarction, less likely to smoke, and had lower left ventricular ejection fraction.

When compared to non-insulin-treated patients, patients taking insulin had higher rates of target vessel failure (5.6% vs 3.3%), major adverse cardiac events (6.0% vs 3.7%), death or myocardial infarction (4.7% vs 2.9%), and cardiac death or myocardial infarction (4.7% vs 2.9%). The insulin-treated group also had higher rates of death (3.5% vs 1.7%) and subacute stent thrombosis (1.1% vs 0.3%). In both the insulin-treated and non-insulin-treated groups, target vessel failure was higher with a hemoglobin level of 7% or higher.

However, according to the authors, “In the regression adjustment to a propensity score model after accounting for baseline variables, the above higher cardiovascular risks with [insulin-treated diabetes patients] were no longer statistically significant.”

In both insulin-treated patients and non-insulin-treated patients, everolimus-eluting stents reduced the rates of cardiovascular risks compared to paclitaxel-eluting stents. The absolute risk reduction for target vessel failure was greater in the insulin-treated group than in the non-insulin-treated group (4.5% vs 1.4%) with everolimus-eluting stents.

The authors noted limitations of the study, mainly that “this study is a prespecified subgroup analysis from the TUXEDO trial, [therefore] the trial was not designed nor powered to evaluate outcome differences in the [insulin-treated] or [non-insulin-treated] subgroups.”

In conclusion, the insulin-treated group had significantly worse outcomes compared to the non-insulin-treated group in the unadjusted analysis. “However, this finding was largely attenuated in the propensity score-adjusted analysis, implying that the increased possibility of adverse cardiovascular events in [insulin-treated] patients is accounted for by the differences in baseline risk factors, DM duration, and DM control. Everolimus-eluting stents reduced the rate of cardiovascular events, including stent thrombosis, when compared with paclitaxel-eluting stents in [insulin-treated] patients.”

References:

1. Kaul U, et al. Paclitaxel-eluting versus everolimus-eluting coronary stents in diabetes. N Engl J Med. 2015;373(18):1709-1719.

2. Bangalore S, et al. Percutaneous coronary intervention in patients with insulin-treated and non-insulin-treated diabetes mellitus. Secondary analysis of the Tuxedo trial. JAMA Cardiol. Epub ahead of print 20 Apr 2016.