Insulin treatment does not appear to be behind the poorer outcomes after stenting in type 2 diabetes, but everolimus-eluting stents (EES) may be better choice for patients on the medication, a TUXEDO substudy found.
The combined rate of cardiac death, target vessel myocardial infarction (MI), or ischemia-driven target vessel revascularization 1 year after stenting was higher for diabetes patients on insulin than their peers on other antidiabetic medications (5.6% versus 3.3%, P=0.02).
This arm also showed more deaths (3.5% versus 1.7%, P=0.01), more death or MI (5.8% versus 3.2%, P=0.009), and more subacute stent thrombosis (1.1% versus 0.3%, P=0.03) over the same period.
Risk adjustment, however, eliminated these differences, reported Sripal Bangalore, MD, MHA, of New York University School of Medicine, and colleagues in their study appearing online in JAMA Cardiology.
This implies that “the increased possibility of adverse cardiovascular events in patients with insulin-treated DM [diabetes mellitus] is accounted for by the differences in baseline risk factors, DM duration, and DM control,” they wrote.
The FREEDOM trial, which showed more cardiovascular events in patients with insulin-treated diabetes, which had raised the question of “perhaps an independent deleterious effect of insulin.”
As such, “the increased risk of cardiovascular events in patients with insulin-treated DM has been attributed to difficult-to-control DM with a greater prevalence of concomitant cardiovascular risk factors as well as a direct atherogenic and thrombogenic effect of insulin,” they wrote.
In the TUXEDO trial, which randomized patients to either a Taxus paclitaxel DES or a Xience EES in India where Taxus stents are still used, 40.8% of the 1,830 enrolled patients were on insulin.
As in the overall results favoring the EES, the insulin-treated patients had fewer adverse outcomes after receiving the everolimus- versus paclitaxel-eluting stents for the following:
- Combined cardiac death, target vessel MI, and target vessel revascularization (3.4% versus 7.9%, P=0.007)
- Major adverse cardiac events (3.9% versus 8.2%, P=0.01)
- MI (1.3% versus 4.4%, P=0.01)
- Stent thrombosis (0.5% versus 3.0%, P=0.009)
- Target lesion revascularization (1.0% versus 5.2%, P=0.001)
Diabetes patients treated without insulin showed similar trends, although the test for interaction was not statistically significant (P>0.05).
The exception was that there was more target vessel-related MI with paclitaxel-eluting stents in this arm (2.0% versus 0.6% for EES, risk ratio 3.57, 95% confidence interval 1.00-12.71).
As prior studies had suggested worse outcomes with EES, “the choice of a drug-eluting stent ([DES], limus- versus taxol-eluting) in patients with insulin-treated DM is controversial even in the era of second-generation DES.”
The present analysis included more patients than the SPIRIT II, SPIRIT III, SPIRIT IV, and COMPARE trials, however — and therefore enjoys a hefty position in the literature of how to revascularize patients with insulin-treated DM.
The results are “very clear,” George Dangas, MD, of Mount Sinai in New York, told MedPage Today. “EES is superior to the Taxus first-generation DES.” Dangas, who was not involved in the study, said he already uses EES in his practice and has not used the paclitaxel-eluting stent in the last 5 years.
Bangalore’s group acknowledged that they still had limitations, as “the trial was not designed nor powered to evaluate outcome differences in the insulin-treated DM or non-insulin-treated DM subgroups.” In addition, the authors suggested, the multivariable model could not eliminate the possibility of unmeasured confounders, such as patient frailty.
Even so, patients with “insulin-treated DM are at particularly high risk for cardiovascular complications and adverse events,” according to Dangas, “and EES-type latest-generation DES should be used and implanted meticulously.”
The TUXEDO trial was funded by Boston Scientific. The study was supported by grants from Abbott Vascular, Boston Scientific, and Medtronic.
Bangalore reported receiving an honorarium from Abbott Vascular.
Dangas declared no relevant conflicts of interest.
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 2016; DOI: 10.1001/jamacardio.2016.0305.