The mTOR Pathway's Influence on Stenting Choices in Diabetics

In non-diabetic patients, researchers have shown sirolimus-eluting stents to be more effective than paclitaxel-eluting stents, leading to better clinical outcomes. Some researchers believe that T2DM attenuates the mammalian target of rapamycin (mTOR) signaling pathway. This could influence the choice of stents, and has created a controversy.

Patients with type 2 diabetes mellitus (T2DM), at elevated risk for symptomatic coronary disease, often need percutaneous coronary intervention (PCI). In non-diabetic patients, researchers have shown sirolimus-eluting stents to be more effective than paclitaxel-eluting stents, leading to better clinical outcomes. Some researchers believe that T2DM attenuates the mammalian target of rapamycin (mTOR) signaling pathway. This could influence the choice of stents, and has created a controversy. Might paclitaxel-eluting stents be preferred over stents eluting rapamycin (now called sirolimus) or its analogues (everolimus or zotarolimus) or vice versa?

The October 2015 issue of the New England Journal of Medicine included a large study that randomized 1830 patients with T2DM and coronary artery disease undergoing PCI to receive paclitaxel-eluting stents or everolimus-eluting stents. They monitored patients for 1 year for target-vessel failure, defined as a composite of cardiac death, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization.

At 1 year, paclitaxel-eluting stents did not meet the criterion for noninferiority to everolimus-eluting stents.

Target vessel failure was more likely to occur in T2DM patients who received paclitaxel-eluting stents than in those who received everolimus-eluting stents. Rates of spontaneous myocardial infarction, stent thrombosis, target-vessel revascularization and target-lesion revascularization were also significantly higher.

The researchers suggest that this study's results answers persistent questions about the older paclitaxel-eluting stent in diabetics. They concluded that there is no advantage for paclitaxel-eluting in patients with diabetes, and no role for paclitaxel-eluting stents in coronary artery disease anymore.

They also suggest that older studies (SYNTAX, FREEDOM and BARI 2D trials) that created a preference for revascularization surgery (CABG) over PCI may need to be revisited.

Clinically, North American and European surgeons have tended to use the newer, -limus eluting stents. Paclitaxel-eluting stents, due to their low cost, are still used extensively in many parts of the world. This study may influence practice and lead to use of the more effective stents.