David Kandzari, MD

In the NEXT study, the 2-year outcomes did not demonstrate any significant difference and, in fact, showed almost identical event rates across all the elements of a composite endpoint for the BP-BES vs. the EES. The reasons for this, in part, are because with existing DES today, we are observing the best event outcomes with regard to safety and efficacy that we’ve ever witnessed. This may also importantly represent changes of practice that may be less quantifiable than just the stents themselves. However it may be, it raises the threshold and makes it very difficult to illustrate superiority for new DES designs. Nevertheless, I think even with larger numbers of patients, if the trajectory of events remain the same, it would be very difficult to demonstrate differences in this patient population.

Douglas Drachman, MD

The NEXT trial compared the outcomes of patients with coronary artery disease (CAD) treated with biodegradable polymers in biolimus-eluting stent designs (BP-BES) versus those treated with durable polymers in everolimus-eluting stent designs (DP-EES). At two years, BP-BES was non-inferior to DP-EES with respect to death or MI, all cause death, MI, definite stent thrombosis, or target lesion revascularization.

In previous randomized controlled trials, such as LEADERS, BP-BES had significantly lower 5-year rates of very late stent thrombosis than durable polymer sirolimus-eluting stents (DP-SES), perhaps indicating that biodegradable polymer confers less long-term inflammation, vascular injury, or predisposition to thrombosis.  In network meta-analyses, however, “real world” patients treated with DP-BES had higher rates of MI and stent thrombosis than those receiving DP-EES. What caused this discrepancy in findings? Do second generation DP drug-eluting stents (e.g. DP-EES) have such marked reduction in stent thrombosis compared with first generation DP stents (e.g. DP-SES) that they overcome the potential advantage of the biodegradable polymer? Or, is there a real world patient selection bias, not identified in network meta-analyses, that predisposes to worse outcomes those patients selected by their physicians for BP-BES?

This controversy set the stage for the presentation of the NEXT trial 2-year outcomes at ACC.14. When subjected to the rigorous scrutiny of randomized-controlled study design, BP-BES and DP-EES had equivalent outcomes: the curves representing 2-year outcomes of the two treatment groups with respect to death or MI were virtually supraimposable. The primary endpoint of the study, however, will be determined at three years. By way of comparison, in the LEADERS trial, the stent thrombosis curve for DP-SES began to separate from that of BP-BES at 2 years, and continued to separate further out to 5 years (2.5% for DP-SES vs. 0.7% for BP-BES). If BP-BES does confer a benefit, we may need to wait for further long-term data in the NEXT trial.  

I would be cautious to forecast whether the NEXT trial 2-year results will change practice. It is reassuring to see that, when subjected to RCT study design, BP-BES appears to be non-inferior to DP-EES. At present, though, there is no compelling finding to advocate whether one stent platform should be selected over another. With further evaluation of the data, subgroup analysis may help us identify particular patients or lesion types where one platform appears to confer a treatment advantage. In addition, it will be important to identify the optimal duration of dual antiplatelet therapy (DAPT) with each of the respective stent platforms, as this may have important impact on patient selection and future treatment protocols, particularly when the need to interrupt DAPT is anticipated. Additionally, traditional technical parameters may influence stent choice: deliverability, radial force, radio-opacity, performance in complex lesion subsets. As always, an assessment of cost-effectiveness may also play an important role on utilization of this new stent technology.

We will eagerly anticipate the presentation of the NEXT trial three year outcomes, and of important subgroup analyses that may promote our understanding of the role of new stent technologies in our evolving treatment of CAD.