Keynote Address Focuses on Newer DES, Problematic Subgroups
In a keynote presentation at TCT 2014, Stephan Windecker, MD, from Bern University Hospital, Switzerland, said that while newer-generation drug-eluting stents (DES) are associated with reduced mortality and improved safety and efficacy compared with the previous generation, treatment limitations remain in certain subgroups.
“During the past 10 years there has been very important progress in drug-eluting stent technology,” he said. “Unsurprisingly, drug-eluting stents are more effective than the other stents, but importantly, there has been further improvement comparing newer-generation drug-eluting stents with earlier-generation drug-eluting stents.”
Benefits outweigh adverse eventsWindecker cited data from previously published studies in which newer-generation DES showed improvement in safety and efficacy with significantly lower rates of target lesion revascularization (TLR), death and MI as well as a lowered risk of restenosis and stent thrombosis. He explained that “ultra-thin” struts, the invention of biocompatible polymer and the utilization of sirolimus-analogues, “without a doubt, have translated into improved clinical outcomes.”
These data, obtained largely in randomized clinical trials “have been corroborated in real clinical practice,” Windecker said, referring to results of the SCAAR registry, in which newer-generation DES significantly outperformed both earlier-generation DES and bare-metal stents (BMS).
In 2013, the European Society for Cardiology (ESC) recommended DES for stable CAD, and in 2014, new-generation DES were indicated for percutaneous treatment of significant coronary lesions in ACS patients as well as recommended over BMS in primary PCI.
The FAME II trial, for which 2-year results recently were published in the New England Journal of Medicine, showed an increase in adverse events in the periprocedural period during which 43% of urgent revascularization procedures were triggered by MI or ECG changes, but those were “largely outweighed” by the benefits of PCI compared with medical therapy, Windecker said.
Using 100 randomized controlled trials comprised of nearly 100,000 patients, Windecker and colleagues compared revascularization methods such as CABG, early PCI techniques and earlier- and newer-generation DES against medical therapy in stable CAD. The resulting paper was published recently in BMJ.
“Interestingly, if you look at the endpoint of all-cause mortality, then this meta-analysis corroborates the findings … that coronary bypass surgery is superior to medical therapy in patients with stable coronary artery disease. But importantly you do see that there is no mortality benefit for early PCI techniques, including earlier-generation drug-eluting stents; whereas in the case of everolimus or zotarolimus drug-eluting stents, there was an association with improved survival,” Windecker said.
Still, Windecker noted that data from an autopsy-based study showed that in comparison to sirolimus-eluting and paclitaxel-eluting stents (PES), everolimus-eluting stents (EES) produced fewer uncovered struts, had lower inflammation scores and less fibrin deposition, but similar frequency of neoatherosclerosis.
“The investigators did not see a difference as it relates to neoatherosclerosis, which may become a pathway for late complications including late restenosis and late stent thrombosis,” he said.
In addition, Windecker said newer-generation DES have limited efficacy in patients with diabetes, citing data from the SPIRIT series and COMPARE trial. In a stratified outcome analysis of these trials, EES showed greater safety and efficacy than PES in patients without diabetes (11.4% vs. 62%; P=.001) but had very similar results in patients with diabetes (10.3% vs. 10.1%; P=.86).
“In the framework in the ESC myocardial revascularization guidelines, we took all this evidence into consideration and now the revascularization recommendation for lesions in the proximal LAD assumes both a class 1A indication for PCI and coronary artery bypass surgery,” Windecker said.
Both therapies carry class 1B indications in left main disease, while three-vessel disease does not carry a recommendation for PCI.
“If we address diabetic patients, there is clear preference to coronary artery bypass surgery in those patients with multivessel disease,” he said. “PCI should be considered only among those patients with less Syntax complexity.”
- Windecker reports
receiving consultant fees/honoraria from Astra Zeneca, Biotronik, Eli Lilly and
St. Jude Medical.