Evidence of Late Catch-up After DES ‘Unequivocal’

SAN FRANCISCO, CALIF.—Angiographic and IVUS data conclusively demonstrate that late catch-up occurs after first- and second-generation DES, said Robert A. Byrne, MB, BCh, PhD, but clinical impact of the resultant delay in arterial healing is of low importance. Byrne also said that findings from several studies including 2 year results of TAXUS II, SIRTAX-LATE and ISAR-TEST 2, 3 and 4 showed late luminal loss extending as far as 5 years after stenting.

Byrne, of Deutsches Herzzentrum in Munich, Germany, said the temporal course of late catch-up, the gradual erosion of procedural gain from PCI, is different depending on modality. Restenosis peaks at roughly 3 months after balloon angioplasty and 6 months following BMS. “Evidence of late catch-up is unequivocal,” he said. “If we look for it, we will find it.”

In a cohort of 1,580 lesions segregated by permanent polymer paclitaxel-eluting stents (PES) (Taxus, Boston Scientific), polymer-free sirolimus-eluting stents (SES) or permanent polymer SES (Cypher, Cordis), the Cypher stent was more effective at 6 to 8 months. However, there is evidence of ongoing late luminal loss with the Cypher and Taxus stents.

“This is something we didn’t see with plain balloon angioplasty or [with] BMS,” Byrne said. “Interestingly, with the polymer-free stent, we didn’t observe this phenomenon.”

Although it is clear late catch-up is a real phenomenon, Byrne said it does not play a major clinical role. Five-year results from the SIRIUS and TAXUS IV trials showed that the curves between DES and BMS are parallel beyond 1 year. Between 1 and 5 years, the rate of target lesion revascularization (TLR) is 4.0% for BMS vs. 4.5% for SES in SIRIUS. In TAXUS IV, the 1- to 5-year rate of TLR was 2.0% for BMS and 1.5% for PES.

Byrne added that in a meta-analysis of 14 trials involving nearly 5,000 patients, the difference in TLR between DES and BMS was 13.4% at 1 year and 13.7% at 5 years.

“The extremely low late luminal loss seen with modern DES coupled with the small magnitude of this delta of late loss beyond 6 to 8 months results in a very small number of patients spilling over the notional TLR threshold at which revascularization becomes necessary or desirable,” Byrne said. “With regard to clinical relevance, we can surmise that in terms of late catch-up, it is low impact. The anti-restenotic effect of DES over BMS is maintained at 5 years. ”

Byrne went on to say that late luminal loss is part of a spectrum of clinical/pathological conditions associated with the pathology of late arterial healing including late stent thrombosis, persistent vasomotor dysfunction and de novo in-stent atherosclerosis. Byrne warned that results from surrogate endpoint efficacy trials comparing different stents would be dependent on the time point at which researchers take measurements.

“This is further evidence of systematic delayed arterial healing following provisional stent implantation. We should bear this in mind when choosing a time point for assessment in trials using surrogate assessments,” he said.