Early vascular responses to abluminal biodegradable polymer-coated versus circumferential durable polymer-coated newer-generation drug-eluting stents in humans: a pathologic study

Abstract

Abstract Background Recent clinical trials are testing strategies for short (1–3 months) dual antiplatelet therapy (DAPT) following newer-generation drug-eluting stent (DES) placement. However, the safety of short DAPT regimens is not supported by biological evidence in humans. Purpose We sought to evaluate early pathologic responses to newer-generation DES by comparing abluminal biodegradable polymer-coated DES (BP-DES) with circumferential durable polymer-coated DES (DP-DES) in human autopsy cases. Methods The study included a total of 37 coronary lesions with thin strut newer-generation DES (DP-DES=23 [XIENCE=18, Resolute Integrity=5] and BP-DES=14 [SYNERGY=9, Ultimaster=5]) with duration of implantation <90 days in 25 autopsy cases. The process of stent healing was precisely evaluated for every single strut in association with underlying tissue characteristics. The degree of strut coverage was defined as follows: grade 0 (bare struts), grade 1 (struts covered with thrombus, fibrin, or other tissues or cells without endothelium), grade 2 (struts covered with single-layered endothelium without underlying smooth muscle cell layers), and grade 3 (struts covered with endothelium and underlying smooth muscle cell layers) (Figure 1). Results Duration of implantation was similar in lesions with DP-DES and those with BP-DES (median=20 vs. 17 days). A total of 1986 struts (DP-DES=1261, BP-DES=725) were pathologically analyzed. Focal grade 2 coverage was observed as early as 5 days after the implantation in both stents. Multilevel mixed-effects ordered logistic regression model demonstrated that BP-DES exhibited greater strut coverage compared with DP-DES (odds ratio; 3.50, 95% CI; 1.31–9.41, P=0.013), which remained significant after adjustment for duration of implantation and underlying tissue characteristics (odds ratio; 2.64, 95% CI; 1.04–6.68, P=0.040). The time course of vessel healing assessed as predictive probability of strut coverage (grade 0–3) stratified by duration of implantation is shown in Figure 2. Predictive probability of grade 2 and 3 coverage was comparably limited at 30 days (DP-DES=17.7% vs. BP-DES=29.0%) and increased at 90 days (DP-DES=76.1% vs. BP-DES=85.9%). Both stents showed few inflammation and similar degree of fibrin deposition. Conclusions The current first pathologic study on early biological responses to newer-generation DES in humans demonstrated that single-layered endothelial coverage begins in days following the stent placement, and abluminal BP-DES potentially exhibit faster strut coverage with smooth muscle cell infiltration than circumferential DP-DES. Nevertheless, vessel healing remains suboptimal at 30 days in both DP- and BP-DES, which progresses with time to become substantial at 90 days. Our results suggest that very short duration of DAPT for 1 month should be applied with caution, taking into account the trade-off between bleeding and thrombotic risks. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science