Pathology of Second-Generation Everolimus-Eluting Stents versus First-Generation Sirolimus- and Paclitaxel-Eluting Stents in Humans

Background — Clinical trials have demonstrated that second-generation cobalt-chromium everolimus-eluting stent (CoCr-EES) is superior to first-generation paclitaxel-eluting stent (PES) and is non-inferior or superior to sirolimus-eluting stent (SES) in terms of safety and efficacy. It remains unclear whether vascular responses to CoCr-EES are different from SES and PES, since the pathology of CoCr-EES has not been described in humans. Methods and Results — A total of 204 lesions (SES=73, PES=85, CoCr-EES=46) from 149 autopsy cases with duration of implant >30 days and (cid:100) 3 years were pathologically analyzed, where comparison of vascular responses was corrected for duration of implant. The observed frequency of late and very late stent thrombosis (LST/VLST) was less in CoCr-EES (4%) versus SES (21%, p=0.029) and PES (26%, p=0.008). Neointimal thickness was comparable among the groups, while the percent uncovered struts was strikingly lower in CoCr-EES (median=2.6%) versus SES (18.0%, p (cid:31) 0.0005) and PES (18.7%, p<0.0005). CoCr-EES showed less inflammation score (with no hypersensitivity) and less fibrin deposition versus SES and PES. The observed frequency of neoatherosclerosis, however, did not differ significantly among the groups (CoCr-EES=29%, SES=35%, PES=19%). CoCr-EES had the least frequency of stent fracture (CoCr-EES=13%, SES=40%, PES=19%; p=0.007 for CoCr-EES versus SES), whereas fracture-related restenosis or thrombosis was comparable among the groups (CoCr-EES=6.5%, SES=5.5%, PES=1.2%). Conclusions — CoCr-EES demonstrated greater strut coverage with less inflammation, less fibrin deposition, and less LST/VLST as compared to SES and PES in human autopsy analysis. Nevertheless, the observed frequencies of neoatherosclerosis and fracture-related adverse pathologic events were comparable in these devices, indicating that careful long-term follow-up remains important even after CoCr-EES placement. toto bbeee eelluucidaaateeed. IInn ttheee cccururrrrenntnt ssttutudydy, wwewe invnvvesestitigagaateeed d d pppathththollologogogic tto SESEESS S annnd dd PPEPESS ininn hhhumumumananan ffibrbrbroaoaathhhereromomoma,a,a, fffororormememed dd wiwiwthththinin The principal findings of the current autopsy study are: (1) CoCr-EES showed a lower frequency of LST/VLST with less uncovered struts, less inflammation (with no hypersensitivity), and less fibrin deposition as compared to SES and PES in humans; (2) greater strut coverage in CoCr-EES versus SES and PES was consistently identified irrespective of lesion characteristics and indications for stenting; (3) neointimal thickness in CoCr-EES was similar to SES and PES, and progressively increased with time; (4) CoCr-EES showed presence of neoatherosclerosis, the frequency of which was comparable to SES and PES; and (5) overall stent fracture was less frequent in CoCr-EES versus SES, whereas the prevalence of fracture-related adverse events (restenosis and thrombosis) in CoCr-EES did not differ from SES and PES. To our knowledge, the current study represents the first report of the pathology of CoCr-EES as compared to SES and PES in human coronary arteries. randomized CoCr-EES versus 1 st -generation ACS, long and/or small unprotected left main coronary A recent randomized comparison of CoCr-EES and BMS in patients with ST-elevation AMI showed a significantly lower incidence of TLR and stent thrombosis in CoCr-EES versus BMS at 1 year following stent implantation. pllatatateleleletetet endndndotottheliliiaalal cell adhesion molecule-1 transssmemmmbmbmbrrarane anndd d PEPS at 14 4 dadaayyss ffoloollooowiiwinngng stetentntnt iiimmppllantaaatiioon. 3330 HHowowweveveeer,, alalll DDEDES S shshsowowowededed ddececcrereasasaeeded exexprprpresesssisisiononons s s ofoof PPPECECECAMAMAM--1-1 aandndnd aantntntititithhrhromommbobobotititic cococofafafactcttororr thrhrhromomombobobomomomodududuliliinnn aasas cccomomompapaparerered d tototo BBBMMSMS, which may atata llleaeaeaststst pppararartltlly y ininndididicacaatetete tthahaht enenendododothththeleleliaiaal l mamamatuturararatititiononon iiis s s stssiillllll iiinsnsnsufufuffifificicicenenent t t ininn CCCoCoor-EES asss EERR. ththrorombmbogogeneniciity y eaearlrly y ini ssetetetititingngngsss isiss ddriririveveven n bybyby ssstettntntnt dddesesesigigign n n ananand dd dededplplployoyoymemementntnt aaandndd ppprororotetetectctctededd the NC (j) . (k, l) Histologic sections from a 67-year-old man who received CoCr-EES in the proximal LAD for non-ST elevation AMI 5 months antemortem, who died of non-cardiac causes. A low-power image (k) shows mild neointimal proliferation and an underlying large NC. All struts are covered with a thin neointima deposition shown at high power image in d n . (e, f) Histologic sections from a 600-yy-yeaeaar--ololold d d mamaman n who received CoCr-EES in the mid LCX 6 months antemortem. A low-power image (e) shows prprprooliferation and underlying fibbbroorccaalcific plaque.e. AAlll ssstttrruruts are covered with ttt prottteeoglycan-rricich h neneoioointnttimima aa wiwwithth aaabbsbseenencce oof fffibriinn, whhhiicich h iis hhigigghlllighthtededed iin n a a hihighghh-p-ppowowwererr iimmmaggge nn h)h)h) seeectctionnsns a wwowomamamann n whwhwhooo rreecececeivivieeed nn