Real-world clinical experience with an everolimus eluting platinum chromium stent with an abluminal biodegradable polymer – a report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) Giovanna Sarno, MD, PhD Uppsala University Hospital and Uppsala Clinical Research Center Uppsala, Sweden

Giovanna Sarno, MD, PhD Istitutional research support from Boston Scientific Corporation

BACKGROUND Time-dependent effects for polymers used in drug-eluting stent (DES) technology have been previously described with an early protective effect against stent thrombosis and a late pro-inflammatory and pro-thrombotic effect. The local reaction to the polymer coating can exacerbate the inflammatory reaction caused by stent implantation, impair endothelialization and lead to increased risk of late ST compared to bare metal stents. Finn AV, Joner M, Nakazawa G, et al. Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization. Circulation 2007;115:2435– 41. Joner M, Finn AV, Farb A, et al. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol 2006;48:193–202. Joner et al. Endothelial cell recovery between comparator polymer-based drug-eluting stents. J Am Coll Cardiol Jul 29;52(5): Drug-eluting stents and late adverse clinical outcomes lessons learned, lessons awaited. J Am Coll Cardiol 2006;47:2112–5

Higher risk of Stent thrombosis in old-generation DES after 1 year BMS N= and Old DES N=18577 and New DES N= and o-DES=old generation drug eluting stents, n-DES=new generation drug eluting stents, BMS=bare metal stents, RR=risk ratio, ns=non significant Cumulative risk of ST (%) n-DES vs BMS: adjusted RR 1.17 ( ), p=ns o-DES vs BMS: adjusted RR 1.81 ( ), p<0.001)

AIM To describe the initial real-world experience with a novel everolimus eluting platinum chromium stent with an abluminal biodegradable polymer (SYNERGY)

Platform Platinum chromium 74μm (0.0029in) Increased Visibility Bioabsorbable Polymer Coating PLGA Abluminal 4 µm thick < 4 month absorption time Drug Everolimus 100μg/cm 2 3 month release time SYNERGY Stent Technology Design

METHODS The SCAAR records consecutive patients from all centers (n=29) performing coronary angiography and PCI in Sweden. Information on restenosis or stent thrombosis in any previously implanted stent anywhere in Sweden is requested for all patients undergoing any subsequent coronary angiography for any clinical indication All implanted SYNERGY stents were compared to all new generation DES (n-DES) with more than 1000 implantations in Sweden between March 2013 and October 2015 for all indications including acute coronary syndromes (ACS) Restenosis, ST, death rates were assessed using propensity score and Cox regression analyses. A subgroup analysis for ST up to 1 year was performed in patients with acute coronary syndromes (ACS) including Non-ST elevation myocardial infarction (NSTEMI), ST-elevation myocardial infarction (STEMI), unstable angina (UA)

STENT CLASSIFICATION SYNERGY stent group, N= 7,886 Other n-DES, N=69,429  BioMatrix, N=1,953  Orsiro, N= 4,946  Promus Element Plus, N= 2,543  Promus Premier, N= 20,414  Xience/ Xpedition, N= 7,971  Resolute/Resolute Integrity, N=19,021  Ultimaster, N=1,156;  Resolute Onyx, N=6,425

Clinical Characteristics SYNERGY n-DES p N Patients <0.01 Age, years, mean68.0 ± ± Women (%)1191(28.0)9697 (25.4) <0.01 Diabetes (%)981 (23.1)8346 (21.9) <0.01 Clinical presentation NSTEMI ‡ (%)1582 (37.2)14384 (37.7) NS STEMI § (%)1017 (23.9)9261 (24.3) NS SA (%)1031 (24.3)9300 (24.4) NS UA (%)412 (9.7)3751 (9.8)NS Other indications205 (4.8)1414 (3.7) <0.01 Clinical history Hypertension (%)2818 (66.4)24107 (63.3) <0.01 Hyperlipidemia (%)2305 (54.3)20428 (53.6) <0.01 Prior MI† (%)1276 (30.0)10606 (27.8) <0.01 Smoker (%)795 (18.7)7057 (18.5) NS Prior CABG* (%)414 (9.7)3589 (9.4) NS Prior PCI (%)1324 (31.2)11117 (29.2) 0.02

Procedural Characteristics SYNERGY n-DES p N < VD¶ (%)1705 (21.6)11824 (20.4)<0.01 LM disease (%)651 (8.3)4277 (7.4)<0.01 Treated vessel RCA║ (%)1390 (32.7)12247 (32.1)NS LM (%)222 (5.2)1810 (4.7)NS LAD† (%)1841 (43.3)16905 (44.4)<0.01 LCX‡ (%)660 (15.5)6129 (16.1)NS Vengraft (%)127 (3.0)981 (2.6)NS Arterial graft (%)7 (0.2)41 (0.1)NS CTO* (%)133 (3.1)1059 (2.8)NS Restenotic lesions (%)191 (4.5)1382 (3.6)<0.01 Bifurcation lesions (%)610 (14.4)5010 (13.1)<0.01 Stent Diameter, mm, mean±SD2.95 ± ± 0.51<0.01 Stent Length, mm, mean±SD22.32 ± ± 7.84<0.01 Stent number per patient, mean±SD2.52 ± ± 1.32<0.01 Procedural success (%)4169 (98,2)37485 (98.4)NS

RESTENOSIS 1.2% vs. 1.0%, adjusted HR: % CI: ; p=0.21). Time after PCI (months) C u m u l a t i v e R a t e o f r e s t e n o s i s 2,0 1,5 1,0 0,5 0,0 n-DES, N=64429 Synergy, N=7886 (1.2% vs. 1.0%, adjusted HR: % CI: ; p=0.21 Restenosis occurred in 525 cases in the total population up to 1 year

0.2% vs. 0.5%, adjusted HR: 0.68; 95% CI: ; p=0.17 n-DES, N=64429 Synergy, N=7886 DEFINITE STENT THROMBOSIS Stent thrombosis occurred in 282 cases in the total population up to 1 year

DEFINITE STENT THROMBOSIS in Acute coronary syndromes Time after PCI (months) C u m u l a t i v e R a t e o f s t e n t t h r o m b o s i s 0,6 0,5 0,4 0,3 0,2 0,1 0,0 0.3% vs. 0.5%; adjusted HR: 0.69; 95% CI: ; p=0.29 Synergy, N= 5294 n-DES, N=44845

ALL CAUSE MORTALITY 5.1% vs. 4.9%, adjusted HR: 1.08; 95% CI: ; p=0.42

CONCLUSIONS In a large real-world population the SYNERGY stent appears to be safe and effective with a low risk of restenosis and ST comparable with other n-DES. The risk of ST up to 1 year is similarly low also in patients with ACS. The advantages of stent devices with bioabsorbable polymer may become more evident in the longer term follow-up 1 A longer term follow-up in this population might show a larger difference in the risk of the very late stent thrombosis between the SYNERGY stent and the other n-DES Serruys, JACC Interv 2013; 6: