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1 FOCUS ARTICLE EuroIntervention 2014;10:38-46 DOI: /EIJV10I1A8 Periopertive mngement of ntipltelet therpy in ptients with coronry stents undergoing crdic nd non-crdic surgery: consensus document from Itlin crdiologicl, surgicl nd nesthesiologicl societies Robert Rossini 1 *, MD, PhD; Giuseppe Musumeci 1, MD; Luigi Oltron Visconti 2, MD; Ezio Brmucci 2, MD; Bttistin Cstiglioni 3, MD; Stefno De Servi 2, MD; Corrdo Lettieri 4, MD; Mddlen Lettino 5, MD; Emnuel Picclug 6, MD; Stefno Svonitto 7, MD; Dniel Trbttoni 8, MD; Dvide Cpodnno 9, MD, PhD; Frncesc Buffoli 4, MD; Alessndro Prolri 10, MD; Ginlorenzo Dionigi 11, MD; Luigi Boni 11, MD; Federico Biglioli 12, MD; Luigi Vldtt 13, MD; Andre Droghetti 14, MD; Antonio Bozzni 15, MD; Crlo Setcci 16, MD; Polo Rvelli 17, MD; Cludio Crescini 18, MD; Giovnni Sturenghi 19, MD; Pietro Scrone 20, MD; Luc Frncetti 21, MD; Fbio D Angelo 22, MD; Frnco Gdd 23, MD; Andre Comel 24, MD; Luc Slvi 25, MD; Luc Lorini 26, MD; Mssimo Antonelli 27, MD; Frncesco Bovenzi 28, MD; Alberto Cremonesi 29, MD; Dominick J. Angiolillo 30, MD; Giulio Gugliumi 1, MD; on behlf of the Itlin Society of Invsive Crdiology (SICI-GISE), Itlin Assocition of Hospitl Crdiologists (ANMCO), Itlin Society for Crdic Surgery (SICCH), Itlin Society of Vsculr nd Endovsculr Surgery (SICVE), Itlin Assocition of Hospitl Surgeons (ACOI), Itlin Society of Surgery (SIC), Itlin Society of Anesthesi nd Intensive Cre Medicine (SIAARTI), Lombrd Society of Surgery (SLC), Itlin Society of Mxillofcil Surgery (SICMF), Itlin Society of Reconstructive Plstic Surgery nd Aesthetics (SICPRE), Itlin Society of Thorcic Surgeons (SICT), Itlin Society of Urology (SIU), Itlin Society of Orthopedics nd Trumtology (SIOT), Itlin Society of Periodontology (SIdP), Itlin Federtion of Scientific Societies of Digestive System Diseses Lombrdi (FISMAD), Assocition of Obstetricins Gynecologists Itlin Hospitl Lombrdi (AOGOI), Society of Ophthlmology Lombrdi (SOL) The uthors ffilitions nd lso the ccompnying supplementry dt cn be found in the online version of this pper t the following website: KEYWORDS ntipltelet therpy spirin coronry rtery disese PCI stent surgery Abstrct Optiml periopertive ntipltelet therpy in ptients with coronry stents undergoing surgery still remins poorly defined nd mtter of debte mong crdiologists, surgeons nd nesthesiologists. Surgery represents one of the most common resons for premture ntipltelet therpy discontinution, which is ssocited with significnt increse in mortlity nd mjor dverse crdic events, in prticulr stent thrombosis. Clinicl prctice guidelines provide little support with regrd to mnging ntipltelet therpy in the periopertive phse in the cse of ptients with non-deferrble surgicl interventions nd/or high hemorrhgic risk. Moreover, stndrd definition of ischemic nd hemorrhgic risk hs never been determined. Finlly, recommendtions shred by crdiologists, surgeons nd nesthesiologists re lcking. The present consensus document provides prcticl recommendtions on the periopertive mngement of ntipltelet therpy in ptients with coronry stents undergoing surgery. Crdiologists, surgeons nd nesthesiologists hve contributed eqully to its cretion. On the bsis of clinicl nd ngiogrphic dt, the individul thrombotic risk hs been defined. All surgicl interventions hve been clssified ccording to their inherent hemorrhgic risk. A consensus on the optiml ntipltelet regimen in the periopertive phse hs been reched on the bsis of the ischemic nd hemorrhgic risk. Aspirin should be continued periopertively in the mjority of surgicl opertions, wheres dul ntipltelet therpy should not be withdrwn for surgery in the cse of low bleeding risk. In selected ptients t high risk for both bleeding nd ischemic events, when orl ntipltelet therpy withdrwl is required, periopertive tretment with short-cting intrvenous glycoprotein IIb/III inhibitors (tirofibn or eptifibtide) should be tken into considertion. *Corresponding uthor: USC Crdiologi, Diprtimento Crdiovscolre, AO Pp Giovnni XXIII, Pizz OMS 1, Bergmo, Itly. E-mil: [email protected] 38 Europ Digitl & Publishing All rights reserved. SUBMITTED 15/08/ REVISION RECEIVED ON 08/10/ ACCEPTED ON 02/12/2013

2 Stent nd surgery Introduction The number of ptients with coronry stents undergoing surgery is incresing significntly. Premture discontinution of ntipltelet therpy, especilly if it occurs within the first months fter stent implnttion, is ssocited with higher risk of stent thrombosis, fered compliction tht might hve drmtic clinicl consequences 1-6. On the other hnd, ntipltelet therpy cn significntly rise intropertive hemorrhgic risk in surgicl or endoscopic procedures 7. Editoril, see pge 17 Periopertive mngement of ntipltelet therpy is often rbitrry nd my be controversil for crdiologists, surgeons nd nesthesiologists. In recent yers, interntionl crdiologicl, nesthesiologicl nd hemtologicl societies hve proposed guidelines nd joint position ppers on the mngement of ntipltelet therpy in ptients undergoing non-crdic surgery However, some limittions of these recommendtions re evident. Elective surgicl procedures should be postponed until completion of the mndtory dul ntipltelet regimen, spirin therpy should be stopped only if hemostsis is difficult to control during surgery, nd multidisciplinry pproch is required (e.g., crdiologist, nesthesiologist, hemtologist, nd surgeon) to determine the ptient s risk nd to choose the best strtegy 13. However, little support is provided with regrd to mnging ntipltelet therpy in the periopertive phse in cse of semi-elective or urgent surgicl or endoscopic procedures, the definition of periopertive bleeding risk is not provided, nd the suggested multidisciplinry pproch on n individul bsis does not llow for stndrd pproch. Moreover, guidelines shred with crdiologists, surgeons nd nesthesiologists re lcking, lthough the surgeon s point of view is crucil. The mngement of the risk rtio between bleeding nd thrombosis requires n exct knowledge of risk strtifiction defined for ech condition, coupled with offering the miniml surgicl impct. The purpose of this mnuscript is to provide prcticl recommendtions for tilored nd stndrdised ntipltelet tretment mngement, even in difficult or unusul scenrios, tht re specific to ech type of surgery (crdic nd non-crdic), which hs been elborted from previously reported consensus document from the Itlin Society of Interventionl Crdiology (GISE) nd the Itlin Assocition of Hospitl Crdiologists (ANMCO) 19. THE GISE-ANMCO CONSENSUS DOCUMENT To overcome the forementioned limittions of existing guidelines, the Itlin Society of Interventionl Crdiology (GISE) nd the Itlin Assocition of Hospitl Crdiologists (ANMCO) promoted the cretion of consensus document with regrd to the optiml ntipltelet regimen in ptients with coronry stents undergoing surgicl nd endoscopic procedures. The Writing Committee ws composed of clinicl nd interventionl crdiologists, surgeons nd nesthesiologists, who met seven times in Miln nd contributed eqully to its cretion 19. Most of the members of the Writing Committee were delegtes of the most importnt ntionl societies of crdiologists, surgeons nd nesthesiologists. Crdiologists defined the thrombotic risk on the bsis of procedurl fetures, such s stent type, time from percutneous coronry interventions (PCI) to surgery, nd clinicl fetures, such s cute coronry syndrome t the time of PCI, previous stent thrombosis, concomitnt dibetes, renl impirment, nd low crdic ejection frction. Surgeons clssified ll interventions ccording to the hemorrhgic risk s low, medium, nd high. Finlly, on the bsis of both ischemic nd thrombotic risk, n greement with regrd to the most pproprite ntipltelet therpy in the periopertive phse ws reched for ech procedure. The mnuscript provides prcticl recommendtions tht re specific to ech type of surgery. The methodology is imed t llowing for tilored nd stndrdised mngement even in difficult or unusul scenrios. This document is n elbortion from the previous Itlin consensus document 19. As distinct from the Itlin published version, the present mnuscript lso received the endorsement of the Itlin Society of Anesthesiology. Anesthesiologists contributed significntly to the pper, thus providing multidisciplinry pproch with the dditionl dvntge of recommendtions coming from different perspectives. Of note, due to lck of evidence from clinicl trils, the present consensus document derives mostly from experts opinion, which represents the min limittion. It hs now been officilly endorsed by 16 crdiology, nesthesiology nd surgery societies. A free English ppliction for I-phone nd I-pd cn be downloded t the site gery/id ?mt=8. STENT AND SURGERY : THE DIMENSION OF THE PROBLEM The number of PCI is incresing worldwide 20,21. Every yer more thn one million PCI re performed in the USA nd Europe 20,21. In more thn 85% of cses coronry stent is implnted 22, nd prolonged ntipltelet therpy is mndtory fter stent implnttion. The most common cuses of discontinution re surgery nd bleeding events which re often ssocited with poor prognosis 23. The mngement of ntipltelet drugs in the periopertive period is relevnt, both from n epidemiologic nd clinicl point of view. It hs been estimted tht 4-8% of ptients undergo surgery within the first yer fter coronry stent implnttion nd 23% within five yers 22. The withdrwl nd sometimes lso the mintennce of ntipltelet therpy my hve drmtic consequences 7,24. Surgery cn led to inflmmtory, hypercogulble nd hypoxic sttes which re ssocited with plque instbility nd periopertive rteril thrombosis 22. On the other hnd, bleeding risk might be 3.4 times higher during dul ntipltelet therpy compred to spirin lone 25. ASSESSMENT OF THE PERIOPERATIVE ISCHAEMIC RISK (THE CARDIOLOGIST S POINT OF VIEW) Aspirin cn significntly reduce the risk of crdio-cerebrovsculr events in secondry prevention 26. Abrupt discontinution of spirin therpy cn be ssocited with rebound effect 27 nd surgicl interventions increse cogultion per se 28. Previous studies demonstrted tht periopertive discontinution of spirin therpy is EuroIntervention 2014;10:

3 EuroIntervention 2014;10:38-46 ssocited with significnt increse in mjor dverse crdic events (MACE) 27,29. Also, in coronry rtery bypss grfting (CABG), mintennce of spirin in the periopertive phse is ssocited with significnt reduction of mortlity 30,31. Dt on the effect of the ssocition of spirin nd clopidogrel re lcking nd derive mostly from post hoc nlyses of rndomised trils nd from registries 32,33. The incidence of periopertive MACE is high, especilly if surgery is performed erly fter coronry stenting 34. The increse of MACE might, in prt, be due to the periopertive discontinution of ntipltelet therpy In Schouten s series, the MACE rte ws 2.6% in the overll popultion, which incresed to 13.3% in ptients undergoing erly surgery 37. However, the protective effect of periopertive ntipltelet therpy did not emerge in other studies 38,39. These (pprently) discordnt dt might be explined by bis in ptient selection: ntipltelet therpy mintennce might identify popultion t high risk for MACE, which seems likely to be the result of complex unidentified interctions between clinicl nd surgicl risk fctors. Previous studies demonstrted tht the risk of periopertive MACE is higher within the first months fter stent implnttion 40, even though dt re not consistent 41. In recent study by Wijeysunder nd collegues 42, the overll rte of 30-dy events ws 2.1%. It demonstrted tht elective non-crdic surgery could be performed resonbly sfely in crefully selected ptients when t lest six months hve elpsed since DES implnttion nd from 46 to 180 dys fter BMS implnttion. INTRA-OPERATIVE MANAGEMENT (THE ANAESTHESIOLOGIST S POINT OF VIEW) In the modern nesthesi scenrio, nesthesiologists re fcing double chllenge: the choice of the best nd sfest nesthesiologicl technique for the ptient, nd how to mnge hemostsis in the periopertive period. Contrry to common belief, t present there is no evidence bout rel superiority of single nesthesi technique in ptients with coronry rtery disese 43-46, neither regrding inhltion vs. intrvenous generl nesthesi nor generl vs. loco-regionl or blended techniques. Nevertheless, there is certin greement towrds preferring blended or loco-regionl nesthesi whenever possible due to its intrinsic better control of periopertive pin nd bility to lower sympthetic stimultion 47,48. However, loco-regionl nesthesi might hve n intrinsic nd unvoidble risk when performed in ptients on ntipltelet therpy 49. The field of loco-regionl nesthesi is gretly ffected by ntipltelet therpy, especilly in terms of neurxil techniques, due to the incresed risk of ctstrophic neurologicl events in the presence of bnorml bleeding sttus. Nowdys, it is well known tht sfe neurxil technique cn be sfely performed in ptients on spirin therpy 49. By contrst, dul ntipltelet therpy with spirin nd clopidogrel during the week preceding surgicl intervention is n ccepted contrindiction to ny form of regionl nesthesi 18,43,47,49. Spinl hemtom hs been described during clopidogrel tretment 45, but the precise risk of spinl or epidurl hemtom with dul ntipltelet therpy is unknown 46. Therefore, the ltest recommendtions of the Americn Society of Locl Anesthesi to stop clopidogrel seven dys prior to surgery re bsed on clinicl judgement nd on isolted reports of epidurl hemtoms fter spinl nlgesi, combined spinl-epidurl nlgesi or both, rther thn on results provided by clinicl trils 18,45,49,50. Afterwrds, loco-regionl nesthesi cn be performed using the neurxil technique in ptients on spirin therpy, wheres dul ntipltelet therpy represents contrindiction. If inhibitors cnnot be discontinued, generl nesthesi is dvisble. THE PERIOPERATIVE HAEMORRHAGIC RISK: THE SURGEON S POINT OF VIEW It is well known tht ntipltelet therpy confers n incresed risk of bleeding 26,32. Conversely, the ssocition between ntipltelet gents nd periopertive bleeding risk hs not been dequtely ddressed. The vst mjority of the vilble dt derives from registries or observtionl studies, which do not hve sufficient sttisticl power. A met-nlysis on the effects of low-dose spirin on periopertive bleeding complictions demonstrted tht spirin incresed the frequency of bleeding complictions by pproximtely 50% 7. However, the definition used in the included studies ws extremely heterogenous nd often did not use stndrd definition. Moreover, when surgeons were blinded regrding spirin ppliction, they could not differentite ptients on spirin from ptients off spirin from bleeding behviour lone 51. The uthors concluded tht, with the possible exception of intrcrnil neurosurgery nd trnsurethrl prosttectomy, where bleeding-relted ftlities fter spirin ingestion were reported 7,24,52, low-dose spirin increses bleeding only quntittively. Additionlly, only few studies nlysed in the met-nlysis were rndomised, nd therefore low-dose spirin might be considered simply risk indictor for incresed comorbidity with n incresed bleeding risk per se 53. Only one double-blind rndomised tril hs investigted the periopertive bleeding risk in ptients undergoing non-crdic surgery while on 75 mg spirin therpy 29. No significnt increse of bleeding events ws identified in those ptients tking spirin s compred with those who were not on ntipltelet therpy. In Albldejo s series, mjor nd minor hemorrhgic complictions were observed in 9.5% of ptients 35. Most bleedings were t the surgicl site (85.2%) nd were ssocited with repet surgery in 18.5% of ptients. The deth rte in ptients with bleeding complictions ws 12.0% (95% CI: 6.6 to 19.7). Another study 37 demonstrted very low rte of excessive blood loss during surgery (1%), wheres blood trnsfusion ws required in 24% of ptients who continued vs. 20% of those who discontinued ntipltelet therpy. Dt on the role of clopidogrel on periopertive bleeding risk re lcking. An incresed hemorrhgic risk emerged in ptients undergoing CABG while on clopidogrel therpy, which ws reduced by stopping the drug t lest five dys prior to intervention 33, However, published dt re not consistent 58. On the bsis of these dt, the ltest guidelines on non-st-elevtion myocrdil infrction of the Europen Society of Crdiology recommend the periopertive 40

4 Stent nd surgery mintennce of clopidogrel in high-risk ptients undergoing coronry rtery bypss grfting (CABG) if coronry ntomy is complex, with specil ttention to reducing bleeding 59,60. The bleeding risk in ptients undergoing non-crdic surgery while on ntipltelet therpy hs been poorly investigted. The few vilble studies indicte n incresed hemorrhgic risk 39,61. Prostte biopsy nd ureteroscopy cn be performed in ptients on spirin therpy without significnt increse of mjor bleeding complictions On the other hnd, in cse of trnsurethrl prosttectomy spirin seems to be ssocited with n incresed risk of lte bleeding events nd need for reintervention 65,66. In cse of bdominl surgery, therpy with clopidogrel significntly increses the post-intervention bleeding risk, but it does not seem to be ssocited with n increse of mortlity due to hemorrhge or need for reintervention 67. In ptients with femorl frcture, periopertive clopidogrel therpy does not seem to be ssocited with significnt increse in mortlity nd morbidity 68. NEW ORAL ANTIPLATELET AGENTS Prsugrel is novel thienopyridine with more rpid onset of ction nd higher ntipltelet effect, s compred to clopidogrel, but it hs been ssocited with n incresed bleeding risk 69,70. In the TRITON-TIMI 38 tril, in the subgroup of ptients undergoing CABG within seven dys fter withdrwl of thienopyridines, the number of CABG-relted bleeding events ws fourfold higher in ptients treted with prsugrel s compred to those treted with clopidogrel. Nevertheless, the risk of mortlity ws reduced 70,71. Ticgrelor is novel non-thienopyridine ntipltelet gent tht inhibits the receptor, through reversible binding mechnism of ction. Like prsugrel, it is chrcterised by more rpid onset of ction, higher ntipltelet ctivity nd clinicl efficcy, s compred to clopidogrel. Ticgrelor does not increse overll bleeding events, but is ssocited with significnt increse of non- CABG-relted bleeding 72,73. As in the TRITON-TIMI 38 tril 74, in the PLATO tril ptients undergoing CABG within seven dys fter discontinution of ntipltelet therpy showed significnt decrese of overll nd crdiovsculr mortlity in the ticgrelor group. Apprently, this protective effect ws not due to different hemorrhgic risk, which ws similr in both groups 74. In ptients undergoing surgery in whom discontinution of ntipltelet therpy is required, prsugrel nd ticgrelor should be stopped seven nd five dys before intervention, respectively. GUIDELINES: WHAT THEY SAY (AND DO NOT SAY) Severl guidelines nd expert recommendtions on the periopertive mngement of ntipltelet therpy hve been published Of note, they derive mostly from expert opinion rther thn from rndomised studies. A multidisciplinry pproch with crdiologists, nesthesiologists nd surgeons is recommended on n individul bsis. The ssessment of the ischemic nd hemorrhgic risk should be provided for ech ptient, in order to tilor the optiml periopertive ntipltelet regimen. If periopertive ntipltelet therpy discontinution is required, bridge therpy with unfrctionted or low moleculr weight heprin is generlly not recommended, s it might be ssocited with incresed bleeding risk, without conferring n nti-ischemic protective effect 75. Of note, the existing guidelines on periopertive ntipltelet therpy hve the following limittions, which negtively ffect their pplicbility in dily clinicl prctice: I) re not shred with crdiologists, surgeons nd nesthesiologists; II) do not provide stndrd clssifiction of surgicl interventions, ccording to the hemorrhgic risk; III) do not provide stndrd clssifiction of the ptient s thrombotic risk; IV) do not provide generl, prcticl dvice on the optiml periopertive regimen on the bsis of the surgicl intervention nd the ischemic risk but rther recommend risk/benefit evlution on n individul bsis; V) provide little support with regrd to mnging ntipltelet therpy in the periopertive phse in cse of non-deferrble nd/or high hemorrhgic risk interventions; VI) do not provide prcticl dvice on the timing nd modlities of ntipltelet therpy discontinution nd resumption. DEVELOPMENT OF THE THROMBOTIC VERSUS BLEEDING RISK ALGORITHM DEFINITION OF THROMBOTIC RISK The genesis of stent thrombosis is multifctoril nd is influenced by ptient chrcteristics, coronry lesions, procedurl fetures, cogultion cscde, nd ntipltelet therpy 9. Therefore, the difficulty of pproprite risk strtifiction for stent thrombosis becomes evident. In the present document, thrombotic risk is defined on the bsis of four fctors (Tble 1): I) type of implnted stent (BMS vs. DES) 76-82, II) time from PCI to surgery 83, III) ngiogrphic fetures of coronry lesions 9,84-86, IV) clinicl chrcteristics 4,6,38,39,87. EuroIntervention 2014;10:38-46 Tble 1. definition. >6 months fter PCI with BMS >1 month <6 months fter PCI with BMS <1 month fter PCI with BMS >12 months fter PCI with DES >6 <12 months fter PCI with DES <6 months fter PCI with DES >12 months fter complex PCI with DES (long stents, multiple stents, overlpping, smll vessels, bifurctions, left min, lst remining vessel) <12 months fter complex PCI with DES (long stents, multiple stents, overlpping, smll vessels, bifurctions, left min, lst remining vessel) PCI in ACS, previous stent thrombosis, LVEF <35%, chronic renl filure nd dibetes mellitus increse the thrombotic risk. Use of second-genertion DES might reduce the thrombotic risk. Ptients submitted to CABG or with ACS mediclly treted re considered t high risk in the first month, t intermedite risk between the 1 st nd 6 th month, nd t low risk fter 6 months. Ptients treted with POBA re considered t high risk within the first 2 weeks, t intermedite risk between 2 nd 4 weeks, nd t low risk fter 4 weeks 1,2,4,6,12,38,39, ACS: cute coronry syndrome; BMS: bre metl stent; CABG: coronry rtery bypss grft; DES; drug-eluting stent; LVEF: left ventriculr ejection frction; PCI: percutneous coronry intervention; POBA: plin old blloon ngioplsty 41

5 EuroIntervention 2014;10:38-46 Of note, second-genertion DES hve been developed with n improved design tht my help to overcome the current limittions of the first-genertion DES 81. Improved stent designs with thinner struts nd more biocomptible polymers my enhnce endothelil coverge nd functionl recovery Due to their sfer profile, s demonstrted by previous studies, second-genertion DES my confer lower thrombotic risk s compred to first-genertion DES, thus llowing n erlier discontinution (beyond six months) of dul ntipltelet therpy, when necessry A lrge retrospective study from Hwn et l hs recently chllenged the concept tht the timing of surgery from PCI nd ntipltelet discontinution re potentil triggers for crdic events t the time of surgery 88. MACE within 30 dys were ssocited with emergency surgery nd dvnced crdic disese but were not ssocited with stent type or timing of surgery beyond six months fter stent implnttion. Moreover, there ws no significnt reltionship between periopertive ntipltelet cesstion nd 30-dy MACE (odds rtio 0.86, 95% confidence intervl ). Although the uthors concluded tht the guideline emphsis on stent type nd surgicl timing for both DES nd BMS should be re-evluted, their findings should be judged with cution becuse they rise from n observtionl study with potentil for residul confounding, where the surgicl popultion ws heterogeneous (e.g., the procedures rnged from minor outptient to emergent in-ptient opertions) nd clinicl decision-mking fctors tht influenced stent selection were lrgely unvilble or limited to dministrtive dt. Moreover, the study ws underpowered to detect true ssocition between periopertive ntipltelet cesstion nd 30-dy MACE. DEFINITION OF BLEEDING RISK On the bsis of the hemorrhgic risk, the min surgicl interventions hve been clssified into three groups: high, medium, nd low risk (Tble 2-Tble 8, Online Tble 1-Online Tble 7). The definition ws mostly derived both from previous published studies, whenever vilble, nd from the experts opinion 9,11,13,54-59,61-66, Tble 2-Tble 8 nd Online Tble 1-Online Tble 7 include generl, prcticl recommendtions, while they do not consider clinicl chrcteristics on n individul bsis. Of note, the overll risk derives from the interction between procedurl nd individul fetures. The present document focuses mostly on periopertive bleeding risk relted to surgicl procedures rther thn to ptient s hemorrhgic profile. Ech tble on surgicl bleeding risk is given to provide the reder with stndrd frme tht might be dpted depending on individul ptients chrcteristics. Once the surgicl hemorrhgic risk hs been defined, it is dvisble to evlute crefully ech ptient s risk on n individul bsis, which might be tken into ccount by using d hoc bleeding risk scores. Severl prcticl bleeding risk scores re vilble nd re mostly bsed on sex, renl function, nd comorbidities Therefore, when pplying these recommendtions to dily clinicl prctice, ech single cse should be crefully evluted in terms of ischemic nd bleeding risk. Resumption of ntipltelet drugs fter surgery my be deferred in cse of cliniclly relevnt bleeding complictions. It could be recommended tht high-risk ptients be referred to centres where the most minimlly invsive therpies such s pure lproscopic, roboticssisted procedures nd new-genertion lsers re vilble. BRIDGE THERAPY Even if controlled clinicl studies re lcking, guidelines nd expert reviews recommend the use of short hlf-life GPI in the periopertive phse in ptients t high thrombotic nd bleeding risk 13,14,17,18. Bridge therpy with iv GPI is reserved to ptients t high risk of stent thrombosis for whom the periopertive discontinution of ntipltelet drugs is required becuse of n uncceptbly high Tble 2. Crdic surgery. Minithorcotomy TAVI (picl pproch) OPCAB CABG Vlve replcement Reintervention Endocrditis CABG in PCI filure Aortic dissections 7 dys prior for prsugrel; b collegil discussion of risk, even with fmily/ptient. References 30,31,33,55-60,74,79-87,89. ASA: spirin; CABG: coronry rtery bypss grfting; OPCAB: off-pump coronry rtery bypss; PCI: percutneous coronry intervention or coronry ngioplsty; TAVI: trnsctheter ortic vlve implnttion 42

6 Stent nd surgery Tble 3. Generl surgery. Hernioplsty, plstic surgery of incisionl hernis, cholecystectomy, ppendectomy nd colectomy, gstric resection, intestinl resection, brest surgery Hemorrhoidectomy, splenectomy, gstrectomy, obesity surgery, rectl resection, thyroidectomy Heptic resection, duodenoceflopncresectomy ASA: Discontinue continue with b with b 7 dys prior for prsugrel; b collegil discussion of risk, even with fmily/ptient. References 66, 101. ASA: spirin continue Bridge therpy with GPIIb/III inhibitors b Bridge therpy with GPIIb/III inhibitors b EuroIntervention 2014;10:38-46 Tble 4. Vsculr surgery. Crotid endrterectomy, bypss or endrterectomy of lower extremity, EVAR, TEVAR, limb mputtions Open bdominl ort surgery Open thorcic nd thorcobdominl surgery Elective surgery: not contrindicted. Consider PTA or stenting continue or consider EVAR Urgency/ emergency continue or consider TEVAR Urgency/emergency continue t lest 30 dys fter PCI Consider PTA or stenting continue or consider EVAR Urgency/ emergency continue or consider TEVAR Urgency/ emergency continue 7 dys prior for prsugrel; References ASA: spirin; EVAR: endovsculr repir for ortic neurysm; PCI: percutneous coronry intervention or coronry ngioplsty; PTA: percutneous trnsluminl ngioplsty; TEVAR: thorcic endovsculr ortic/neurysm repir bleeding risk 1,2. Svonitto et l 22,131 crried out prospective study on 60 ptients with DES considered t high risk for stent thrombosis, nd cndidtes for mjor surgery. All ptients received GPI therpy with tirofibn in the periopertive phse. No crdic ischemic event ws observed. The rtes of bleeding nd trnsfusion were low, in reltion to the types of surgery, nd no bleeding complictions requiring new surgery were observed. Similr studies on more limited ptient popultions hve been performed with eptifibtide Bsed on the results of these studies, in highly selected ptients, bridge therpy with iv tirofibn or eptifibtide cn resonbly be recommended. GPI infusion, t the dose reported in the summry of product chrcteristics (decresed by 50% in ptients with renl filure nd incresed pre-/post-surgery bleeding risk) should strt three dys prior to surgicl intervention, wheres clopidogrel nd ticgrelor should be discontinued five dys prior to surgery (seven dys with prsugrel). GPI infusion should be stopped t lest four hours prior to surgery (eight hours in ptients with cretinine clernce <30 ml/min). inhibitors should be resumed within hours fter the intervention, (300 mg for clopidogrel, 60 mg for prsugrel nd 180 mg for ticgrelor). In selected cses (especilly in bdominl surgery, if gstrointestinl function hs not yet recovered), infusion with tirofibn or eptifibtide cn be restrted (with loding dose) few hours fter the end of the intervention, fter creful evlution of the bleeding risk. After complete intestinl recnlistion, therpy with inhibitors cn be resumed, nd, fter two hours, 43

7 EuroIntervention 2014;10:38-46 Tble 5. Orthopedic surgery. Hnd surgery Shoulder nd knee rthroscopy Minor spine surgery l Prosthetic shoulder surgery Mjor spine surgery Knee surgery (nterior crucite ligment, osteotomies) Foot surgery Mjor prosthetic surgery (hip or knee) Mjor trumtology (pelvis, long bones) Frctures of the proximl femur in the elderly - Discontinue 5 dys before hours, with loding dose - Discontinue 5 dys before - Discontinue 5 dys before with loding dose b with loding dose b with loding dose b continue, c 7 dys prior for prsugrel; b collegil discussion of risk, even with fmily/ptient; c in cse of femur frcture my be pproprite to proceed immeditely to surgery, despite dul ntipltelet therpy, without witing for the 5-dy suspension. References 68, ASA: spirin. Tble 6. Urology surgery. Flexible cystoscopy, Ureterl ctheteristion, Ureteroscopy Prostte biopsy, Orchiectomy, Circumcision Rdicl nd prtil nephrectomy, Percutneous nephrostomy, Percutneous lithotripsy, Cystectomy nd rdicl prosttectomy, TURP, TURBT, Penectomy, Prtil orchiectomy loding dose hours, Elective surgery: not contrindicted continue with loding dose b, if possible with loding dose b if ASA is discontinued Elective surgery: not contrindicted continue with loding dose b with loding dose b 7 dys prior for prsugrel; b collegil discussion of risk, even with fmily/ptient. References 62-66, ASA: spirin; TURP: trnsurethrl resection of prostte; TURBT: trnsurethrl resection of bldder tumour the infusion of tirofibn or eptifibtide cn be stopped. Of note, GPI re potent ntipltelet gents nd might be ssocited with n incresed risk of bleeding during their infusion. Afterwrds, they might be contrindicted in ptients with n ctive, cliniclly relevnt bleeding (i.e., mcrohemturi). This therpy should be prescribed by crdiologists nd dministered in crdiology wrd. GPI dministrtion is currently off-lbel s bridge therpy in the periopertive period 29. The periopertive mintennce of spirin therpy, which might be dministered iv, is strongly recommended in the vst mjority of interventions. As ischemic complictions occur most frequently soon fter surgery, close clinicl nd electrocrdiogrphic monitoring of the ptient is strongly recommended. 44

8 Stent nd surgery Tble 7. Thorcic surgery. Wedge resection Dignostic videothorcoscopy Chest wll resection Lobectomy Pneumonectomy Medistinoscopy Sternotomy Medistinl mss excision Oesophgectomy Pleuropneumonectomy Decortiction of lung - Discontinue 5 dys before - Discontinue 5 dys before - Discontinue 5 dys before with loding dose b with loding dose b with loding dose 7 dys prior for prsugrel; b collegil discussion of risk, even with fmily/ptient. References 8-10,12-15,90. ASA: spirin with loding dose EuroIntervention 2014;10:38-46 Tble 8. Digestive endoscopy. EGD or colonoscopy +/ biopsy Echoendoscopy without biopsy Polypectomy/polyps <1 cm ERCP, stent, dilted ppill without sphincterotomy Endoscopy + fine needle spirtion biopsy (FNA) for solid lesions Stenosis dilttion (oesophgel, colorectl) Gstroenteric stents Argon plsm cogultion tretment Polypectomy/polyps >1 cm PEG (percutneous endoscopic gstrostomy) Binding/vricel sclerosis Binding/hemorrhoids sclerosis Dilttion in chlsi Mucosectomy/submucosl resection Echogrphy with FNA biopsy of pncretic cystic lesions Ampullectomy of the mpull of Vter continue Elective surgery: not contrindicted continue b b Bridge therpy with GP IIb/III inhibitors b continue Bridge therpy with GP IIb/III inhibitors b Bridge therpy with GP IIb/III inhibitors b 7 dys prior for prsugrel; b collegil discussion of risk, even with fmily/ptient. References ASA: spirin; EGD: oesophgo-gstro-duodenoscopy; ERCP: endoscopic retrogrde cholngiopncretogrphy Antithrombotic therpy with unfrctionted or low moleculr weight heprin is not recommended, unless dministered s prophylxis for venous thromboembolism. Cngrelor is new potent ntipltelet gent tht inhibits the receptor competitively. On the bsis of the BRIDGE tril results, it might be used in future s bridge therpy in ptients undergoing surgery, in whom the periopertive discontinution of orl ntipltelet drugs is necessry 135. Limittions The present consensus document derives mostly from experts opinions rther thn from the results of rndomised trils, which 45

9 EuroIntervention 2014;10:38-46 represents its min limittion. Moreover, mny procedures require more urgent mngement ccording to the severity of the clinicl presenttion, nd often the distinction between deferrble nd un-deferrble surgery is not cler issue nd cn be misleding both for the surgeon nd for the crdiologist. Finlly, the hemorrhgic risk is determined not only by the type of surgicl intervention, but lso by the ptient s clinicl chrcteristics, which hve not been considered in the bleeding risk ssessment. Acknowledgement This mnuscript nd supplementry dt hve been dpted with permission from Rossini et l 19. Conflict of interest sttement R. Rossini received pyment s n individul for consulting fees or honorri from Eli Lilly nd Co., nd Diichi Snkyo, Inc nd Astr Zenec. L.O. Visconti received pyment s n individul for consulting fees or honorri from Eli Lilly, nd Diichi Snkyo, Astr Zenec, Menrini, Byer, Pfizer, BMS nd Boehringer. D. Angiolillo reports receiving pyment s n individul for: ) consulting fees or honorri from Bristol Myers Squibb, Snofi- Aventis, Eli Lilly, Diichi Snkyo, The Medicines Compny, AstrZenec, Merck, Evolv, Abbott Vsculr nd PLx Phrm; b) prticiption in review ctivities from Johnson & Johnson, St. Jude, nd Sunovion. He lso reports receiving institutionl pyments for grnts from Bristol Myers Squibb, Snofi-Aventis, Glxo Smith Kline, Otsuk, Eli Lilly, Diichi Snkyo, The Medicines Compny, AstrZenec, Evolv; nd hving other finncil reltionships with the Jmes nd Esther King Biomedicl Reserch Progrm. D. Cpodnno reports receiving honorri for lectures/ consulting from Eli Lilly nd Co., The Medicines Compny, nd AstrZenec. G. Gugliumi reports receiving consulting fees from Boston Scientific, St. Jude Medicl nd AstrZenec nd receiving grnt support from St. Jude Medicl, Medtronic Vsculr, Boston Scientific nd Abbott Vsculr. M. Lettino reports speker s fees nd being n dvisory bord member for AZ, Byer, Boehringer, Diichi Snkyo, Eli Lilly, The Medicines Compny, BMS, MSD, Pfizer. G. Musumeci reports receiving honorri for lectures from Eli Lilly nd Co., Diichi Snkyo, AstrZenec, St. Jude Medicl nd Abbott Vsculr. L. Frncetti reports receiving pyment s n individul for consulting from Vles sp. S. Svonitto reports receiving reserch grnts from Eli Lilly, Novrtis, nd Iroko. B. Cstiglioni reports receiving pyment s n individul for speker fees from CID. G. Sturenghi reports receiving pyment s n individul for consulting fees or honorri from Heidelberg Engineering, OD-OS, Optos, Oculr Instruments, Quentel Medicl, Crl Zeiss Meditec, Alcon, Allergn, Byer, Boheringer, Genentech, GSK, QLT, Novrtis nd Roche. All the other uthors hve no conflicts of interest to report. References The references cn be found in the online version of the pper. Online dt supplement Appendix. Acknowledgements. Online Tble 1. Mxillofcil surgery. Online Tble 2. Plstic surgery. Online Tble 3. Gynecology. Online Tble 4. Neurosurgery. Online Tble 5. Interventionl pulmonology. Online Tble 6. Dentistry. Online Tble 7. Ophthlmology. 46

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12 Stent nd surgery ntipltelet therpy re ssocited with n increse in mjor dverse crdic events. J Am Coll Crdiol. 2007;49: Anwruddin S, Askri AT, Sudye H, Btizy L, Houghtling PL, Almoudi M, Militello M, Muhmmd K, Kpdi S, Ellis SG. Chrcteriztion of post-opertive risk ssocited with prior drugeluting stent use. JACC Crdiovsc Interv. 2009;2: vn Kuijk JP, Flu WJ, Schouten O, Hoeks SE, Schenkeveld L, de Jegere PP, Bx JJ, vn Domburg RT, Serruys PW, Poldermns D. Timing of noncrdic surgery fter coronry rtery stenting with bre metl or drug-eluting stents. Am J Crdiol. 2009;104: Cruden NL, Hrding SA, Flpn AD, Grhm C, Wild SH, Slck R, Pell JP, Newby DE; Scottish Coronry Revsculristion Register Steering Committee. Previous coronry stent implnttion nd crdic events in ptients undergoing noncrdic surgery. Circ Crdiovsc Interv. 2010;3: Rbbitts JA, Nuttll GA, Brown MJ, Hnson AC, Oliver WC, Holmes DR, Rihl CS. Crdic risk of noncrdic surgery fter percutneous coronry intervention with drug-eluting stents. 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Endoscopy nd ntipltelet gents. Europen Society of Gstrointestinl Endoscopy (ESGE) Guideline. Endoscopy. 2011;43: Guerci Ph, Audibert G, Mertes PM. Mngement of chronic nticogulnt nd ntipltelet tretment before scheduled neurosurgery. Neurochirurgie. 2009;55:H Korinth MC. Low-dose spirin before intrcrnil surgery - results of survey mong neurosurgeons in Germny. Act Neurochir. 2006;148: Lehot JJ, Piriou V, Durnd de Gevigney G, Corit P. Ptient t risk of endocoronry stent thrombosis during periopertive period: frequent sitution. Ann Fr Anesth Renim. 2005;24: Di Roio C, Gillc N, Pélissou I, Crillon R, Diller F. Drugeluting stent, intrventriculr hemorrhge, ventriculr dringe, fvourble outcome. Ann Fr Anesth Renim. 2007;26:91-2. EuroIntervention 2014;10:

15 EuroIntervention 2014;10: Mntz J, Smm CM. The ntionl STRATAGEM study: the success needs everyone s contribution! Ann Fr Anesth Renim. 2006;25: Herth FJ, Becker HD, Ernst A. Aspirin does not increse bleeding complictions fter trnsbronchil biopsy. Chest. 2002;122: Chinsky K. Bleeding risk nd bronchoscopy: in serch of the evidence in evidence-bsed medicine. Chest. 2005;127: Johnson JR, Chin R, Conforti J. Bronchoscopic myths nd legends: nti-pltelet medictions. Clinicl Pulmonry Medicine. 2005;12: Ernst A, Eberhrdt R, Whidi M, Becker HD, Herth FJ. Effect of routine clopidogrel use on bleeding complictions fter trnsbronchil biopsy in humns. Chest. 2006;129: Pototski M, Amenábr JM. Dentl mngement of ptients receiving nticogultion or ntipltelet tretment. J Orl Sci. 2007;49: Eld S, Chckrtchi T, Shpir L, Findler M. A criticlly severe gingivl bleeding following non-surgicl periodontl tretment in ptients medicted with nti-pltelet. J Clin Periodontol. 2008;35: Lillis T, Ziks A, Koskins K, Tsirlis A, Ginnoglou G. Sfety of dentl extrctions during uninterrupted single or dul ntipltelet tretment. Am J Crdiol. 2011;108: Krishnn B, Shenoy NA, Alexnder M. Exodonti nd ntipltelet therpy. J Orl Mxillofc Surg. 2008;66: Npens JJ, Hong CH, Brennn MT, Furney SL, Fox PC, Lockhrt PB. The frequency of bleeding complictions fter invsive dentl tretment in ptients receiving single nd dul ntipltelet therpy. J Am Dent Assoc. 2009;140: Kobyshi H. Evlution of the need to discontinue ntipltelet nd nticogulnt medictions before ctrct surgery. J Ctrct Refrct Surg. 2010;36: Brequet IS, Schs D, Shenkmn B, Priel A, Wsserzug Y, Budnik I, Moisseiev J, Slomon O. Risk ssessment of simple phcoemulsifiction in ptients on combined nticogulnt nd ntipltelet therpy. J Ctrct Refrct Surg. 2011;37: Mson JO 3rd, Frederick PA, Neimkin MG, White MF Jr, Feist RM, Thomley ML, Albert MA Jr. Incidence of hemorrhgic complictions fter intrvitrel bevcizumb (vstin) or rnibizumb (lucentis) injections on systemiclly nticogulted ptients. Retin. 2010;30: Kumr N, Jivn S, Thoms P, McLure H. Sub-Tenon s nesthesi with spirin, wrfrin, nd clopidogrel. J Ctrct Refrct Surg. 2006;32: Joseph JJ, Pilli A, Brmley D. Clopidogrel in orthopedic ptients: review of current prctice in Scotlnd. Thromb J. 2007;5: Collinge CA, Kelly KC, Little B, Wever T, Schuster RD. The effects of clopidogrel (Plvix) nd other orl nticogulnts on erly hip frcture surgery. J Orthop Trum. 2012;26: Kriotis I, Philippou P, Volnis D, Serfetinides E, Delks D. Sfety of ultrsound-guided trnsrectl extended prostte biopsy in ptients receiving low-dose spirin. Int Brz J Urol. 2010;36: Enver MK, Hoh I, Chinegwundoh FI. The mngement of spirin in trnsurethrl prosttectomy: current prctice in the UK. Ann R Coll Surg Engl. 2006;88: Crmignni L, Picozzi S, Stubinski R, Csellto S, Bozzini G, Lunelli L, Aren D. Endoscopic resection of bldder cncer in ptients receiving double pltelet ntiggregnt therpy. Surg Endosc. 2011;25: Subherwl S, Bch RG, Chen AY, Gge BF, Ro SV, Newby LK, Wng TY, Gibler WB, Ohmn EM, Roe MT, Pollck CV Jr, Peterson ED, Alexnder KP. Bseline risk of mjor bleeding in non-st-segment-elevtion myocrdil infrction: the CRUSADE (Cn Rpid risk strtifiction of Unstble ngin ptients Suppress ADverse outcomes with Erly implementtion of the ACC/AHA Guidelines) Bleeding Score. Circultion. 2009;119: Mehrn R, Pocock SJ, Nikolsky E, Clyton T, Dngs GD, Kirtne AJ, Prise H, Fhy M, Mnoukin SV, Feit F, Ohmn ME, Witzenbichler B, Gugliumi G, Lnsky AJ, Stone GW. A risk score to predict bleeding in ptients with cute coronry syndromes. J Am Coll Crdiol. 2010;55: Pisters R, Lne DA, Nieuwlt R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to ssess 1-yer risk of mjor bleeding in ptients with tril fibrilltion: the Euro Hert Survey. Chest. 2010;138: Svonitto S, D Urbno M, Crcciolo M, Brlocco F, Mrini G, Nicheltti M, Klugmnn S, De Servi S. Urgent surgery in ptients with recently implnted coronry drug-eluting stent: phse II study of bridging ntipltelet therpy with tirofibn during temporry withdrwl of clopidogrel. Br J Anesth. 2010;104: Wessler JD, Sldn F, Giuglino RP. Bridging therpy fter recent stent implnttion: cse report nd review of dt. Crdiovsc Revsc Med. 2012;13: Pickett AM, Tylor DA, Ackmn ML. Prolonged infusion of eptifibtide s bridge therpy between bre-metl stent insertion nd crdiovsculr surgery: cse report nd review of the literture. Phrmcotherpy. 2010;30:127e-33e Biglke B, Seizer P, Geisler T, Lindemnn S, Gwz M, My AE. Periopertive ntipltelet therpy in ptients t risk for coronry stent thrombosis undergoing noncrdic surgery. Clin Res Crdiol. 2009;98: Angiolillo DJ, Firstenberg MS, Price MJ, Tumml PE, Hutyr M, Welsby IJ, Voeltz MD, Chndn H, Rmih C, Brtko M, Cnnon L, Dyke C, Liu T, Montlescot G, Mnoukin SV, Prts J, Topol EJ; BRIDGE Investigtors. Bridging ntipltelet therpy with cngrelor in ptients undergoing crdic surgery: rndomized controlled tril. JAMA. 2012;307:

16 Stent nd surgery Authors ffilitions 1. Diprtimento Crdiovscolre, AO Pp Giovnni XXIII, Bergmo, Itly; 2. Divisione di Crdiologi, IRCCS Fondzione Policlinico S. Mtteo, Pvi, Itly; 3. U.O. di Crdiologi 2, Ospedle di Circolo, Vrese, Itly; 4. Divisione di Crdiologi, Ospedle Crlo Pom, Mntu, Itly; 5. U.O.C. Crdiologi Clinic I, Humnits Reserch Hospitl, Rozzno (MI), Itly; 6. Divisione di Crdiologi, Ospedle L. Scco, Miln, Itly; 7. Division of Crdiology, A. Mnzoni Hospitl, Lecco, Itly; 8. Diprtimento di Scienze Crdiovscolri, Centro Crdiologico Monzino, IRCCS, Miln, Itly; 9. Diprtimento di Crdiologi, Ospedle Ferrtto, Università di Ctni, Ctni, Itly; 10. Diprtimento di Scienze Crdiovscolri, Centro Crdiologico Monzino, IRCCS, Università degli Studi, Miln, Itly, 11. Chirurgi I Aziend Ospedliero Universitri Fondzione Mcchi di Vrese, Vrese, Itly; 12. U.O. di Chirurgi Mxillo-Fccile, Ospedle Sn Polo, Miln, Itly; 13. Diprtimento di Biotecnologie e Scienze dell Vit, Università dell Insubri, Vrese, Itly; 14. Divisione di Chirurgi Torcic, Ospedle Crlo Pom, Mntu, Itly; 15. Divisione di Chirurgi Vscolre, IRCCS Fondzione Policlinico S. Mtteo, Pvi, Itly; 16. Vsculr nd Endovsculr Surgery Unit, Deprtment of Medicine, Surgery nd Neuroscience, University of Sien, Sien, Itly; 17. U.O. di Endocrinologi ed Endoscopi Digestiv, AO Pp Giovnni XXIII, Bergmo, Itly; 18. U.O. di Ostetrici Ginecologi, Ospedle di Treviglio, Treviglio, Itly; 19. Clinic Oculistic, Diprtimento di Scienze Cliniche L. Scco, Università degli Studi di Milno, Ospedle L. Scco, Miln, Itly; 20. Servizio di Neurochirurgi, Fondzione IRCCS Cá Grnd, Ospedle Mggiore Policlinico, Miln, Itly; 21. Diprtimento di Scienze Biomediche, Chirurgiche e Odontoitriche, Clinic Odontoitric IRCCS Istituto Ortopedico Glezzi, Università di Miln, Itly; 22. Diprtimento di Biotecnologie e Scienze dell Vit, Università dell Insubri, Vrese, Itly; 23. Fondzione IRCCS C Grnd Ospedle Mggiore Policlinico di Milno, Miln, Itly; 24. Divisione di Pneumologi, Ospedle Crlo Pom, Mntu, Itly; 25. U.O. di Anestesi e Terpi Intensiv, IRCCS Centro Crdiologico Monzino, Miln, Itly; 26. Diprtimento di Anestesi, AO Pp Giovnni XXIII, Bergmo, Itly; 27. Istituto di Terpi Intensiv e Anestesi, Università Cttolic-Policlinico Universitrio A.Gemelli, Rome, Itly; 28. U.O. di Crdiologi, Ospedle Cmpo di Mrte, Lucc, Itly; 29. Diprtimento Crdiovscolre, GVM Cre nd Reserch - Mri Cecili Hospitl, Cotignol (RA), Itly; 30. University of Florid, College of Medicine-Jcksonville, Jcksonville, FL, USA EuroIntervention 2014;10:38-46 Appendix Supplement to: Periopertive mngement of ntipltelet therpy in ptients with coronry stents undergoing crdic nd non-crdic surgery: consensus document from Itlin crdiologicl, surgicl nd nesthesiologicl societies Acknowledgements Piersilvio Geromett 1, Enrico Guffnti 2, Gid Beltrmini 3, Luc Devlle 4, Sergiomri Gini 5, Stefno Corbell 6, Antonio Cstelli 7, Emnuel Menozzi 7, Alessndro Loctelli 8, Lorenzo Mntovni 9, Nicolin Russo 10, Gennro Svoi U.O. di Crdiochirurgi, Humnits Gvzzeni, Bergmo, Itly; 2. Chirurgi II, Ospedle di Circolo, Vrese, Itly; 3. U.O. di Chirurgi Mxillo-Fccile, Ospedle Sn Polo, Miln, Itly; 4. U.S.C. di Chirurgi Plstic, AO Pp Giovnni XXIII, Bergmo, Itly; 5. U.O. di Neurochirurgi, Ospedle Mggiore Policlinico, Miln, Itly; 6. Diprtimento di Tecnologie per l Slute, Università degli Studi di Milno, Clinic Odontoitric, IRCCS Istituto Ortopedico Glezzi, Miln, Itly; 7. U.O. di Anestesi e Rinimzione, Ospedle L. Scco, Miln, Itly; 8. Diprtimento Crdiovscolre, Ospedle Snt Croce, Cuneo, Itly; 9. Diprtimento di Anestesi, AO Pp Giovnni XXIII, Bergmo, Itly. 10. Diprtimento Crdiovscolre, AO Pp Giovnni XXIII, Bergmo, Itly; 11. UOSC Terpi Intensiv AORN A. Crdrelli, Nples, Itly. Società Itlin di Crdiologi Invsiv (Alberto Cremonesi, Diprtimento Crdiovscolre, GVM Cre nd Reserch - Mri Cecili Hospitl, Cotignol, Itly) Associzione Nzionle Medici Crdiologi Ospedlieri (Frncesco Bovenzi, U.O. di Crdiologi, Ospedle Cmpo di Mrte, Lucc, Itly) Società Itlin di Chirurgi (Ginluigi Melotti, Chirurgi Generle, Ospedle di Bggiovr [NOCSAE], USL Moden, Itly) Associzione Chirurghi Ospedlieri Itlini (Stefno Brtoli, Chirurgi Vscolre ASL RM C; Luigi Presenti, U.O. Chirurgi Generle, Ospedle Giovnni Polo II, Olbi, Itly; Muro Longoni, U.O.C. di Chirurgi Generle I, P.O. di Sesto Sn Giovnni A.O. di Vimercte, Itly) Società Lombrd di Chirurgi (Gimpietro Creperio, Chirurgi Generle, Ospedle Erb-Renldi di Menggio, Itly) Società Itlin di Chirurgi Crdic (Lorenzo Menicnti, Deprtment of Crdic Surgery, IRCCS Policlinico Sn Donto, Miln; Itly) Società Itlin di Anestesi, Anlgesi, Rinimzione e Terpi Intensiv (Mssimo Antonelli, Terpi Intensiv e Anestesi, Università Cttolic-Policlinico Universitrio A. Gemelli, Rome, Itly) Società Itlin Chirurgi Mxillo-fccile (Giuseppe Ferronto, Chirurgi Mxillofccile, Aziend Ospedlier - Università di Pdov, Pdu, Itly) Società Itlin di Chirurgi Plstic ed Estetic (Enrico Robotti, USC Chirurgi Plstic, AO Pp Giovnni XXIII, Bergmo, Itly) 7

17 EuroIntervention 2014;10:38-46 Società Itlin di Chirurgi Torcic (Dvide Dell Amore, U.O. Chirurgi Torcic Antonio Vio Ospedle G.B. Morggni-L. Pierntoni, Forlì, Itly) Società Itlin di Chirurgi Vscolre ed Endovscolre (Crlo Setcci, Chirurgi vscolre ed endovscolre, Aziend Ospedlier Universitri Senese, Sien, Itly) Società Itlin di Ortopedi e Trumtologi (Polo Cherubino, Dip. Scienze Ortopediche e Trumtologiche M. Boni, Università degli Studi dell Insubri, Ospedle di Circolo, Vrese, Itly) Federzione Itlin delle Società scientifiche delle Mlttie dell Apprto Digerente (Mrco Soncini, Gincrlo Spinzi, Murizio Vecchi) Associzione Ostetrici Ginecologi Ospedlieri Itlini Lombrdi (Cludio Crescini, U.O. Ostetrici Ginecologi Ospedle di Treviglio (BG), Itly) Società Oftlmologic Lombrd (Giovnni Sturenghi, Divisione di Oculistic, Ospedle L. Scco, Miln, Itly) Società Itlin di Prodontologi (Luc Frncetti, Servizio di Odontostomtologi, Diprtimento di Tecnologie per l Slute, Università degli Studi di Milno, Istituto Ortopedico Glezzi, Miln, Itly) Società Itlin di Urologi (Frncesco Rocco, UO Urologi, Ospedle Mggiore, Policlinico Miln, Itly) Società Itlin di Neurochirurgi (Frnco Servdei, Aziend Ospedlier Universitri di Prm, Itly) Online Tble 1. Mxillofcil surgery. Closed reduction of zygomtic rch frcture, closed reduction of mndibulr frcture; lipofilling; rthrocentesis nd temporomndibulr joint rthroscopy, skin cncer surgery Implntology nd orl surgery, closed reduction of nsl bone frcture, open reduction of jw frcture; protidectomy, orthognthic surgery, fcil renimtion prlysis in cute nd chronic Rdicl nd reconstructive cncer surgery of hed nd neck; open reduction of frcture orbito-zygomtic rch; silodenectomy submndibulr 7 dys prior for prsugrel; b collegil discussion of risk, even with fmily/ptient. References ASA: spirin continue b b continue 8

18 Stent nd surgery Online Tble 2. Plstic surgery. Excision nd suturing smll epithelioms nd smll benign skin lesions, scrring correction, tretment of soft tissue pthology of the hnd (crpl tunnel, trigger finger, tendon nd rticulr cysts, Dupuytren). Upper blephroplsty, lower blephroplsty, rhinoplsty, otoplsty, brest reconstruction fter totl removl (mstectomy) or prt (qudrntectomy) for oncologicl resons, positioning with rtificil implnts. Brest ugmenttion; lifting; flp microsurgicl brest reconstruction, removl of tumours of considerble extent of fce nd neck soft tissues nd plstic reconstruction using microsurgicl flp Tretment of brest bnormlities (symmetry, tuberous brests, tubulr brests, etc). Tretment of gynecomsti. Lower, upper limbs liposuction nd bdomen of medium entity. Functionl tretment of trum (cr ccidents, surgery outcomes, etc.), loss of substnce fter demolishing of medium entity in the detil of the fce, the region of peri-oculr (eyelid scrs with functionl ltertion), upper nd lower limbs peribuccl, by locl flps, skin grft, with or without use of rtificil derml substitute. Tret leg ulcers (ASA Clss II - I). Correcting scrs nd depressions (lipofilling) of medium entity. Surgicl tretment of burns (10% <X <15%). Fcelift, brest reduction, bdominoplsty Functionl tretment of trum (cr ccidents, surgery outcomes, etc.), loss of substnce fter demolishing of substntil entity, especilly of fce nd upper nd lower limbs, bdomen, bck, using microsurgicl flps or multi-tissue pedicled flps of substntil entity. Lower limbs, upper bdomen serious liposuction. Surgicl tretment of burns (>15%). Tret leg ulcers (ASA Clss V - IV - III). Correcting scrs nd depressions (lipofilling) of significnt entity. Post surgery Britric surgery - Discontinue 5 dys before - Discontinue 5 dys before - Discontinue 5 dys before continue b continue Bridge therpy with GP IIb/III inhibitors b Bridge therpy with GP IIb/III inhibitors b 7 dys prior for prsugrel; b collegil discussion of risk, even with fmily/ptient. References: 8-10, 12-15, 66. ASA: spirin; ASA clss: Americn Society of Anesthesiology clssifiction EuroIntervention 2014;10:38-46 Online Tble 3. Gynecology. Dignostic hysteroscopy with endometril biopsy nd polypectomy, rectoscopic hysteroscopy polypectomy, metroplsty, dilttion nd curettge of uterus (D & C), Cervicl conistion with dithermy loop (LEEP), Mrsupilistion / Brtholins glnd/cyst removl, lproscopic removl / lprotomic nnex for benign disese, lproscopy / lprotomy for mild endometriosis, tubl sterilistion hysteroscopic/ lproscopic, dignostic lproscopy or with miniml opertion (simple dhesiolysis, endometriotic implnts DTC) Resettoscopic hysteroscopy /myomectomy, endometril bltion Lproscopy / lprotomy for endometriosis (intermedite) Simple bdominl hysterectomy for benign disese Simple vginl hysterectomy for benign disese / prolpse Fscil vginl reprtive surgery (repir cystocele / rectocele) Reprtive vginl prosthetic surgery Rdicl Vulvr Surgery Omentectomy Lprotomy or lproscopic hysterectomy for lrge uteri (>750 g) Myomectomy lprotomic / lproscopic Lproscopy / lprotomy for severe/deep endometriosis Debulking surgery for ovrin cncer Rdicl surgery for crcinom of cervix nd endometrium Pelvic/ lombo-ortic lymphdenectomy Pelvic eviscertion continue - Discontinue 5 dys before - Discontinue 5 dys before - Discontinue 5 dys before 7 dys prior for prsugrel; b collegil discussion of risk, even with fmily/ptient. ASA: spirin; DTC: dithermocogultion continue b b continue Bridge therpy with GP IIb/III inhibitors b Bridge therpy with GP IIb/III inhibitors b 9

19 EuroIntervention 2014;10:38-46 Online Tble 4. Neurosurgery. Spinl neurosurgery: disc hernition, lminectomy ( 2 spces) without rthrodesis Crnil neurosurgery: externl ventriculr derivtion, intrventriculr ctheter plcement for intrcrnil pressure monitoring, intrventriculr reservoir plcement Spinl neurosurgery: lminectomy >2 spces, spinl rthrodesis (ny type) Crnil neurosurgery: ventriculoperitonel shunt, removl of extrdurl lesion Spinl nd crnil neurosurgery: removl of intrdurl lesions (intrcerebrl tumours, intrprenchyml hemorrhge) with with - Restrt of ntipltelet therpy to be discussed (with loding dose) 7 dys prior for prsugrel; b collegil discussion of risk, even with fmily/ptient. References ASA: spirin Urgency: hemorrhge, cerebrl oedem - Restrt of ntipltelet therpy to be discussed () b Urgency: brin/spinl hemtom - Restrt of ntipltelet therpy to be discussed () b - Restrt of ntipltelet therpy to be discussed () b Urgency: intrcerebrl hemtom (pltelet trnsfusion to be discussed) Urgency: hemorrhge, cerebrl oedem continue Urgency: hemtom brin injury/ spinl - Restrt of ntipltelet therpy to be discussed () b - Restrt of ntipltelet therpy to be discussed () b Urgency: intrcerebrl hemtom (pltelet trnsfusion to be discussed) Online Tble 5. Interventionl pulmonology. Bronchoscopic inspection Bronchospirtion Broncholveolr lvge Bronchil biopsy Trnsbronchil needle spirtion Lung nd trnsbronchil biopsy Rigid bronchoscopy Medicl thorcoscopy Elective procedure: postpone Non-deferrble procedure: continue Elective procedure: postpone Non-deferrble procedure: with b Elective procedure: postpone with b 7 dys prior for prsugrel; b collegil discussion of risk, even with fmily/ptient. References ASA: spirin Elective procedure: postpone Non-deferrble procedure: continue Elective procedure: postpone Non-deferrble procedure: Elective procedure: postpone Non-deferrble procedure: 10

20 Stent nd surgery Online Tble 6. Dentistry. Non-surgicl periodontl therpy (including suprgingivl scling); Endodontic therpy; Rubber dm positioning Surgicl periodontl therpy (resective surgery, regenertive surgery, mucogingivl surgery) Orl surgery in generl (teeth extrctions, pre-prosthetic reconstructive surgery), implnt surgery continue continue continue continue continue continue EuroIntervention 2014;10:38-46 References ASA: spirin Online Tble 7. Ophthlmology. Intrvitrel injections Ctrct surgery Peribulbr nesthesi Vitrectomy Trbeculectomy Elective surgery: not contrindicted continue b continue with loding dose 7 dys prior for prsugrel; b collegil discussion of risk, even with fmily/ptient. References ASA: spirin 11