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  1. 1. EditorialAntiplatelet Therapy in Patients With Coronary Stent UndergoingUrologic Surgery: Is It Still No Man’s Land?Richard Naspro a,*, Roberta Rossini b, Giuseppe Musumeci b, Franco Gadda c,Luigi Filippo Da Pozzo aaDepartment of Urology, AO Papa Giovanni XXIII, Bergamo, Italy; bDepartment of Cardiology, AO Papa Giovanni XXIII, Bergamo, Italy; cUrology Unit,Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, ItalyPercutaneous coronary intervention (PCI) in patients withcoronary artery disease is on the increase worldwide. Everyyear, >1 million PCIs are performed in United States andEurope [1,2]. In >85% of cases, a coronary stent is implanted[3], and prolonged antiplatelet therapy is mandatory afterstent implantation. International guidelines advocate dualantiplatelet therapy (DAPT) for 4 wk after bare metal stent(BMS) implantation and for 6–12 wk after drug-elutingstent (DES) implantation [4]. Premature withdrawal ofantiplatelet therapy is associated with a significantly higherrisk of cardiac ischemic events because of stent thrombosis(ST). This rare, but life-threatening complication occursmost of the time as acute myocardial infarction, with amortality of 10–40%. Occurrence of ST can be up to 90 timeshigher after premature discontinuation of DAPT [5]. Aprevious study assessing the prevalence and causes ofpremature discontinuation of DAPT after DES implantationshowed that premature discontinuation was not a rareevent (1 of 10 patients). The most common causes ofdiscontinuation were surgery and bleeding events and wereoften associated with a poor prognosis [6].The management of antiplatelet drugs in the periopera-tive period is relevant from both an epidemiological and aclinical point of view. The incidence of noncardiac surgeryafter BMS or DES implantation is 5% at 1 yr and 23% at 5 yr[3]. The number of patients on antiplatelet therapy who willrequire urologic procedures is progressively increasing asthe ages of the peak incidence of PCI and of various forms ofurologic cancer coincide. Urologic conditions are verydiverse, spanning from benign but troublesome conditions(eg, severe bladder outlet obstruction [BOO], complicatedurinary stones) to very complex oncologic diseases thatrequire major and mandatory surgery. Therefore, it ischallenging to weigh the exact impact of hemorrhage orthrombosis/ischemia risk according to surgical priority. Onthe one hand, the withdrawal (and sometimes also themaintenance) of the antiplatelet therapy may have dramat-ic consequences, as bleeding risk is increased in patientsundergoing surgery on antiplatelet therapy [7,8]. Bleedingrisk is 3.4 times higher during DAPT compared with aspirinalone [9]. On the other hand, surgery can lead toinflammatory, hypercoagulable, and hypoxic states thatare associated with plaque instability and perioperativearterial thrombosis [3].1. Clinical implicationsIn recent years, international cardiologic, anesthesiologic,and hematologic societies have proposed guidelines andpublished joint position papers on the management of DAPTin patients undergoing noncardiac surgery [4,10–16].However, these recommendations provide little supportwith regard to managing antiplatelet therapy in theperioperative phase in urgent operations and/or patientsat high hemorrhagic risk. In particular, guidelines sharedwith urologists and cardiologists are lacking [17].Elective surgical procedures ought to be postponed untilafter the completion of DAPT. Unfortunately, many proce-dures require more urgent management according toseverity, and often the distinction between deferrableand undeferrable surgery is not clear and can be misleadingfor both the surgeon and the patient.The management of the risk ratio between bleeding andthrombosis requires an exact knowledge of risk stratifica-tion defined for each condition, paired with offering theminimal surgical impact. In this respect, it could beE U R O P E A N U R O L O G Y 6 4 ( 2 0 1 3 ) 1 0 1 – 1 0 5available at www.sciencedirect.comjournal homepage: www.europeanurology.com* Corresponding author. Department of Urology, AO Papa Giovanni XXIII, Bergamo, Italy. Tel. +39 0352673471; Fax: +39 035266419.E-mail address: nasprorichard@gmail.com (R. Naspro).0302-2838/$ – see back matter # 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.http://dx.doi.org/10.1016/j.eururo.2013.01.026
  2. 2. recommended that high-risk patients be referred to centersat which the most minimally invasive therapies—such aspure laparoscopic procedures, robot-assisted procedures,and new-generation lasers—are available. These proce-dures, coupled with a high-volume cardiologic team, canallow the reduction of blood loss in case of maintenance ofthe antiplatelet therapy and permit prompt resumption ofthe antiplatelet drugs if they have been discontinued.2. Evidence-based state of the artA consensus document on the optimal antiplatelet regimenin patients with coronary stents undergoing urologicinterventions has been recently proposed by a multidisci-plinary panel composed of urologists and cardiologists, whocontributed equally to its creation [6]. The document wasendorsed by the Italian Society of Urology, InterventionalCardiology, and Cardiology. An ST risk was graded consider-ing procedural features such as stent type, time from PCI tourologic surgery, and clinical aspects such as concomitantdiabetes, renal impairment, low cardiac ejection fraction, andage. Most urologic interventions were classified according tothe bleeding risk (Table 1).The document [6] follows the pivotal paper by Gupta andcoworkers [18] but is the first consensus document toprovide practical recommendations on the management ofantiplatelet therapy in patients with coronary stents whoare undergoing diverse urologic interventions. To ourknowledge, it is also the first consensus document sharedby urologic and cardiologic societies. Briefly, ST risk isstratified as low, intermediate, and high (Table 2), and themost appropriate antiplatelet therapy and management isdefined for each intervention on the basis of the ischemicand hemorrhagic risk (Table 3).This stratification allows detailed definition of theoptimal antiplatelet regimen that should be maintainedin the perioperative period, thus avoiding arbitrarymanagement. Of note, it is important to define the idealtiming of the urologic intervention, as elective proceduresshould be delayed until a low cardiac ischemic risk isreached.The main difference between the classification of Guptaet al. and the Italian hemorrhagic classification is thedefinition of the hemorrhagic risk for transurethral resec-tion of the prostate (TURP) and transurethral resection ofbladder tumor. The former classification considers themintermediate bleeding risk procedures, and the latterconsiders them high risk, highlighting the particularity ofendoscopic procedures.3. Transurethral resection of the prostate: thechallenging issueCurrently, any surgical treatment of BOO should be deferredwhenever possible following PCI. Nevertheless, somepatients require surgery because of the presence of oneor a combination of the following: an indwelling catheter,severe infection, bladder stones, and severe and unsustain-able lower urinary tract symptoms.To date, TURP is still considered the gold standard for thetreatment of BOO in spite of the growing number ofTable 1 – Stratification of urologic procedures according tobleeding risk. Reproduced with permission from the Publisher,Il Pensiero Scientifico Editore [6].Low riskFlexible cystoscopyUreteral catheterizationUreteroscopyIntermediate riskProstate biopsyOrchiectomyCircumcisionHigh riskRadical and partial nephrectomyPercutaneous nephrostomyPercutaneous lithotripsyCystectomyRadical prostatectomyOpen simple prostatectomyTURPTURBTPenectomyPartial orchiectomyTURBT = transurethral resection of bladder tumor; TURP = transurethralresection of the prostate.Table 2 – Definition of thrombotic risk in patients with coronary stents. Reproduced with permission from the Publisher, Il PensieroScientifico Editore [6].Low risk Intermediate risk High risk 6 months after PCI with BMS 12 months after PCI with DES. 1 month, 6 months after PCI with BMS 6, 12 months after PCI with DES 12 months after complex PCI with DES (long stents,multiple stents, overlapping, small vessels, biforcations,left main, last remaining vessel). 1 month after PCI with BMS 6 months after PCI with DES 12 months after complex PCI with DES(long stents, multiple stents, overlapping,small vessels, biforcations, left main, lastremaining vessel).PCI in ACS, previous stent thrombosis, LVEF 35%, chronic renal failure, diabetes increase the thrombotic risk.Patients submitted to CABG or with ACS medically treated are considered at high risk in the first month, at intermediate risk between 1st and 6th month, and atlow risk after 6 months.Patients treated with POBA are considered at high risk within the first 2 weeks, at intermediate risk between 2 and 4 weeks, and at low risk after 4 weeks.PCI = percutaneous coronary intervention; BMS = bare metal stent; DES = drug-eluting stent; LVEF = left ventricular ejection fraction; CABG = coronary arterybypass grafting; ACS = acute coronary syndrome; POBA = plain old balloon angioplasty.E U R O P E A N U R O L O G Y 6 4 ( 2 0 1 3 ) 1 0 1 – 1 0 5102
  3. 3. alternative minimally invasive surgical therapies [19,20].Although morbidity following TURP is relatively low (1%),in recent TURP series, clot retention with major bleedinghas been reported in 5% of cases, with a reinterventionrate of 1.3–5% and a requirement for blood derivatives in7% of cases. When stratifying these findings accordingto patients with coagulation disorders and cardiologiccomorbidities, complications are expected to be muchhigher, especially when antiplatelet therapy is continued[18,21]. Currently, no clear evidence has emerged from theliterature regarding the safety of TURP in patients onantiplatelet therapy, and the available data are limitedand not consistent. Therefore, TURP must be considereda potentially dangerous procedure in high-risk cardiologicpatients with an increased risk of troublesome postopera-tive bleeding when aspirin is not discontinued periopera-tively [22,23]. In these patients, TURP may cause fatalbleeding, in contrast with most major surgical procedureswith a safer profile [7].To reduce perioperative morbidity, Ehrlich and cow-orkers advocated the safety of perioperative aspirindiscontinuation followed by early initiation after TURP[24]. It is interesting to note that the authors did not registeran increase in either postoperative bleeding complicationsor cardiac events. However, the population included in thestudy probably did not represent a high-risk group ofpatients. The risk of clinically significant bleeding can alsobe reduced by using alternative sources of energy such aslasers, as recommended by the updated European Associa-tion of Urology (EAU) guidelines [20]. In particular,holmium laser enucleation of the prostate and laservaporization using potassium-titanyl-phosphate–greenlight (80-120-180 W) have accumulated enough evidenceto support their use in patients receiving anticoagulantmedication or with a high cardiovascular risk. Bothprocedures provide a safe perioperative profile withreduced bleeding even without discontinuation of clopido-grel, aspirin, or warfarin therapy, while guaranteeing adisobstruction not inferior to standard TURP [25–27]. Thesefindings need to be highlighted, as the optimal managementof these patients is a daily quest for most urologists.4. Antiplatelet therapy: Stop or maintain?Antiplatelet therapy (especially aspirin) is to be main-tained whenever possible, especially when the ischemicrisk is intermediate or high, because of the extremelyenhanced risk of ST. In case of withdrawal of theantiplatelet therapy in the perioperative phase, cardiolo-gists recommend restarting the drugs with a loading doseas soon as possible after the intervention (ideally, 24–48 hlater).Table 3 – Perioperative antiplatelet therapy in patients with coronary stents who are undergoing urologic surgery. Reproduced withpermission from the Publisher, Il Pensiero Scientifico Editore [6].Hemorrhagic risk Thrombotic riskLow risk Intermediate risk High riskLow riskFlexible cystoscopyUreteral catheterizationUreteroscopyASA: continueP2Y12 receptor inhibitors:–Discontinue 5 days beforea–Resume within 24–72 hours,with a loading doseElective surgery: not contraindicatedASA: continueP2Y12 receptor inhibitors: continueElective surgery: postponeNon deferrable surgery:ASA: continueP2Y12 receptor inhibitors: continueIntermediate riskProstate biopsyOrchiectomyCircumcisionASA: discontinueP2Y12 receptor inhibitors:–Discontinue 5 days beforea–Resume within 24–72 hours,with a loading doseElective surgery: postponeNon deferrable surgery:ASA: continueP2Y12 receptor inhibitors:–Discontinue 5 days beforea–Resume within 24–72 hours,with a loading dosebElective surgery: postponeNon deferrable surgery:ASA: continueP2Y12receptor inhibitors:–Discontinue 5 days beforea–Resume within 24–72 hours,with a loading dosebBridge therapy with GPIIb/IIIa inhibitorsbHigh riskRadical and partial nephrectomyPercutaneous nephrostomyPercutaneous lithotripsyCystectomyRadical prostatectomyOpen simple prostatectomyTURPTURBTPenectomyPartial orchiectomyASA: discontinueP2Y12 receptor inhibitors:–Discontinue 5 days beforea–Resume within 24–72 hours,with a loading doseElective surgery: postponeNon deferrable surgery:ASA: continue (if possible)P2Y12 receptor inhibitors:–Discontinue 5 days beforea–Resume within 24–72 hours,with a loading dosebBridge therapy with GPIIb/IIIainhibitorsbif ASA is discontinuedElective surgery: postponeNon deferrable surgery:ASA: continueP2Y12 receptor inhibitors:–Discontinue 5 days beforea–Resume within 24–72 hours,with a loading dosebBridge therapy with GPIIb/IIIa inhibitorsbASA = aspirin; TURP = transurethral resection of the prostate; TURBT = transurethral resection of bladder tumor; GP = glycoprotein.a7 days prior for prasugrel.bCollegial discussion of risk, even with family/patient.E U R O P E A N U R O L O G Y 6 4 ( 2 0 1 3 ) 1 0 1 – 1 0 5 103
  4. 4. In selected cases, such as patients with high ischemic andhemorrhagic risk for whom the discontinuation of the oralantiplatelet therapy is necessary, the ‘‘bridge therapy’’ isadvocated [6]. This therapy consists of intravenous, pro-longed infusion of glycoprotein (GP) IIb/IIIa inhibitor(tirofiban or eptifibatide), a potent short active antiplateletdrug that acts as the oral antiplatelet therapies do, thuspreventing ST. Patients undergoing bridge therapy stoptaking DAPT or only the second antiplatelet agent 5 d beforesurgery (7 d in case of therapy with prasugrel). Theintravenous infusion of GP IIb/IIIa inhibitor starts 3 d beforethe intervention and is stopped 4 h before surgery (8 h in thecase of creatinine clearance 30 ml/min). Oral antiplatelettherapy should be resumed within 24–48 h after theintervention. Of note, GP IIb/IIIa inhibitors have potentantiplatelet effects and are associated with an increase risk ofbleeding during their infusion. Afterward, they might becontraindicated in patients with active, clinically relevantbleeding (ie, macrohematuria). This therapy should beprescribed by cardiologists and administered in a cardiologicward. Its administration as ‘‘bridge therapy’’ in the perioper-ative period is currently off-label [28].5. ConclusionsThe risk of ST is significantly increased after prematurediscontinuation of DAPT. The management of antiplatelettherapy in patients with coronary stents undergoing urologicprocedures isstillchallengingandrequiresthoroughurologicand cardiologic assessment. It appears evident that the rightdirection is toward the application in clinical practice of theconsensus documents that are available. The documentendorsed by cardiologists, urologists, and anesthesiologistsrecommends perioperative discontinuation of antiplateletdrugs if the known or assumed perioperative bleeding risksand their sequels are expected to be similar to, or more severethan, the observed cardiovascular thrombotic risks afterantiplatelet therapy withdrawal.In this respect, a dedicated chapter in the EAU guidelinescould be considered in the future to help in the managementof this delicate cohort of patients to minimize risks for boththe patients and the surgeons. A prospective case registrycould be a helpful tool to improve the management ofpatientsreceiving DAPT.Topotentiallyimprovethequalityofevidence derived from the consensus document, randomizedstudies could be considered merely from a methodologicalpoint of view. However, in our opinion, a comparisonbetween surgery performed with and without DAPT is notethical for patients with benign disease because of theextremely increased risk of ST. The only comparison can bebetween traditional compared with minimally invasivesurgery during DAPT in high-risk cardiovascular patients.Conflicts of interest: Richard Naspro has received honoraria as a speakerfrom Lumenis during the European Association of Urology Congress(2008, 2011, and 2012) and the American Urological AssociationCongress (2011). Roberta Rossini, Giuseppe Musumeci, Franco Gadda,and Luigi Filippo Da Pozzo have nothing to disclose.References[1] Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and strokestatistics—2011 update: a report from the American Heart Associ-ation. Circulation 2011;123:e18–209.[2] Moschovitis A, Cook S, Meier B. Percutaneous coronary interven-tions in Europe in 2006. Eurointervention 2010;6:189–94.[3] Savonitto S, Caracciolo M, Cattaneo M, De Servi S. Management ofpatients with recently implanted coronary stents on dual antiplate-let therapy who need to undergo major surgery. 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