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Editorial

Antiplatelet Therapy in Patients With Coronary Stent Undergoing

Urologic Surgery: Is It Still No Man’s Land?

Richard Naspro a,*, Roberta Rossini b, Giuseppe Musumeci b, Franco Gadda c,Luigi Filippo Da Pozzo a

a Department of Urology, AO Papa Giovanni XXIII, Bergamo, Italy; b Department of Cardiology, AO Papa Giovanni XXIII, Bergamo, Italy; c Urology Unit,

Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy

Percutaneous coronary intervention (PCI) in patients with

coronary artery disease is on the increase worldwide. Every

year, >1 million PCIs are performed in United States and

Europe [1,2]. In>85% of cases, a coronary stent is implanted

[3], and prolonged antiplatelet therapy is mandatory after

stent implantation. International guidelines advocate dual

antiplatelet therapy (DAPT) for�4 wk after bare metal stent

(BMS) implantation and for 6–12 wk after drug-eluting

stent (DES) implantation [4]. Premature withdrawal of

antiplatelet therapy is associated with a significantly higher

risk of cardiac ischemic events because of stent thrombosis

(ST). This rare, but life-threatening complication occurs

most of the time as acute myocardial infarction, with a

mortality of 10–40%. Occurrence of ST can be up to 90 times

higher after premature discontinuation of DAPT [5]. A

previous study assessing the prevalence and causes of

premature discontinuation of DAPT after DES implantation

showed that premature discontinuation was not a rare

event (>1 of 10 patients). The most common causes of

discontinuation were surgery and bleeding events and were

often associated with a poor prognosis [6].

The management of antiplatelet drugs in the periopera-

tive period is relevant from both an epidemiological and a

clinical point of view. The incidence of noncardiac surgery

after BMS or DES implantation is 5% at 1 yr and 23% at 5 yr

[3]. The number of patients on antiplatelet therapy who will

require urologic procedures is progressively increasing as

the ages of the peak incidence of PCI and of various forms of

urologic cancer coincide. Urologic conditions are very

diverse, spanning from benign but troublesome conditions

(eg, severe bladder outlet obstruction [BOO], complicated

urinary stones) to very complex oncologic diseases that

require major and mandatory surgery. Therefore, it is

* Corresponding author. Department of Urology, AO Papa Giovanni XXIII, BE-mail address: [email protected] (R. Naspro).

0302-2838/$ – see back matter # 2013 European Association of Urology. Phttp://dx.doi.org/10.1016/j.eururo.2013.01.026

challenging to weigh the exact impact of hemorrhage or

thrombosis/ischemia risk according to surgical priority. On

the one hand, the withdrawal (and sometimes also the

maintenance) of the antiplatelet therapy may have dramat-

ic consequences, as bleeding risk is increased in patients

undergoing surgery on antiplatelet therapy [7,8]. Bleeding

risk is 3.4 times higher during DAPT compared with aspirin

alone [9]. On the other hand, surgery can lead to

inflammatory, hypercoagulable, and hypoxic states that

are associated with plaque instability and perioperative

arterial thrombosis [3].

1. Clinical implications

In recent years, international cardiologic, anesthesiologic,

and hematologic societies have proposed guidelines and

published joint position papers on the management of DAPT

in patients undergoing noncardiac surgery [4,10–16].

However, these recommendations provide little support

with regard to managing antiplatelet therapy in the

perioperative phase in urgent operations and/or patients

at high hemorrhagic risk. In particular, guidelines shared

with urologists and cardiologists are lacking [17].

Elective surgical procedures ought to be postponed until

after the completion of DAPT. Unfortunately, many proce-

dures require more urgent management according to

severity, and often the distinction between deferrable

and undeferrable surgery is not clear and can be misleading

for both the surgeon and the patient.

The management of the risk ratio between bleeding and

thrombosis requires an exact knowledge of risk stratifica-

tion defined for each condition, paired with offering the

minimal surgical impact. In this respect, it could be

ergamo, Italy. Tel. +39 0352673471; Fax: +39 035266419.

ublished by Elsevier B.V. All rights reserved.

http://dx.doi.org/10.1016/j.eururo.2013.01.026

mailto:[email protected]

http://dx.doi.org/10.1016/j.eururo.2013.01.026

Table 1 – Stratification of urologic procedures according tobleeding risk. Reproduced with permission from the Publisher,Il Pensiero Scientifico Editore [6].

Low risk

Flexible cystoscopy

Ureteral catheterization

Ureteroscopy

Intermediate risk

Prostate biopsy

Orchiectomy

Circumcision

High risk

Radical and partial nephrectomy

Percutaneous nephrostomy

Percutaneous lithotripsy

Cystectomy

Radical prostatectomy

Open simple prostatectomy

TURP

TURBT

Penectomy

Partial orchiectomy

TURBT = transurethral resection of bladder tumor; TURP = transurethral

resection of the prostate.


recommended that high-risk patients be referred to centers

at which the most minimally invasive therapies—such as

pure laparoscopic procedures, robot-assisted procedures,

and new-generation lasers—are available. These proce-

dures, coupled with a high-volume cardiologic team, can

allow the reduction of blood loss in case of maintenance of

the antiplatelet therapy and permit prompt resumption of

the antiplatelet drugs if they have been discontinued.

2. Evidence-based state of the art

A consensus document on the optimal antiplatelet regimen

in patients with coronary stents undergoing urologic

interventions has been recently proposed by a multidisci-

plinary panel composed of urologists and cardiologists, who

contributed equally to its creation [6]. The document was

endorsed by the Italian Society of Urology, Interventional

Cardiology, and Cardiology. An ST risk was graded consider-

ing procedural features such as stent type, time from PCI to

Table 2 – Definition of thrombotic risk in patients with coronary stenScientifico Editore [6].

Low risk Intermediate r

� >6 months after PCI with BMS

� >12 months after PCI with DES.

� >1 month, < 6 months after PCI

� >6, <12 months after PCI with D

� >12 months after complex PCI w

multiple stents, overlapping, small

left main, last remaining vessel).

PCI in ACS, previous stent thrombosis, LVEF <35%, chronic renal failure, diabetes

Patients submitted to CABG or with ACS medically treated are considered at high r

low risk after 6 months.

Patients treated with POBA are considered at high risk within the first 2 weeks,

PCI = percutaneous coronary intervention; BMS = bare metal stent; DES = drug-el

bypass grafting; ACS = acute coronary syndrome; POBA = plain old balloon angio

urologic surgery, and clinical aspects such as concomitant

diabetes, renal impairment, low cardiac ejection fraction, and

age. Most urologic interventions were classified according to

the bleeding risk (Table 1).

The document [6] follows the pivotal paper by Gupta and

coworkers [18] but is the first consensus document to

provide practical recommendations on the management of

antiplatelet therapy in patients with coronary stents who

are undergoing diverse urologic interventions. To our

knowledge, it is also the first consensus document shared

by urologic and cardiologic societies. Briefly, ST risk is

stratified as low, intermediate, and high (Table 2), and the

most appropriate antiplatelet therapy and management is

defined for each intervention on the basis of the ischemic

and hemorrhagic risk (Table 3).

This stratification allows detailed definition of the

optimal antiplatelet regimen that should be maintained

in the perioperative period, thus avoiding arbitrary

management. Of note, it is important to define the ideal

timing of the urologic intervention, as elective procedures

should be delayed until a low cardiac ischemic risk is

reached.

The main difference between the classification of Gupta

et al. and the Italian hemorrhagic classification is the

definition of the hemorrhagic risk for transurethral resec-

tion of the prostate (TURP) and transurethral resection of

bladder tumor. The former classification considers them

intermediate bleeding risk procedures, and the latter

considers them high risk, highlighting the particularity of

endoscopic procedures.

3. Transurethral resection of the prostate: the

challenging issue

Currently, any surgical treatment of BOO should be deferred

whenever possible following PCI. Nevertheless, some

patients require surgery because of the presence of one

or 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 the

treatment of BOO in spite of the growing number of

ts. Reproduced with permission from the Publisher, Il Pensiero

isk High risk

with BMS

ES

ith DES (long stents,

vessels, biforcations,

� <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, last

remaining vessel).

increase the thrombotic risk.

isk in the first month, at intermediate risk between 1st and 6th month, and at

at intermediate risk between 2 and 4 weeks, and at low risk after 4 weeks.

uting stent; LVEF = left ventricular ejection fraction; CABG = coronary artery

plasty.

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 risk

Low risk Intermediate risk High risk

Low risk

Flexible cystoscopy

Ureteral catheterization

Ureteroscopy

ASA: continue

P2Y12 receptor inhibitors:

–Discontinue 5 days beforea

–Resume within 24–72 hours,

with a loading dose

Elective surgery: not contraindicated

ASA: continue

P2Y12 receptor inhibitors: continue

Elective surgery: postpone

Non deferrable surgery:

ASA: continue

P2Y12 receptor inhibitors: continue

Intermediate risk

Prostate biopsy

Orchiectomy

Circumcision

ASA: discontinue




with a loading dose



ASA: continue




with a loading doseb



ASA: continue





Bridge therapy with GPIIb/IIIa inhibitorsb

High risk

Radical and partial nephrectomy

Percutaneous nephrostomy

Percutaneous lithotripsy

Cystectomy

Radical prostatectomy

Open simple prostatectomy

TURP

TURBT

Penectomy

Partial orchiectomy

ASA: discontinue




with a loading dose



ASA: continue (if possible)





Bridge therapy with GPIIb/IIIa

inhibitorsb if ASA is discontinued



ASA: continue





Bridge therapy with GPIIb/IIIa inhibitorsb

ASA = aspirin; TURP = transurethral resection of the prostate; TURBT = transurethral resection of bladder tumor; GP = glycoprotein.a 7 days prior for prasugrel.b Collegial 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

alternative minimally invasive surgical therapies [19,20].

Although morbidity following TURP is relatively low (<1%),

in recent TURP series, clot retention with major bleeding

has been reported in �5% of cases, with a reintervention

rate of 1.3–5% and a requirement for blood derivatives in

�7% of cases. When stratifying these findings according

to patients with coagulation disorders and cardiologic

comorbidities, complications are expected to be much

higher, especially when antiplatelet therapy is continued

[18,21]. Currently, no clear evidence has emerged from the

literature regarding the safety of TURP in patients on

antiplatelet therapy, and the available data are limited

and not consistent. Therefore, TURP must be considered

a potentially dangerous procedure in high-risk cardiologic

patients with an increased risk of troublesome postopera-

tive bleeding when aspirin is not discontinued periopera-

tively [22,23]. In these patients, TURP may cause fatal

bleeding, in contrast with most major surgical procedures

with a safer profile [7].

To reduce perioperative morbidity, Ehrlich and cow-

orkers advocated the safety of perioperative aspirin

discontinuation followed by early initiation after TURP

[24]. It is interesting to note that the authors did not register

an increase in either postoperative bleeding complications

or cardiac events. However, the population included in the

study probably did not represent a high-risk group of

patients. The risk of clinically significant bleeding can also

be reduced by using alternative sources of energy such as

lasers, as recommended by the updated European Associa-

tion of Urology (EAU) guidelines [20]. In particular,

holmium laser enucleation of the prostate and laser

vaporization using potassium-titanyl-phosphate–green

light (80-120-180 W) have accumulated enough evidence

to support their use in patients receiving anticoagulant

medication or with a high cardiovascular risk. Both

procedures provide a safe perioperative profile with

reduced bleeding even without discontinuation of clopido-

grel, aspirin, or warfarin therapy, while guaranteeing a

disobstruction not inferior to standard TURP [25–27]. These

findings need to be highlighted, as the optimal management

of 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 ischemic

risk is intermediate or high, because of the extremely

enhanced risk of ST. In case of withdrawal of the

antiplatelet therapy in the perioperative phase, cardiolo-

gists recommend restarting the drugs with a loading dose

as soon as possible after the intervention (ideally, 24–48 h

later).


In selected cases, such as patients with high ischemic and

hemorrhagic risk for whom the discontinuation of the oral

antiplatelet therapy is necessary, the ‘‘bridge therapy’’ is

advocated [6]. This therapy consists of intravenous, pro-

longed infusion of glycoprotein (GP) IIb/IIIa inhibitor

(tirofiban or eptifibatide), a potent short active antiplatelet

drug that acts as the oral antiplatelet therapies do, thus

preventing ST. Patients undergoing bridge therapy stop

taking DAPT or only the second antiplatelet agent 5 d before

surgery (7 d in case of therapy with prasugrel). The

intravenous infusion of GP IIb/IIIa inhibitor starts 3 d before

the intervention and is stopped 4 h before surgery (8 h in the

case of creatinine clearance <30 ml/min). Oral antiplatelet

therapy should be resumed within 24–48 h after the

intervention. Of note, GP IIb/IIIa inhibitors have potent

antiplatelet effects and are associated with an increase risk of

bleeding during their infusion. Afterward, they might be

contraindicated in patients with active, clinically relevant

bleeding (ie, macrohematuria). This therapy should be

prescribed by cardiologists and administered in a cardiologic

ward. Its administration as ‘‘bridge therapy’’ in the perioper-

ative period is currently off-label [28].

5. Conclusions

The risk of ST is significantly increased after premature

discontinuation of DAPT. The management of antiplatelet

therapy in patients with coronary stents undergoing urologic

procedures is still challenging and requires thorough urologic

and cardiologic assessment. It appears evident that the right

direction is toward the application in clinical practice of the

consensus documents that are available. The document

endorsed by cardiologists, urologists, and anesthesiologists

recommends perioperative discontinuation of antiplatelet

drugs if the known or assumed perioperative bleeding risks

and their sequels are expected to be similar to, or more severe

than, the observed cardiovascular thrombotic risks after

antiplatelet therapy withdrawal.

In this respect, a dedicated chapter in the EAU guidelines

could be considered in the future to help in the management

of this delicate cohort of patients to minimize risks for both

the patients and the surgeons. A prospective case registry

could be a helpful tool to improve the management of

patients receiving DAPT. To potentially improve the quality of

evidence derived from the consensus document, randomized

studies could be considered merely from a methodological

point of view. However, in our opinion, a comparison

between surgery performed with and without DAPT is not

ethical for patients with benign disease because of the

extremely increased risk of ST. The only comparison can be

between traditional compared with minimally invasive

surgery during DAPT in high-risk cardiovascular patients.

Conflicts of interest: Richard Naspro has received honoraria as a speaker

from Lumenis during the European Association of Urology Congress

(2008, 2011, and 2012) and the American Urological Association

Congress (2011). Roberta Rossini, Giuseppe Musumeci, Franco Gadda,

and Luigi Filippo Da Pozzo have nothing to disclose.

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