1. 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
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
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* 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. 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
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
Table 1 – Stratification of urologic procedures according to
bleeding 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.
Table 2 – Definition of thrombotic risk in patients with coronary stents. Reproduced with permission from the Publisher, Il Pensiero
Scientifico 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, last
remaining 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 at
low 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 artery
bypass grafting; ACS = acute coronary syndrome; POBA = plain old balloon angioplasty.
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3. 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).
Table 3 – Perioperative antiplatelet therapy in patients with coronary stents who are undergoing urologic surgery. Reproduced with
permission 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
P2Y12 receptor inhibitors:
–Discontinue 5 days beforea
–Resume within 24–72 hours,
with a loading dose
Elective surgery: postpone
Non deferrable surgery:
ASA: continue
P2Y12 receptor inhibitors:
–Discontinue 5 days beforea
–Resume within 24–72 hours,
with a loading doseb
Elective surgery: postpone
Non deferrable surgery:
ASA: continue
P2Y12
receptor inhibitors:
–Discontinue 5 days beforea
–Resume within 24–72 hours,
with a loading doseb
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
P2Y12 receptor inhibitors:
–Discontinue 5 days beforea
–Resume within 24–72 hours,
with a loading dose
Elective surgery: postpone
Non deferrable surgery:
ASA: continue (if possible)
P2Y12 receptor inhibitors:
–Discontinue 5 days beforea
–Resume within 24–72 hours,
with a loading doseb
Bridge therapy with GPIIb/IIIa
inhibitorsb
if ASA is discontinued
Elective surgery: postpone
Non deferrable surgery:
ASA: continue
P2Y12 receptor inhibitors:
–Discontinue 5 days beforea
–Resume within 24–72 hours,
with a loading doseb
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.
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4. 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 isstillchallengingandrequiresthoroughurologic
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
patientsreceiving DAPT.Topotentiallyimprovethequalityof
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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