Keywords
antiplatelet therapy - stent - surgery - bridging - cangrelor
Introduction
Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is the standard of care to prevent thrombotic complications in patients
undergoing percutaneous coronary intervention (PCI) with stent implantation.[1] Perioperative management of DAPT in patients undergoing nondeferrable surgery still
raises relevant safety concerns. On one hand, discontinuation of DAPT to reduce bleeding
complications is associated with an enhanced risk of thrombotic events, while maintenance
of DAPT to avoid perioperative thrombotic complications increases the risk of bleeding
and the need for transfusions, which are both known determinants of poor prognosis.[2] A strategy of temporary transition with an intravenous antiplatelet agent may represent
a desirable treatment option in patients deemed at high thrombotic risk undergoing
nondeferrable relevant bleeding risk surgery requiring a predictable interruption
of platelet inhibition.[3]
[4]
[5]
[6] The European Society of Cardiology (ESC) guidelines recommend a bridging strategy
with an intravenous antiplatelet agent if both oral antiplatelet agents have to be
discontinued perioperatively, especially within 1 month after PCI.[5] However, currently there are no antiplatelet agents approved by drug regulating
agencies for such bridging indication.
Cangrelor is an intravenous, rapidly acting, and reversible potent P2Y12 platelet receptor antagonist approved for the reduction of thrombotic cardiovascular
events in P2Y12 inhibitor naïve patients undergoing PCI.[7]
[8] Cangrelor also has a very short half-life (3–6 minutes) with an offset of its antiplatelet
effects within 60 minutes making it an attractive option for bridging therapy. Accordingly,
a dose-finding investigation was conducted to identify a regimen of cangrelor associated
with a “thienopyridine-like” effect for bridging purposes, hence not as potent as
that used for its PCI indication which is known to lead to near complete P2Y12 inhibition. Such identified bridging dosing regimen of cangrelor (0.75 μg/kg/min)
was tested in a prospective randomized double-blind study among thienopyridine-treated
patients undergoing coronary artery bypass grafting surgery (CABG) showing to achieve
adequate levels of platelet inhibition during the washout phase from oral P2Y12 inhibitors until the time of surgery without safety (bleeding or nonbleeding) concerns.[9] However, there is limited reported data on the use of cangrelor among patients undergoing
noncardiac surgery (NCS).[10]
[11]
[12]
[13]
[14]
[15]
[16] On this background, we report the results of a prospective, multicenter registry
describing real-world experience of a prespecified bridging protocol using cangrelor
conducted in patients referred to nondeferrable intermediate to high bleeding risk
surgery requiring withdrawal of DAPT.
Materials and Methods
Study Population
We prospectively collected data from nine Italian centers that had included patients
undergoing surgery using cangrelor as a bridging strategy in the perioperative phase
([Table 1]). All patients were still on DAPT due to recent coronary stent implantation and
required nondeferrable, intermediate to high bleeding risk surgery demanding discontinuation
of one or both antiplatelet agents. Patients with prohibitive hemorrhagic risk profile
or active bleeding were not considered suitable for bridging therapy with cangrelor.
Guidelines indicate that the perioperative management of antithrombotic therapy needs
to be defined in a multidisciplinary manner to better state the trade-off between
ischemia and bleeding.[17]
[18]
[19] To predict the individual risk of thrombotic complications against the anticipated
risk of surgical bleeding complications, a multidisciplinary consensus document among
cardiologists, surgeons, and anesthesiologists on practical recommendations for standardizing
management of antithrombotic therapy management in patients treated with coronary
stents (Surgery After Stenting 2) was used (https://itunes.apple.com/us/app/stent-surgery/id551350096?mt1⁄48).20,21
Briefly, the document defined the thrombotic risk (low, intermediate, or high) by
combining angiographic and clinical features, time from stent implantation, type of
implanted stent, and perioperative need for DAPT discontinuation. Moreover, surgical
bleeding risk was defined into low, intermediate, or high according to the inherent
hemorrhagic risk of over 250 cardiac and noncardiac surgical procedures based on the
amount of blood loss and the anticipated difficulty in achieving adequate local hemostasis.[20]
[21]
Table 1
Baseline characteristics of the patient population and the management of cangrelor
infusion during the perioperative phase
|
Patient
|
Age
|
No of stents
|
ACS
|
P2Yy12 inhibitor
|
Type of surgery
|
PCI-surgery time interval
(days)
|
Reason for bridge
|
P2Y12 discontinuation time (days)
|
Surgery on aspirin
|
Discontinuation cangrelor-surgery time (hours)
|
Cangrelor
reintroduction
|
Cangrelor reintroduction-surgery time (hours)
|
Bridge after surgery time (hours)
|
|
1
|
68
|
2
|
1
|
T
|
Lobectomy
|
76
|
A
|
5
|
1
|
9
|
1
|
24
|
12
|
|
2
|
79
|
2
|
1
|
T
|
Prostatectomy
|
80
|
A
|
5
|
1
|
7
|
1
|
18
|
12
|
|
3
|
63
|
2
|
0
|
C
|
CABG
|
7
|
B
|
5
|
1
|
10
|
0
|
–
|
|
4
|
74
|
5
|
1
|
C
|
Emicolectomy
|
21
|
B
|
6
|
1
|
6
|
1
|
6
|
108
|
|
5
|
60
|
2
|
0
|
C
|
Nasal surgery
|
257
|
C
|
6
|
0
|
8
|
1
|
12
|
24
|
|
6
|
76
|
3
|
1
|
T
|
Gastrectomy
|
51
|
A
|
5
|
1
|
6
|
1
|
6
|
72
|
|
7
|
83
|
4
|
1
|
T
|
MV replacement
|
6
|
B
|
2
|
1
|
8
|
1
|
8
|
41
|
|
8
|
54
|
1
|
T
|
Hip prostesys
|
658
|
D
|
6
|
1
|
9
|
1
|
7
|
24
|
|
9
|
52
|
1
|
P
|
CABG + valve repair
|
35
|
A
|
6
|
1
|
8
|
0
|
–
|
|
10
|
72
|
3
|
1
|
T
|
CABG + valve repair
|
13
|
B
|
5
|
1
|
8
|
0
|
–
|
|
11
|
81
|
1
|
T
|
CABG
|
51
|
A
|
6
|
1
|
8
|
1
|
8
|
61
|
|
12
|
73
|
6
|
1
|
T
|
AVR
|
210
|
D
|
5
|
1
|
8
|
0
|
–
|
|
13
|
71
|
1
|
T
|
Prostatectomy
|
40
|
A
|
5
|
1
|
6
|
1
|
8
|
66
|
|
14
|
79
|
3
|
1
|
C
|
Hip prostesys
|
48
|
A
|
5
|
1
|
8
|
1
|
9
|
12
|
|
15
|
69
|
3
|
1
|
T
|
Gastric endoscopy
|
39
|
A
|
5
|
1
|
3
|
0
|
–
|
|
16
|
69
|
1
|
T
|
CABG
|
2
|
A
|
2
|
1
|
3
|
0
|
–
|
|
17
|
66
|
1
|
T
|
CABG
|
2
|
A
|
2
|
1
|
3
|
0
|
–
|
|
18
|
59
|
1
|
T
|
CABG
|
2
|
A
|
2
|
1
|
3
|
0
|
–
|
|
19
|
87
|
1
|
C
|
ERCP
|
30
|
A
|
7
|
1
|
10
|
1
|
7
|
12
|
|
20
|
74
|
3
|
0
|
C
|
Nefrectomy
|
139
|
E
|
5
|
1
|
6
|
1
|
4
|
21
|
|
21
|
74
|
3
|
1
|
C
|
Gastrectomy
|
30
|
B
|
5
|
1
|
6
|
1
|
12
|
120
|
|
22
|
70
|
4
|
1
|
T
|
Limb amputation
|
57
|
A
|
4
|
1
|
3
|
0
|
–
|
|
23
|
81
|
3
|
0
|
C
|
Bladder endoscopic surgery
|
10
|
E
|
2
|
1
|
6
|
0
|
–
|
|
24
|
88
|
1
|
T
|
Renal endoscopic surgery
|
49
|
A
|
6
|
1
|
6
|
0
|
–
|
Abbreviations: A, ACS < 3 mo; ACS, acute coronary syndrome; AVR, aortic valve replacement;
B, PCI < 1 mo; C, clopidogrel; C, stent failure occurrence; CABG, coronary artery
by-pass graft; D, previous bioresorbable scaffold implantation; E, complex PCI; ERCP,
endoscopic retrograde cholangiopancreatography; MV, mitral valve; P, prasugrel; PCI,
percutaneous coronary intervention; ST, stent thrombosis; T, ticagrelor.
Bridging Protocol
A standardized bridging protocol using cangrelor infusion before and eventually after
surgery was reserved for patients deemed at high thrombotic risk undergoing nondeferrable
surgery at intermediate to high risk of bleeding, which requires a predictable interruption
of platelet inhibition at the time of surgery[21]
[22] ([Fig. 1]). According to International Guidelines, clopidogrel and ticagrelor were discontinued
for 5 days before surgery, while prasugrel was discontinued for 7 days.[5] In line with expert consensus recommendation, cangrelor at a bridging dose regimen
(0.75 μg/kg/min infusion without a bolus) was initiated 2 to 3 days following clopidogrel
and ticagrelor discontinuation and 3 to 4 days after prasugrel discontinuation.[9]
[22] As a matter of fact, previous data reported a broad variability in platelet reactivity
after discontinuation of thienopyridine therapy, meaning that a considerable number
of patients are not adequately protected when stopping thienopyridine therapy for
up to a week.[9] Cangrelor infusion was discontinued up 1 to 10 hours before surgery. Otherwise,
according to BRIDGE Trial design, a lower P2Y12 inhibitor discontinuation time and PCI-to-surgery time intervals were allowed in
patients referred to nonemergent CABG planned between 48 hours but no longer than
7 days following coronary stent implantation.[9] Since thrombotic complications occur most frequently soon after surgery, close clinical
and electrocardiographic monitoring in an intensive care unit was emphasized in the
postoperative period. Complete blood count assessments were performed daily to monitor
hemoglobin levels. Once successful hemostasis was achieved, oral P2Y12 inhibiting therapy was resumed within 24 to 48 hours. Clopidogrel was preferred over
prasugrel or ticagrelor in this setting of increased bleeding risk patients. In particular,
to avoid a potential drug–drug interaction with cangrelor, clopidogrel 600 mg loading
dose (LD) was administered immediately after discontinuation of cangrelor.[22]
[23] If oral P2Y12 inhibiting therapy was temporarily not administrable (i.e., in case of failed gastrointestinal
function recovery or prolonged maintenance of drainages), intravenous infusion of
cangrelor was resumed, after careful evaluation of the bleeding risk.
Fig. 1 Standardized bridging protocol using cangrelor infusion before and eventually after
nondeferrable surgery which required discontinuation of one or both antiplatelet agents
in patients with previous PCI.[21] PCI, percutaneous coronary intervention.
Study End Points
Clinical events during the perioperative phase (up to 48 hours from surgery) and at
30-days follow-up were prospectively collected. Cardiac death, periprocedural and
spontaneous myocardial infarction (MI), urgent target-lesion revascularization (TLR),
and definite stent thrombosis (ST) were assessed according to the Academic Research
Consortium Criteria and the American College of Cardiology/American Heart Association
(ACC/AHA) cardiovascular end points data standards.[24] Major ischemic adverse cardiac events (MACE) were defined as the composite of cardiac
death, MI, and TLR.
Bleeding events were defined using the Global Use of Strategies to Open Occluded Coronary
Arteries (GUSTO) and Bleeding Academic Research Consortium (BARC) definition.[25] Major bleedings were defined as GUSTO-defined severe/life-threatening bleedings
and the composite of BARC-defined type 3b, type 3c, and type 5 bleedings. For the
purpose of the study, CABG-related bleeding (BARC type 4) was included in the major
bleeding category in case of fatal bleeding, reoperation following closure of sternotomy
for the purpose of controlling bleeding, transfusion of ≥5 units or relevant chest
tube output. Mild bleedings were defined as GUSTO-defined moderate bleedings and BARC-defined
type 3a. The amount of blood loss from drainages, the hemoglobin drops, and the need
for blood transfusion were also assessed.
Statistical Analysis
All efficacy and safety end points were collected during the perioperative phase (evaluated
within 48 hours from surgery) and at 30 days follow-up. Quantitative variables were
summarized as mean ± standard deviation, while categorical ones as count and percentages
in each category.
Results
Patient Characteristics and Perioperative Management
Between December 2017 and April 2019, 24 patients were identified to be at high thrombotic
risk and required nondeferrable intermediate-high bleeding risk surgery. Baseline
characteristics of the patient population and data on cangrelor infusion during the
perioperative phase are shown in [Table 1]. Mean age was 72 ± 9 years and 79% were men. In the majority (83%) of patients,
the index PCI was performed due to an acute coronary syndrome (ACS) and 2.1 ± 1.5
stents per patient were implanted. The average time from PCI to surgery was 80 ± 136
days. Two-thirds of the patients were on ticagrelor 90 mg bid (n = 14, 58% of cases), one-third on clopidogrel (n = 9, 38% of the cases), and a minority on prasugrel (n = 1, 4% of cases). All patients were also on aspirin 100 mg/qd. According to a multidisciplinary
evaluation and SAS2 criteria,[20] high thrombotic risk categories included: PCI within 1 month (patients number 3–4-7–10–21),
ACS within 3 months (patients number 1–2-6–9-11–13 to 19–22–24), prior stent failure
due to definite subacute ST (patient number 5), previous complex PCI with multiple
stents implantation and left main involvement (patients number 20–23), and use of
a bioresorbable vascular scaffold (BRS) (patients number 8–12) ([Fig. 2]). Intermediate to high bleeding risk surgeries, deemed nondeferrable from a surgical
point-of-view especially due to recently encountered neoplastic pathology, included:
pulmonary lobectomy (patient number 1), prostatectomy (patients number 2–13), colectomy
(patient number 4), endoscopic surgery (patients number 15–23–24), gastrectomy (patients
number 6–21), nephrectomy (patient number 20), paranasal sinus surgery (patient number
5), hip replacement (patients number 8–14), endoscopy sphincterotomy (patient number
19), and limb amputation (patient number 22) ([Fig. 3]). Eight patients (numbers 3–7-9 to 12–16 to 18) were planned for nonemergent CABG
and valvular repair. The average time of P2Y12 inhibitor discontinuation was 4.5 ± 1.7 days prior to surgery. All patients but one
maintained aspirin through the perioperative phase. Cangrelor infusion was started
at the bridging dose (0.75 µg/kg/min) 2.9 ± 0.9 days before planned surgery and was
discontinued 6.6 ± 1.5 hours prior to surgical incision. After surgery, drainages
were left in all but six patients. In 55% of patients, cangrelor was resumed within
24 hours from surgery (mean time 8.6 ± 6.1 hours) for a mean of 39 ± 38 hours. Drainages
were removed after discontinuation of cangrelor to reduce bleeding complications.
Within 2 hours from postoperative cangrelor discontinuation, a 600 mg clopidogrel
LD was administered in all patients. In all other patients, clopidogrel was resumed
at 36 ± 22 hours after surgery once successful hemostasis was achieved.
Fig. 2 High thrombotic risk categories included in the studied patient population undergoing
to bridging with cangrelor for nondeferrable relevant bleeding risk surgery.
Fig. 3 Nondeferrable, intermediate-high bleeding risk surgeries included in the studied
patient population undergoing bridging with cangrelor for high ischemic risk.
Outcomes
Adverse events are reported in [Table 2]. Prior to surgery, one cardiac death occurred due to fatal ST elevation MI at 3 hours
after cangrelor discontinuation. The patient was still on aspirin 100 mg/qd, whereas
ticagrelor 90 mg/bid had been discontinued 5 days prior to nonemergent surgery. This
70-year-old female patient was afflicted by chronic limb-threatening ischemia (CLTI)
with lower extremities rest pain (Radford stage IV). She experienced a failed attempt
of revascularization complicated with an ACS treated with an effective complex PCI
(four stents implanted) on the left main and left descending artery. Due to progression
of CLTI disease to incapacitating pain and nonhealing wounds (Radford stage V) but
with no signs of infection she was scheduled for a nonemergent but nondeferrable lower
limb amputation 57 days after the PCI.[26] No other major ischemic adverse outcomes occurred up to 30 days follow-up. The average
hemoglobin drop was 1.8 ± 1.8 g/dL and nine patients required periprocedural blood
transfusions which was consistent with the type of surgery performed, known to need
a larger spending of blood products, as orthopaedic, general, and cardiac surgery.[27] One-third of patients experienced periprocedural BARC 3/GUSTO moderate bleeding
events due to drainages output, but a hemoglobin drop ≥3 g/dL was observed in only
three cases. No fatal, life-threatening, or intracranial bleedings occurred. No patient
required re-operation or experienced hemodynamic compromise due to bleeding.
Table 2
Clinical ischemic and bleeding events during the perioperative phase (up to 48 h from
surgery) and at 30-d follow-up
|
<48 h
|
>48 h to 30 d
|
|
Ischemic events
|
|
MACE
|
1 (4%)
|
0 (0%)
|
|
Cardiac death
|
1 (4%)
|
0 (0%)
|
|
MI
|
1 (4%)
|
0 (0%)
|
|
Urgent TLR
|
0 (0%)
|
|
ST
|
1 (4%)
|
0 (0%)
|
|
Bleeding events
|
|
GUSTO-defined severe/life-threatening
|
0 (%)
|
|
BARC-defined type 5
|
0 (%)
|
|
GUSTO-defined moderate
|
9 (38%)
|
4 (17%)
|
|
BARC-defined type 3a
|
9 (38%)
|
4 (17%)
|
|
BARC-defined type 3b-3c
|
3 (13%)
|
2 (8%)
|
|
Hemoglobin drop (g/dL)
|
1.8 ± 1.7
|
–
|
|
Need for blood transfusion
|
9 (38%)
|
4 (17%)
|
Abbreviations: BARC, Bleeding Academic Research Consortium; GUSTO, Global Use of Strategies
to Open Occluded Coronary Arteries; MACE, major adverse ischemic events; MI, myocardial
infarction; ST, stent thrombosis; TLR, target lesion revascularization.
Note: Variables are presented as count and percentages or mean values ± standard deviation.
Discussion
To the best of our knowledge, this is the largest multicenter experience on a bridging
protocol with cangrelor in stented patients at high ischemic risk undergoing nondeferrable
intermediate-high bleeding risk surgery. In the present case series, a reassuring
safety bleeding profile of cangrelor was demonstrated, with no identified fatal/life-threatening
bleedings or major blood loss requiring re-operation occurring in the perioperative
phase.
Compared with patients without CAD, those who have previous PCI are at higher risk
for MACE when undergoing surgery.[6]
[28]
[29] The risk of an ischemic event (e.g., ST, MI, and cardiac death) associated with
surgery is strictly dependent on time from PCI, patient's surgical and cardiac risk,
and the need for DAPT interruption.[2]
[3]
[4] Moreover, surgery itself is associated with proinflammatory and prothrombotic effects
regardless of previous stenting.[2]
[3]
[4] Several observational studies have reported that the surgical risk in PCI treated
patients stabilizes after 3 to 6 months; furthermore, selected patients without high-risk
clinical or lesion characteristics showed the same perioperative risk of patients
without CAD already beyond the first month after any type of stent implantation.[21]
[30] In fact, current ESC guidelines recommend P2Y12 inhibitor discontinuation 1 month after PCI, irrespective of the stent type, if aspirin
can be maintained throughout the perioperative period.[5] In patients with recent MI or other high ischemic risk features requiring DAPT,
elective surgery should be postponed for up to 6 months.[5] A bridging strategy with an intravenous antiplatelet agent is required if both oral
antiplatelet agents have to be discontinued perioperatively, especially within 1 month
after PCI.[5] However, there are no specific recommendations on perioperative antiplatelet therapy
provided in those patients with high ischemic risk features requiring nondeferrable
high hemorrhagic risk surgery between 1 and 6 months from PCI.[5]
[18]
[19] As a matter of fact, maintaining antiplatelet therapy to minimize ischemic complications
confers an increased risk of bleeding and need for transfusions, which are both determinants
of poor prognosis, including higher mortality risk.[4]
[25]
[31]
[32] In this setting, a strategy of temporary transition with a potent and effective
intravenous antiplatelet agent with a predictable and safe interruption of platelet
inhibition may represent an appropriate treatment option.[4]
[5]
[6]
Currently, the only intravenous antiplatelet agents available for clinical use and
potentially usable for bridging include cangrelor and glycoprotein IIb/IIIa inhibitors
(GPI). However, cangrelor is a more attractive agent for bridging. In fact, it has
a very short half-life with rapid resumption of platelet function (within 60 minutes),
it does not require renal dosing adjustments and has a specific dosing regimen for
bridging identified from a dose-finding investigation aimed at achieving “thienopyridine-like”
levels of platelet inhibition; moreover, cangrelor has been specifically tested in
a prospective, randomized, double-blind, placebo-controlled trial of patients undergoing
CABG.[9]
[33] Conversely, the short-acting GPIs (i.e., eptifibatide and tirofiban) have a longer
half-life and slower offset of action (i.e., 4–6 hours) compared with cangrelor, require
renal dosing adjustments, and are used at the ACS dosing regimen given that there
is no dedicated bridging dose.[34] Moreover, GPIs are known to be associated with an increased risk of thrombocytopenia,
particularly with prolonged infusion, a phenomenon associated with worse outcomes,
including mortality.[35] Overall, these pharmacologic characteristics enhance the risk of bleeding complications
associated with GPI use which has never been tested for bridging in a randomized study.[9]
[31]
[36] Accordingly, after a multidisciplinary assessment, we selected high thrombotic risk
patients with previous PCI undergoing nondeferrable surgery. On one hand, these patients
cannot safely interrupt oral antiplatelet therapy, on the other, they required a predictable
interruption of platelet inhibition at the time of surgery to minimize blood loss.[5]
[21] We tailored this strategy mainly for patients with a recent PCI or ACS with a clear
indication to urgent cardiac or NCS with intermediate to high bleeding risk. Subsequently,
we applied a prespecified bridging protocol with cangrelor infusion with a strict
patient monitoring during the perioperative phase.[22]
To date, there is no randomized trial of bridging with cangrelor in NCS, and limited
observational experience are available with heterogenous prescribing and monitoring
practices, which may contribute to suboptimal outcomes.[10]
[11]
[12]
[13]
[14]
[15]
[16] Likewise, data on bridging use of short-acting GPIs are heterogeneous as well with
regard to type of surgery, inclusion criteria, time windows between stent implantation
or ACS and surgery, and antiplatelet strategies during the perioperative period which
may partly explain the reported variability in success rates.[37] Despite the inclusion of a similar miscellaneous of surgical procedures, we believed
that the strength of our study is a standardize case by case approach evaluation to
weight the ischemic and bleeding risk and the use of a bridging protocol with a close
postoperative monitoring which could have had a positive impact on our study findings.[19]
[20] Moreover, the possibility of restoration of a switch-on/switch-off infusion of a
reversible antiplatelet agent (i.e., cangrelor) immediately after surgery when oral
P2Y12 inhibiting therapy was temporarily not administrable, potentially allowed a safer
monitoring in the postoperative phase when a careful balance between thrombotic and
bleeding risk is particularly relevant.[20] As a matter of fact, differently from previously reported worrisome increase in
bleeding rates during bridging therapy with cangrelor,[10]
[11]
[37] we showed no fatal/life-threatening bleedings or major blood loss requiring re-operation
and a restrained mean hemoglobin drop. Additionally, one-third of patients experienced
periprocedural BARC 3/GUSTO moderate bleeding events due to drainages output, mostly
with a hemoglobin drop <3 g/dL and below the hemorrhages/transfusion rates (up 65%)
reported in previous observational studies on GPIs.[37] We reported one cardiac death due to fatal ACS after cangrelor discontinuation 3 hours
before surgery, which occurred after almost 2 months from PCI, while on aspirin. On
one hand, these data underline the risk of DAPT discontinuation even beyond 1 month
especially in patients treated with complex PCI. In these patients, bridging with
cangrelor up to 1 hour prior to surgical incision should be considered, even though
the risk of thrombotic events might occur in perioperative phase, when cangrelor in
suspended. On the other, previous studies on bridging therapy with cangrelor and eptifibatide
had already highlighted such high ischemic risk profile reporting up to 3 to 6% rates
of death or MI.[37] To note, preoperative administration of tirofiban was associated with more favorable
efficacy with the cost of increased bleeding complications, although different study
designs and populations may partly or totally explain the variability in success rates
reported in those studies.[37] Undoubtedly, a strict selection of patient eligible for a bridging strategy needs
to be fulfilled, excluding cases with lower bleeding risk profile to avoid overestimation
of bleeding complications occurrence in predictable intermediate-to-low bleeding risk
surgeries.[20]
[38] Moreover, due to the well-known consistently elevated morbidity and mortality with
no bridge therapy,[2]
[3]
[4]
[28]
[29] more studies are warranted to support the efficacy and safety of our proposed standardized
bridging strategy by identifying the patient population that would receive the maximum
clinical benefit. Two multicenter observational registries will assess the impact
of DAPT discontinuation on ischemic and bleeding events in stented patients referred
to nondeferrable surgery. The MARS registry (ClinicalTrials.gov Identifier: NCT03981835)
will study the current perioperative DAPT management strategies in the United States,
including bridging, and outcome data after NCS. The MONET Italian study (ClinicalTrials.gov
Identifier: NCT03445273) will evaluate outcomes after any type of surgery according
to the actual application of the SAS2 indications and the clinical and angiographic
risk of previous PCI. Furthermore, the ongoing randomized, double-blind, placebo-controlled
MONET BRIDGE study (ClinicalTrials.gov Identifier: NCT03862651) aims to assess the
efficacy and safety profile of a bridging strategy with cangrelor in patients who
discontinue DAPT before surgery within 12 months from coronary stent implantation.
Limitations
Limitations of this study include the restricted number of patients and the heterogeneity
between the enrolled patients and type of surgeries. However, prescribing and monitoring
practices were standardized leading to more homogenous and consistent patient management
which could have contributed to our overall favorable observations. Nevertheless,
albeit within a certain time window, exact timing of initiation and discontinuation
of cangrelor infusion was left at the discretion of the treating physician. Furthermore,
any perioperative platelet function test and transfusion was suggested. Despite the
lack of evidence to guide the prophylactic use of platelet transfusions before major
surgery, they should be considered according to the threshold of platelet count and
in case of severe thrombocytopenia or critical bleeding.[39]
[40] Moreover, due to a large individual variation in the magnitude and duration of the
antiplatelet effect, platelet function testing may be considered to help guide timing
of starting cangrelor infusion after a P2Y12 discontinuation, especially in case of planned cardiac surgery.[5]
[22] Finally, data interpretation warrants caution due to the lack of a control group.
Despite the abovementioned limitations, we think that our paper may add useful information
to the current literature, reporting for the first time a strategy with a standardize
case by case approach evaluation to weight the ischemic and bleeding risk and the
use of a bridging protocol with a close postoperative monitoring. Moreover, this data
might help to identify the patient population that would receive maximum benefit from
bridging antiplatelet therapy, determine optimal administration strategy, monitoring
therapy, and management of adverse events to delineate large prospective studies which
are required in such challenging setting.[41]
Conclusion
Perioperative antiplatelet bridging therapy with cangrelor is a feasible approach
for stented patients at high thrombotic risk referred to nondeferrable intermediate-high
bleeding risk surgery requiring DAPT discontinuation. Larger studies are warranted
to support the safety of this strategy.
