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Cardiovascular and bleeding risk of non-cardiac surgery in patients on antiplatelet therapy
G Model JJCC-866; No. of Pages 5
ARTICLE IN PRESS Journal of Cardiology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of Cardiology journal homepage: www.elsevier.com/locate/jjcc
Original article
Cardiovascular and bleeding risk of non-cardiac surgery in patients on antiplatelet therapy Kei Yamamoto (MD), Hiroshi Wada (MD), Kenichi Sakakura (MD), Nahoko Ikeda (MD), Yoko Yamada (MD), Takuji Katayama (MD), Yoshitaka Sugawara (MD), Takeshi Mitsuhashi (MD), Junya Ako (MD), Shin-ichi Momomura (MD, FJCC) ∗ Division of Cardiovascular Medicine, Saitama Medical Center, Jichi Medical University, Saitama, Japan
a r t i c l e
i n f o
Article history: Received 30 September 2013 Received in revised form 17 January 2014 Accepted 4 February 2014 Available online xxx Keywords: Non cardiac surgery Bleeding Stent thrombosis Antiplatelet therapy Heparin-bridge
a b s t r a c t Background: The perioperative risk of non-cardiac surgery (NCS) in the patients on antiplatelet therapy after percutaneous coronary intervention (PCI) remains unclear. Methods: This study was a retrospective and single center study. Between January 2008 and December 2011, 198 patients who had already received PCI underwent NCS in our hospital. Among them, 63 patients underwent surgery on dual antiplatelet therapy (DAPT group) and 88 patients on single antiplatelet therapy (SAPT group). We compared bleeding events and cardiovascular events during perioperative period between the two groups. Results: There was no stent thrombosis in either group. The bleeding events in the DAPT group were significantly higher than that in the SAPT group (9.5% vs 2.3%, p = 0.049). There was no difference in events between with or without heparin-bridge in the SAPT group. Conclusions: The frequency of bleeding events was higher in the DAPT group. Both bleeding and cardiovascular events with aspirin alone were low in our study. It may be safe to undergo NCS with SAPT after PCI. © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Introduction Antiplatelet therapy (APT) plays a central role in the treatment of patients receiving stent deployment [1]. The most important stent thrombosis (ST) predictor is premature discontinuation of dual antiplatelet therapy (DAPT) [2,3]. Apart from non-compliance, the most common reason for early discontinuation of either DAPT or single antiplatelet therapy (SAPT) is the need for non-cardiac surgery (NCS), accounting for one-third of cases [3]. According to current American College of Cardiology/American Heart Association (ACC/AHA) guidelines, approximately two-thirds of all NCS procedures in the first year after index percutaneous coronary intervention (PCI) are classified as moderate to high risk for major adverse cardiac events (MACE) [4–6]. MACE, particularly ST, is a concern after discontinuation of APT; however, its continuation is associated with bleeding risk. The perioperative management
∗ Corresponding author at: Division of Cardiovascular Medicine, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Omiya-ku, Saitama-city, Saitama 330-8503, Japan. Tel.: +81 48 647 2111; fax: +81 48 648 5188. E-mail addresses: [email protected], [email protected] (S.-i. Momomura).
of APT remains controversial because there is limited amount of evidence to suggest what strategies are effective in preventing bleeding or cardiovascular events. In this study, we investigated NCS outcomes in patients who had received either bare-metal stents (BMS) or drug-eluting stents (DES), comparing between DAPT and SAPT. Methods Study patients The present study included 198 patients who had undergone NCS after successful PCI between January 2008 and December 2011, and the data were retrospectively analyzed. The local ethics committee approved this study. All patients had already undergone PCI with either BMS or DES. The treating physician determined the type of stent used at the PCI procedure. Patients with a BMS were prescribed aspirin (100 mg/day) and thyenopyridine (ticropidin 200 mg/day or clopidogrel 75 mg/day) for 30 days. Patients with a DES usually were prescribed aspirin and thienopyridine clopidogrel for 6 months or longer, at the discretion of the treating physician. NCS were performed after stent deployment during
http://dx.doi.org/10.1016/j.jjcc.2014.02.027 0914-5087/© 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Yamamoto K, et al. Cardiovascular and bleeding risk of non-cardiac surgery in patients on antiplatelet therapy. J Cardiol (2014), http://dx.doi.org/10.1016/j.jjcc.2014.02.027
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328 ± 290 days. If the patients took DAPT before surgery in SAPT group, only thyenopyridine was discontinued 5–14 days before surgery.
analyzed using Student’s t-test. Statistical analyses were performed using StatView (SAS Institute Inc., Cary, NC, USA).
Inclusion criteria
Results
The inclusion criteria were (1) patients who underwent NCS after stent deployment and (2) patients who received DES or BMS. NCS was defined as surgical procedure in the operation room and required local or general anesthesia (abdominal, aortic, urologic, etc.). The type of DES included both first-generation (sirolimuseluting stent and paclitaxel-eluting stent) and second-generation (zotarolimus-eluting stent, everolimus-eluting stent, and biolimuseluting stent).
A total of 1794 patients underwent stent deployment in our institution between January 1st, 2008 and December 31st, 2011. Among them, 198 patients also underwent NCS; the DAPT group included 63 patients and the SAPT group included 88 patients (Fig. 1). Mean age was 69.4 ± 8.3 years in the DAPT group and 70.3 ± 8.7 years in the SAPT group, and 70.4 ± 7.8 years overall (p = ns) (Table 1). The number of DES implantations was 53 (84.1%) in the DAPT group and 54 (61.3%) in the SAPT group. Patients taking anti-coagulants were 15.9% in the DAPT group and 11.4% in the SAPT group (Table 2). Aortic surgery and abdominal surgery were performed more frequently in the SAPT group, while peripheral vascular surgery and urologic surgery were more frequently seen in the DAPT group (Table 3). The frequency of bleeding was significantly higher in the DAPT group (9.5%) compared with the SAPT group (2.3%, p = 0.049). Two patients who suffered bleeding during operation in the SAPT group did not use heparin-bridge in the perioperative period. Of these two patients, blood transfusion was required in one patient, and re-operation was required in the other (Tables 4 and 5). Seven out of eight patients who had bleeding events were patients who received DES. No patient died from bleeding (Table 6). No patient experienced ST in either group during the observational period. NCS after stent deployment was performed during 328 ± 290 days.
Exclusion criteria The exclusion criteria were the patients who underwent body surface surgery (ophthalmology and dermatology), and patients who did not require hospitalization. We excluded the patients who received only balloon angioplasty or aspiration. Event definitions The perioperative complications were defined as the occurrence of MACE and bleeding in hospital. Any perioperative myocardial infarction (MI) and ST was considered as MACE. ST was defined according to the Academic Research Consortium definition [7]. Bleeding complications were categorized as major and minor bleeding as previously reported [8]. In brief, major bleeding was defined as bleeding requiring transfusion, intracranial bleeding, clinical overt signs of hemorrhage associated with a drop in hemoglobin of 5 g/dl, and fatal bleeding that resulted directly in death in 7 days. Minor bleeding was defined as clinically overt bleeding resulting in hemoglobin drop of 3–5 g/dl [8]. Statistics Descriptive results were expressed as frequency and percentage for categorical variables, and they were compared using the chi square test (or Fisher exact test for small samples). For continuous variables, statistics were expressed as mean ± SD and were
Discussion The present study showed that the risk of bleeding during the perioperative period was significantly higher in the DAPT group. There was no difference in risk between with or without heparinbridge in the SAPT group. Current guidelines of the European Society of Cardiology or ACC/AHA provide information on how to manage cardiovascular risk during the non-cardiac perioperative period [6,9]. Given the lack of prospective randomized clinical trials, recommendations are mostly dependent on experts’ opinions and retrospective studies.
Fig. 1. The flowchart of this study. APT, antiplatelet therapy; DAPT, dual antiplatelet therapy; SAPT, single antiplatelet therapy.
Please cite this article in press as: Yamamoto K, et al. Cardiovascular and bleeding risk of non-cardiac surgery in patients on antiplatelet therapy. J Cardiol (2014), http://dx.doi.org/10.1016/j.jjcc.2014.02.027
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Table 1 The baseline characteristics 1.
Age (years) Male BMI (kg/m2 ) Medical history Ischemic heart disease Congestive heart failure Renal impairment (Cre > 2.0 mg/dl) Diabetes mellitus Hypertension Dysplipidemia History of MI History of stroke Medical therapy ACE-inhibitor/ARB Beta blocker Statin Diuretics Calcium antagonist Insulin
Overall (n = 151)
DAPT (n = 63)
SAPT (n = 88)
p
70.4 ± 8.8 124 (82.1%) 23.9 ± 3.4
69.4 ± 8.3 43 (68.3%) 23.9 ± 3.4
70.3 ± 8.7 81 (92.0%) 23.9 ± 3.3
ns 0.002 ns
151 (100%) 36 (23.8%) 33 (21.8%)
63 (100%) 24 (38.1%) 21 (33.3%)
88 (100%) 12 (13.6%) 12 (13.6%)
ns 0.0005 0.004
63 (41.7%) 125 (82.8%) 124 (82.1%) 75 (49.6%) 16 (10.6%)
29 (46.0%) 57 (90.4%) 53 (84.1%) 47 (74.6%) 7 (11.1%)
34 (38.6%) 68 (77.3%) 71 (80.7%) 32 (36.4%) 9 (10.2%)
ns 0.03 ns <0.0001 ns
104 (68.9%) 103 (68.2%) 138 (91.4%) 45 (29.8%) 62 (41.1%) 29 (19.2%)
52 (82.5%) 48 (76.2%) 61 (96.8%) 28 (44.4%) 29 (46.0%) 19 (30.2%)
52 (59.1%) 55 (62.5%) 77 (87.5%) 17 (19.3%) 33 (37.5%) 10 (11.4%)
0.002 ns 0.04 0.0009 ns 0.004
Table 2 The baseline characteristics 2. Overall (n = 151) Medical therapy 2 Aspirin Thienopyridine Anti-coagulant Coronary stent BMS DES SES PES ZES EES BES Duration from PCI (day)
DAPT (n = 63)
SAPT (n = 88)
151 (100%) 114 (75.5%) 20 (13.2%)
63 (100%) 63 (100%) 10 (15.9%)
88 (100%) 51 (58.0%) 10 (11.4%)
44 (26.4%) 107 (70.9%) 39 31 3 27 1 328 ± 290
10 (15.9%) 53 (84.1%) 20 17 0 15 1 356 ± 406
34 (38.6%) 54 (61.3%) 19 14 3 20 0 357 ± 347
Overall (n = 151)
DAPT (n = 63)
SAPT (n = 88)
45 (29.8%) 20 (13.2%) 25 (16.6%) 21 (13.9%) 15 (9.9%) 7 (4.6%) 4 (2.6%) 2 (1.3%) 5 (3.3%) 6 (4.0%)
2 (3.2%) 6 (9.5%) 15 (23.8%) 16 (25.4%) 11 (17.5%) 5 (7.9%) 4 (6.3%) 1 (1.6%) 0 4 (3.2%)
43 (48.8%) 14 (15.9%) 10 (11.4%) 5 (5.8%) 4 (4.5%) 2 (2.3%) 0 1 (1.1%) 5 (5.7%) 2 (2.3%)
p ns 0.001 ns 0.002
ns
Table 3 The baseline characteristics 3 (type of surgery).
Type of surgery Aorta Abdominal Vessel peripheral Urologic Pacemaker/ICD/CRT-D Orthopedics ENT (ear/nose/throat) Neurosurgery Oral and maxillofacial Other
p <0.0001
Bleeding events Van Kuijk et al. [10] showed that the mean bleeding risk from studies in which adequate information was available was 4.1% for SAPT versus 14.7% for DAPT. In a meta-analysis by Burger et al. [11], including a total of 49,590 patients undergoing NCS, it was
concluded that aspirin continuation led to increased bleeding events by a factor of 1.5. However, this increase did not lead to a higher level of the severity of bleeding complications or fatal bleeding except in intracranial surgery and possibly transurethral prostatectomy. Tokushige et al. showed that Japanese patients who underwent NCS in the DAPT group had bleeding events more
Table 4 The clinical outcome. The frequency of bleeding and stent thrombosis. Overall (n = 151)
DAPT (n = 63)
SAPT (n = 88)
p
Major bleeding Minor bleeding CVD event
5 (3.3%) 3 (2.0%) 0
4 (6.3%) 2 (3.2%) 0
1 (1.1%) 1 (1.1%) 0
ns ns ns
Total
8 (5.3%)
6 (9.5%)
2 (2.3%)
0.049
Please cite this article in press as: Yamamoto K, et al. Cardiovascular and bleeding risk of non-cardiac surgery in patients on antiplatelet therapy. J Cardiol (2014), http://dx.doi.org/10.1016/j.jjcc.2014.02.027
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Table 5 The clinical outcome. The frequency of bleeding and stent thrombosis. Overall (n = 151)
DAPT (n = 63)
SAPT (n = 88) Heparin(+) (n = 20)
Heparin(−) (n = 68)
Major bleeding Minor bleeding CVD event
5 (3.3%) 3 (2.0%) 0
4 (6.3%) 2 (3.2%) 0
0 0 0
1 (1.4%) 1 (1.4%) 0
Total
8 (5.3%)
6 (9.5%)
0
2 (2.8%)
Table 6 The characteristics of cases of bleeding events. Patient
Age
Gender
Type of surgery
Stent
Antiplatelet therapy
Anti coagulant
Emergency
Time from PCI
Bleeding
Complication
A B C D E F
59 72 70 79 70 75
M F M M M M
AAA ENT (ear/nose/throat) Urologic Abdominal Urologic Neurosurgery
BMS DES DES DES DES DES
SAPT DAPT DAPT DAPT DAPT DAPT
Warfarin (off) Warfarin (heparin-bridge) N N N N
N N N Y N Y
94 days 558 days 219 days 512 days 191 days 246 days
Minor Major Minor Major Minor Major
G
75
M
Neurosurgery
DES
SAPT
N
N
388 days
Major
H
66
M
Orthopedics
DES
DAPT
N
N
798 days
Major
Hb 12.4 → 8.5 Transfusion 4U Discontinue clopdgrel Transfusion Discontinue clopdgrel Intra-cranial bleeding + re-operation Intra-cranial bleeding + re-operation Transfusion 4U
frequently than the SAPT group [12]. Moreover, withdrawal of aspirin was associated with a higher incidence of cardiac, cerebral, and peripheral vascular events [11]. Similar to previous reports, our study showed the frequency of bleeding risk in the DAPT group was significantly higher than that in the SAPT group. APT should be reduced to single in surgeries which have high risk of bleeding.
procedure and duration of discontinuation of APT was determined by the treating physician. Although SAPT appeared relatively safe in this study, there are no data to support safety of SAPT in neurosurgery, which allows little safety margin for bleeding. Further study is warranted to evaluate appropriate APT in patients who received intracoronary stents.
Stent thrombosis
Conclusions
In a prospective multicenter observational study of 1134 NCS procedures (82% performed within 1 year after PCI), MACE occurred in 10.9% of patients [13]. A multivariate analysis identified complete APT interruption 5 days prior to NCS as well as creatinine clearance 30 ml/min, pre-operative hemoglobin 10 g/dl, and urgent and high-risk surgery as significant predictors for MACE. Activation of hemostasis is associated with persistent high on-treatment platelet reactivity, a well-known risk factor for ST [14]. Although there was no event of ST in our study, the risk of ST is of concern in patients receiving no APT in the perioperative period.
The frequency of bleeding events was higher in the DAPT group. Both bleeding and cardiovascular events with aspirin alone were low in our study. It may be safe to undergo NCS with SAPT after PCI.
Heparin-bridge It remains unclear whether heparin-bridge is useful. A 103patient study (unknown stent type: 77%) undergoing NCS 1 year after PCI evaluated addition of either unfractionated or lowmolecular weight heparin (LMWH) perioperatively in addition to continuation of some type of APT (aspirin 85%, clopidogrel 44%) [15]. Although the incidence of significant bleeding was low, the risk of overall adverse events was high (approximately 44%). A previous study showed that heparin-bridge alternative for anticoagulation before pacemaker or defibrillator surgery did not reduce thromboembolic events and increased bleeding events [16]. In the present study, the heparin-bridge alternative for APT did not significantly change the bleeding or cardiovascular risk. Given the paucity of data, the value of heparin or LMWH is uncertain. Limitations Our study has the inherent limitations of a retrospective design. There is a possibility of referral bias, and the care of the patients was not controlled by a study protocol. The type of stent used at the PCI
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Please cite this article in press as: Yamamoto K, et al. Cardiovascular and bleeding risk of non-cardiac surgery in patients on antiplatelet therapy. J Cardiol (2014), http://dx.doi.org/10.1016/j.jjcc.2014.02.027
ARTICLE IN PRESS Journal of Cardiology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of Cardiology journal homepage: www.elsevier.com/locate/jjcc
Original article
Cardiovascular and bleeding risk of non-cardiac surgery in patients on antiplatelet therapy Kei Yamamoto (MD), Hiroshi Wada (MD), Kenichi Sakakura (MD), Nahoko Ikeda (MD), Yoko Yamada (MD), Takuji Katayama (MD), Yoshitaka Sugawara (MD), Takeshi Mitsuhashi (MD), Junya Ako (MD), Shin-ichi Momomura (MD, FJCC) ∗ Division of Cardiovascular Medicine, Saitama Medical Center, Jichi Medical University, Saitama, Japan
a r t i c l e
i n f o
Article history: Received 30 September 2013 Received in revised form 17 January 2014 Accepted 4 February 2014 Available online xxx Keywords: Non cardiac surgery Bleeding Stent thrombosis Antiplatelet therapy Heparin-bridge
a b s t r a c t Background: The perioperative risk of non-cardiac surgery (NCS) in the patients on antiplatelet therapy after percutaneous coronary intervention (PCI) remains unclear. Methods: This study was a retrospective and single center study. Between January 2008 and December 2011, 198 patients who had already received PCI underwent NCS in our hospital. Among them, 63 patients underwent surgery on dual antiplatelet therapy (DAPT group) and 88 patients on single antiplatelet therapy (SAPT group). We compared bleeding events and cardiovascular events during perioperative period between the two groups. Results: There was no stent thrombosis in either group. The bleeding events in the DAPT group were significantly higher than that in the SAPT group (9.5% vs 2.3%, p = 0.049). There was no difference in events between with or without heparin-bridge in the SAPT group. Conclusions: The frequency of bleeding events was higher in the DAPT group. Both bleeding and cardiovascular events with aspirin alone were low in our study. It may be safe to undergo NCS with SAPT after PCI. © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Introduction Antiplatelet therapy (APT) plays a central role in the treatment of patients receiving stent deployment [1]. The most important stent thrombosis (ST) predictor is premature discontinuation of dual antiplatelet therapy (DAPT) [2,3]. Apart from non-compliance, the most common reason for early discontinuation of either DAPT or single antiplatelet therapy (SAPT) is the need for non-cardiac surgery (NCS), accounting for one-third of cases [3]. According to current American College of Cardiology/American Heart Association (ACC/AHA) guidelines, approximately two-thirds of all NCS procedures in the first year after index percutaneous coronary intervention (PCI) are classified as moderate to high risk for major adverse cardiac events (MACE) [4–6]. MACE, particularly ST, is a concern after discontinuation of APT; however, its continuation is associated with bleeding risk. The perioperative management
∗ Corresponding author at: Division of Cardiovascular Medicine, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Omiya-ku, Saitama-city, Saitama 330-8503, Japan. Tel.: +81 48 647 2111; fax: +81 48 648 5188. E-mail addresses: [email protected], [email protected] (S.-i. Momomura).
of APT remains controversial because there is limited amount of evidence to suggest what strategies are effective in preventing bleeding or cardiovascular events. In this study, we investigated NCS outcomes in patients who had received either bare-metal stents (BMS) or drug-eluting stents (DES), comparing between DAPT and SAPT. Methods Study patients The present study included 198 patients who had undergone NCS after successful PCI between January 2008 and December 2011, and the data were retrospectively analyzed. The local ethics committee approved this study. All patients had already undergone PCI with either BMS or DES. The treating physician determined the type of stent used at the PCI procedure. Patients with a BMS were prescribed aspirin (100 mg/day) and thyenopyridine (ticropidin 200 mg/day or clopidogrel 75 mg/day) for 30 days. Patients with a DES usually were prescribed aspirin and thienopyridine clopidogrel for 6 months or longer, at the discretion of the treating physician. NCS were performed after stent deployment during
http://dx.doi.org/10.1016/j.jjcc.2014.02.027 0914-5087/© 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Yamamoto K, et al. Cardiovascular and bleeding risk of non-cardiac surgery in patients on antiplatelet therapy. J Cardiol (2014), http://dx.doi.org/10.1016/j.jjcc.2014.02.027
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328 ± 290 days. If the patients took DAPT before surgery in SAPT group, only thyenopyridine was discontinued 5–14 days before surgery.
analyzed using Student’s t-test. Statistical analyses were performed using StatView (SAS Institute Inc., Cary, NC, USA).
Inclusion criteria
Results
The inclusion criteria were (1) patients who underwent NCS after stent deployment and (2) patients who received DES or BMS. NCS was defined as surgical procedure in the operation room and required local or general anesthesia (abdominal, aortic, urologic, etc.). The type of DES included both first-generation (sirolimuseluting stent and paclitaxel-eluting stent) and second-generation (zotarolimus-eluting stent, everolimus-eluting stent, and biolimuseluting stent).
A total of 1794 patients underwent stent deployment in our institution between January 1st, 2008 and December 31st, 2011. Among them, 198 patients also underwent NCS; the DAPT group included 63 patients and the SAPT group included 88 patients (Fig. 1). Mean age was 69.4 ± 8.3 years in the DAPT group and 70.3 ± 8.7 years in the SAPT group, and 70.4 ± 7.8 years overall (p = ns) (Table 1). The number of DES implantations was 53 (84.1%) in the DAPT group and 54 (61.3%) in the SAPT group. Patients taking anti-coagulants were 15.9% in the DAPT group and 11.4% in the SAPT group (Table 2). Aortic surgery and abdominal surgery were performed more frequently in the SAPT group, while peripheral vascular surgery and urologic surgery were more frequently seen in the DAPT group (Table 3). The frequency of bleeding was significantly higher in the DAPT group (9.5%) compared with the SAPT group (2.3%, p = 0.049). Two patients who suffered bleeding during operation in the SAPT group did not use heparin-bridge in the perioperative period. Of these two patients, blood transfusion was required in one patient, and re-operation was required in the other (Tables 4 and 5). Seven out of eight patients who had bleeding events were patients who received DES. No patient died from bleeding (Table 6). No patient experienced ST in either group during the observational period. NCS after stent deployment was performed during 328 ± 290 days.
Exclusion criteria The exclusion criteria were the patients who underwent body surface surgery (ophthalmology and dermatology), and patients who did not require hospitalization. We excluded the patients who received only balloon angioplasty or aspiration. Event definitions The perioperative complications were defined as the occurrence of MACE and bleeding in hospital. Any perioperative myocardial infarction (MI) and ST was considered as MACE. ST was defined according to the Academic Research Consortium definition [7]. Bleeding complications were categorized as major and minor bleeding as previously reported [8]. In brief, major bleeding was defined as bleeding requiring transfusion, intracranial bleeding, clinical overt signs of hemorrhage associated with a drop in hemoglobin of 5 g/dl, and fatal bleeding that resulted directly in death in 7 days. Minor bleeding was defined as clinically overt bleeding resulting in hemoglobin drop of 3–5 g/dl [8]. Statistics Descriptive results were expressed as frequency and percentage for categorical variables, and they were compared using the chi square test (or Fisher exact test for small samples). For continuous variables, statistics were expressed as mean ± SD and were
Discussion The present study showed that the risk of bleeding during the perioperative period was significantly higher in the DAPT group. There was no difference in risk between with or without heparinbridge in the SAPT group. Current guidelines of the European Society of Cardiology or ACC/AHA provide information on how to manage cardiovascular risk during the non-cardiac perioperative period [6,9]. Given the lack of prospective randomized clinical trials, recommendations are mostly dependent on experts’ opinions and retrospective studies.
Fig. 1. The flowchart of this study. APT, antiplatelet therapy; DAPT, dual antiplatelet therapy; SAPT, single antiplatelet therapy.
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Table 1 The baseline characteristics 1.
Age (years) Male BMI (kg/m2 ) Medical history Ischemic heart disease Congestive heart failure Renal impairment (Cre > 2.0 mg/dl) Diabetes mellitus Hypertension Dysplipidemia History of MI History of stroke Medical therapy ACE-inhibitor/ARB Beta blocker Statin Diuretics Calcium antagonist Insulin
Overall (n = 151)
DAPT (n = 63)
SAPT (n = 88)
p
70.4 ± 8.8 124 (82.1%) 23.9 ± 3.4
69.4 ± 8.3 43 (68.3%) 23.9 ± 3.4
70.3 ± 8.7 81 (92.0%) 23.9 ± 3.3
ns 0.002 ns
151 (100%) 36 (23.8%) 33 (21.8%)
63 (100%) 24 (38.1%) 21 (33.3%)
88 (100%) 12 (13.6%) 12 (13.6%)
ns 0.0005 0.004
63 (41.7%) 125 (82.8%) 124 (82.1%) 75 (49.6%) 16 (10.6%)
29 (46.0%) 57 (90.4%) 53 (84.1%) 47 (74.6%) 7 (11.1%)
34 (38.6%) 68 (77.3%) 71 (80.7%) 32 (36.4%) 9 (10.2%)
ns 0.03 ns <0.0001 ns
104 (68.9%) 103 (68.2%) 138 (91.4%) 45 (29.8%) 62 (41.1%) 29 (19.2%)
52 (82.5%) 48 (76.2%) 61 (96.8%) 28 (44.4%) 29 (46.0%) 19 (30.2%)
52 (59.1%) 55 (62.5%) 77 (87.5%) 17 (19.3%) 33 (37.5%) 10 (11.4%)
0.002 ns 0.04 0.0009 ns 0.004
Table 2 The baseline characteristics 2. Overall (n = 151) Medical therapy 2 Aspirin Thienopyridine Anti-coagulant Coronary stent BMS DES SES PES ZES EES BES Duration from PCI (day)
DAPT (n = 63)
SAPT (n = 88)
151 (100%) 114 (75.5%) 20 (13.2%)
63 (100%) 63 (100%) 10 (15.9%)
88 (100%) 51 (58.0%) 10 (11.4%)
44 (26.4%) 107 (70.9%) 39 31 3 27 1 328 ± 290
10 (15.9%) 53 (84.1%) 20 17 0 15 1 356 ± 406
34 (38.6%) 54 (61.3%) 19 14 3 20 0 357 ± 347
Overall (n = 151)
DAPT (n = 63)
SAPT (n = 88)
45 (29.8%) 20 (13.2%) 25 (16.6%) 21 (13.9%) 15 (9.9%) 7 (4.6%) 4 (2.6%) 2 (1.3%) 5 (3.3%) 6 (4.0%)
2 (3.2%) 6 (9.5%) 15 (23.8%) 16 (25.4%) 11 (17.5%) 5 (7.9%) 4 (6.3%) 1 (1.6%) 0 4 (3.2%)
43 (48.8%) 14 (15.9%) 10 (11.4%) 5 (5.8%) 4 (4.5%) 2 (2.3%) 0 1 (1.1%) 5 (5.7%) 2 (2.3%)
p ns 0.001 ns 0.002
ns
Table 3 The baseline characteristics 3 (type of surgery).
Type of surgery Aorta Abdominal Vessel peripheral Urologic Pacemaker/ICD/CRT-D Orthopedics ENT (ear/nose/throat) Neurosurgery Oral and maxillofacial Other
p <0.0001
Bleeding events Van Kuijk et al. [10] showed that the mean bleeding risk from studies in which adequate information was available was 4.1% for SAPT versus 14.7% for DAPT. In a meta-analysis by Burger et al. [11], including a total of 49,590 patients undergoing NCS, it was
concluded that aspirin continuation led to increased bleeding events by a factor of 1.5. However, this increase did not lead to a higher level of the severity of bleeding complications or fatal bleeding except in intracranial surgery and possibly transurethral prostatectomy. Tokushige et al. showed that Japanese patients who underwent NCS in the DAPT group had bleeding events more
Table 4 The clinical outcome. The frequency of bleeding and stent thrombosis. Overall (n = 151)
DAPT (n = 63)
SAPT (n = 88)
p
Major bleeding Minor bleeding CVD event
5 (3.3%) 3 (2.0%) 0
4 (6.3%) 2 (3.2%) 0
1 (1.1%) 1 (1.1%) 0
ns ns ns
Total
8 (5.3%)
6 (9.5%)
2 (2.3%)
0.049
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Table 5 The clinical outcome. The frequency of bleeding and stent thrombosis. Overall (n = 151)
DAPT (n = 63)
SAPT (n = 88) Heparin(+) (n = 20)
Heparin(−) (n = 68)
Major bleeding Minor bleeding CVD event
5 (3.3%) 3 (2.0%) 0
4 (6.3%) 2 (3.2%) 0
0 0 0
1 (1.4%) 1 (1.4%) 0
Total
8 (5.3%)
6 (9.5%)
0
2 (2.8%)
Table 6 The characteristics of cases of bleeding events. Patient
Age
Gender
Type of surgery
Stent
Antiplatelet therapy
Anti coagulant
Emergency
Time from PCI
Bleeding
Complication
A B C D E F
59 72 70 79 70 75
M F M M M M
AAA ENT (ear/nose/throat) Urologic Abdominal Urologic Neurosurgery
BMS DES DES DES DES DES
SAPT DAPT DAPT DAPT DAPT DAPT
Warfarin (off) Warfarin (heparin-bridge) N N N N
N N N Y N Y
94 days 558 days 219 days 512 days 191 days 246 days
Minor Major Minor Major Minor Major
G
75
M
Neurosurgery
DES
SAPT
N
N
388 days
Major
H
66
M
Orthopedics
DES
DAPT
N
N
798 days
Major
Hb 12.4 → 8.5 Transfusion 4U Discontinue clopdgrel Transfusion Discontinue clopdgrel Intra-cranial bleeding + re-operation Intra-cranial bleeding + re-operation Transfusion 4U
frequently than the SAPT group [12]. Moreover, withdrawal of aspirin was associated with a higher incidence of cardiac, cerebral, and peripheral vascular events [11]. Similar to previous reports, our study showed the frequency of bleeding risk in the DAPT group was significantly higher than that in the SAPT group. APT should be reduced to single in surgeries which have high risk of bleeding.
procedure and duration of discontinuation of APT was determined by the treating physician. Although SAPT appeared relatively safe in this study, there are no data to support safety of SAPT in neurosurgery, which allows little safety margin for bleeding. Further study is warranted to evaluate appropriate APT in patients who received intracoronary stents.
Stent thrombosis
Conclusions
In a prospective multicenter observational study of 1134 NCS procedures (82% performed within 1 year after PCI), MACE occurred in 10.9% of patients [13]. A multivariate analysis identified complete APT interruption 5 days prior to NCS as well as creatinine clearance 30 ml/min, pre-operative hemoglobin 10 g/dl, and urgent and high-risk surgery as significant predictors for MACE. Activation of hemostasis is associated with persistent high on-treatment platelet reactivity, a well-known risk factor for ST [14]. Although there was no event of ST in our study, the risk of ST is of concern in patients receiving no APT in the perioperative period.
The frequency of bleeding events was higher in the DAPT group. Both bleeding and cardiovascular events with aspirin alone were low in our study. It may be safe to undergo NCS with SAPT after PCI.
Heparin-bridge It remains unclear whether heparin-bridge is useful. A 103patient study (unknown stent type: 77%) undergoing NCS 1 year after PCI evaluated addition of either unfractionated or lowmolecular weight heparin (LMWH) perioperatively in addition to continuation of some type of APT (aspirin 85%, clopidogrel 44%) [15]. Although the incidence of significant bleeding was low, the risk of overall adverse events was high (approximately 44%). A previous study showed that heparin-bridge alternative for anticoagulation before pacemaker or defibrillator surgery did not reduce thromboembolic events and increased bleeding events [16]. In the present study, the heparin-bridge alternative for APT did not significantly change the bleeding or cardiovascular risk. Given the paucity of data, the value of heparin or LMWH is uncertain. Limitations Our study has the inherent limitations of a retrospective design. There is a possibility of referral bias, and the care of the patients was not controlled by a study protocol. The type of stent used at the PCI
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Please cite this article in press as: Yamamoto K, et al. Cardiovascular and bleeding risk of non-cardiac surgery in patients on antiplatelet therapy. J Cardiol (2014), http://dx.doi.org/10.1016/j.jjcc.2014.02.027