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Cardiac Risk of Noncardiac Surgery After Percutaneous Coronary Intervention With Second-Generation Drug-Eluting Stents

Smith, Bradford B., MD*; Warner, Matthew A., MD*; Warner, Nafisseh S., MD*; Hanson, Andrew C., BS; Smith, Mark M., MD*; Rihal, Charanjit S., MD; Gulati, Rajiv, MD, PhD; Bell, Malcolm R., MD; Nuttall, Gregory A., MD*

doi: 10.1213/ANE.0000000000003408
Cardiovascular and Thoracic Anesthesiology: Original Clinical Research Report
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BACKGROUND: Noncardiac surgery (NCS) following percutaneous coronary intervention (PCI) with stenting is sometimes associated with major adverse cardiac events (MACEs). Second-generation drug-eluting stents (DES) were developed to decrease the incidence of MACE seen with bare metal and first-generation DES.

METHODS: The medical records of all adult patients who underwent second-generation DES placement between July 29, 2008 and July 28, 2011 followed by NCS between September 22, 2008 and July 1, 2013 were reviewed. All episodes of MACE following surgery were recorded.

RESULTS: A total of 282 patients (74.8% male) were identified who underwent NCS after PCI with second-generation DES. MACE occurred in 15 patients (5.3%), including 11 deaths. The incidence of MACE changed significantly with time from PCI to NCS: 17.1%, 10.0%, 0.0%, and 3.1% for patients undergoing NCS at 0–90, 91–180, 181–365, and ≥366 days, respectively. Compared with those having NCS ≥366 days after PCI, the odds ratio for MACE (95% confidence interval) was 6.4 (1.9 to 21.3) at 0–90 days and 3.4 (0.8 to 15.3) at 91–180 days. Seven days prior to NCS, 146 (52%) patients were on dual antiplatelet therapy (DAPT), 106 (38%) were on aspirin, and 30 (11%) did not receive antiplatelet therapy. Excessive surgical bleeding occurred in 19 cases (6.7%). While observed bleeding rates were lowest in those not receiving antiplatelet therapy, there were no statistically significant differences based on the presence or absence of antiplatelet therapy (3% [1/30] for no antiplatelet therapy compared to 6% [6/106] for aspirin monotherapy and 8% [12/146] for DAPT; Fisher exact test: P = .655).

CONCLUSIONS: The incidence of MACE in patients with second-generation DES undergoing NCS was 5.3% and was highest in the first 180 days following DES implantation. The rate of excessive surgical bleeding was 6.7% with the highest observed rate in those on DAPT. However, differences by the presence or absence of antiplatelet therapy were not significant, and future large observational studies will be necessary to further define bleeding risk with continued DAPT.

From the *Department of Anesthesiology and Perioperative Medicine

Division of Biomedical Statistics and Informatics

Division of Cardiology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.

Published ahead of print 9 March 2018.

Accepted for publication March 9, 2018.

Funding: None.

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website.

Reprints will not be available from the authors.

Address correspondence to Gregory A. Nuttall, MD, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905. Address e-mail to Gnuttall@mayo.edu.

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KEY POINTS

  • Question: What is the rate and temporal relationship of major adverse cardiac events (MACEs) and bleeding complications in patients undergoing noncardiac surgery (NCS) after placement of second-generation drug-eluting stents?
  • Findings: The incidence of MACE changed significantly with time from percutaneous coronary intervention to NCS: 17.1%, 10.0%, 0.0%, and 3.1% for patients undergoing NCS at 0–90, 91–180, 181–365, and ≥366 days, respectively. Compared with those having NCS ≥366 days after percutaneous coronary intervention, the odds ratio for MACE (95% confidence interval) was 6.4 (1.9–21.3) at 0–90 days and 3.4 (0.8–15.3) at 91–180 days. The rate of excessive surgical bleeding was 6.7% with the highest observed rate in those on dual antiplatelet therapy although not statistically significant.
  • Meaning: The incidence of MACE was highest in the first 180 days following second-generation drug-eluting stent implantation, and elective NCS in this population should be considered with caution.

Noncardiac surgery (NCS) following percutaneous coronary intervention (PCI) with stenting is associated with major adverse cardiac events (MACEs) including death, myocardial infarction (MI), stent thrombosis, and need for repeat revascularization.1 Cessation of dual antiplatelet therapy (DAPT) increases the risk of stent thrombosis, and these effects are likely magnified by the prothrombotic state associated with the perioperative period.2,3 Continuation of DAPT may predispose patients to excessive surgical bleeding.

It has been shown that the incidence of MACE after bare metal stent (BMS) placement is lowest when NCS is performed >90 days following stent placement.4 A study examining the risk of MACE after placement of first-generation drug-eluting stents (DESs) found no significant association with the time from stenting to NCS, but observed rates of MACE were lowest after 1 year.5 Subsequent prospective studies have found a high rate of MACE following NCS.6–8 Many studies concluded that maintaining antiplatelet therapy throughout the perioperative period is essential to avoid MACE with little effect on the rate of bleeding complications.6,7,9

Recently, second-generation DES have been introduced into clinical practice in an effort to decrease the incidence of in-stent restenosis, MI, and stent thrombosis.10 The optimal timing of NCS following PCI with second-generation DES is debatable.3,11 Previous retrospective studies examining the risk of MACE after placement of DES have shown a similar rate of MACE when comparing first- and second-generation DES.1,12–15 Prospective studies evaluating BMS and DES report higher rates of MACE following NCS than retrospective studies.6–8 Data regarding the incidence of MACE and bleeding complications in patients undergoing NCS after placement of second-generation DES is limited.14,16–18 The objective of this study was to assess the rate and temporal relationship of MACE and bleeding complications in patients undergoing NCS after placement of second-generation DES.

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METHODS

This retrospective study was conducted under approval from the institutional review board at the Mayo Clinic in Rochester, Minnesota. Inclusion criteria included adult patients (≥18 years old) with documented permission to use their medical records in research who underwent second-generation DES placement (predominantly the Xience V stent, Abbott Vascular, Santa Clara, CA) at our institution between July 29, 2008 and July 28, 2011 followed by NCS between September 22, 2008 and July 1, 2013. Exclusion criteria included absence of research consent and previous inclusion in the study, such that patients were only included once. Patients were identified by crossmatching the Mayo Clinic PCI and surgical database.

Electronic medical records of identified patients were reviewed for demographic data, including risk factors for coronary artery disease, prior MI, previous coronary artery bypass grafting (CABG), history of congestive heart failure, cerebrovascular disease, chronic kidney disease, and preoperative hemoglobin. Angiographic data including type of stent, number of stents placed, stent location, percent residual stenosis, successful PCI of all coronary lesions, and thrombolysis in myocardial infarction (TIMI) flow post-PCI19 were obtained. The presenting condition at the time of PCI (ie, elective versus urgent PCI presence or absence of pre-PCI cardiogenic shock) was extracted. The administration of antiplatelet therapy (aspirin, clopidogrel, prasugrel, ticlopidine, abciximab, and eptifibatide) prior to NCS (categorized as continued until <7 days before NCS, discontinued 7–30 days before NCS, and not used during the month before NCS), preoperative anticoagulation (coumadin and heparin), postoperative anticoagulation (heparin) and preoperative β-blocker, calcium channel blocker, angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, and statin use was also reported. Type of NCS was categorized according to the 2014 American Heart Association (AHA) and American College of Cardiology (ACC) Guidelines as low-risk procedures and elevated risk procedures.2 Low-risk procedures, or those with a rate of MACE ≤1%, included cataract, plastic, breast, endoscopy, and miscellaneous surgery.2,20,21 Elevated risk procedures (MACE >1%) included orthopedic, vascular, intraperitoneal, neurosurgery, intrathoracic, head and neck, urologic, other abdominal, and obstetric/gynecologic surgery. Data regarding anesthetic type (general anesthesia, monitored anesthesia care, and regional anesthesia), urgency of NCS (nonemergent or emergent), American Society of Anesthesiologist functional class, estimated blood loss, perioperative blood product administration, and length of surgery were also collected.

Coronary angiography and intracoronary stent deployment were performed using standard percutaneous techniques.22 Patients were prescribed long-term aspirin therapy in addition to clopidogrel, ticlopidine, or prasugrel following DES deployment. All patients undergoing PCI at the Mayo Clinic are prospectively followed up in a PCI registry. Demographic, clinical, and angiographic data are recorded by trained data technicians, and 10% of records are audited twice yearly for quality control. Patients are prospectively contacted with follow-up events such as rehospitalization, MACE, subsequent procedures, and medication compliance recorded.

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Definitions

Perioperative complications following NCS were identified as MACE (MI, stent thrombosis, repeat revascularization through angiography or CABG during the hospital stay or within 24 hours of discharge, and 30 day all-cause mortality) and excessive surgical bleeding (estimated blood loss ≥1000 mL, fatal bleeding, symptomatic or bleeding in a closed space, transfusion of ≥2 blood products intraoperatively or within 48 hours postoperatively, bleeding that requires subsequent surgical exploration, or bleeding that causes hemodynamic instability).23 A perioperative MI was defined by an elevated cardiac biomarker (troponin or creatine kinase myocardial band) with at least 1 of the following: electrocardiographic changes consistent with ischemia, echocardiographic evidence of new regional wall motion abnormalities, symptoms of ischemia, or identification of an intracoronary thrombus by angiography.24 If ST elevation was identified, a diagnosis of ST segment elevation MI (STEMI) was made, and if ST segment elevation was not present, a diagnosis of non-ST segment elevation MI (NSTEMI) was made. Postoperative screening for MACE with serum cardiac biomarker surveillance was at the discretion of individual providers. Perioperative blood product transfusion included intraoperative transfusion and transfusion within 24 hours postoperatively of red blood cells (RBCs), platelets, fresh frozen plasma, cryoprecipitate, or autologous RBC salvage.

Successful PCI was defined by significant enlargement of the coronary artery lumen at the target site of all coronary lesions as reported. Final residual stenosis in the stented coronary artery by visual estimation was recorded with a stenosis diameter reduction to <20% defined as an optimal angiographic result.25 TIMI score was utilized to access coronary flow following PCI and was reported by the performing physician with a score of 3 indicating normal coronary flow.19,26 Stent thrombosis was defined as angiographic evidence of 1 or more luminal filling defects in the previously stented coronary artery or a diagnosis of MI consistent with electrocardiographic changes in the coronary distribution of the previously stented artery. Cardiogenic shock prior to PCI was defined by persistent hypotension necessitating support with vasoactive and inotropic medications (with or without the use of mechanical circulatory support devices) in the setting of reduced cardiac indices despite normal or elevated ventricular filling pressures.27 At our institution, mechanical support devices prior to PCI placed at the discretion of the primary provider most commonly include intra-aortic balloon pumps and less commonly microaxial pumps such as Impella (Abiomed, Danvers, MA).

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Statistical Analysis

To assess whether the risk for MACE after NCS was associated with the duration of time from PCI to NCS, the time from PCI to NCS was assessed as a continuous variable as well as categorically (≤90, 91–180, 181–365, and ≥366 days). These time categories were chosen for the following reasons: <90 days because of the significantly increased rate of MACE in patients with BMSs during this time interval; 91–180 days as this would be consistent with the pharmacokinetics of drug elution and 2016 ACC/AHA and European Society of Cardiology and European Society of Anaesthesiology guidelines recommend delaying elective surgery for at least 180 days following new-generation DES placement; and >1 year because of the previous 2014 AHA/ACC recommendations to delay elective surgery for at least 1 year after DES placement, especially in the setting of acute coronary syndrome (ACS).2

Patient and procedural characteristics were summarized and compared across timing groups. Continuous variables were compared using rank-sum tests, and categorical variables were compared using χ2 tests or Fisher exact tests as appropriate. Univariable logistic regression was used to assess the association between MACE and timing from PCI to NCS. Due to the limited number of MACE, no multivariable analyses were performed. In all cases, 2-sided tests with P < .05 were considered statistically significant. This article adheres to the applicable statistical guidelines.28

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RESULTS

Clinical Characteristics

During the study period, a total of 282 patients (74.8% male) were identified who underwent NCS after PCI with second-generation DES. Relationships between patient characteristics and the timing of NCS after second-generation DES placement were evaluated and reported in Supplemental Digital Content, Table 1, http://links.lww.com/AA/C356.

Table 1

Table 1

Prior to NCS, DES had been placed for ACS in 147 (52%) cases versus electively in 135 (48%) cases. Twelve patients (4%) were in cardiogenic shock prior to PCI. A single stent was deployed in 59% of cases, 2 stents in 26%, and 3 or more stents in 15%. The left anterior descending artery was stented in 45% of cases, the right coronary artery in 34%, and the circumflex artery was stented in 18%. Ninety percent of stents deployed had <5% residual stenosis with 97% having successful PCI in all coronary lesions. The majority (95%) of second-generation DES deployed were Xience V everolimus DESs. Other second-generation DES was Endeavor (Medtronic, Minneapolis, MN) zotarolimus DES.

The median time from PCI to NCS was 387 days (interquartile range, 171–517 days). Forty-one patients (14%) had NCS 0–90 days following PCI, 30 patients (11%) had NCS 91–180 days after PCI, 51 patients (18%) had NCS 181–365 days after PCI, and 160 patients (57%) had NCS ≥366 days after PCI. The majority of NCS were elevated risk procedures (90%) with orthopedic (24%), vascular (16%), and intraperitoneal surgery (12%) being most common. Twenty-six of the 282 total surgical procedures (9%) were performed emergently. Of the 41 cases of NCS performed ≤90 days after PCI, 11 (27%) were performed emergently, with the remaining being time-sensitive procedures. There was a significant association between time from PCI to NCS and duration of NCS. Mean (SD) duration of NCS in minutes was 68 (59), 82 (91), 109 (87), and 114 (94) for patients undergoing NCS at 0–90, 91–180, 181–365, and ≥365 days, respectively.

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Perioperative MACE

Figure 1

Figure 1

One or more MACE was identified in 15 patients (5.3%) including 1 STEMI, 3 NSTEMIs, 3 stent thromboses, 2 repeat revascularizations, and 11 deaths (Table 1). Each case of MI, other than one (indeterminate), occurred in the territory of the previously deployed DES as evidenced by repeat catheterization or electrocardiogram (ECG) changes consistent with ischemia in the previously stented territory. The incidence of MACE changed significantly with time from index PCI to NCS: 17.1%, 10.0%, 0.0%, and 3.1% for patients undergoing NCS at 0–90, 91–180, 181–365, and ≥366 days, respectively, with an odds ratio (95% CI) of 6.4 (1.9–21.3) at 0–90 days and 3.4 (0.8–15.3) at 91–180 days when compared to the reference group of those having NCS ≥366 days after PCI (Figure 1; Table 1). Of the 11 cases of NCS emergently performed ≤90 days following PCI, 4 (36.4%; exact binomial CI, 10.9%–69.2%) experienced MACE. After exclusion of emergent surgeries, the rate of MACE remained highest at 0–90 days followed by 91–180 days, but these relationships were no longer significant (Table 1). Postoperative serum troponin levels were obtained in 36 patients (13%), and only 6 resulted in significant elevation when trended over 6 hours.

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Antiplatelet Therapy

Antiplatelet therapy use in the month prior to surgery is outlined in Supplemental Digital Content, Table 1, http://links.lww.com/AA/C356. Antiplatelet therapy was continued in the month prior to NCS in the majority of patients (95%) with 252 patients (89%) having taken some form of antiplatelet therapy in the 7 days prior to NCS. DAPT within 7 days of the procedure was highest for those undergoing surgery within 90 days of the PCI and lowest for those undergoing surgery ≥366 days after second-generation DES placement. The rate of MACE was 6.8% (10/146) in patients who were on DAPT <7 days prior to NCS, 2.8% (3/106) in patients who were on aspirin <7 days prior to NCS, and 6.7% (2/30) in those who were not receiving antiplatelet medication within 7 days prior to NCS (Fisher exact test P = .315).

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Surgical Bleeding Events and Transfusion

There were 19 cases (6.7%) of excessive surgical bleeding (Table 2). Nine patients (47%) underwent orthopedic surgery, 3 vascular surgery (16%), 3 intraperitoneal surgery (16%), 2 neurosurgery (11%), and 2 underwent miscellaneous procedures; 6 patients (32%) had a preoperative hemoglobin <10 g/dL and 6 patients (32%) had preoperative chronic kidney disease. The rate of excessive bleeding was 8.2% (12/146) in patients who were on DAPT <7 days prior to NCS, 5.7% (6/106) in patients who were on aspirin alone, and 3.3% (1/30) in those not receiving any antiplatelet medication in the 7 days prior to NCS (Fisher exact test P = .655). Two patients with excessive surgical bleeding received a preoperative eptifibatide infusion as NCS was <7 days following PCI, 5 patients (26%) received perioperative anticoagulation in the form of an intravenous heparin infusion, and 1 patient with excessive surgical bleeding also experienced MACE.

Table 2

Table 2

Table 3

Table 3

Thirty-six (13%) of the 282 study patients required erythrocyte transfusion, while 11 patients (4%) required transfusion of platelets, fresh frozen plasma, or cryoprecipitate, and 4 patients (1%) received autologous RBC salvage transfusion intraoperatively (Table 3). The frequency of erythrocyte transfusion was 15.1% (22/146) in patients who were on DAPT <7 days prior to NCS, 12.3% (13/106) in patients who were on aspirin alone, and 3.3% (1/30) in those not receiving any antiplatelet medication in the 7 days prior to NCS (Fisher exact test P = .222).

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DISCUSSION

In this study, the rate of MACE following NCS was 5.3% and was highest in the first 180 days following second-generation DES implantation. The rate of excessive surgical bleeding was 6.7%. The incidence of perioperative RBC transfusion and excessive bleeding were not statistically different based on the presence or absence of antiplatelet therapy, and the lowest observed rates were seen in those not receiving antiplatelet therapy in the 7 days prior to NCS though sample size was limited.

Second-generation DES have been brought into clinical practice in an effort to decrease late in-stent restenosis, MI, and stent thrombosis seen with first-generation DES, ie, by more rapid release of antiproliferative drug, reducing neointimal proliferation, and improved stent design.17,29,30 Previous reported rates of MACE following first-generation DES placement at our institution were 5.4%, and rates of MACE were lowest after 1 year. The Xience V everolimus-eluting stent was introduced in 2008 in our clinical practice, largely replacing first-generation DES. This stent releases approximately 25% of the everolimus in first 24 hours following deployment with the remaining (75%) antiproliferative drug being released in the first month following PCI. There is no detectable antiproliferative drug 4 months following stent deployment.31 Thus, after 4 months, this second-generation DES behaves similar to BMSs and allows rapid reendothelialization of the stent.

The 2016 ACC/AHA Guideline Focused recommends delaying elective NCS optimally for 180 days (Class I recommendation, Level of evidence: B) while elective NCS can be considered 90 days following DES implantation (class IIb recommendation, level of evidence: C).11 The findings of this study show that the rate of MACE was highest in patients who underwent NCS 0–90 days following second-generation DES implantation (17%). The observed risk of MACE was still elevated when NCS was performed 91–180 days following PCI (10%) though not significantly different from the risk observed when NCS was performed ≥365 days following PCI (3%). Thus, elective NCS <180 days following PCI should be considered with caution. When eliminating emergent NCS, there was no statistically significant difference in the incidence of MACE irrespective of the timing between stent placement and surgery although rates were highest in those undergoing surgery at <180 days.

A previous retrospective study evaluating NCS following placement of second-generation DES specifically found the rate of MACE to be 2.2% with a rate of stent thrombosis (reported separately) of 0.7%.14 They did not find a significant difference in the rate of MACE when corrected for time from PCI to NCS, but they did note a greater risk for adverse outcomes with intermediate- and high-risk surgery. Major bleeding events occurred in 5.8%, while rates of major bleeding and MACE were similar regardless of antiplatelet therapy. Additional retrospective studies evaluating first–and second-generation DES found the rate of MACE to be 4.3%1 and 2.1%.15 They also found increased MACE during the first 180 days following DES placement.

A matched-cohort study in patients with DES (first and second generation) compared to controls without ischemic heart disease undergoing similar NCS found that patients with prior DES had an increased risk of MI and cardiac death, especially ≤30 days following PCI.12 This may indicate that surgery type and surgical urgency increased adverse events more than prior DES implementation alone. Furthermore, patient characteristics from a Danish population differ significantly with regard to obesity, history of tobacco use, and diabetes mellitus. Another matched-cohort study evaluating patients with BMS and DES (first and second generation) undergoing NCS found a rate of MACE in patients with DES similar to our study at 5.3%. MACE rates were highest ≤60 days following stent deployment. In addition, patients with prior stents were more likely to have major bleeding events.13

Prospective studies evaluating MACE following NCS and PCI with all types of stents have found a higher rate of MACE (range, 10.9%–40.8%) when compared to retrospective studies.6–8 A prospective study by Albaladejo et al6 evaluated a cohort of 1134 patients and found a MACE rate (including cerebrovascular events) of 10.9%. Factors associated with increased MACE included preoperative anemia, severe renal failure, urgent surgery, high risk surgery, and interruption of antiplatelet agents for >5 days preoperatively. Stent type (BMS versus DES) was not associated with increased MACE. A major difference between the study by Albaladejo et al6 and prospective studies by Wąsowicz et al8 and Vicenzi et al7 is patients in the study by Albaladejo et al6 were not screened with postoperative serum cardiac biomarkers through a surveillance protocol. Provider-specific or clinically based troponin measurement versus routine troponin surveillance has been shown to underestimate the incidence of postoperative cardiac events.32 This may explain why the rate of MACE, and rate of NSTEMI, is significantly higher in studies by Wąsowicz et al8 and Vicenzi et al.7 The optimal perioperative management strategy for DAPT is difficult. Recent prospective and retrospective studies conclude that maintaining antiplatelet therapy throughout the perioperative period may be essential to avoiding major cardiovascular complications without increasing bleeding complications.6,7,9,33,34

The 2016 ACC/AHA guideline focused update recommend that in elective NCS after DES, discontinuation of DAPT may be considered after 180 days (class IIb recommendation, level of evidence: C), but aspirin should be continued perioperatively and the P2Y12 platelet receptor inhibitor be restarted as soon as possible after surgery (class I, level of evidence: C). The 2014 European Society of Cardiology/European Society of Anaesthesiology guidelines recommend DAPT to be continued for 3–12 months following new-generation DES implantation and for 1 year when PCI was performed following ACS unless the risk of life-threatening surgical bleeding is unacceptably high (class IIa recommendation, level of evidence C). The 2016 Canadian Cardiovascular Society Guidelines on Perioperative Cardiac Risk Assessment and Management for Patients Who Undergo Noncardiac Surgery recommend against the continuation of aspirin to prevent cardiac events except in patients with recent coronary stents (6 weeks for BMS and 3–12 months for DES) and those scheduled for carotid endarterectomy (strong recommendation; high-quality evidence).35 Similar to prior studies, the rate of MACE in this study was highest in the first 180 days following DES implantation even when the majority of these patients were on DAPT.11,36

Our overall rate of excessive surgical bleeding events (6.7%) is less than prospective studies6–8 but similar to a recent retrospective study.14 Excessive surgical bleeding did not differ significantly between those who received antiplatelet therapy in the 7 days prior to NCS versus not, despite a trend toward less bleeding in the absence of antiplatelet therapy (3% vs 6% vs 8% for none versus single antiplatelet therapy versus DAPT; Fisher exact test P = .655). The majority of patients received antiplatelet therapy within 7 days of NCS, and hence, the small sample size of patients not receiving antiplatelet therapy (n = 30) makes any inference from these results difficult. Other factors including surgery type (47% orthopedic surgery and 16% vascular surgery), preoperative anemia (32%), preoperative chronic kidney disease (32%), and perioperative use of systemic anticoagulation (26%) may have contributed to excessive surgical bleeding events. Only 1 patient with excessive surgical bleeding had MACE. A major dilemma in the effort to decrease MACE in patients with DES undergoing NCS is the unclear mechanism of perioperative MI.37 Wąsowicz et al8 noted a high rate of NSTEMI in their prospective cohort and postulated that this was indicative of coronary artery supply–demand mismatch from perioperative bleeding. There is a concern for in-stent thrombosis, but the role that antiplatelet therapy plays in reducing this risk is unclear.33 Antiplatelet interruption combined with the prothrombotic state during the perioperative period leads to platelet aggregation, increasing the risk of perioperative MI.6 The majority of our postoperative MIs had evidence of MI in the territory supplied by the stented coronary artery by either angiographic or ECG evidence.

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Limitations

Our study has inherent limitations associated with a retrospective analysis with missing data and charting inaccuracies. Some patients who underwent PCI at our institution may have gone elsewhere for NCS and were lost to our study. Many patients present to our tertiary referral center specifically for perioperative care and then receive follow-up care elsewhere, and MACE follow-up may be incomplete. Perioperative MI usually occurs within 48 hours of surgery, and typical symptoms may be concealed due to concomitant sedation and analgesia.38 During the study period, the presence of routine postoperative cardiac biomarkers and ECGs varied among providers, and thus, less clinically obvious MACE (eg, minor perioperative NSTEMI secondary to demand ischemia) may have been underdiagnosed. If standardized surveillance protocols to evaluate for postoperative MI and subsequent MACE were in place, the rate of MACE in our study may have been more consistent with the aforementioned studies. The low rate of MACE in this study limited our ability to detect differences in the rate of MACE between groups and perform risk adjustment. Based on the observed rate of MACE in patients having NCS ≥366 days following second-generation DES implementation (3.1%), and the observed rates in each timing category (≤90, 91–180, 181–365, and ≥366 days), we have determined that a total sample size of 1410 patients (205, 150, 255, and 800 patients in the ≤90, 91–181, 181–365, and ≥366 groups, respectively) would be required to provide statistical power of ≥80% to detect an odds ratio of 3.0 for the comparisons of each of group (≤90, 91–180, 181–365, and ≥366 days) to the reference group of ≥366. This estimate is based on the current postoperative surveillance of MACE at our institution, which may underestimate postoperative MI due to the lack of standardized surveillance protocols. A large multicenter prospective registry would significantly improve our understanding of the risk factors for MACE, further define the optimal window for NCS after PCI, and clarify perioperative antiplatelet strategies for patients presenting for NCS following DES placement. Assessment of differences in excessive surgical bleeding by the presence or absence of antiplatelet therapy was limited by the small number of patients not receiving antiplatelet therapy in the 7 days prior to NCS. The low incidence of both MACE and excessive surgical bleeding made multivariable adjustments for the outcomes of interest unfeasible. Other second-generation DESs are available; therefore, it is important to apply our data largely to the Xience V stent.

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CONCLUSIONS

The rate of MACE in patients with second-generation DES undergoing NCS was 5.3%, similar to that reported with first-generation DES. The rate of MACE following NCS was highest in the first 180 days following DES implantation even when the majority of these patients were on DAPT at the time of surgery. While higher bleeding rates were observed in those maintained on DAPT, between-group differences were nonsignificant.

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DISCLOSURES

Name: Bradford B. Smith, MD.

Contribution: This authorhelped design the study, acquire and analyze the data, and draft the manuscript.

Name: Matthew A. Warner, MD.

Contribution: This authorhelped design the study, acquire and analyze the data, and draft the manuscript.

Name: Nafisseh S. Warner, MD.

Contribution: This authorhelped draft and revise the manuscript.

Name: Andrew C. Hanson, BS.

Contribution: This authorhelped acquire and analyze the data and draft and revise the manuscript.

Name: Mark M. Smith, MD.

Contribution: This authorhelped draft and revise the manuscript.

Name: Charanjit S. Rihal, MD.

Contribution: This authorhelped draft and revise the manuscript.

Name: Rajiv Gulati, MD, PhD.

Contribution: This authorhelped draft and revise the manuscript.

Name: Malcolm R. Bell, MD.

Contribution: This authorhelped draft and revise the manuscript.

Name: Gregory A. Nuttall, MD.

Contribution: This authorhelped design the study, acquire and analyze the data, and draft the manuscript.

This manuscript was handled by:W. Scott Beattie, PhD, MD, FRCPC.

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REFERENCES

1. Hawn MT, Graham LA, Richman JS, Itani KM, Henderson WG, Maddox TM. Risk of major adverse cardiac events following noncardiac surgery in patients with coronary stents. JAMA. 2013;310:1462–1472.
2. Fleisher LA, Fleischmann KE, Auerbach AD, et al. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130:e278–e333.
3. Kristensen SD, Knuuti J, Saraste A, et al; Authors/Task Force Members. 2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management: The Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). Eur Heart J. 2014;35:2383–2431.
4. Nuttall GA, Brown MJ, Stombaugh JW, et al. Time and cardiac risk of surgery after bare-metal stent percutaneous coronary intervention. Anesthesiology. 2008;109:588–595.
5. Rabbitts JA, Nuttall GA, Brown MJ, et al. Cardiac risk of noncardiac surgery after percutaneous coronary intervention with drug-eluting stents. Anesthesiology. 2008;109:596–604.
6. Albaladejo P, Marret E, Samama CM, et al. Non-cardiac surgery in patients with coronary stents: the RECO study. Heart. 2011;97:1566–1572.
7. Vicenzi MN, Meislitzer T, Heitzinger B, Halaj M, Fleisher LA, Metzler H. Coronary artery stenting and non-cardiac surgery—a prospective outcome study. Br J Anaesth. 2006;96:686–693.
8. Wąsowicz M, Syed S, Wijeysundera DN, et al. Effectiveness of platelet inhibition on major adverse cardiac events in non-cardiac surgery after percutaneous coronary intervention: a prospective cohort study. Br J Anaesth. 2016;116:493–500.
9. Graham MM, Sessler DI, Parlow JL, et al. Aspirin in patients with previous percutaneous coronary intervention undergoing noncardiac surgery. Ann Intern Med. 2018;168:237–244.
10. Palmerini T, Sangiorgi D, Valgimigli M, et al. Short- versus long-term dual antiplatelet therapy after drug-eluting stent implantation: an individual patient data pairwise and network meta-analysis. J Am Coll Cardiol. 2015;65:1092–1102.
11. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. Circulation. 2016;134:e123–e155.
12. Egholm G, Kristensen SD, Thim T, et al. Risk associated with surgery within 12 months after coronary drug-eluting stent implantation. J Am Coll Cardiol. 2016;68:2622–2632.
13. Holcomb CN, Graham LA, Richman JS, Itani KM, Maddox TM, Hawn MT. The incremental risk of coronary stents on postoperative adverse events: a matched cohort study. Ann Surg. 2016;263:924–930.
14. Lo N, Kotsia A, Christopoulos G, et al. Perioperative complications after noncardiac surgery in patients with insertion of second-generation drug-eluting stents. Am J Cardiol. 2014;114:230–235.
15. Wijeysundera DN, Wijeysundera HC, Yun L, et al. Risk of elective major noncardiac surgery after coronary stent insertion: a population-based study. Circulation. 2012;126:1355–1362.
16. Palmerini T, Biondi-Zoccai G, Della Riva D, et al. Stent thrombosis with drug-eluting stents: is the paradigm shifting? J Am Coll Cardiol. 2013;62:1915–1921.
17. Vetter TR, Short RT III, Hawn MT, Marques MB. Perioperative management of the patient with a coronary artery stent. Anesthesiology. 2014;121:1093–1098.
18. Saia F, Belotti LM, Guastaroba P, et al. Risk of adverse cardiac and bleeding events following cardiac and noncardiac surgery in patients with coronary stent: how important is the interplay between stent type and time from stenting to surgery? Circ Cardiovasc Qual Outcomes. 2016;9:39–47.
19. TIMI Study Group. The Thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings. N Engl J Med. 1985;312:932–936.
20. Fleisher LA, Beckman JA, Brown KA, et al; ACC/AHA TASK FORCE MEMBERS. ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery): Developed in Collaboration With the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. Circulation. 2007;116:1971–1996.
21. Gupta PK, Gupta H, Sundaram A, et al. Development and validation of a risk calculator for prediction of cardiac risk after surgery. Circulation. 2011;124:381–387.
22. Orford JL, Lennon R, Melby S, et al. Frequency and correlates of coronary stent thrombosis in the modern era: analysis of a single center registry. J Am Coll Cardiol. 2002;40:1567–1572.
23. Schulman S, Angerås U, Bergqvist D, Eriksson B, Lassen MR, Fisher W; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost. 2010;8:202–204.
24. Thygesen K, Alpert JS, Jaffe AS, et al; Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction. Third universal definition of myocardial infarction. Circulation. 2012;126:2020–2035.
25. Smith SC Jr, Feldman TE, Hirshfeld JW Jr, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; ACC/AHA/SCAI Writing Committee to Update 2001 Guidelines for Percutaneous Coronary Intervention. ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update 2001 Guidelines for Percutaneous Coronary Intervention). Circulation. 2006;113:e166–e286.
26. Gibson CM, Cannon CP, Daley WL, et al. TIMI frame count: a quantitative method of assessing coronary artery flow. Circulation. 1996;93:879–888.
27. Reynolds HR, Hochman JS. Cardiogenic shock: current concepts and improving outcomes. Circulation. 2008;117:686–697.
28. Lang TA, Altman DG. Basic statistical reporting for articles published in biomedical journals: the “Statistical Analyses and Methods in the Published Literature” or the SAMPL Guidelines. Int J Nurs Stud. 2015;52:5–9.
29. Räber L, Magro M, Stefanini GG, et al. Very late coronary stent thrombosis of a newer-generation everolimus-eluting stent compared with early-generation drug-eluting stents: a prospective cohort study. Circulation. 2012;125:1110–1121.
30. Kedhi E, Joesoef KS, McFadden E, et al. Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice (COMPARE): a randomised trial. Lancet. 2010;375:201–209.
31. Sheiban I, Villata G, Bollati M, Sillano D, Lotrionte M, Biondi-Zoccai G. Next-generation drug-eluting stents in coronary artery disease: focus on everolimus-eluting stent (Xience V). Vasc Health Risk Manag. 2008;4:31–38.
32. Beattie WS, Karkouti K, Tait G, et al. Use of clinically based troponin underestimates the cardiac injury in non-cardiac surgery: a single-centre cohort study in 51,701 consecutive patients. Can J Anaesth. 2012;59:1013–1022.
33. Childers CP, Maggard-Gibbons M, Shekelle PG. Antiplatelet therapy in patients with coronary stents undergoing elective noncardiac surgery: continue, stop, or something in between? JAMA. 2017;318:120–121.
34. Chassot PG, Delabays A, Spahn DR. Perioperative antiplatelet therapy: the case for continuing therapy in patients at risk of myocardial infarction. Br J Anaesth. 2007;99:316–328.
35. Duceppe E, Parlow J, MacDonald P, et al. Canadian cardiovascular society guidelines on perioperative cardiac risk assessment and management for patients who undergo noncardiac surgery. Can J Cardiol. 2017;33:17–32.
36. Tokushige A, Shiomi H, Morimoto T, et al; CREDO-Kyoto PCI/CABG Registry Cohort-2 Investigators. Incidence and outcome of surgical procedures after coronary bare-metal and drug-eluting stent implantation: a report from the CREDO-Kyoto PCI/CABG registry cohort-2. Circ Cardiovasc Interv. 2012;5:237–246.
37. Devereaux PJ, Eikelboom J. Insights into myocardial infarction after noncardiac surgery in patients with a prior coronary artery stent. Br J Anaesth. 2016;116:584–586.
38. Devereaux PJ, Xavier D, Pogue J, et al; POISE (PeriOperative ISchemic Evaluation) Investigators. Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study. Ann Intern Med. 2011;154:523–528.

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