Cardiac Events After Non-Cardiac Surgery in Patients With Previous Coronary Intervention in the Drug-Eluting Stent Era

ABSTRACT: The peri-operative risk for patients with coronary drug-eluting stents (DES) who subsequently have non-cardiac surgery (NCS) is unclear. We performed this retrospective study of all patients in our institution who had coronary intervention and subsequent NCS from 2003 through December 2008 to evaluate the incidence of major adverse cardiac events (MACE) in patients who received DES compared to those who received bare-metal stents (BMS) or had percutaneous transluminal coronary angioplasty (PTCA) during the same time period. The main outcome measures were 30-day post-operative myocardial infarction, stent thrombosis, target vessel revascularization (TVR) and cardiac death. During the 6-year study period, 1,770 coronary interventions were performed and 238 patients subsequently had NCS in 8 days to 49 months. Eighteen patients had PTCA, 79 BMS and 141 DES. Acute myocardial infarction occurred in 1 patient who had PTCA, 2 who had BMS and 14 who had DES (p = 0.10). Stent thrombosis occurred in 6 patients who had DES and none who had BMS (p = 0.09). Seven patients who had DES had TVR compared to 1 patient who had BMS and none who had PTCA (p = 0.41). Cardiac mortality occurred in 2 patients who had DES and none who had PTCA or BMS (p = 0.35). In conclusion, the 30-day MACE in patients who received coronary DES and undergone NCS were not significantly different compared to those who received BMS or had PTCA only, with a trend toward higher stent thrombosis in the DES group. 

J INVASIVE CARDIOL 2011;23:283–286

Key words: acute myocardial infarction, bare-metal stents, cardiac outcomes, stent thrombosis

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Bare-metal stents (BMS) were the cornerstone of percutaneous stenotic coronary artery disease treatment after the successful implantation of the first coronary stent in 1986 by Ulrich Sigwart.¹ Studies showed that 6–12 weeks from the time of BMS placement, patients can undergo non-cardiac surgery (NCS) with a lower risk of serious peri-operative cardiac events.^2–4 Restenosis rates with BMS, although lower than angioplasty, were still high,⁵ which led to the development of drug-eluting stents (DES) that have a restenosis rate in the single digits.^6,7 These latter stents were approved for use in Europe in 2002 and in the United States in 2003.⁸ Patients continued to have NCS generally 3 months after sirolimus coronary DES and 6 months after paclitaxel DES. In 2004, alarming reports emerged about the occurrence of very late DES stent thrombosis not typically seen with BMS.^9,10 The U.S. Food and Drug Administration (FDA) revised its recommendations and advised that dual antiplatelet therapy should be taken for at least 1 year after DES implantation in order to reduce the risk of stent thrombosis.¹¹ The cardiac risk of patient with DES undergoing NCS is unclear. We have thus undertaken this study to evaluate the cardiac events in this patient population.

Methods

Study population. All patients who had coronary intervention at the Roudebush Veterans Affairs (VA) Medical Center during a 6-year period from 2003 (the year the FDA approved DES) through 2008 were included in this study. Patients who only received coronary evaluation using intravascular ultrasound or pressure-wire assessment for coronary lesions without coronary angioplasty or stenting were excluded.

Methods. The Indiana University and the Roudebush VA Medical Center institutional review board approvals were initially obtained to review the electronic medical records of all patients who had coronary intervention during the study period. The records were reviewed and all patients who subsequently had NCS or procedure were included. The demographics, history and physical examination, electrocardiograms, lab tests including cardiac markers and any further cardiac evaluation notes were reviewed. VA patients get their medical treatment through the VA health system, and any surgery or procedure done either in this hospital or another hospital can be easily traced through the patient computerized medical records.

Endpoints. The primary outcome measures were 30-day post-operative acute myocardial infarction, stent thrombosis, target vessel revascularization and cardiac mortality.

Definitions. Non-cardiac surgery was classified into low-, intermediate- and high-risk according to the American College of Cardiology-American Heart Association classification.¹²Acute myocardial infarction was diagnosed according to the universal definition of myocardial infarction¹³ by detection of a rise and/or fall of cardiac biomarkers with at least one value above the 99th percentile of the upper reference limit together with evidence of myocardial ischemia with at least one of the following: (a) symptoms of ischemia; (b) electrocardiogram (ECG) changes indicative of new ischemia [new ST-T changes or new left bundle branch block]; (c) development of pathological Q-waves in the ECG; or (d) imaging evidence of new loss of viable myocardium or new regional wall motion abnormality. Stent thrombosis was diagnosed according to the Academic Research Consortium (ARC) classification¹⁴ as definite (either angiographic or pathologic confirmation), probable (unexplained death < 30 days of stenting or > 30 days if there was documented ischemia in the territory of the implanted stent in absence of any other cause), or possible (unexplained death > 30 days after index procedure). The timing was classified as early (within 1 month of stent implantation), late (30 days to 1 year post-stenting) or very late (> 1 year post-stent implantation). Death was only classified as cardiac if a cardiac cause was clearly identified or there was an autopsy result to that effect.

Statistical analysis. All data relating to the study were summarized using descriptive statistics, such as means, proportions, ranges, and standard deviations. Analysis of variance methods were used at the 5% level of significance to compare mean values of DES, BMS and PTCA for age and time from percutaneous coronary intervention (PCI) to surgery. Tukey’s multiple comparison tests were used for post hoc analysis. Chi-square and Fisher’s exact test at the 5% significance level were employed to compare the proportions and the count data of all interested variables. All statistical analysis tests were performed with the Statistical Analysis Software 9.1 (SAS Institute, Cary, North Carolina).

Results

During the 6-year study period from January 2003 through December 2008, 1,770 patients underwent coronary intervention. Subsequently, 238 patients had NCS following the intervention (18 angioplasties, 79 BMS, 55 Cypher DES and 86 Taxus Express DES). Table 1 shows the baseline characteristics of these patients. There was no difference in the baseline characteristics or antiplatelet therapy between the 3 groups.

Table 2 shows the surgery-related characteristics. There was no difference in the time from PCI to surgery, surgeries with general anesthesia, or the risk of surgery between the groups. Fewer patients in the DES group received regional anesthesia compared to the other 2 groups.

The 30-day major adverse cardiac outcomes are shown in Figure 1. The time from stenting to surgery ranged from 8 days to 49 months. Acute myocardial infarction (MI) occurred in 1 patient (5.5%) who had PTCA, 2 (2.5%) who had BMS and 14 (9.9%) who had DES (p = 0.10). There was no difference in MI in patients who had low-, intermediate- or high-risk surgeries (p = 0.42). Of these 17 patients with MI (Table 3), 6 had ST-elevation MI and 11 had non-ST elevation MI; 5 had definite and 1 probable stent thrombosis. The latter died a few hours after surgery after complaining of chest pain and suffering a VF arrest. All stent thrombosis events occurred in the DES group (p = 0.09). Stent thrombosis occurred within 24 hours of surgery in 5 of the 6 patients; the sixth developed stent thrombosis on the third day after surgery. Very late stent thrombosis (> 12 months after PCI) occurred in 4 of these patients. At the time of surgery, 1 patient was on aspirin and clopidogrel, 1 was on aspirin only and 4 were off both antiplatelets; aspirin was stopped 5–10 days before surgery and clopidogrel for longer periods. Aspirin and clopidogrel were restarted in those patients immediately after the diagnosis of MI. In patients who did not sustain MI, aspirin was restarted 2–7 days after surgery and clopidogrel at the same time if the patient was on it pre-operatively.

Seven patients (5%) who had DES had TVR, compared to 1 patient (1.3%) who had BMS and none who had PTCA (p = 0.41). The TVR was mainly driven by revascularization for stent thrombosis.

Cardiac mortality in the first 30 post-operative days occurred in 2 patients (1.4%) who had DES and none who had PTCA or BMS (p = 0.35). The first had chest pain a few hours after a left sub-occipital craniotomy and resection of a vestibular schwannoma and ECG showed anterior ST-elevation MI; this progressed into cardiac arrest and the patient could not be revived. The second patient had cardiopulmonary arrest at home 3 weeks after a left above-knee amputation and sustained hypoxic brain injury. ECG after the event showed ST-segment depression and T-wave inversion inferolaterally. The patient died 2 days after the event. Of the 6 patients who had stent thrombosis, all of which occurred in the post-operative period while in-hospital, 1 died (17%) after the event. During the study period, 22 patients died (9%) following their surgery (1–40 months), of which cardiac death was attributed to 8 of them (3%).

Discussion

This study shows that the 30-day MACE in patients who had coronary DES and subsequent NCS are not different from those who had BMS or PTCA only. There was a trend toward more stent thrombosis in the DES group, which did not reach statistical significance.

MI occurred in 17 patients, of whom 6 had STEMI. All of the STEMI patients had DES and were due to stent thrombosis; 5 had definite stent thrombosis and one had probable stent thrombosis, showing an overall study incidence of 2.7% (6 patients of 220 who had either DES or BMS), with an incidence of 4.2% in the DES group. These patients had their DES 8 days to 49 months prior to NCS. There have been very few reports in the literature about the incidence of DES thrombosis in patients undergoing non-cardiac surgery. In 78 patients who had DES implantation and subsequently underwent NCS, Assali et al¹⁵ found that the incidence of stent thrombosis was 2.6%. Kim et al¹⁶ studied 239 patient who had stenting and subsequently had NCS (138 DES and 101 BMS), and found that 3 patients (2.2%) in the DES group and 0 in the BMS group developed post-operative cardiac events. The incidence of stent thrombosis in the DES group in our study is higher than what was reported in the above studies. TVR in the first post-operative month occurred in 7 patients (5%) who had DES compared to 1 patient (1.3%) who had BMS and none who had PTCA only, and was not statistically different between the 2 groups. The increased number of TVR in the DES group was mainly driven by revascularization of peri-operative stent thrombosis. When stent thrombosis occurred, it was catastrophic. Of the 6 patients with stent thrombosis, all of which occurred while the patients were still in-hospital, 1 patient (17%) died following the event. This is in concordance with the mortality after stent thrombosis in non-surgical patients with either DES or BMS. In a study by Ong et al,¹⁷ patients with angiographic DES subacute thrombosis had a 30-day mortality of 15%; patients with presumed clinical subacute thrombosis had a 30-day mortality of 75%. Cutlip et al,¹⁸ Karillon et al¹⁹ and Moussa et al²⁰ found that the 30-day mortality in patients with BMS was 18.9%, 26%, and 24%, respectively, when stent thrombosis occurred.

Comparing cardiac outcomes between patients who had low-, intermediate- or high-risk surgeries, there was no difference in MI between the 3 groups. Differences in the other outcomes between the 3 groups could not be calculated due to the small number of events.

Our study shows that there is an increased but insignificant trend of stent thrombosis in patients who undergo NCS following coronary DES implantation and that it can occur years after coronary stenting. There was no significant difference in cardiac outcomes when DES was used compared to BMS. Our findings are concordant with results from pooled randomized controlled trials and observational studies^21–23 in non-surgical patients in which there was no increased incidence of cardiac mortality when these first-generation DES were used compared to BMS. More studies are needed to evaluate the cardiac outcomes in this patient population.

Study limitations. This is a single-center, retrospective study that has the inherent limitations of a retrospective design. Ideally, one would like to study the cardiac outcomes in a prospective, randomized study comparing BMS and different types of DES. Such a comparison would have to overcome the multiple patient complexities; in reality, such a trial may be difficult as surgery is not usually planned before patients undergo coronary stenting. The total number of events is small and this precluded performing multivariate analysis and evaluating long-term outcomes.

Acknowledgment. The authors of this manuscript would like to thank Mrs. Vicki Williams, the research nurse in our department, for her administrative work with this research project.

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From ¹the Krannert Institute of Cardiology and the Roudebush VA Medical Center, Indiana University School of Medicine, Indianapolis, and ²the Department of Biostatistics, Tulane University School of Medicine, New Orleans, Louisiana.
The authors report no conflicts of interest regarding the content herein.
Manuscript submitted January 31, 2011, provisional acceptance given March 9, 2011, final version accepted May 11, 2011.
Address for correspondence: Islam A. Bolad, MBBS, MD, 1481 West 10th Street, 111C, Indianapolis, IN 46202. Email: ibolad@iupui.edu