Outcome of Non-Cardiac Surgery After Stent Implantation in the DES Era: Results of the Surgery After Stent (SAS) Registry

ABSTRACT: Background. Optimal management of patients needing non-cardiac surgery after coronary stenting has not been established. Objective. To assess the perioperative outcome of patients undergoing non-cardiac surgery after coronary bare-metal stent (BMS) or drug-eluting stent (DES) implantation. Methods. We enrolled consecutive patients undergoing non-cardiac surgery (up to 2008) after coronary stenting in a single-center registry, prospectively registering clinical and procedural data about revascularization and retrospectively recording surgical details, perioperative therapy and in-hospital outcome after surgery. At our institution, we implant BMS for planned surgery at time of revascularization, and use antiplatelet therapy for surgery required within 1 month of BMS or within 12 months of DES implantation. The primary endpoint was defined as perioperative occurrence of major adverse events, both cardiovascular (death, myocardial infarction, stent thrombosis and repeated revascularization) and hemorrhagic (bleeding requiring transfusions or surgical hemostasis). Results. We enrolled 101 patients: 70 treated with BMS (group 1) and 31 with DES (group 2). The mean interval between stenting and surgery was 288 days. The average number of antiplatelet drugs used during the operative period was higher in group 2 than group 1 (p = 0.02). Fifteen patients (15%) experienced major adverse events (5.9% had non-ST elevation myocardial infarction, 12% received blood transfusions), without a significant difference between the 2 groups (p = 0.72). At multivariate analysis, the predictor of primary endpoint was time interval between stenting and surgery (p = 0.022). Conclusion. We found similar outcomes for non-cardiac surgery after coronary stenting when BMS were selected for planned surgery and dual antiplatelet therapy was used, if indicated, during the operative period.

Approximately 5% of patients who receive coronary stents are expected to require non-cardiac surgery within 1 year of percutaneous coronary intervention (PCI).¹ Notably, the optimal management of patients with coronary artery disease treated by stent implantation and requiring non-cardiac surgery has not yet been established. In particular, the optimal antiplatelet therapy to be maintained during the perioperative period has not been elucidated. Antiplatelet therapy in the perioperative period might be associated with an increased risk of bleeding complications; on the other hand, its reduction exposes the patient to the hypercoagulative state associated with surgery, which may trigger stent thrombosis.²

The clinical relevance of such issues is magnified in the contemporary era with the use of drug-eluting-stents (DES) along with bare-metal stents (BMS), since double-antiplatelet therapy is considered to be necessary to prevent thrombosis for a longer period after DES implantation.³

The American Heart Association (AHA) and American College of Cardiology (ACC) recommend delaying non-cardiac surgery for 1 year after DES implantation and for 6 weeks after BMS implantation.⁴ This recommendation, however, is supported by only a few studies with small populations. Moreover, data on the outcome of patients with DES undergoing non-cardiac surgery are limited and often report a high rate of adverse events.^5–13

The objective of this study was to analyze the perioperative outcome of patients in a single-center registry who received BMS versus DES and thereafter required non-cardiac surgery.

Methods

Consecutive patients at the Institute of Cardiology, Catholic University of the Sacred Heart, in Rome, Italy, who were treated by PCI with stent implantation between January 1, 2005 and December 31, 2007 were screened by matching the PCI database (Cardioplanet V.3.08, Ebit AET SpA, Genoa, Italy) with the hospital database recording all the surgical procedures.

Patient clinical data, including cardiac risk factors, cardiac history, known need of non-cardiac surgery at time of angioplasty, angiographic and procedural data about coronary angioplasty (including number of lesions treated, number and type of stent placed) were prospectively recorded in the database.

At our Institute, patients with planned surgery at the time of PCI generally receive BMS; maintenance of double antiplatelet therapy is recommended for at least 1 month after BMS implantation and for at least 12 months after DES stent implantation. As a consequence, surgery is deferred beyond such time intervals if elective (and patients operated on single antiplatelet therapy after 1 month since BMS and after 1 year since DES implantation) or performed under dual antiplatelet therapy if urgently required before 1 month or 1 year after BMS and DES implantation, respectively. Finally, when the surgical team refused (on the basis of the specific hemorrhagic risk of the operation) to operate with the patient on antiplatelet therapy, surgery was performed using subcutaneous low-molecular-weight heparin.

We grouped the patients according to the implanted stent (BMS = group 1; DES = group 2) and according to the timing between stenting and surgery (patients were classified as “early surgery” if within 6 weeks of BMS implantation or within 1 year of DES implantation or “late surgery” if their surgery was at least 6 weeks after BMS implantation or 1 year after DES implantation).

Data on surgical procedure, perioperative antiplatelet therapy, type of anesthesia and in-hospital clinical outcomes after surgery were retrospectively collected by screening of medical records. Cardiac risk stratification for non-cardiac surgical procedures was categorized in agreement with ACC/AHA guidelines (Table 1),⁴ while hemorrhagic risk of surgical procedure was evaluated according to Chassot et al (Table 2).¹⁴

Troponin T levels and echocardiographic assessments were performed after non-cardiac surgery in the presence of any suspicion of cardiac complication in low- and intermediate-risk surgery and routinely after high-risk surgery.

Aspirin and thienopiridines exert an irreversible inhibition on platelet function. Platelet half-life is about 7–10 days. We considered patients on antiplatelet therapy during the operative period if aspirin and/or thienopiridine were administered within 5 days before surgery.¹⁵

Endpoints. The primary endpoint was the incidence of major adverse events, defined as the combination of major adverse cardiovascular events (MACE) and/or hemorrhagic complications during hospitalization for non-cardiac surgery. MACE were defined as: death, non-fatal myocardial infarction, stent thrombosis or repeated target vessel revascularization. Myocardial infarction was defined as rise and/or fall of cardiac troponin levels with at least one value above the 99th percentile of the upper reference limit.¹⁶ Stent thrombosis was classified according to the standard definition proposed by Academic Research Consortium¹⁷ as definite (symptoms suggestive of an acute coronary syndrome and angiographic or pathologic confirmation of stent thrombosis), probable (unexplained death within 30 days post-procedure or acute myocardial infarction involving the target-vessel territory without angiographic confirmation), possible (all unexplained deaths occurring at least 30 days post-procedure) and as acute (0–24 hours after stent implantation), subacute (> 24 hours to 30 days after stent implantation), late (31–360 days after stenting), or very late (> 360 days after stenting).

Hemorrhagic complications were defined as the occurrence of perioperative bleeding requiring blood transfusion or surgical hemostasis. Blood transfusions were administered according to current guidelines.¹⁸

Statistical analysis. Statistical analysis was conducted using the SPSS 15.0. statistical software package. Data were reported as means ± standard deviation or medians (ranges) as appropriate.

Parametric Student’s t-test was used to compare normally distributed variables. Chi-square or Fisher’s exact test were used to compare categorical variables.

Univariate and multivariate analyses were performed to identify factors potentially related to the occurrence of MACE, bleeding complications and major adverse events. The potential variables that were considered included cardiovascular risk factors, left ventricular ejection fraction, angiographic and procedural data about PCI, cardiovascular and hemorrhagic risk of surgery, time between revascularization and surgery and perioperative antiplatelet therapy.

Results

Characteristics of the study population and non-cardiac surgery details. A total of 101 patients (21 females) were enrolled. Seventy patients (69%) received BMS (group 1) and 31 patients (31%) received DES (group 2). Fifteen patients (15%) had planned surgery at time of revascularization (all receiving BMS). The mean interval between coronary revascularization and surgery was 288 days (interquartile range, 6–911 days), with no significant difference between the two groups (p = 0.41). The characteristics of the entire study population and of groups 1 and 2 are reported in Table 3. Patients treated with BMS tended to have more acute or recent myocardial infarction at the time of stent implantation and were the only patients to have planned surgery at the time of PCI.

The cardiac and hemorrhagic surgical risks of the study population are reported in Table 3 and were not significantly different between the two groups.

Regarding the type of anesthesia adopted during surgery, about half the patients received general anesthesia, with no significant difference between group 1 and group 2 (Table 3). Forty-six patients (45%) had non-cardiac surgery under double antiplatelet therapy, thirty-nine patients (39%) under single antiplatelet therapy, and 16 patients (16%) had no antiplatelet therapy. The average number of antiplatelet drugs during surgery was significantly higher in group 2 compared with group 1 (1.55 versus 1.19, respectively; p = 0.02) (Figure 1).

Clinical outcome after non-cardiac surgery. Of the 101 patients in the study population, we observed that no deaths or potential life-threatening events occurred; actually, nobody died, had definite stent thrombosis, or required target vessel revascularization or urgent surgical hemostasis. However, fifteen patients experienced major adverse events (15%) in terms of cardiovascular and/or hemorrhagic complications (16% in group 1 and 13% in group 2; p = 0.72).

MACE occurred in 6 patients (6%) who experienced non-ST elevation myocardial infarction (NSTEMI), with no difference between the two groups (6% in group 1 versus 6% in group 2; p = 0.88). These events were diagnosed when chest pain and/or dyspnea with rise and/or fall of cardiac troponin levels (according to the current definition of myocardial infarction) occurred after surgery, irrespective of the presence of electrocardiographic (ECG) changes. Actually, the majority of patients had myocardial infarction in absence of ECG changes. One patient in Group 1 had NSTEMI before surgical intervention with T-wave inversion in leads V1-V4 at ECG, and developed T-wave inversion in V5-V6 with typical chest pain and new rise and fall of troponin 3 days after surgery. According to the current definition of stent thrombosis, these acute myocardial infarctions should be classified as probable stent thromboses (2 subacute, 3 late and 1 very late stent thrombosis). All patients with post-operative myocardial infarction had an uncomplicated clinical course on medical treatment and were discharged alive in the absence of Q-wave development on ECG. At univariate analysis, the variables associated with MACE were number of antiplatelet therapy during perioperative period (p = 0.01) and cardiovascular risk stratification of surgery (p = 0.05).

Hemorrhagic complications occurred in terms of blood transfusions in the post-operative period. Twelve patients (11%) required blood transfusions (14% in group 1 versus 6% in group 2; p = 0.26). Group 1 patients required a total of 22 blood transfusion bags, with a mean of 2.2 bags/patient, while group 2 patients required a total of 4 bags, with a mean of 2 bags/patient. We observed no significant difference between the two groups (p = 0.29). No patient had complications due to blood transfusions.

At univariate analysis, patients with major adverse events compared to those with uncomplicated clinical courses had significantly shorter time intervals to surgery and higher frequency of planned non-cardiac surgery (Table 4). At multivariate analysis, the only variable associated with major adverse events was shorter time interval between PCI and surgery (p = 0.022).

According to the timing between stenting and surgery in the whole population, we observed a statistically significant difference between the incidence of major adverse events in the patients subgrouped into the “early surgery” category and the incidence of major adverse events in the patients subgrouped into the “late surgery” category (p = 0.011; Figure 2).

Interestingly, the incidence of major adverse events was significantly higher in the subgroup of patients with BMS operated within 6 weeks compared to those operated after that time (Figure 3). Conversely, no significant difference was observed in the rate of major adverse events occurring in patients with DES who were operated upon before and after 1 year post-stenting (Figure 3).

Study limitations. A prospective, protocol-driven study could have strengthened our observations compared to the retrospective evaluation that we performed. The number of patients with DES included in the study is small; despite the low event rate, we can’t provide any strong message regarding a low risk for non-cardiac surgery after DES implantation. Serial troponins and ECG evaluations were not routinely performed in all patients, neither before surgery nor at prespecified time points following the surgical procedures. Cardiac markers and ECG were assessed according to clinical suspicion of myocardial damage (for example, chest pain or dyspnea). Therefore, an elevated level of troponin after surgery without a documented normal pre-operative level could result in a false positive for myocardial infarction.

Discussion

The present registry reports the clinical outcome observed after non-cardiac surgery in consecutive patients who received coronary stents at our Institution during a 3-year period. The main findings are that using a strategy of selecting BMS for patients with planned surgery at the time of PCI and keeping perioperative dual antiplatelet therapy when indicated, we observed:

1. no death, definite stent thrombosis, urgent coronary revascularization or surgical hemostasis; and 2. major adverse event rate was similar between patients with DES and BMS.

Non-cardiac surgery after coronary stenting is known to be associated with an increased risk of adverse outcomes in the perioperative period.^1,2,5–13 Dual antiplatelet therapy is needed after coronary stent implantation to reduce the risk of stent thrombosis with important differences according to the type of implanted stent. In particular, patients with BMS are prescribed clopidogrel for at least 1 month and lifelong aspirin, while patients with DES are recommended to receive clopidogrel for at least 1 year and lifelong aspirin.³ Nevertheless, antiplatelet therapy in the perioperative period might be associated with an increased risk for hemorrhagic complications so that its maintenance is often controverted in the daily practice. On the other hand, aspirin and/or clopidogrel withdrawal exposes patients to a higher risk of stent thrombosis. Recent guidelines recommend delaying elective non-cardiac surgery for 1 year after DES implantation and for 6 weeks after BMS implantation.⁴ This recommendation is supported by our data showing that shorter time to surgery is the only independent predictor of major adverse events, that higher major adverse events are associated with early surgery and that significant higher major adverse events are observed in patients with BMS operated within 6 weeks. Similar findings have been reported by a large registry on patients with BMS.⁵ Such observations suggest that the selection of BMS in patients who are known to need surgery is a rational approach and should be associated, according to current guidelines, with a surgery deferral period of 6 weeks. Unfortunately, patients requiring surgery within 6 weeks of stent implantation have a rather high perioperative risk and further studies are needed to assess what might be the optimal perioperative management.

Yet, many patients are treated by coronary stenting in the absence of known need for surgery, so that a relevant number of them are expected to require surgery after DES implantation; optimal management of these patients may be clinically useful. Our Institution’s policy is to maintain DES patients on dual antiplatelet therapy for 12 months; therefore, the average number of antiplatelet drugs was significantly higher compared to patients with BMS. We observed a similar outcome after non-cardiac surgery in patients with DES or BMS. This finding fits with the data by Schouten et al⁶ and by Cruden et al,¹⁹ who recently reported similar outcomes after non-cardiac surgery in patients with DES as compared to patients with BMS. Interestingly, the cut-off of 1 year for surgery deferral after DES implantation is not clearly established. In our study as well as in a larger study from Mayo Clinic,⁷ no significant difference was observed in the clinical outcomes of patients with DES operated before or after 1 year.

Conclusion

Patients with previous BMS or DES implantation appear to have similar outcomes after non-cardiac surgery in a study population characterized by an approach of BMS selection for planned surgery and perioperative double antiplatelet treatment in patients with DES.

References

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From the Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy. ^*The first two authors equally contributed to the present manuscript. The authors report no conflicts of interest regarding the content herein. Manuscript submitted August 3, 2010, provisional acceptance given September 3, 2010, final version accepted November 8, 2010. Address for correspondence: Francesco Burzotta, MD, PhD, Via Prati Fiscali 158, 00141 Rome, Italy. E-mail: f.burzotta@rm.unicatt.it