Author + information
- Olaf Schouten, MD,
- Ron T. van Domburg, PhD,
- Jeroen J. Bax, MD, PhD,
- Peter J. de Jaegere, MD, PhD,
- Martin Dunkelgrun, MD,
- Harm H.H. Feringa, MD,
- Sanne E. Hoeks, MSc and
- Don Poldermans, MD, PhD⁎ ()
- ↵⁎Erasmus Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, the Netherlands
To the Editor:
Noncardiac surgery early after percutaneous coronary intervention (PCI) with stenting has been associated with adverse cardiac events in the perioperative period (1,2). However, these reports were on patients with bare-metal stents, did not include drug-eluting stents, and did not compare patients who continued their antiplatelet therapy during surgery with those who interrupted this therapy. Therefore, we conducted the current study.
Patients who underwent noncardiac surgery between 1999 and 2005 and had a successful PCI because of unstable coronary artery disease within the 2 years before surgery were enrolled. The data on PCI procedures were part of a prospectively maintained registry including a total of 574 procedures. Data on the surgical procedure, as well as 30-day cardiovascular outcome, were retrospectively collected by screening of medical charts. The medical ethics committee of our hospital approved the study. All patients underwent PCI using either bare-metal or drug-eluting stents (paclitaxel or sirolimus). Patient characteristics included the indication for PCI, the number of affected and stented coronary arteries, whether the procedure was successful, left ventricular function, and medication use during and after PCI. In addition, cardiac risk factors were scored. Patients with bare-metal stents were prescribed lifelong aspirin and clopidogrel for at least 1 month at the discretion of the treating physician (median 30 days, interquartile range 30 to 90 days). Patients with drug-eluting stents usually received lifelong aspirin as well as clopidogrel for at least 3 months (sirolimus, median 90 days, interquartile range 60 to 180 days) to 6 months (paclitaxel, median 180 days, interquartile range 180 to 180 days), or longer at the discretion of the treating physician.
The surgical procedures were categorized according to surgical risk, based on the definition of the Revised Cardiac Risk Index (3). Furthermore, the cardiac risk factors and medication use assessed during the initial PCI procedures were updated at the time of operation and were used to assess the Revised Cardiac Risk Index for each patient (3). Importantly, there was no protocol for perioperative antiplatelet use in the population studied. Consequently, some patients received aspirin and/or clopidogrel throughout the surgical procedure, whereas in other patients aspirin and clopidogrel were stopped 1 week before operation.
Medical charts were reviewed for the composite end points of 30-day major adverse cardiac events (MACE), defined as nonfatal myocardial infarction and/or cardiac death as previously defined according to guidelines of the American College of Cardiology/European Society of Cardiology (4). Patients with an increased cardiac risk (i.e., previous PCI) were routinely screened for postoperative cardiac end points using serial troponin T and electrocardiographic monitoring on days 1, 3, and 7 after surgery. Additional tests were performed at the discretion of the treating physician. Blood loss during operation and the necessity and quantity of perioperative transfusion requirements were noted in all patients.
In total, 192 patients underwent surgery within 2 years after the initial PCI procedure (Table 1).Patients were arbitrarily divided in an early-surgery group (defined as noncardiac surgery during which clopidogrel was required during the trials that led to approval of these devices and according to their labels: bare-metal stents 1 month, sirolimus-eluting stents 3 months, paclitaxel-eluting stents 6 months) and a late-surgery group. Thirty patients underwent early surgery according to this classification.
During the first 30 postoperative days, 5 patients (2.6%) experienced a MACE (all fatal, see Table 2for characteristics of these patients). In the early-surgery group, 4 MACEs (13.3%) occurred, whereas in the late-surgery group, only 1 MACE (0.6%) occurred (Fisher exact test p = 0.002) (Table 3).In 91 patients (47%), antiplatelet medication was interrupted during the perioperative period. There was no significant difference in surgical risk between patients in whom antiplatelet therapy (both clopidogrel and aspirin) was interrupted versus those in whom antiplatelet therapy was continued. The interruption was associated with a significantly higher incidence of MACE in patients who stopped versus those who continued (5.5% vs. 0%, Fisher exact test p = 0.023). In the group of patients with a MACE, all 5 patients discontinued antiplatelet therapy, whereas in the group without a MACE, only 46% (86 of 187) patients discontinued their antiplatelet therapy. In particular, in patients in whom antiplatelet therapy was stopped before the required time for clopidogrel use (early-surgery group), the discontinuation of antiplatelet therapy had a detrimental effect: an incidence of MACEs of 30.7% in the discontinuation group versus 0% in patients who continued antiplatelet therapy (Fisher exact test p = 0.026) (Table 4).Again, all 4 patients with a MACE discontinued antiplatelet therapy, whereas only 35% (9 of 26) of the patients without a MACE discontinued antiplatelet therapy.
There was no difference in the incidence of MACE between patients with drug-eluting stents and those with bare-metal stents (2.2% vs. 3.0%, p = 0.70); neither was there a significant difference within the early-surgery group (28.6% for bare-metal stents and 8.7% for drug eluting stents, p = 0.23). Remarkably, in 57% of the patients with bare-metal stents, antiplatelet therapy was interrupted in the early-surgery group, whereas antiplatelet therapy was interrupted in 39.1% of the drug-eluting stent group.
Excessive blood loss during surgery was noted in the medical charts of 2 patients (1 receiving antiplatelet therapy). Blood transfusion was required in 44 patients (24% vs. 20% for those who continued vs. those who discontinued antiplatelet therapy, respectively, p = 0.50). In patients requiring blood transfusion, the number of units of homologues’ blood did not differ between those who continued versus those who discontinued antiplatelet therapy (median 2 vs. 3 U, p = 0.51).
This study showed an association between early noncardiac surgery after coronary artery stenting and perioperative adverse cardiovascular events. Importantly, in patients undergoing early surgery, discontinuation of antiplatelet therapy during the perioperative period may be a major cause of the increase in MACE. The type of stent (i.e., bare-metal or drug-eluting) did not influence cardiovascular outcome in this cohort of patients.
In recent studies, an association between early noncardiac surgery after PCI and adverse cardiac outcome has been reported as well (1,2,5). However, these reports did not include the use of drug-eluting stents. The excessive risk of early surgery after PCI might be attributable to the high risk of in-stent thrombosis during the perioperative period. This thrombosis risk is possibly increased by the stress response to major surgery. The stress response includes sympathetic activation promoting shear stress on arterial plaques, enhanced vascular reactivity conducive to vasospasm, reduced fibrinolytic activity, platelet activation, and hypercoagulability. Because procoagulant clotting factors increase while fibrinolysis decreases, the surgical patient is in a hypercoaguable state. Furthermore, coronary stenting results in denudation of the endothelial surface. This might also contribute to the high risk of patients with early surgery because re-endothelization takes up to 8 weeks. This hypothesis is supported by our finding that all MACEs in the early-surgery group occurred in patients in whom antiplatelet therapy was discontinued, including 3 events in the 17 patients with bare-metal stents in whom antiplatelet therapy was discontinued and 2 events in 9 patients with drug-eluting stents without antiplatelet therapy. In contrast to our findings, Reddy et al. (5) did not show an association between discontinuation of antiplatelet therapy and perioperative MACEs in 56 patients with prior bare-metal stenting. This might have been attributable to the small number of events in their study.
The small number of events is also a limitation of the current study. Multivariate analysis could not be performed because of this small number. However, the difference found between those patients who continued their antiplatelet therapy and those who did not deserves attention, and, until more evidence is available, antiplatelet therapy during surgery should be continued unless there is an absolute contraindication.
Please note: Dr. Schouten is supported by an unrestricted research grant from The Netherlands Organization for Health Research and Development (ZonMw), the Hague, the Netherlands, and an unrestricted research grant from “Lijf & Leven” Foundation, Rotterdam, the Netherlands. Dr. Dunkelgrun is supported by an unrestricted research grant (#2003B143) from the Netherlands Heart Foundation, the Hague, the Netherlands. Harold L. Dauerman, MD, served as Guest Editor for this article.
- American College of Cardiology Foundation
- Kaluza G.L.,
- Joseph J.,
- Lee J.R.,
- Raizner M.E.,
- Raizner A.E.
- Wilson S.H.,
- Fasseas P.,
- Orford J.L.,
- et al.
- Lee T.H.,
- Marcantonio E.R.,
- Mangione C.M.,
- et al.
- Alpert J.S.,
- Thygesen K.,
- Antman E.,
- Bassand J.P.