Therapeutic Advances in Cardiovascular Disease http://tak.sagepub.com/
Late and very late drug-eluting stent thrombosis in the immediate postoperative period after antiplatelet withdrawal: a retrospective study Hesham R. Omar, Collin Sprenker, Rachel Karlnoski, Enrico M. Camporesi and Devanand Mangar Ther Adv Cardiovasc Dis published online 10 July 2014 DOI: 10.1177/1753944714542592 The online version of this article can be found at: http://tak.sagepub.com/content/early/2014/07/10/1753944714542592
Published by: http://www.sagepublications.com
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TAK0010.1177/1753944714542592Therapeutic Advances in Cardiovascular DiseaseOmar et al.
Therapeutic Advances in Cardiovascular Disease
Late and very late drug-eluting stent thrombosis in the immediate postoperative period after antiplatelet withdrawal: a retrospective study
Original Research
Ther Adv Cardiovasc Dis 1–8 DOI: 10.1177/ 1753944714542592 © The Author(s), 2014. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Hesham R. Omar, Collin Sprenker, Rachel Karlnoski, Enrico M. Camporesi and Devanand Mangar
Abstract Background: Late (31–360 days after deployment) and very late (>360 days after deployment) stent thrombosis is a feared complication after drug-eluting stent (DES) deployment. The American College of Cardiology/American Heart Association guidelines recommend dual antiplatelet therapy for 12 months due to the lack of protection beyond this period in randomized trials. The perioperative period is a unique state of generalized hypercoagulability which can predispose people to DES thrombosis when combined with the rebound hypercoagulable effect of antiplatelet withdrawal. Methods: A retrospective chart review was performed to detect incidences of late and very late postoperative DES thrombosis after elective noncardiac surgery. Only definite and probable cases of stent thrombosis were included. All cases were analyzed for patient demographics, comorbidities, type of surgery, intervention history, preoperative antiplatelets management, postoperative course and outcome. Results: A total of six patients with prior DES deployment (10–42 months earlier, average 30 months) developed DES thrombosis (five very late and one late) in the immediate postoperative period. All patients had stable coronary artery disease and were cleared for surgery (intermediate cardiac risk surgery) by their cardiologist. In all patients, antiplatelets were discontinued 4–7 days (average 5.6 days) prior to surgery to minimize operative bleeding. Five of six patients developed ST-segment elevation myocardial infarction. Half of the patients had simultaneous two-vessel DES thrombosis and two cases had single vessel thrombosis. Three patients developed ventricular fibrillation and cardiac arrest. One-third of the patients died during the index hospitalization. Coronary thrombectomy and angioplasty was successful in the remaining four cases. The incidence of postoperative late and very late DES thrombosis among all patients undergoing noncardiac surgery who were older than 40 years was 0.006%. Conclusion: Caution should be exercised when attempting to withdraw antiplatelets preoperatively in patients with DES even when the recommended 12-month period of dual antiplatelet therapy (DAPT) has elapsed. The significant morbidity and mortality of this complication warrants further research to study the ideal perioperative management of antiplatelets in patients with prior DES deployment over 1 year who are still receiving DAPT. Keywords: stent thrombosis, drug-eluting stent, antiplatelet withdrawal Introduction Despite the success of drug-eluting sent (DES) compared with bare metal stent (BMS) in suppressing neointimal proliferation and reducing instent restenosis, concerns have arisen because of
the significantly higher risk of late and very late DES thrombosis. This has been more recognized with first-generation DES. Nevertheless, reports emerge that describe this complication with second-generation DES. The risk of stent thrombosis
Correspondence to: Hesham R. Omar, MD Internal Medicine Department, Mercy Medical Center, Clinton, IA 52732, USA hesham.omar@ apogeephysicians.com Collin Sprenker, BS Rachel Karlnoski, PhD Florida Gulf to Bay Anesthesiology Associates LLC, Tampa, FL, USA Enrico M. Camporesi, MD Department of Surgery/ Anesthesiology, Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, USA Devanand Mangar, MD Tampa General Hospital and Florida Gulf to Bay Anesthesiology Associates LLC, Tampa, FL, USA
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Therapeutic Advances in Cardiovascular Disease is increased in the perioperative period secondary to catecholamine production, promoting vasospasm, increased platelet activation and decreased fibrinolysis. Additionally, preoperative interruption of antiplatelet therapy to decrease bleeding complications can trigger a rebound increase in platelet activation and platelet aggregation further increasing the risk of stent thrombosis [Collet et al. 2004; Ferrari et al. 2005]. Published reports that illustrate simultaneous two-vessel and three-vessel stent thrombosis suggest that this phenomenon is due to a generalized hypercoagulable state in a setting of a predisposed stent. Cessation of dual antiplatelet therapy (DAPT) was found to be the single most significant predictor of stent thrombosis in prior trials [Park et al. 2006]. The American College of Cardiology (ACC)/American Heart Association (AHA) recommend DAPT for 12 months after DES deployment due to lack of evidence for protection beyond that period in randomized trials [Park et al. 2010]. However, there are no studies to demonstrate the safety of antiplatelet withdrawal in patients with prior DES deployed for longer than 12 months who are anticipating surgery. We were vigorously exposed to this dilemma and have encountered six cases with acute postoperative DES thrombosis due to preoperative antiplatelet withdrawal. We attempted to study the magnitude, prevalence, causes and outcome of this complication at our institution.
identified culprit lesion and/or any unexplained death within 30 days. Possible is defined in the case of any unexplained death after 30 days [Cutlip et al. 2007]. Only definite and probable cases were classified as stent thrombosis in this study. Cases with possible stent thrombosis were excluded. Myocardial infarction was classified as ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) according to the third universal definition of myocardial infarction [Thygesen et al. 2012]. The collected cases were analyzed for patient demographics, comorbidities, type of surgery, DES type, time of coronary stenting, type of antiplatelet medication the patient received and onset of withdrawal, intraoperative hemodynamic and telemetric events, postoperative course and final outcome. We also investigated the patients’ baseline degree of severity of coronary artery disease based on historical data (according to a preoperative interview with primary cardiologist) or noninvasive cardiac stress testing. Our main objective was to study the magnitude, causes, presentation and outcome of late and very late DES thrombosis in the perioperative period. We also attempted to calculate the incidence of postoperative late and very late DES thrombosis among all surgical cases. Continuous data were presented as mean (±standard deviation) and dichotomous data were expressed as numbers and percentages.
Methods The Institutional Review Board at Tampa General Hospital approved the study and waived the need for patient consent. A retrospective chart review was performed for patients admitted to Tampa General Hospital for elective surgical procedures between January 2005 and August 2012 who suffered late and very late DES thrombosis in the immediate postoperative period. Stent thrombosis is defined on the basis of the Academic Research Consortium definitions [Cutlip et al. 2007]. According to the timing of presentation, stent thrombosis is considered late when it occurs 31–360 days after deployment, or very late when it occurs after 360 days. According to the level of certainty, stent thrombosis can be definite, probable or possible. Definite is classified in the presence of acute coronary syndrome and either angiographic or pathological (autopsy) confirmation of stent thrombosis. Probable is classified in case of an acute myocardial infarction involving the target-vessel territory without angiographic confirmation of thrombosis or other
Results Study population A total of six patients developed DES thrombosis in the immediate postoperative period during the study timeframe. They were five men and one woman, with a mean age of 59 years (range 54– 69) and a mean body mass index of 35 kg/m² (range 25–45). One third of the patients had diabetes mellitus. Other comorbidities are listed in Table 1. The patients had DES deployed 10–42 months prior to surgery with a mean of 30 months. In patients with simultaneous DES thrombosis, the date of the last deployed DES was used as ‘onset of stenting’ if DES were placed on separate occasions. Five cases had first-generation DES (Taxus or Cypher) and one case had second-generation DES (Endeavor). All patients were referred to their primary cardiologist for preoperative cardiac evaluation and risk stratification. No patient had unstable coronary artery disease prior to surgery. Stability was based on patients’ symptomatology and a prior
2 http://tac.sagepub.com
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64
55
5
6
Female
Male
Male
Male
Male
Male
Sex
45
32
45
27
25
34
BMI
Yes
Yes
No
No
No
No
DM
AFib, HTN, hypertriglyceridemia, sleep apnea, bilateral knee osteoarthritis HTN, hyperlipidemia, colon cancer, jaundice due to biliary obstruction HTN, CHF, PVD, hyperlipidemia, GERD, cervical spondylitic myelopathy HTN, hyperlipidemia, depression, GERD, HTN, CABG, PVD, hyperlipidemia, GERD, DJD, COPD, sleep apnea HTN, DVT, DJD, incisional hernia, GERD
Other comorbidities
286
Roux en- Y hepaticojejunostomy
180 170
217
Gastric banding Hip replacement
Hernia repair
215
233
Bilateral knee replacement
Spondylosis
Duration of surgery (min)*
Surgery
50
350
50
< 50
200
400
EBL (ml)
50–55
40
68
LVEF preop%
35
55–60
20–25
20
LVEF postop%
125
0.7§
100
None (no ST shifts)
None (no ST shifts) None (no ST shifts)
Occasional SB (no ST shifts)
None (no ST shifts)
lead II and ST depression in aVL > lead I suggests that the RCA is the culprit vessel). ECG of case no. 3 shows no ST elevation. ECG of case no. 4 shows high take off coved ST segments in leads I and aVL with reciprocal ST depression in V1–V3, suggesting high lateral STEMI. ECG of case no. 5 shows anterior STEMI with RBBB, suggesting a very proximal LAD lesion. ECG of case no. 6 shows high lateral STEMI (ST-segment elevation in leads I and aVL with reciprocal depression in the inferior leads). RBBB; right bundle branch block; LAD, left anterior descending coronary artery; RCA, right coronary artery; STEMI, ST-segment elevation myocardial infarction. Panels for patients 1 and 2 are adapted with permission and modification from Elsevier Science [Omar et al. 2012, 2014].
are limited data in the literature regarding DES thrombosis in the immediate postoperative period and are mostly related to antiplatelet withdrawal. It should be noted that the main evidence of increased postoperative bleeding from DAPT is mainly related to cardiac surgery. Data regarding the risk of operative bleeding after noncardiac surgery are limited and controversial. A meta-analysis by Burger and colleagues found that continuation of aspirin led to an increased rate of bleeding by a factor of 1.5, however it did not lead to a higher level of the severity of bleeding complications,
with the exception of intracranial surgery, and possibly transurethral prostatectomy [Burger et al. 2005]. Stone and colleagues found no difference in incidence of transfusion and reoperation for bleeding in 10,406 patients who underwent vascular surgery and were randomized to either aspirin alone, clopidogrel alone, aspirin and clopidogrel, or neither [Stone et al. 2011a]. Perioperative antiplatelet management remains controversial and usually represents a debate between cardiologists and surgeons. This has provoked some countries to develop national societal guidelines with partnership between cardiologists and surgeons for
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HR Omar, C Sprenker et al.
Figure 2. Coronary angiography (CA) of case no. 1 reveals mid LCX and proximal LAD drug-eluting stent thrombosis with sparing of a mid-LAD bare metal stent that shows in-stent restenosis (a). CA of case no. 2 reveals subtotal proximal LAD occlusion with an evident thrombus (b) and total mid RCA occlusion (c). CA of case no. 3 shows in-stent thrombosis and total occlusion of the LCX and diagonal branch (d). CA of case no. 4 shows total occlusion of the ramus intermedius branch (e). CA of case no. 6 shows in-stent thrombosis and total LAD occlusion (f). Panels (a–c) are adapted with permission from Elsevier Science [Omar et al. 2012, 2014].
ideal perioperative antiplatelet management. For example, the national society of interventional cardiology in Italy recommended that DAPT should not be withdrawn before low bleeding risk surgeries, whereas at least aspirin should be continued in the majority of surgeries [Rossini et al. 2012]. We do agree that there is no evidence from randomized trials to support continuing DAPT for longer than 1 year after DES deployment. Withdrawing antiplatelets immediately before surgery carries more risk than elective withdrawal due to the rebound increase in platelet function in the hypercoagulable perioperative state. We are occasionally met with a patient who is still prescribed DAPT indefinitely and is coming for our advice before a noncardiac surgery to decide on antiplatelet withdrawal. This decision is variable among cardiologists due to the absence of societal guidelines in this specific instance. A question to be answered is whether discontinuing antiplatelet therapy after 12 months can be generalized to all patients with DES. In our opinion, patients with DES who are still on DAPT and
are anticipating surgery should be approached more cautiously with proper risk/benefit assessment, even if the recommended 1-year period of DAPT has elapsed. In cases in whom operative risk of bleeding is minimal, we propose continuing DAPT if the patient is on it. When operative bleeding is a concern, then continuing a single antiplatelet agent with aspirin might be a reasonable alternative. We aim to draw attention to this serious complication and warn of the consequences of preoperative discontinuation of DAPT in patients with DES. Future randomized trials are mandatory in this specific group of patients to test the risks and benefits associated with implementing either approach. Funding This research received no specific grant from any funding agency in the public, commercial, or notfor-profit sectors. Conflict of interest statement The authors declare no conflicts of interest in preparing this article.
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Therapeutic Advances in Cardiovascular Disease References Bavry, A., Kumbhani, D., Helton, T., Borek, P., Mood, G. et al. (2006) Late thrombosis of drugeluting stents: a meta-analysis of randomized clinical trials. Am J Med 119: 1056–1061. Burger, W., Chemnitius, J., Kneissl, G. and Rücker, G. (2005) Low-dose aspirin for secondary cardiovascular prevention - cardiovascular risks after its perioperative withdrawal versus bleeding risks with its continuation - review and meta-analysis. J Intern Med 257: 399–414. Collet, J., Montalescot, G., Blanchet, B., Tanguy, M., Golmard, J., Choussat, R. et al. (2004) Impact of prior use or recent withdrawal of oral antiplatelet agents on acute coronary syndromes. Circulation 110: 2361–2367. Cutlip, D., Windecker, S., Mehran, R., Boam, A., Cohen, D., van Es, G. et al. (2007) Academic Research Consortium. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 115: 2344–2351. Daemen, J., Wenaweser, P., Tsuchida, K., Abrecht, L., Vaina, S., Morger, C. et al. (2007) Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study. Lancet 369: 667–678. Ferrari, E., Benhamou, M., Cerboni, P. and Marcel, B. (2005) Coronary syndromes following aspirin withdrawal: a special risk for late stent thrombosis. J Am Coll Cardiol 45: 456–459. Fleisher, L., Beckman, J., Brown, K., Calkins, H., Chaikof, E., Fleischmann, K. et al. (2008) 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). Anesth Analg 106: 685–712. Kimura, T., Morimoto, T., Nakagawa, Y., Kawai, K., Miyazaki, S. et al. (2012) Very late stent thrombosis and late target lesion revascularization after sirolimuseluting stent implantation: five-year outcome of the j-Cypher Registry. Circulation 125: 584–591. Omar, H., Mangar, D., Karlnoski, R., Abdelmalak, H. and Camporesi, E. (2012) Simultaneous left anterior descending and right coronary stent thrombosis after aspirin withdrawal. Am J Emerg Med 30: 2093.e5–8.
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Omar, H., Mangar, D., Sullebarger, J., Sprenker, C. and Camporesi, E. (2014) Postoperative simultaneous very late two-vessel drug eluting stent thrombosis with sparing of a bare metal stent in a Jehovah’s Witness after clopidogrel withdrawal. J Cardiol 9: 57–60.
Park, D., Park, S., Park, K., Lee, B., Kim, Y., Lee, C. et al. (2006) Frequency of and risk factors for stent thrombosis after drug-eluting stent implantation during long-term follow-up. Am J Cardiol 98: 352–356. Park, S., Park, D., Kim, Y., Kang, S., Lee, S., Lee, C. et al. (2010) Duration of dual antiplatelet therapy after implantation of drug-eluting stents. N Engl J Med 362: 1374–1382. Räber, L., Jüni, P., Nüesch, E., Kalesan, B., Wenaweser, P., Moschovitis, A. et al. (2011) Longterm comparison of everolimus-eluting and sirolimuseluting stents for coronary revascularization. J Am Coll Cardiol 57: 2143–2151. Rossini, R., Bramucci, E., Castiglioni, B., De Servi, S., Lettieri, C., Lettino, M. et al. (2012) Coronary stenting and surgery: perioperative management of antiplatelet therapy in patients undergoing surgery after coronary stent implantation. G Ital Cardiol 13: 528–551. Siddiqi, O. and Faxon, D. (2012) Very late stent thrombosis: current concepts. Curr Opin Cardiol 27: 634–641. Smits, P., Kedhi, E., Royaards, K., Joesoef, K., Wassing, J., Rademaker-Havinga, T. et al. (2011) 2-year follow-up of a randomized controlled trial of everolimus- and paclitaxel-eluting stents for coronary revascularization in daily practice. COMPARE (Comparison of the everolimus eluting XIENCE-V stent with the paclitaxel eluting TAXUS LIBERTÉ stent in all-comers: a randomized open label trial). J Am Coll Cardiol 58: 11–18. Stone, D., Goodney, P., Schanzer, A., Nolan, B., Adams, J., Powell, R. et al. (2011a) Vascular Study Group of New England. Clopidogrel is not associated with major bleeding complications during peripheral arterial surgery. J Vasc Surg 54: 779–784. Stone, G.W., Rizvi, A., Sudhir, K., Newman, W., Applegate, R.J., Cannon, L.A. et al. (2011b) SPIRIT IV Investigators. Randomized comparison of everolimus- and paclitaxel-eluting stents. 2-year follow-up from the SPIRIT (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) IV trial. J Am Coll Cardiol 58:19–25. Thygesen, K., Alpert, J., Jaffe, A., Simoons, M., Chaitman, B., White, H. et al. (2012) Third universal definition of myocardial infarction. Circulation 126: 2020–2035. Yeung, A., Leon, M., Jain, A., Tolleson, T., Spriggs, D., Mc Laurin, B. et al. (2011) RESOLUTE US Investigators. Clinical evaluation of the Resolute zotarolimus-eluting coronary stent system in the treatment of de novo lesions in native coronary arteries: the RESOLUTE US clinical trial. J Am Coll Cardiol 57: 1778–1783.
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Late and very late drug-eluting stent thrombosis in the immediate postoperative period after antiplatelet withdrawal: a retrospective study Hesham R. Omar, Collin Sprenker, Rachel Karlnoski, Enrico M. Camporesi and Devanand Mangar Ther Adv Cardiovasc Dis published online 10 July 2014 DOI: 10.1177/1753944714542592 The online version of this article can be found at: http://tak.sagepub.com/content/early/2014/07/10/1753944714542592
Published by: http://www.sagepublications.com
Additional services and information for Therapeutic Advances in Cardiovascular Disease can be found at: Email Alerts: http://tak.sagepub.com/cgi/alerts Subscriptions: http://tak.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav Citations: http://tak.sagepub.com/content/early/2014/07/10/1753944714542592.refs.html
>> OnlineFirst Version of Record - Jul 10, 2014 What is This?
Downloaded from tak.sagepub.com at University of Waikato Library on July 12, 2014
542592
research-article2014
TAK0010.1177/1753944714542592Therapeutic Advances in Cardiovascular DiseaseOmar et al.
Therapeutic Advances in Cardiovascular Disease
Late and very late drug-eluting stent thrombosis in the immediate postoperative period after antiplatelet withdrawal: a retrospective study
Original Research
Ther Adv Cardiovasc Dis 1–8 DOI: 10.1177/ 1753944714542592 © The Author(s), 2014. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Hesham R. Omar, Collin Sprenker, Rachel Karlnoski, Enrico M. Camporesi and Devanand Mangar
Abstract Background: Late (31–360 days after deployment) and very late (>360 days after deployment) stent thrombosis is a feared complication after drug-eluting stent (DES) deployment. The American College of Cardiology/American Heart Association guidelines recommend dual antiplatelet therapy for 12 months due to the lack of protection beyond this period in randomized trials. The perioperative period is a unique state of generalized hypercoagulability which can predispose people to DES thrombosis when combined with the rebound hypercoagulable effect of antiplatelet withdrawal. Methods: A retrospective chart review was performed to detect incidences of late and very late postoperative DES thrombosis after elective noncardiac surgery. Only definite and probable cases of stent thrombosis were included. All cases were analyzed for patient demographics, comorbidities, type of surgery, intervention history, preoperative antiplatelets management, postoperative course and outcome. Results: A total of six patients with prior DES deployment (10–42 months earlier, average 30 months) developed DES thrombosis (five very late and one late) in the immediate postoperative period. All patients had stable coronary artery disease and were cleared for surgery (intermediate cardiac risk surgery) by their cardiologist. In all patients, antiplatelets were discontinued 4–7 days (average 5.6 days) prior to surgery to minimize operative bleeding. Five of six patients developed ST-segment elevation myocardial infarction. Half of the patients had simultaneous two-vessel DES thrombosis and two cases had single vessel thrombosis. Three patients developed ventricular fibrillation and cardiac arrest. One-third of the patients died during the index hospitalization. Coronary thrombectomy and angioplasty was successful in the remaining four cases. The incidence of postoperative late and very late DES thrombosis among all patients undergoing noncardiac surgery who were older than 40 years was 0.006%. Conclusion: Caution should be exercised when attempting to withdraw antiplatelets preoperatively in patients with DES even when the recommended 12-month period of dual antiplatelet therapy (DAPT) has elapsed. The significant morbidity and mortality of this complication warrants further research to study the ideal perioperative management of antiplatelets in patients with prior DES deployment over 1 year who are still receiving DAPT. Keywords: stent thrombosis, drug-eluting stent, antiplatelet withdrawal Introduction Despite the success of drug-eluting sent (DES) compared with bare metal stent (BMS) in suppressing neointimal proliferation and reducing instent restenosis, concerns have arisen because of
the significantly higher risk of late and very late DES thrombosis. This has been more recognized with first-generation DES. Nevertheless, reports emerge that describe this complication with second-generation DES. The risk of stent thrombosis
Correspondence to: Hesham R. Omar, MD Internal Medicine Department, Mercy Medical Center, Clinton, IA 52732, USA hesham.omar@ apogeephysicians.com Collin Sprenker, BS Rachel Karlnoski, PhD Florida Gulf to Bay Anesthesiology Associates LLC, Tampa, FL, USA Enrico M. Camporesi, MD Department of Surgery/ Anesthesiology, Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, USA Devanand Mangar, MD Tampa General Hospital and Florida Gulf to Bay Anesthesiology Associates LLC, Tampa, FL, USA
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Therapeutic Advances in Cardiovascular Disease is increased in the perioperative period secondary to catecholamine production, promoting vasospasm, increased platelet activation and decreased fibrinolysis. Additionally, preoperative interruption of antiplatelet therapy to decrease bleeding complications can trigger a rebound increase in platelet activation and platelet aggregation further increasing the risk of stent thrombosis [Collet et al. 2004; Ferrari et al. 2005]. Published reports that illustrate simultaneous two-vessel and three-vessel stent thrombosis suggest that this phenomenon is due to a generalized hypercoagulable state in a setting of a predisposed stent. Cessation of dual antiplatelet therapy (DAPT) was found to be the single most significant predictor of stent thrombosis in prior trials [Park et al. 2006]. The American College of Cardiology (ACC)/American Heart Association (AHA) recommend DAPT for 12 months after DES deployment due to lack of evidence for protection beyond that period in randomized trials [Park et al. 2010]. However, there are no studies to demonstrate the safety of antiplatelet withdrawal in patients with prior DES deployed for longer than 12 months who are anticipating surgery. We were vigorously exposed to this dilemma and have encountered six cases with acute postoperative DES thrombosis due to preoperative antiplatelet withdrawal. We attempted to study the magnitude, prevalence, causes and outcome of this complication at our institution.
identified culprit lesion and/or any unexplained death within 30 days. Possible is defined in the case of any unexplained death after 30 days [Cutlip et al. 2007]. Only definite and probable cases were classified as stent thrombosis in this study. Cases with possible stent thrombosis were excluded. Myocardial infarction was classified as ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) according to the third universal definition of myocardial infarction [Thygesen et al. 2012]. The collected cases were analyzed for patient demographics, comorbidities, type of surgery, DES type, time of coronary stenting, type of antiplatelet medication the patient received and onset of withdrawal, intraoperative hemodynamic and telemetric events, postoperative course and final outcome. We also investigated the patients’ baseline degree of severity of coronary artery disease based on historical data (according to a preoperative interview with primary cardiologist) or noninvasive cardiac stress testing. Our main objective was to study the magnitude, causes, presentation and outcome of late and very late DES thrombosis in the perioperative period. We also attempted to calculate the incidence of postoperative late and very late DES thrombosis among all surgical cases. Continuous data were presented as mean (±standard deviation) and dichotomous data were expressed as numbers and percentages.
Methods The Institutional Review Board at Tampa General Hospital approved the study and waived the need for patient consent. A retrospective chart review was performed for patients admitted to Tampa General Hospital for elective surgical procedures between January 2005 and August 2012 who suffered late and very late DES thrombosis in the immediate postoperative period. Stent thrombosis is defined on the basis of the Academic Research Consortium definitions [Cutlip et al. 2007]. According to the timing of presentation, stent thrombosis is considered late when it occurs 31–360 days after deployment, or very late when it occurs after 360 days. According to the level of certainty, stent thrombosis can be definite, probable or possible. Definite is classified in the presence of acute coronary syndrome and either angiographic or pathological (autopsy) confirmation of stent thrombosis. Probable is classified in case of an acute myocardial infarction involving the target-vessel territory without angiographic confirmation of thrombosis or other
Results Study population A total of six patients developed DES thrombosis in the immediate postoperative period during the study timeframe. They were five men and one woman, with a mean age of 59 years (range 54– 69) and a mean body mass index of 35 kg/m² (range 25–45). One third of the patients had diabetes mellitus. Other comorbidities are listed in Table 1. The patients had DES deployed 10–42 months prior to surgery with a mean of 30 months. In patients with simultaneous DES thrombosis, the date of the last deployed DES was used as ‘onset of stenting’ if DES were placed on separate occasions. Five cases had first-generation DES (Taxus or Cypher) and one case had second-generation DES (Endeavor). All patients were referred to their primary cardiologist for preoperative cardiac evaluation and risk stratification. No patient had unstable coronary artery disease prior to surgery. Stability was based on patients’ symptomatology and a prior
2 http://tac.sagepub.com
Downloaded from tak.sagepub.com at University of Waikato Library on July 12, 2014
64
55
5
6
Female
Male
Male
Male
Male
Male
Sex
45
32
45
27
25
34
BMI
Yes
Yes
No
No
No
No
DM
AFib, HTN, hypertriglyceridemia, sleep apnea, bilateral knee osteoarthritis HTN, hyperlipidemia, colon cancer, jaundice due to biliary obstruction HTN, CHF, PVD, hyperlipidemia, GERD, cervical spondylitic myelopathy HTN, hyperlipidemia, depression, GERD, HTN, CABG, PVD, hyperlipidemia, GERD, DJD, COPD, sleep apnea HTN, DVT, DJD, incisional hernia, GERD
Other comorbidities
286
Roux en- Y hepaticojejunostomy
180 170
217
Gastric banding Hip replacement
Hernia repair
215
233
Bilateral knee replacement
Spondylosis
Duration of surgery (min)*
Surgery
50
350
50
< 50
200
400
EBL (ml)
50–55
40
68
LVEF preop%
35
55–60
20–25
20
LVEF postop%
125
0.7§
100
None (no ST shifts)
None (no ST shifts) None (no ST shifts)
Occasional SB (no ST shifts)
None (no ST shifts)
lead II and ST depression in aVL > lead I suggests that the RCA is the culprit vessel). ECG of case no. 3 shows no ST elevation. ECG of case no. 4 shows high take off coved ST segments in leads I and aVL with reciprocal ST depression in V1–V3, suggesting high lateral STEMI. ECG of case no. 5 shows anterior STEMI with RBBB, suggesting a very proximal LAD lesion. ECG of case no. 6 shows high lateral STEMI (ST-segment elevation in leads I and aVL with reciprocal depression in the inferior leads). RBBB; right bundle branch block; LAD, left anterior descending coronary artery; RCA, right coronary artery; STEMI, ST-segment elevation myocardial infarction. Panels for patients 1 and 2 are adapted with permission and modification from Elsevier Science [Omar et al. 2012, 2014].
are limited data in the literature regarding DES thrombosis in the immediate postoperative period and are mostly related to antiplatelet withdrawal. It should be noted that the main evidence of increased postoperative bleeding from DAPT is mainly related to cardiac surgery. Data regarding the risk of operative bleeding after noncardiac surgery are limited and controversial. A meta-analysis by Burger and colleagues found that continuation of aspirin led to an increased rate of bleeding by a factor of 1.5, however it did not lead to a higher level of the severity of bleeding complications,
with the exception of intracranial surgery, and possibly transurethral prostatectomy [Burger et al. 2005]. Stone and colleagues found no difference in incidence of transfusion and reoperation for bleeding in 10,406 patients who underwent vascular surgery and were randomized to either aspirin alone, clopidogrel alone, aspirin and clopidogrel, or neither [Stone et al. 2011a]. Perioperative antiplatelet management remains controversial and usually represents a debate between cardiologists and surgeons. This has provoked some countries to develop national societal guidelines with partnership between cardiologists and surgeons for
6 http://tac.sagepub.com
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HR Omar, C Sprenker et al.
Figure 2. Coronary angiography (CA) of case no. 1 reveals mid LCX and proximal LAD drug-eluting stent thrombosis with sparing of a mid-LAD bare metal stent that shows in-stent restenosis (a). CA of case no. 2 reveals subtotal proximal LAD occlusion with an evident thrombus (b) and total mid RCA occlusion (c). CA of case no. 3 shows in-stent thrombosis and total occlusion of the LCX and diagonal branch (d). CA of case no. 4 shows total occlusion of the ramus intermedius branch (e). CA of case no. 6 shows in-stent thrombosis and total LAD occlusion (f). Panels (a–c) are adapted with permission from Elsevier Science [Omar et al. 2012, 2014].
ideal perioperative antiplatelet management. For example, the national society of interventional cardiology in Italy recommended that DAPT should not be withdrawn before low bleeding risk surgeries, whereas at least aspirin should be continued in the majority of surgeries [Rossini et al. 2012]. We do agree that there is no evidence from randomized trials to support continuing DAPT for longer than 1 year after DES deployment. Withdrawing antiplatelets immediately before surgery carries more risk than elective withdrawal due to the rebound increase in platelet function in the hypercoagulable perioperative state. We are occasionally met with a patient who is still prescribed DAPT indefinitely and is coming for our advice before a noncardiac surgery to decide on antiplatelet withdrawal. This decision is variable among cardiologists due to the absence of societal guidelines in this specific instance. A question to be answered is whether discontinuing antiplatelet therapy after 12 months can be generalized to all patients with DES. In our opinion, patients with DES who are still on DAPT and
are anticipating surgery should be approached more cautiously with proper risk/benefit assessment, even if the recommended 1-year period of DAPT has elapsed. In cases in whom operative risk of bleeding is minimal, we propose continuing DAPT if the patient is on it. When operative bleeding is a concern, then continuing a single antiplatelet agent with aspirin might be a reasonable alternative. We aim to draw attention to this serious complication and warn of the consequences of preoperative discontinuation of DAPT in patients with DES. Future randomized trials are mandatory in this specific group of patients to test the risks and benefits associated with implementing either approach. Funding This research received no specific grant from any funding agency in the public, commercial, or notfor-profit sectors. Conflict of interest statement The authors declare no conflicts of interest in preparing this article.
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