Drug-Eluting Stent Management Dilemmas II

How Do you Manage the Patient with Recent Drug Eluting Stent Placement Who Requires Urgent Non-cardiac Surgery? H. Vernon (Skip) Anderson, MD The topic of interest is the recent DES patient who requires urgent surgery, usually non-cardiac surgery, and how do you deal with this patient. Balloon angioplasty (POBA) was done for many years in patients requiring non-cardiac surgery, and the patients did very well with that mode of revascularization. In fact, sometimes POBA was recommended over coronary bypass as being better suited and less risky for patients needing non-cardiac surgery, even if POBA would not have otherwise been the first choice. Initially after bare metal stents (BMS) were introduced and came to be accepted, this practice continued mostly unchanged, where patients would be revascularized with BMS and then have their non-cardiac surgeries performed shortly thereafter. The first hint of a problem came in 2000 with a publication by Kaluza and colleagues.(1) This group reported 40 patients who had non-cardiac surgery performed between 1-39 days after a BMS was implanted, with the average being 13 days later (approximately 2 weeks). Astoundingly, there were 7 infarctions, 11 major bleeds, and 8 deaths. Soon after that initial report, groups at the Mayo Clinic and the Washington Hospital Center reviewed their own experiences which confirmed high rates of early adverse events with stents in patients undergoing non-cardiac surgery.(2,3) The data seemed to indicate that there was an early period of high vulnerability if the non-cardiac surgery was done within 3-to-6 weeks after stenting, but was less of a problem or not a problem at all if the non-cardiac surgery was delayed beyond this vulnerable period. (See Figure 1) Recent evaluations have tended to support the later date of 6 weeks for BMS. As drug eluting stents (DES) have supplanted BMS in the majority of coronary stent cases, the focus has shifted to those devices. We now know that with DES in general there is an early vulnerable period during which stent thrombosis can occur, followed by a later period of low-frequency but relatively constant “late” stent thrombosis.(See Figure 2) The usual strategy for dealing with this situation is to maintain dual antiplatelet therapy (DAPT) with aspirin and a thieneopyridine for a long time following DES implantation. This typically means a year or more of DAPT treatment. The potential problem with this prolonged DAPT strategy is that it can increase the bleeding risks for the non-cardiac surgery. Therefore, the issue boils down to one of ‘balance.’ The clinician has to balance the potential benefits of DES with the risks both of early and late stent thrombosis and also bleeding due to the prolonged DAPT. There are several strategic approaches that have been developed to help guide the management of patients who need surgery in the setting of coronary stents. Two of these are shown in Figure 3. Both strategic approaches take into account the possibility of using either BMS or DES, and the approach shown in Figure 3B also includes consideration of no coronary revascularization at all or revascularization using only POBA and avoiding stents altogether. Both approaches also use the recommended time limits of 6 weeks delay for BMS and 1 year delay (12 months) for DES. Other modulating factors are the estimated risks of stent thrombosis (low, moderate, or high) and of course the urgency of the anticipated surgery. There are no completely right or completely wrong answers for this situation. Clinicians must struggle to balance all of the issues in the care of the specific patient. References 1. Kaluza GL, Joseph J, Lee JR, Raizner ME, Raizner AE. Catastrophic outcomes of noncardiac surgery soon after coronary stenting. J Am Coll Cardiol 2000; 35: 1288–1294. 2. Wilson SH, Fasseas P, Orford JL, Lennon RJ, Horlocker T, Charnoff NE, Melby S, Berger PB. Clinical outcome of patients undergoing non-cardiac surgery in the two months following coronary stenting. J Am Coll Cardiol 2003;42:234-240. 3. Sharma AK, Ajani AE, Hamwi SM, Maniar P, Lakhani SV, Waksman R, Lindsay J. Major noncardiac surgery following coronary stenting: when is it safe to operate? Cathet Cardiovasc Interv 2004;63:141-145. 4. Daemen J, Wenaweser P, Tsuchida K, Abrecht L, Vaina S, Morger C, Kukreja N, Jüni P, Sianos G, Hellige G, van Domburg RT, Hess OM, Boersma E, Meier B, Windecker S, Serruys PW. 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 2007;369:667–668. 5. Riddell JW, Chiche L, Plaud B, Hamon M. Coronary stents and noncardiac surgery. Circulation 2007; 116: e378–e382. 6. Brilakis ES, Banerjee S, Berger PB. Perioperative management of patients with coronary stents. J Am Coll Cardiol 2007; 49:2145–2150. Figure 1. Early vulnerability for coronary stent thrombosis with non-cardiac surgery. (A)From Ref. 2. (B)From Ref. 3. ------ Figure 2. Periods of stent thrombosis following drug eluting stent (DES) placement. From Ref 4. ------ Figure 3. Suggested approaches to patients who require non-cardiac surgery and have recent implantation of coronary stents. (A) From Ref. # 5. (B) From Ref. # 6. Additional Risk Factors for Stent Thrombosis Coronary Anatomy Bifurcation stenting Ostial stenting Small ( 18 mm) stent length Overlapping stents Multiple stents Suboptimal result Stent-indication Acute coronary syndrome Patient Diabetes Renal impairment Advanced age Low ejection fraction Prior brachytherapy _______________________________________ Also in this session How Do you Manage the High-Risk DES Patient who Requires Coumadin Therapy? By Cindy Grines, MD _______________________________________

Discussion: Drug-eluting Stent Management Dilemmas Part II

Moderated by Howard Cohen, MD Howard Cohen: Thank you Cindy and Skip that was great. Any questions from the audience? Bob Bersin: In our region what I am seeing, for example in a patient who gets a DES and then needs urgent surgery, is that some of the clinicians are stopping the clopidogrel and administering a 2B3A, like Integrilin up until the time of the operation to help protect them against early stent thrombosis, when it is a very fresh DES. Can we hear some comments about either that or the use of subcutaneous Lovenox? Any discussion of these bridging agents to surgery when surgery had not been anticipated? Cindy Grines: I see that being used by some of my partners as well as others using 2B3As. I mean there is at least some rationale for using the 2B3As, clopidogrel and antiplatelet agents, but of course there are no studies to prove that it is worthwhile. One of the things that concerns me is abrupt withdrawal of the 2B3A and then doing the surgery on patients who really are still unprotected. You know Bill, you might want to comment about the EXCITE trial, since I think it was when you gave the oral 2B3As that there was an increase event rate, increase ischemic event rate that was thought to be due to these ups and downs in terms of the platelet inhibition. Is that correct? Yes. And then with regard to Lovenox, I think there is even less rational for doing that because it is an antithrombin agent. Jim Zidar, didn’t you do a trial of stent, high risk stenting with….? Jim Zidar: I would like to hear from Steve Steinhubl he has probably more exposure…..(inaudible……) what should we be doing? I think Bob’s question is really something that we are seeing, we are seeing a lot of clinicians sort of playing this game of what are we supposed to be using and Steve you thought of this for the last 10 years, made a lot of career about it. What should we be doing for practical? I see these papers but I am not sure they help me that much when you look back retrospectively at what the Mayo Clinic is doing or. I have a struggle especially with non-cardiac surgery that is elective. Steve Steinhubl: Thanks for all the pressure. Although I have thought about this issue a lot I have to admit I truly don’t know the right answer. Obviously Cindy has thought about this even more so. I certainly agree with everything she said. I am concerned that anesthesia societies do recommend enoxaparin and unfractionated heparin bridging and in fact we have very good data from the ACS trials that, that is a great way to make your platelets hyper-responsive upon discontinuation. In all of the early ACS trials when you stop unfractionated heparin, in particular with no antiplatelet therapy, you have a clustering of thrombotic events. In the case of surgery you are then you end up just adding additional prothrombotic stressors onto a patient. I know that there are several single center trials looking at tirofiban or eptifibatide bridging. In these trials I again agree with Cindy that there are certainly concerns with stopping the 2B3A inhibitor and sending a patient to surgery with hyperactive platelets. The Medicines Company is studying cangrelor, which is a very short acting P2Y12 inhibitor. We are looking at cangrelor as pre-operative bridging therapy in a trial called BRIDGE. Its PK/PD profile appears ideal for this role but there remain a lot of things we still don’t know. So this has been a long non-answer, because I don’t really know what to do but I definitely don’t like bridging with enoxaparin or unfractionated heparin and I tended not to bridge with a 2B3A inhibitor except in the rare case when a patient had gotten left main stent or some very high risk bifurcation stenting. Alex Zapolonski: I don’t want to comment on what to do to transition Plavix to something else, but I do want to comment on the fact that for cardiac surgery we are using a simple test that costs $40. It is from a company from Accumetrics and it gives us very, very accurate information as to whether there is really platelet inhibition or there isn’t. The surprising thing is that about 30% of the time the platelet inhibition is zero in patients that have been Plavix for two years. So we are faced with this situation in which we were originally going to delay these patients for 5-6 days prior to cardiac surgery, but with the test we don’t have to worry about it and the patients don’t bleed. So basically we are relying on a drug that 30% of the time is not active. _______________________________