Conversations in Cardiology: Thrombus Troubles During STEMI

The management of a patient with a large intracoronary thrombus during ST-elevation myocardial infarction (STEMI) or acute coronary syndromes (ACS) has remained troublesome and controversial. Studies of routine thrombus aspiration have not demonstrated consistent benefit, yet many interventionalists feel obligated to remove massive clot for fear of showering the fragments distally and producing an ischemic downward spiral starting with no reflow. Our expert cath lab colleagues’ group comments on their current practice for managing thrombus.

The Question

I received a question from an interventional cardiologist practicing on the East Coast. He asked, “Last week I had a 66-year-old patient with high blood pressure, diabetes mellitus, obesity, and paroxysmal atrial fibrillation (PAF) (controlled) who presented with an acute inferior wall STEMI. Moderate chest pain started at 8 pm, was relieved, then restarted the next day at 2 pm and he came to the emergency department (ED) at 4 pm (16 hours after initial pain onset). Coronary angiography showed an uninvolved left coronary system with a totally occluded proximal right coronary artery (RCA) with large clot burden (Figure 1). He had significant residual clots after thrombectomy (Figure 2). My enigma was whether to stent the RCA, or treat with heparin and glycoprotein (GP) IIb/IIIa and bring patient back for definitive treatment. 

“I did not immediately stent, but treated the patient with 24 hours of heparin and tirofiban and repeated angio the next day, which showed residual clot (Figures 3-4). I stented the vessel, but there was significant clot distally (Figure 5). Intravascular ultrasound (IVUS) also showed clot in the vessel, but no distal coronary arterial disease (CAD). I stopped and treated with dual antiplatelet therapy (DAPT) and discharged him 4 days later. What would your colleagues in the interventional community do?”

1. Would anyone not do thromboaspiration? Is there a role for intracoronary (IC) lytics, GP blockers, or other drugs?
2. With residual clot after thromboaspiration and return of TIMI-3 flow, can I wait 24 hours or longer before returning to cath lab and then stent?
3. Should I add GP blockers to heparin for the 24 hours before coming back to the lab?
4. Finally, with residual distal clot after stenting, should I have stented more in the region of the distal clot or continued heparin/GP blockers for another 24-48 hours?
5. How long should I treat with DAPT in these patients?”

The Answers

Mort Kern, Long Beach, Calif.: This is a common and difficult problem with no single answer. To your questions:

1. My guess is most Interventionalists would perform thromboaspiration based on the large clot burden despite the randomized trials showing no benefit. I do not use IC lytics, GP blockers, or heparin, except in the most dire straits.
2. Prolonged heparin can be used and has been reported to demonstrate clot resolution. However, bleeding from femoral sites complicates this approach. Radial access should be used, if not for this reason alone.
3. GP blockers probably will potentiate results of heparin on clot resolution, but bleeding risk goes up even more.
4. Stenting to cover all diseased segments despite clot might ensure any plaque that remains obstructing or stimulating clot (from erosive plaque surface) is treated. Many might be uncomfortable leaving artery with visible clot by angio and IVUS. 
5. DAPT is mandatory, of course, but duration should be standard for the practice; 1 year is reasonable. I see no special need to continue it longer.

Sam Butman, Mesa, Ariz.: I would have done and have done pretty much what Mort wrote other than 1) GP IIb/IIIa inhibitors for sure; 2) Possibly thought about a follow-up aspiration at second sitting. These would be predicated to a large degree on the TIMI flow grade at each sitting, with less ‘futzing’ [read fooling around] in the vessel being my choice if there is brisk flow.

Fred Resnic, Lahey Clinic, Burlington, Mass.: Great question, and not an uncommon conundrum for every one of us. That is an impressive volume of thrombus in the RCA! I think this case particularly highlights the putative safety benefits of transradial percutaneous coronary intervention (PCI) for STEMI, as demonstrated in the subgroup analysis in RIVAL and in RIFLE-STEACS. In this situation of heavy thrombus burden, I would advocate for aspiration thrombectomy and stenting, in front of the site of ruptured plaque, if identifiable. I would treat with GP IIb/IIIa inhibitors and DAPT with either ticagrelor or prasugrel. I don’t know how much residual thrombus I would tolerate post stenting, but it wouldn’t be a huge volume. Having said that, I don’t think I can argue against the strategy adopted by the interventionalist who opted for restoring flow without stenting, followed by “marinating” the patient with unfractionated heparin (UFH) and GP IIb/IIIa inhibition plus DAPT, and then returning to the lab for definitive mechanical treatment of the lesion seems quite reasonable. 

Bob Applegate, Wake Forest University, Winston-Salem, North Carolina: I also agree with aspiration first. Whether to “marinate” the vessel with anticoagulant and antiplatelet therapy prior to deferred stenting will be dictated by the clinical scenario. Ongoing chest pain and ST changes would, in my mind, argue for definitive initial therapy, including stenting. We did a case last year, a non-STEMI, with an enormous clot burden in the distal left main (LM). Cardiothoracic (CT) surgery wanted to defer and relook after 48 hours of heparin and eptifibatide (we went radial). Forty-eight hours later, the clot was gone, and intracoronary ultrasonic (ICUS) showed a minimal lumen area (MLA) of the distal LM of about 10 mm2. No other disease present. I have now seen him at 6 months and 1 year, and he is playing basketball with his grandkids!

Mike Kutcher, Wake Forest University, Winston-Salem, North Carolina: I agree with Fred about the merits of a transradial PCI for STEMI, which allows you to be more aggressive with antiplatelet and anticoagulation therapy. In this case, I would choose to give intracoronary abciximab up front, then aspiration, then IVUS to identify plaque, then stenting if the plaque rupture is identified, with further aspiration if necessary — followed by a 12-hour abciximab IV infusion, heparin, and DAPT. Abciximab may be more effective than a small-molecule IIb/IIIa agent. If any concerns, I’d bring the patient back to the lab the next day. I also agree the strategy of the interventionalist of record was also appropriate. The patient would warrant a clotting dysfunction work-up — but I have to admit this is almost never definitive.

George Vetrovec, VCU Pauley Heart Center, Richmond, Virginia: I would do about the same as Mort. 1) Aspiration to achieve flow and to determine lesion length. Later presentations often have higher clot burden. I remain amazed that in subanalyses, aspiration was not found beneficial, but it may be because these patients tend to do less well, so whatever is done, it is hard to change the outcome. 2) Heparin and GP inhibitors, definitely. 3) Time delay to intervention would likely depend on TIMI flow. If TIMI-3 flow post aspiration, I might consider deferring and bringing back, but not mandatory. 4) When stenting, I would make every effort to use one long stent to cover lesions and clot. 5) Only 1 inflation to maximally necessary pressure with a long 1-2 minutes of inflation time to minimize the risk of embolization. Though never totally proven and not 100% effective, I believe that the clinical observation is that not the first inflation but a subsequent inflation in a thrombotic lesion is most likely to cause embolization and slow flow.

Regarding the distal clot post PCI, I likely would not have tried to remove it with aspiration, particularly if there is TIMI-3 flow despite the clot. By this time, the clot is likely more organized and harder to aspirate. In addition, I would be concerned about mobilizing the residual clot and lastly, my long-time experience is that if an artery has good flow, the body will resolve over time and it seems by experience that the vessel will re-clot because of the residual thrombus in the setting of good flow. Lastly, I would use DAPT, ideally with prasugrel for this case. 

Bonnie Weiner, Worchester, Mass.: I am not so convinced that aspiration makes any difference, even in this setting. I would see if flow was reestablished after wiring the vessel before deciding. I suspect there is little harm, but no clear benefit. If I went in with the strategy of no initial stent, then I agree that anticoagulation and antiplatelet agents (not totally sure GP IIb/IIIa are much better than the newer oral agents) would be the next step and would bring back for relook. If at that time there was still a lot of clot, this might be the rare situation where I would think about an embolic protection device (EPD). I would also direct stent and treat it like a saphenous vein graft (SVG). Large stent at “low” but adequate pressure to try to minimize cheese grating. No reason for prolonged DAPT.

Colin Berry, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK: If TIMI-3 flow can be achieved following initial percutaneous transluminal coronary angioplasty (PTCA) and/or thrombectomy, then in cases of very large residual clot burden, deferral of stent implantation for a few hours may be helpful.¹ DANAMI-3 DEFER² didn’t support this approach in all comers with acute STEMI, but in higher risk patients with large thrombus and TIMI-3 flow, our experience suggests deferral of stenting combined with pharmacotherapy may be helpful. Low-dose infusion of intracoronary alteplase (10 mg or 20 mg) is one other “off-label” option. We are currently assessing this in a Phase 2 placebo-controlled trial.³ Just some thoughts for individualized patient management in difficult circumstances!

Gary Mintz, Columbia University, New York, New York: One comment about thrombectomy. Despite what it looks like angiographically, there is almost always a larger residual thrombus burden in this setting whether after manual thrombectomy or rheolytic thrombectomy.⁴

Lloyd Klein, Rush University, Chicago, Ill.: I am not a big fan of thrombectomy, but this would be the case I would use it in. This is mainly a visceral choice, not an evidence-based one. Intellectually, I think the odds of mechanical disruption of the clot by a large catheter is balanced by any prevention of distal embolization by extracting the clot. I also agree with eptifibatide or abciximab for 24-48 hours post procedure. I would definitely implant a stent in this setting. I also would strongly consider returning the patient to the lab if any chest pain occurred.

Mitchell W. Krucoff, Duke University, Raleigh, North Carolina: I agree with all that none of us know the right answer in this complex kind of setting. In the TAMI 7 study with parenteral systemic lyrics, patients underwent initial cath and if TIMI-3 flow, no PTCA (no stents then) was performed. Patients were maintained on heparin and ASA (no thienopyridines then) and re-cathed pre-discharge (an average of 6.5 days later). In 8% of patients, there was no residual stenotic lesion at all. On the other hand, in almost 11%, the site re-occluded with severe clinical consequences in the interim. 

Personally, I am inclined to deal with the thrombotic mass in its earliest (least organized) stages, e.g., with the index procedure, although I’d sweat a lot with this bulky thrombus. In the total absence of data, I am an “abciximab magic” believer and use it “religiously” with very bulky thrombus. I also abrogate accepted clinical trials failures with both thrombus aspiration and in large, straight, proximal or mid RCA locations, I have, several times, used distal protection with flow baskets. I use 3 steps: 1) Aspirate just enough to see the distal vessel to understand landing zone and create “abciximab flow” good humors; 2) Deploy an oversized Spider distal protection basket (Medtronic) proximal to the posterior descending artery (PDA); 3) Direct stent to high pressure for a single, long, high-pressure inflation (anticipating balloon growth with compliant balloon delivery systems). Of course, my fourth step is 4) Pray a lot, which we also showed did not demonstrate measurable therapeutic value in a prospective, randomized trial5, but I do it anyway.

Mort Kern: Mike [Kutcher], is the data for IC abciximab much stronger than IC eptifibatide? I know from past anecdotes that there is talk about this, but is there real data?

Mike Kutcher: Good point, Mort. Abciximab has a longer antiplatelet effect; that is why I use it.

Gus Pichard, Medstar Washington Hospital Center, Washington, D.C.:

1. Remember that GP IIb/IIIas are NOT thrombolytics. They will prevent additional new thrombus and allow spontaneous lysis to go on. For that reason, they are indicated in cases like this.
2. If a clinically compromised patient, and there is a need to clear the thrombus burden expeditiously, IC lytics are the best (I prefer tenecteplase [TNK], at half the standard dose for STEMI).
3. Stents are effective to treat atherosclerotic plaque. I try to never use stents for “thrombus”.
4. Aspiration with large-bore catheters or Guideliner (Vascular Solutions) can be quite effective in cases of large thrombus burden not effectively removed by aspiration catheters.

The Bottom Line

For the STEMI patient, the most critical step is to restore blood flow as soon as possible. Afterward, there is no consensus on how to get the best results for residual thrombus. If the operator starts with a wire and small balloon, then aspirates the thrombus bulk and proceeds to let the body’s own intrinsic thrombolytic system dissolve the clot with the aid of heparin/GP blockers to prevent further clotting, this seems reasonable. Stenting over a big clot always leaves residual thrombotic material, but with the potent anticoagulant and antiplatelet therapy we have today, recurrent thrombotic occlusion is uncommon, if not rare. The most important aspect of care for the patient with thrombus after immediate reperfusion without stenting is the attention to maintaining anticoagulation in the first days while the thrombotic vessel heals, reduces the residual clot burden, and becomes amenable for further stenting of the remaining obstructive CAD. 

I hope this discussion is helpful for those encountering this situation. My appreciation to my interventional colleagues for their insightful comments.

References

1. Carrick D, Oldroyd KG, McEntegart M, Haig C, Petrie MC, Eteiba H, et al. A randomized trial of deferred stenting versus immediate stenting to prevent no- or slow-reflow in acute ST-segment elevation myocardial infarction (DEFER-STEMI). J Am Coll Cardiol. 2014 May 27; 63(20): 2088-2098. doi: 10.1016/j.jacc.2014.02.530.
2. Kelbæk H, Høfsten DE, Køber L, Helqvist S, Kløvgaard L, Holmvang L, et al. Deferred versus conventional stent implantation in patients with ST-segment elevation myocardial infarction (DANAMI 3-DEFER): an open-label, randomised controlled trial. Lancet. 2016 May 28; 387(10034): 2199-2206. doi: 10.1016/S0140-6736(16)30072-1.
3. A Trial of Low-dose Adjunctive alTeplase During prIMary PCI (T-TIME). ClinicalTrials.gov. Available online at https://clinicaltrials.gov/ct2/show/NCT02257294?term=t-time&rank=1. Accessed December 28, 2016.
4. Parodi G, Valenti R, Migliorini A, Maehara A, Vergara R, Carrabba N, et al. Comparison of manual thrombus aspiration with rheolytic thrombectomy in acute myocardial infarction. Circ Cardiovasc Interv. 2013 Jun; 6(3): 224-230. doi: 10.1161/CIRCINTERVENTIONS.112.000172.
5. Krucoff MW, Crater SW, Gallup D, Blankenship JC, Cuffe M, Guarneri M, et al. Music, imagery, touch, and prayer as adjuncts to interventional cardiac care: the Monitoring and Actualisation of Noetic Trainings (MANTRA) II randomised study. Lancet. 2005 Jul 16-22; 366(9481): 211-217.

Disclosure: Dr. Kern reports he is a consultant and speaker for St. Jude Medical and Philips Volcano, and a consultant for Opsens, ACIST Medical, Heartflow, and Merit Medical.