Cath-Lab Complications: New Analysis Pinpoints Rate and Risks of Intraprocedural Thrombotic Events in ACS
Pooled patient data from 2 bivalirudin vs heparin trials is shedding a light on intraprocedural thrombotic events in the setting of STEMI and non–ST-elevation acute coronary syndromes. In particular, the analysis addresses which components of this composite endpoint occur the most frequently—and at what price for patients.
Jeffrey Wessler, MD, of Columbia University Medical Center (New York, NY), and colleagues, writing in an early-online publication in JACC: Cardiovascular Interventions, define intraprocedural thrombotic events (IPTE) as new or worsened thrombus, abrupt closure, distal embolization, no-reflow/slow flow, and stent thrombosis during PCI.
“IPTE occur frequently—one in every 13 patients undergoing PCI for high-risk ACS,” Wessler observed to TCTMD. Getting a better understanding of what types of events are occurring may lead to better ways of mitigating their impact, the authors say.
Senior investigator on the study, Ajay J. Kirtane, MD, SM, also of Columbia, acknowledged that most operators are already well aware that IPTE are unwelcome news in the cath lab.
“Every interventional cardiologist can tell you if that event happens . . . that wouldn’t be a good thing,” he told TCTMD. “What’s not clear when you use a composite endpoint is whether 1 component or another in particular is more relevant or important when it comes to clinical outcomes.”
Fortunately, he added, the individual component events are very rare, which was what drove investigators to combine datasets from the HORIZONS-AMI and ACUITY trials. Both studies tested strategies involving bivalirudin, heparin, or glycoprotein IIb/IIIa inhibitors (GPIs) in the setting of PCI for STEMI and NSTE-ACS, respectively. IPTE events overall occurred in 7.7% of 6,951 patients in the combined dataset: in 12.2% of STEMI patients and 3.5% of NSTE-ACS patients.
Occurrence of IPTE was associated with a 2-fold higher 30-day MACE and a 3-fold higher death rate, compared with patients who did not experience an IPTE. Rates of reinfarction, stent thrombosis, and non-CABG bleeding were also significantly higher. These latter numbers are worth noting, Kirtane observed, since they hint at a practice pattern whereby interventionalists who encounter a stent thrombosis during the PCI escalate pharmacotherapies and require more time to complete the procedure, both of which also increase the bleeding risk.
Commenting on the study by email, Rod Stables, MD, of the Liverpool Heart and Chest Hospital, UK, pointed out that the reverse is also true: “Having a bleed as an index event then increases the risk of a subsequent ischemic event,” due to hypotension and low flow; stoppage of antiplatelet agents leading to an increased risk of stent thrombosis; or blood transfusions that increase the risk for thrombotic MACE.
Most Common IPTE
The most common IPTE type was no-reflow/slow flow, making up more than half of the IPTE (58%). This was followed by new/worsened thrombus (35%), distal embolization (35%), abrupt closure (20%), and intraprocedural stent thrombosis (9.5%). Of note, more than one IPTE tended to happen in the same patient, with 23% of patients who experienced the phenomenon having at least 2 component events and 20% having more than 2 types of IPTE.
Importantly, all of the individual components of IPTE were independently associated with death, major bleeding, and MACE at 30 days. This association was strongest for stent thrombosis occurring during the procedure.
Mitigating the Risks
These findings should prompt operators to figure out the best therapies for helping them avoid these events. According to Kirtane, the current evidence base supports a role for GPIs in this setting, and more recently, for cangrelor. “But at the same time, you need to make sure that can be done safely—the more antithrombotic therapy you add, the more patients risk having a bleed,” he said.
Indeed, when risk of IPTE was analyzed in relation to study drugs, investigators showed that while there were no differences in IPTE occurrence among patients randomized to bivalirudin plus GPIs or patients randomized to heparin, numbers of IPTE were higher among patients assigned to bivalirudin alone and lower among patients randomized to GPI.
“This is a useful study that, to some extent, sets the scene for what—in my opinion—is the next big thing in STEMI PCI,” Stables commented. “That is, how do we recognise, in real-time, the case that is not going so well, to spot the patients with the greatest potential for the occurrence of adverse events? This recognition could then be the prelude for the application of some additional, targeted therapy.”
Currently, Stables continued, primary PCI in STEMI “is a bit formulaic—every patient gets the basic package and then we just see how they fare. Research to date has been a little unimaginative; we test a drug, for example a GPI, or a technology, like thrombectomy, in trials that demand unselected, universal application. That means 1 group gets 100% use and the other 0% use.”
Instead, Stables told TCTMD, “we need to be more selective with the range of ‘extra’ treatment options,” including use of GPIs, oral or IV P2Y12 inhibitors, vasoldilators, coronary sinus counter-pulsation, and balloon pumps as well as potentially consider delayed stenting as a means of minimizing intraprocedural complications—a strategy previously explored by Berry and colleagues in the DEFER-STEMI trial.
In an accompanying editorial, Neal S. Kleiman, MD, of Houston Methodist DeBakey Heart and Vascular Center in Texas, lists many of the same strategies as Stables for reducing risks of IPTE in the cath lab. There are also emerging drug targets, including glycoprotein Ib/V/IX, the platelet receptor responsible for mediating platelet adhesion, and glycoprotein VI, the principal platelet receptor for collagen, he notes, plus “a variety of newly identified platelet signaling targets that are downstream from previously identified receptors.”
All of these approaches must walk the knife edge faced by all antiplatelet drugs that have gone before, balancing the risk of excess bleeding against reducing ischemic events, Kleiman stresses.
That is not to say prevention of IPTE is not a worthy goal: extrapolating the numbers from Wessler et al’s analysis to PCI volumes in the United States, nearly 29,000 cases likely occur every year, Kleiman writes. “A back of the envelope calculation of attributable risk percentage reveals that 48% of MACE, 70% of the deaths, and 62.5% of the stent thromboses that occur by 30 days could be prevented if IPTE were eliminated.”
He concludes: “Focusing on the target group suggested by the current paper would allow further refinement of PCI as it would allow newer therapies which might carry a higher bleeding risk or be otherwise more resource-intensive to be developed for the patients at highest risk.”
Note: Several coauthors of the paper are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.
1. Wessler JD, Généreux P, Mehran R, et al. Which intraprocedural thrombotic events impact clinical outcomes following percutaneous coronary intervention in acute coronary syndromes? A pooled analysis of the HORIZONS-AMI and ACUITY trials. J Am Coll Cardiol Interv. 2016;Epub ahead of print.
2. What happens in the cath lab stays in the cath lab or does it? Intraprocedural thrombotic events in patients with acute coronary syndromes [editorial]. J Am Coll Cardiol Interv. 2016;Epub ahead of print.
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- Kirtane reports institutional research grants to Columbia University from Abbott Vascular, Abiomed, Boston Scientific, Eli Lilly, Medtronic, St. Jude Medical, and Vascular Dynamics.
- Kleiman reports being a consultant to Medicure.
- Stables reports research grants from AstraZeneca and The Medicines Company and Speakers fees from AstraZeneca.