Thoughtful Insights at TCT: Uncertainty Surrounds Antithrombotic Therapy in PCI Patients Who Require Anticoagulation
Washington, DC—Interventional cardiologists are awaiting the results of ongoing trials to help answer questions about the ideal type and duration of antithrombotic therapy for patients undergoing percutaneous coronary intervention (PCI) who have indications for oral anticoagulation, according to discussions held during the “Adjunctive Pharmacology Conundrums” session on the final day of TCT 2014.
Three case presentations, each accompanied by a “thoughtful insights” presentation and panel discussion, covered the preferred pharmacotherapy during and after STEMI, the duration of dual antiplatelet therapy (DAPT) in complex patients, and DES implantation in patients with chronic atrial fibrillation (A-fib).
However, the common thread tying these presentations all together was the question of what to do for patients who require both DAPT and oral anticoagulation.
One of the moderators of the session, TCT Course Director Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), pointed out that even though the benefits of warfarin and novel oral anticoagulants are well established, there is little information on what happens when they are combined with DAPT.
“I think we need a lot more data before we can be confident that we know what we’re doing,” he said.
Questions Remain on Combining DAPT, Anticoagulation
Following a case presentation on a patient with STEMI already on rivaroxaban who received BMS, Neal S. Kleiman, MD, of Houston Methodist DeBakey Heart and Vascular Center (Houston, TX), highlighted the problem facing clinicians who have to decide on how to treat patients who are candidates for DAPT and oral anticoagulation.
With 4 approved oral anticoagulants (warfarin, rivaroxaban, dabigatran, and apixaban), 3 P2Y12 antagonists (clopidogrel, prasugrel, and ticagrelor), and aspirin, there are 39 possible therapeutic combinations without taking dose or duration into consideration, he said. Throwing edoxaban—which has not yet been approved—into the mix would bring the total to more than 50 potential combinations.
Dr. Kleiman introduced some key pieces of evidence to consider when tackling the question of antithrombotic therapy in these patients, including data from a Danish registry study suggesting that patients do at least as well—if not better—on warfarin and clopidogrel as they do on triple therapy including aspirin.
The ISAR-TRIPLE trial presented at TCT 2014 provided some information to inform this issue by randomizing patients on both aspirin and vitamin K antagonist therapy after DES implantation to a short or long duration of clopidogrel. There were no differences between the groups in ischemic or bleeding outcomes.
Another important piece of the puzzle, Dr. Kleiman said, is the WOEST trial, in which PCI patients on oral anticoagulation did better in terms of both bleeding and clinical outcomes when they received clopidogrel alone instead of clopidogrel plus aspirin.
He and other panelists pointed out some limitations of that study, including the small sample size resulting in a lack of statistical power to look at ischemic outcomes, the inclusion of patients with relatively simple lesions, the aggressive antiplatelet regimen in the control arm, and the lack of information on the use of more potent antiplatelet agents. In addition, Dr. Stone expressed skepticism about the size of the effects seen in the trial.
Because of the shortcomings of the existing evidence regarding the combination of oral anticoagulation and DAPT, Pascal Vranckx, MD, PhD, of Hartcentrum Hasselt (Hasselt, Belgium), said “the efficacy and safety of different antithrombotic regimens in individuals with more than 1 indication for antithrombotic therapy is still unresolved.”
While awaiting the results of numerous ongoing trials expected to resolve some of the remaining uncertainty—including RE-DUAL PCI, PIONEER AF-PCI, MUSICA-2, and others—Dr. Kleiman said a good approach to managing the dilemma is to look at the recently released joint consensus document from the European Society of Cardiology Working Group on Thrombosis and other groups on using antithrombotic therapy in A-fib patients presenting with ACS or undergoing PCI or valve interventions.
“That [document] outlines a very pragmatic approach that’s largely patient-centered, assessing the patient’s… thrombotic risk, as well as whether they’ve had stable angina or an acute coronary syndrome,” he said.
Device Alternatives to Stroke Prevention
Dr. Vranckx’s “thoughtful insights” presentation followed a case study involving a man with paroxysmal A-fib who underwent a series of procedures including staged PCI for 3-vessel disease and LAA closure, first with the Lariat device (SentreHEART; Redwood City, CA), then, to correct leakage, with the Amplatzer plug (St. Jude; St. Paul, MN).
Presented by Matthew J. Price, MD, of the Scripps Clinic (La Jolla, CA), the case raised questions about not just pharmacologic therapy but also device treatments to minimize stroke risk. Patients with complex disease were not well represented in WOEST and might represent an important population for alternative stroke prevention strategies like transcatheter LAA ligation and plugging of the LAA with the as of yet unapproved Watchman device (Boston Scientific; Natick, MA), particularly if there are contraindications to oral anticoagulation.
Dr. Stone noted that the first long-term combined data from the PROTECT AF and PREVAIL trials of Watchman yielded mixed results, with less ischemic protection with the device than with warfarin but a lower risk of cardiovascular/unexplained mortality with the device. So even though Watchman might not be as protective as warfarin, it might be a good alternative in high-risk cases. As for LAA ligation with Lariat, however, outcomes data are almost unknown, he added.
Dr. Price agreed with the lack of outcomes data for Lariat, and said, “What we have to take away is [that] the profound excitement or uptake of the Lariat procedure with zero data in the United States… is reflective of the profound unmet clinical need… for patients who are at risk for oral anticoagulation.”
Optimal DAPT Duration Murky
Aside from the best composition of antithrombotic regimens, the optimal duration of DAPT after stent implantation has not been resolved, either in patients with A-fib or PCI patients in general, a situation that has interventional cardiologists “very confused,” according to Roxana Mehran, MD, of Mount Sinai Medical Center (New York, NY), who also moderated the session.
A third case study involved a man with 2-week history of substernal chest pain who was already on warfarin (INR 2.8) and aspirin—and experiencing intermittent nose bleeding that could be stopped by prolonged compression. Diagnostic angiography showed a large proximal lesion with moderate calcification in the LAD, so, after being cleared by an ear, nose, and throat consult, he received DES and remained on DAPT for 6 months.
In his “thoughtful insights” presentation following the case, Daniel I. Simon, MD, of University Hospitals Case Medical Center (Cleveland, OH), noted that there is some evidence suggesting that earlier discontinuation of DAPT does not appear to be associated with higher risks of MACE or stent thrombosis, and that extended DAPT could increase bleeding without any ischemic benefits.
Some trials have already explored the question of DAPT duration—EXCELLENT, PRODIGY, DES-LATE, and OPTIMIZE—and have shown no ischemic benefit with longer durations and reductions in major bleeding with shorter durations (except in OPTIMIZE). But much more information is forthcoming and the issue is far from settled, Dr. Simon noted.
“The randomized evidence to date does not support prolonged DAPT, but I think it’s very important to emphasize that definitive conclusions regarding duration await the results of multiple pending trials, including DAPT, OPTIDUAL, [ISAR-SAFE], ARCTIC, ITALIC, and SCORE,” he said.
Eric R. Bates, MD, of the University of Michigan Health System (Ann Arbor, MI), suggested that the decision about how long to keep a patient on DAPT needs to be personalized.
“I think we’re asking too much from guidelines and from clinical trials to give us direction on individual patient care. I don’t think we’re ever going to solve this completely,” he said. “So I think you pretty much have to take everything you know about it, and use the art of medicine and figure out what’s best for a given patient.”
Frederick Feit, MD, of NYU Langone Medical Center (New York, NY), agreed that determining the optimal duration should be done on a case-by-case basis, and he questioned whether the much-anticipated DAPT Study—which will be presented at the upcoming meeting of the American Heart Association—will provide conclusive guidance.
“[To] those of you who are staying tuned to DAPT like it’s the Super Bowl, it’s going to be a tie and it’s going to be a boring tie,” he said.
- Dr. Kleiman reports no relevant conflicts of interest.
- Dr. Price reports receiving consulting honoraria from AstraZeneca, Boston Scientific, Daiichi Sankyo, St. Jude Medical, and WL Gore; institutional research support from Boston Scientific, SentreHEART, and St. Jude Medical; and speaker’s honoraria from AstraZeneca and Daiichi Sankyo/Eli Lilly.
- Dr. Simon reports receiving grant/research support from the Medtronic Foundation and consulting fees/honoraria from Cordis, Janssen, Medtronic, and Merck.
- Dr. Vranckx reports receiving consulting fees/honoraria from Bayer HealthCare, Bristol-Myers Squibb/Pfizer, and The Medicines Company.
- Dr. Stone reports receiving consultant fees/honoraria/speaker’s bureau fees from Reva and TherOx and having equity in Artasis, Biostar Funds, Caliber, Guided Delivery Systems, MedFocus Funds, Micardia, and VNT.
- Dr. Bates reports receiving consultant fees/honoraria/speaker’s bureau fees from AstraZeneca, Daiichi Sankyo/Eli Lilly, Merck/Schering Plough, and Sanofi Aventis.
- Dr. Feit reports receiving consultant fees/honoraria/speaker’s bureau fees from The Medicines Company and having equity in Boston Scientific, Medtronic, and The Medicines Company.
- Dr. Mehran reports relationships with multiple pharmaceutical and device companies.