In this issue of Cardiovascular Revascularization Medicine , Yang et al. report the results from their randomized single-center clinical trial comparing the impact of dual antiplatelet therapy (DAPT) for six months with ticagrelor and aspirin versus one month of DAPT with clopidogrel and aspirin on thrombus burden detected by optical coherence tomography (OCT) in patients with peripheral arterial disease (PAD). The authors found ticagrelor to be associated with a significantly reduced white thrombus burden at 6-month follow-up OCT (median volume/stent length 0.067 vs. 0.014 mm 3 /mm, p=0.05). Whether this reduced white thrombus volume is clinically meaningful remains unknown. They found no significant differences between groups in Rutherford classification or ABI at 6-month follow-up; however, the study was not sufficiently powered to detect differences in clinical outcomes.
The reduction in thrombus volume seen with ticagrelor is hypothesis-generating in light of its contrast with the results of the large, double-blind randomized EUCLID clinical trial, which found no significant differences in cardiovascular death, myocardial infarction, ischemic stroke, or major bleeding. The results of this negative trial led to premature termination of this OCT study by the sponsor. Conversely, ticagrelor treatment has become the cornerstone for treating acute coronary syndrome (ACS) patients with and without undergoing PCI. From the pathophysiological point of view, PAD differs from coronary artery disease. For example, previous coronary studies in ACS patients with high thrombotic burden studied with OCT at baseline and follow-up have consistently shown thrombus resolution at very short-term follow-up (within a week). On the other hand, in this report of patients with PAD, a substantial amount of thrombus is seen at 6 months. These are important considerations when reading the present report and comparing it with previous reports from the coronary literature; insights from cardiovascular studies cannot always be applied to PAD.
OCT offers a high-resolution intravascular imaging modality that can serve as an adjunctive tool during the index procedure and follow-up. At baseline, OCT is effective at assessment of stent expansion, malapposition, and can identify geographic miss, dissection, tissue protrusion or intraluminal mass. On follow-up, OCT can exclude the presence of intraluminal mass. When an intraluminal mass is present, with current OCT technology, the ability to accurately differentiate thrombus from plaque (vessel wall) components may be limited. It may be difficult to differentiate by OCT whether the content of the intraluminal mass is white versus red thrombus or artifact. Components of thrombus can be variable and are often mixed. Despite the high resolution of OCT, significant inter- and intra-observer variability exists in respect to the evaluation of stent strut coverage. Further, at follow-up, OCT cannot discern tissue coverage of struts (i.e., neointima) from thrombogenic fibrin deposition, potentially limiting the ability of OCT to guide DAPT duration. OCT-guided antiplatelet therapy discontinuation has been previously reported in patients with coronary artery disease. However, platelet function with PAD is different when compared to coronary disease.
This study provided hypothesis-generating findings; however, it is difficult to draw significant conclusions from this pilot study given the small sample size. It generates interest, however, on how the current standard of care for DAPT regimen in patients with PAD following revascularization can be further improved. Perhaps OCT guidance can help tailor antiplatelet therapy, suggesting when a longer duration of therapy or alternative agent may be needed. While sufficient evidence currently does not exist to use OCT to guide discontinuation of DAPT, OCT-identified features, including severe malapposition or inadequate stent expansion, may guide when a longer duration of DAPT may be favored. Additionally in cases of stent thrombosis in coronaries, if no primary issue with the stent can be identified on OCT, switching to an alternative antiplatelet agent should be considered. Whether this can be applied to PAD must be evaluated.
From the current study however, it is unclear whether the increased potency of ticagrelor, the prolonged duration of DAPT, or the combination of the two played a role in reduced white thrombus burden. Further research is needed to assess whether OCT-guided medication regimens can lead to improved clinical outcomes.
Cardiovascular Revascularization Medicine, 2018-10-01, Volume 19, Issue 7, Pages 733-734, Copyright © 2018