There are three main outcomes in the present study. In the PSM cohort, (1) IVUS was associated with decreased MACE, but without statistical significance. (2) Ticagrelor significantly lowered the risk of MACCE compared with clopidogrel, especially in the angiography-guided group. The result differed slightly in the IVUS-guided group. (3) Ticagrelor increased the overall bleeding risk, mainly driven by BARC2 bleeding.
Recurrent thrombotic events after PCI tend to be associated with MI and death[12]. Ticagrelor has been recommended after PCI, given its more potent antiplatelet effect compared with clopidogrel[13, 14]. However, ticagrelor often poses a higher risk of bleeding[2, 15], including in our study. In fact, we also observed discrepancies regarding the advantage of ticagrelor in reducing thrombotic events over clopidogrel in the subgroup of patients with different bleeding and ischemia risks. [4] [16].
Patients treated with IVUS could be seen as at low risk for ischemia. Mechanical factors, such as under-expansion, malapposition, edge dissection, or residual plaque burden, may be correlated with stent thrombosis[17, 18]. IVUS could detect and fix these mechanical complications to reduce thrombotic events. Also, in the present study, IVUS-guided DES implantation tended to reduce MACE compared to angiography guidance, although the difference did not reach statistical significance. One explanation could be that the MLA was not analyzed, which is a crucial predictor of stent thrombosis [19], since this data was incomplete in our operative recordings. And unplanned revascularization was not included in our MACE, this may underestimate the effect of IVUS. Additionally and notably, in most previous IVUS studies, DAPT with clopidogrel and aspirin were prescribed after PCI[7, 20]. A recent study that compared the hard endpoint of cardiac death and MI between IVUS and angiography at 3 years; ticagrelor and prasugrel was used in the study, while the total proportion was less than 40%[9]. Although the benefit of IVUS was clarified, further analysis regarding the influence of different antiplatelet regimens on the clinical outcomes was not performed. However, ticagrelor accounted for nearly half both in the IVUS-guided group and the angiography-guided group in our PSM cohort. The superiority of ticagrelor over clopidogrel was confirmed in our study; the improvement in thrombotic events with ticagrelor might be associated with the absence of a statistically significant difference of MACE in the IVUS-guided group.
The present findings indicate that ticagrelor could be not the most beneficial treatment for patients who receive implanted stents with IVUS guidance and who are at low risk for ischemia, given the higher risk of bleeding with the use of the more potent antiplatelet agent. When patients who did or did not use IVUS was analyzed separately in our study, the efficacy of ticagrelor was only significant in the angiography-guided subgroup. The result supply clinicians with evidence for an antiplatelet regimen alternative when balancing the treatment regimen with the risks of bleeding and thromboembolic events after PCI-DES. Indeed, concerns about the increased bleeding risk in special patients often lead clinicants to prescribe a less potent P2Y12 inhibitor, potentially leaving patients undertreated and exposing them to a higher incidence of thrombotic complications. Therefore, to better balance the ischemia and bleeding risk, our study result might provide the new ideas with clinicians.
There were several explanations for this finding. Firstly, patients who treated with DES implantation with IVUS guidance were considered at low risk of ischemia due to decreased thrombogenic factors. On the other hand, IVUS could lead a larger MLA, which might in turn improve blood flow and microcirculation. In one study, the favorable effect of ticagrelor on MACE was deemed to be partly owing to the inhibition of adenosine and the consequent improved microcirculation[21]. The collective findings indicate the weakened benefit of ticagrelor in patients who receive stents with IVUS guidance.
Secondly, when endothelial cells are injured, subcutaneous components were released in the bloodstream and some changes of the mechanical microenvironment caused by stents can contribute to platelet aggregation[22]. Therefore, a more potent antiplatelet agent was recommended for preventing thrombosis after PCI[14]. IVUS could precisely guide stents and balloons to the target lesion. Although IVUS tends to be used with more complex procedures involving longer and larger stents with larger balloons and higher inflation pressure, no increased thrombotic complications have been described[23]. The precise PCI strategy achieved by IVUS with mild damage to the vascular wall might reduce injury and inflammation of endothelial cells. Thus, IVUS guidance can reduce platelet aggregation and thrombogenesis, which could further alleviate the demand for potent platelet agents. This deduction was supported by the findings of the ADAPT study[24], which demonstrated a significantly low risk of thrombotic events in patients whose stents were guided by IVUS versus those guided by angiography. The less potent P2Y12 inhibitor, clopidogrel, was prescribed for the whole study cohort and clopidogrel hypo-responsiveness was more frequently seen in the IVUS-guided group. Our comparative data obtained by matching patients concerning stent size still revealed a beneficial tendency with IVUS. To some extent, IVUS attenuated the superiority of ticagrelor.
Finally, except for the target lesion, recurrent thrombotic events arise from high-risk plaques at non-culprit lesions, which are characterized by a large plaque burden, small MLD, and thin-cap fibroatheromas [25]. IVUS can detect these high-risk plaques outside stents, which can drive the selection of a more appropriate medical management to decrease residue risk [26]. This personalized medicine management could alleviate the advantage of a potent antiplatelet agent.
The clinical outcomes of ticagrelor over clopidogrel based on IVUS-guided PCI for patients with ACS has been unclear. Our findings provide insight on the choice between ticagrelor and clopidogrel for clinicians. The beneficial role of ticagrelor in reducing thrombotic events comes at the expense of increased bleeding risk. Clopidogrel may be a suitable alternative for patients with ACS whose stent implantation is guided by IVUS. This study result may provide further ideas for personalized treatment.
Limitations
This was a single central observational study. Although the baseline, lesion, and procedural features were well balanced using PSM, unknown confounders were possible. First, the decision whether to use IVUS guidance and IVUS guidance criteria were solely at the operators’ discretion. Second, the endpoint of MI could not be conclusively determined in the same treated vessel guided with IVUS. Third, our study was conclusive only for the composite endpoint related to thrombotic events. Difference for individual endpoints did not reach statistical significance. At last, the current study result would only be hypothesis-generating.