Discussion
thrombosis, PAD, CAD, thrombus, restenosis
THROMBOSIS, PROLIFERATION, DISEASE, PAD, THROMBUS, EVENTS, RESTENOSIS, CAD
The current trial involving patients who had undergone successful FP EVT showed that the sarpogrelate plus aspirin (sarpogrelate group) is non-inferior to the clopidogrel plus aspirin (clopidogrel group) in terms of 6-month target lesion restenosis. The limb-related events and cardiovascular events of the two groups were also comparable.After EVT for PAD, antiplatelet agents are used for three purposes, including prevention of early thrombosis, maintenance of long-term patency, and prevention of cardiovascular events. While aspirin- or clopidogrel-based monotherapy or DAPT is commonly used for these purposesThe best antithrombotic treatment for FP intervention remains a matter of debate. The ACC/AHASarpogrelate is an attractive drug choice for PAD considering its inhibitory effects on antiplatelet aggregation and vasoconstriction that prevent early thrombus and anti-vascular smooth muscle proliferation properties that prevent intimal hyperplasiaTo the best of our knowledge, this study was the first to show the efficacy of SR sarpogrelate after PAD EVT. We enrolled 272 patients at 10 tertiary centers in Korea, which represents the current trend of EVT for FP disease in Korea. Further comparison with data from the Western population would highlight racial or ethnic differences in EVT for PAD. The sarpogrelate group showed a tendency of less restenosis at 6 months than the clopidogrel group (13% vs 19%) without statistically significant difference. Secondary endpoints of safety outcomes were very rare in both groups, showing that both DAPT regimens are safe after FP EVT.Interestingly, in subgroup analysis, clopidogrel and aspirin showed better efficacy for reducing restenosis in CAD patients than sarpogrelate and aspirin together. A larger-scale study is needed to prove this concept. Multivariate analysis revealed TASC C/D lesions (vs A/B lesions) and only balloon angioplasty (vs stenting) were significant risk factors for restenosis at 6 months.Another noteworthy point is that a sarpogrelate SR formulation requiring once-daily dosing rather than thrice-daily was used in our study. Multiple dosing is a well-known risk factor for medication nonadherence, especially in chronic diseasesThis study has limitations. First, although a reasonable number of participants proved the non-inferiority of SR sarpogrelate to clopidogrel, this study was performed on a limited population in Korea. For generalization, multinational studies in a large population are needed. Second, the primary endpoint was restenosis at 6 months, and thus, only short-term follow-up data were available for this study. Post hoc data collection and 2-year analysis is anticipated and may reveal additional information. Third, the method of EVT was chosen at the discretion of the physician, and the study was not powered to compare the effectiveness of sarpogrelate and clopidogrel within each type of EVT (i.e. drug-coated balloons, drug-eluting stents, bare-metal stents, and plain balloon angioplasty). As in coronary beds, different medication regimens may prove more beneficial after different types of EVT. Fourth, although we had planned for a 10% dropout rate, only 78% of the randomized patients completed the six months intervention. This may have contributed to the insignificant results of the sensitivity analysis in the FAS analysis. In addition, a higher dropout rate in the per-protocol analysis could have resulted in a larger type I error than we expected, diluting the actual difference between the two intervention groups. Thus, larger-scale trials are warranted to confirm our results. Lastly, the noninferiority margin of our study was based on an expert panel discussion on the clinically meaningful difference in restenosis rate in FP lesions. While the selection of noninferiority margin needs to consider the standard treatment's effect estimate by pooling the relevant placebo-controlled randomized trial results, this was not possible as there was only one trial with inadequate sample sizeIn conclusion, results from the current trial suggest that sarpogrelate plus aspirin is non-inferior in preventing early restenosis after FP EVT compared to clopidogrel plus aspirin. Additional clinical trials in larger multinational, multiethnicity trial populations are warranted to generalize these findings.