In this pooled individual patient-level analysis from two large-sized, contemporary, real-world registries, we observed that DAPT duration was highly variable. As compared with guideline-recommended DAPT duration (at least 1 year), shorter DAPT duration was associated with a significantly increased risk of MACE without benefit of major bleeding.
LMCA lesions are one of the most complex anatomic subsets in real-world clinical settings. Recent clinical studies suggested that PCI with second-generation DES for LMCA disease provided favorable procedural and long-term clinical outcomes2,3. However, there have been few studies on long-term duration and effect of DAPT in the contemporary PCI practice with second-generation DES for treatment of LMCA disease. In a recent study, DAPT for > 12 months after an index procedure was associated with a reduced risk of ischemic events among patients with LMCA bifurcation stenting, compared with DAPT for ≤ 12 months13. However, this study might have been hampered by the use of first-generation DES, exclusion of LMCA ostial and shaft lesions, and non-assessment of bleeding events. Moreover, since events that occurred within 12 months were excluded, the exact relationship of shorter or longer duration of DAPT with clinical events could not be assessed. In contrast, in the recent EXCEL trial report, continuation of DAPT beyond 12 months was not found to be associated with a reduced risk of ischemic events (death, MI, or stroke) after PCI with everolimus-eluting stents in patients with LMCA disease14. However, this study was a subgroup analysis including a relatively limited number of patients, and bleeding events were also not assessed. In the current study, we investigated the clinical outcomes including ischemic and bleeding events according to different durations of DAPT in patients receiving PCI with contemporary second-generation DES for LMCA disease using two large-scaled real-world registries. Following PCI, most patients (84.8%) maintained DAPT for at least 6 months according to the current guidelines. After multiple treatment propensity score weighting, with the DAPT 12–24 months as the reference group, DAPT for < 6 months was significantly associated with a higher risk of MACE without clinical benefit of major bleeding.
Recently, several RCTs have reported the potential benefit of reduced DAPT duration in patients receiving contemporary second-generation DES15,16. Most studies have shown that antiplatelet monotherapy was associated with lower incidence of clinically relevant bleeding compared to DAPT with increasing risk of ischemic events. However, the observed results from several studies with regard to the shortening of DAPT in the complex PCI groups were conflicting and the number of patients with LMCA disease was too small to provide clinically meaningful insights. In the RAIN registry (veRy thin stents for patients with left mAIn or bifurcatioN in real life) subgroup analysis, the incidence of MACE was significantly higher in the ≤ 3 months DAPT group compared to the 3–12 and > 12 months DAPT groups, which was mainly driven by the differences in MI and ST17. Theoretically, despite the use of second-generation DES, PCI for LMCA disease is more prone to develop stent malapposition due to large diameter and bifurcation compared to non-LMCA lesions, which might result in insufficient strut coverage and the potential risk of thrombus formation. In previous studies, especially among patients with two-stent strategy implying a high probability of stent malapposition and underexpansion, fatal ischemic events substantially increased when DAPT was discontinued18. A similar signal of association between shorter DAPT and higher ischemic events was also observed in our study, which might have a paramount clinical significance with regard to the optimal DAPT duration in patients with complex PCI for LMCA disease. Our findings should be further addressed through adequately powered RCTs involving complex high-risk PCI.
There have been several score systems (e.g. DAPT score, Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy [PRECISE-DAPT score]) and validation studies to determine the optimal duration of DAPT19,20. In a previous study, DAPT > 12 months was associated with a lower MACE rate than DAPT ≤ 12 months within a population with DAPT score ≥ 2, but not within a population with DAPT score < 213. In our study, spline analysis showed that maintaining up to 12.6 months of DAPT appears to reduce MACE according to the best cutoff based on the highest Youden’s index. This finding may support the current guideline recommendations of at least 12 months DAPT for complex PCI to balance the risks between ischemic and bleeding events. The IDEAL-LM trial (Improved Drug-Eluting stent for All-comers Left Main trial; NCT02303717) will additional information on the optimal duration of DAPT in patients undergoing PCI for LMCA disease.
There are several limitations of our study. First, although multiple propensity score treatment analysis was performed, this study was an observational, nonrandomized study; therefore, it might be vulnerable to the inherent limitations including selection bias and unmeasured confounders. Thus, overall observed findings should be interpretated as provisional and hypothesis-generating only. These findings should be confirmed or refuted through large-sized RCTs. Second, owing to the limited number of clinical events, our study was underpowered to detect clinically relevant difference with regard to hard clinical endpoints including death, ST, or major bleeding. Third, we could not investigate the PRECISE-DAPT score owing to some missing variables. Fourth, we could not systematically measure the detailed information of the atherosclerotic burden and complexity, such as SYNTAX score. Finally, in the current study, potent P2Y12 inhibitors, such as prasugrel and ticagrelor, were less frequently used. In recent study, novel P2Y12 inhibitor monotherapy was shown to reduce major bleeding events without increasing ischemic events in patients with complex PCI21. This concept should be further tested in patients with complex PCI including LMCA disease.
In conclusion, in this merged individual patient-level analysis of two large-scaled real-world registries, shorter duration of DAPT was significantly associated with increased risk of MACE without benefit of major bleeding compared to the guideline-directed DAPT duration (at least 1 year) in patients with LMCA disease who have undergone PCI with second-generation DES. Future RCTs to determine the optimal duration of DAPT for patients receiving complex PCI including LMCA disease, are warranted.