To date, few studies have explored the potential benefit of withholding stent implantation in acute myocardial infarction when primary percutaneous coronary intervention (PCI) strategy was chosen [29].
Accordingly, this study was conducted aiming to compare the effects of immediate versus deferral of stenting and explore the benefits of delaying stenting in 1ry PCI and the better duration of delay after recanalization of the infarct related artery in a subset of patients with heavy thrombus burden.
We have found that the incidence of no/slow-reflow was significantly higher in the immediate stenting group as the percentage of patients with final TIMI flow grade 3 was significantly higher in both deferred stenting groups (group A and B) than in immediate stenting (group C) (82.2% vs. 76%, respectively), the same was found with the percentage of patients with final MBG grade 3. Also, in the DEFER-STEMI study, deferral of stenting 4–16 h caused a reduction in occurrence of no-reflow when compared to immediate stenting (5.9% vs. 28.6%) [16]. This was also consistent with Tang et al. [30] Who found a significant reduction in thrombus burden prior to stenting after 7 days of deferral, with subsequent higher percentage of final TIMI III flow in the deferral group after stenting.
In their landmark trial, DANAMI-3-DEFER, Kelbæk et al. [19] in 2016 tested deferral of stenting in a study population of patients undergoing 1ry PCI randomized to either immediate or deferred stenting, and it showed no benefit and resulted in a class III recommendation for routine deferral of stenting in the latest guidelines.
In the current study, and others’ as DEFER-STEMI trial [16], the population study selected had heavy thrombus burden (TIMI thrombus grade ≥ 2), which we thought would be the subset of patients that would benefit from stent implantation deferral. 56% in our patients’ population had TIMI grade 4 thrombus and 31% had TIMI grade 5 thrombus burden, with no significant difference between the 3 studied groups regarding neither baseline thrombus grade nor TIMI flow in the IRA. The angiographic findings of our trial showed that after the 1st procedure; the percentage of patients with TIMI flow grade 3 was significantly higher in groups A and B compared to group C (90% and 92% vs. 76%, p value = 0.034) Also thrombus regression was evident in patients’ 2nd coronary angiography, with nearly half of the patients presented at 2nd procedure with thrombus grade 2. We have also found that regarding the thrombus resolution at the 2nd procedure; group B (7 days deferral) was significantly better than group A (4–16 h deferral), this delineates the only merit of the prolonged interval of deferral in group B, leaving a longer time for the drugs to act on and help in thrombus resolution. However, after the 2nd procedure no significant difference was found between the two groups regarding the TIMI flow as well as the MBG.
In the current study, median lesion length was significantly higher in group C compared to each of groups A and group B. This was consistent with other studies as DEFER-STEMI trial [16] which showed reduced lesion length after stent deferral, however no significant difference was found between groups A and B. This is mostly caused by the spontaneous (auto-thrombolysis) and the pharmacologic induced angiographic changes in the vessel with time after deferral of stenting, resulting in shorter implanted stents with better long-term prognosis and lower rates of in-stent restenosis.
In the current study, in group A (4–16 h deferral), stenting of the IRA was avoided in 4 (8%) patients, while in group B (7 days deferral), stenting was avoided in 10 (20%) patients, which can be explained by the thrombus resolution that occurred after deferral with the subsequent relief of the vasospasm that occurs with the heavy thrombus burden.
In DEFER-STEMI trial [16] stenting was deemed unnecessary in 3 patients in the deferral group representing 6%, also in DANAMI-3-DEFER [19], despite the negative overall results of the Routine deferral of stenting, it showed that in the deferral group stenting was deemed unnecessary in 15% of patients.
While for the other secondary endpoints, the current study showed that regarding the in-hospital outcome; no significant difference was found between the 3 groups regarding over-all MACE, bleeding and CIN. While in respect to 6-months follow-up group C (immediate stenting) showed significantly higher risk of developing MACE (composite endpoint) than group A (4–16 h deferral) (34.7% vs. 14.6%; adjusted HR, 2.59; 95% CI, 1.07–6.25; p = 0.034), also the same group showed significantly higher risk of developing MACE than group B (7 days deferral) (34.7% vs. 16.3%; adjusted HR, 2.43; 95% CI, 1.05–5.64; p = 0.038). There was no statistical difference in the risk of developing MACE between groups A and B during the follow-up period. The most frequent event reported in group C was heart failure, which can be explained by the lesser percentage of achievement of TIMI grade 3 flow after revascularization of the IRA in comparison with the deferral groups.
In Tang et al. [30], no MACE occurred during period of hospitalization in both groups. After 6 months follow up, there was no significant difference in the occurrence of MACE, but lower incidence of heart failure in the deferral group was noticed (5.0% vs. 19.1%), which is consistent with our study as mentioned.
This was also associated in the current study with the fact that the median LVEF at 6 months was significantly lower in group C (immediate stenting) compared to each of groups A and B (deferred stenting) p = 0.021, however no significant difference was found between groups A and B. And the median change in LVEF between the initial echocardiography and the one performed 6 months later was significantly lower in group C compared to groups A and B, however no significant difference was found between groups A and B. In DANAMI-3-DEFER trial [19], an improvement in LVEF at 18 months with deferred stenting was observed in a smaller subset that underwent imaging. While in DEFER-STEMI trial [16], regarding the MRI findings; when compared with immediate stenting, myocardial salvage (percentage of left ventricular mass) (19.7% [IQR: 13.8% to 26.0%] vs. 14.7% [IQR: 8.1% to 23.2%]) and salvage index (68% (IQR: 54% to 82%) vs. 56% (IQR: 31% to 72%)) were higher in the deferred stenting arm after 6 months.
Improved angiographic outcomes provided by delayed stenting, such as the higher percentage of post-PCI TIMI grade 3 flow, have been associated with a reduction in death, myocardial infarction and repeat revascularization after PCI [31]. A potential mechanical explanation for the improvement associated with delayed stenting may actually be the reduction in thrombus burden. In all the studies where quantitative coronary analysis was performed a significant reduction in thrombus burden was observed before and after the interval required for delayed stenting [30].
In the light of the results of our study, and other former studies that we mentioned, deferral of stenting is proved to be a valuable strategy in primary PCI patients with heavy thrombus burden, selection of the candidates is of great importance as DANAMI-3-DEFER [19] proved that routine deferral of stenting in primary PCI was of no value. But our study proves among others that it could be used as a bailout strategy in patients with heavy thrombus burden with resulting improved coronary flow, myocardial recovery, and reduction in lesion length or even the mere need for stent implantation.