Previous meta-analyses based on ITDM patients with cardiac problems were well appreciated [2, 13].
Nevertheless, even though the authors assessed stent thrombosis in their previous work, this particular outcome was not assessed in detail. We therefore came up with the new idea of systematically comparing early, late and very late stent thrombosis post-PCI in patients with ITDM and NITDM.
In the previous analysis, stent thrombosis was shown to be significantly higher in patients with ITDM compared with NITDM (OR 1.66, 95% CI 1.16–2.38, P = 0.005 for short-term ST; OR 1.59, 95% CI 1.21–2.10; P = 0.001 for long-term ST) .
When data were closely assessed, it could be seen that stent thrombosis was definitely significantly higher in patients with ITDM compared with NITDM. This result was obtained when definite and probable or possible stent thromboses were analyzed all together. However, in the current analysis, when stent thrombosis was assessed based on the time period following PCI, early stent thrombosis was significantly higher in patients with insulin therapy (OR 1.81, 95% CI 1.04–3.15; P = 0.04). However, late (OR 1.44, 95% CI 0.73–2.84; P = 0.30) and very late stent thromboses (OR 0.80, 95% CI 0.33–1.92; P = 0.62) were not significantly different in patients with ITDM and NITDM.
Several reasons have been suggested for the high level of stent thrombosis in patients with ITDM: Patients on insulin therapy have more advanced disease, and their risk of complications after PCI is higher according to their high risk profile. Also, iatrogenic hyperinsulinemia might promote proinflammatory macrophage responses and stimulate hormonal hyperactivity, which might in return disturb the balanced synthesis and release of endothelial mediators. Insulin therapy might also cause platelet hyperactivity, which can then increase the chance of stent thrombosis after PCI with DES.
Reasons that have been considered for a similar rate of late and very late stent thrombosis in this analysis could be that:
The total number of studies reporting these outcomes were few and not sufficient to reach a robust result in terms of very late stent thromboses, which were only reported in four studies;
This issue is controversial, and the number of studies favoring ITDM was similar to the number of studies favoring NITDM, resulting in an insignificant result for favoring either ITDM or NITDM in case of late and very late stent thrombosis;
The total number of early stent thromboses in patients with ITDM was indeed higher compared with late and very late stent thrombosis.
In other studies where early and late stent thromboses were reported following PCI in patients with and without insulin therapy, for example, in the E-five registry , 14 patients out of a total of 644 (2.17%) patients with ITDM experienced stent thrombosis as defined by the Academic Research Consortium (ARC), whereas 25 out of 1919 (1.30%) patients with NITDM experienced stent thrombosis as defined by the ARC. However, when stent thrombosis was further divided into early and late stent thrombosis, 1.6% of patients with ITDM experienced early stent thrombosis and 1.0% of the patients with NITDM experienced early stent thrombosis, whereas 0.8% and 0.3% of the patients with ITDM and NITDM, respectively, experienced late ST. Even if the percentage of patients with ITDM experienced more thrombosis, the percentage was reduced when stent thrombosis was further divided, especially in the case of late stent thrombosis.
The results of the SPIRIT IV Trial were different from those of the E-five registry . The early stent thrombosis rate was 0.48% with EES in ITDM and 0.85% with PES in ITDM, and there was no late stent thrombosis in ITDM. However, in patients with NITDM, early stent thrombosis was 0.35% with EES and 0.36% with PES, whereas late stent thrombosis was 0.18% with EES and 0.76% with PES. A conclusion could be that there was no late stent thrombosis in patients with ITDM who were implanted with DES.
In the 2-year results from the Prospectively Pooled Analysis of the International Global RESOLUTE Program , 0.9% of patients with ITDM and 0.8% of patients with NITDM experienced early stent thrombosis, whereas 0.2% and 0.1% of patients with ITDM and NITDM, respectively, experienced late stent thrombosis. The number of patients who experienced late stent thrombosis events was similar between the ITDM and NITDM groups, further supporting this analysis.
In contrast, insights from a sub-study of the Cypher Stent Japan Post-Marketing Surveillance (Cypher J-PMS) Registry  showed no early, late or very late stent thrombosis in the ITDM group, whereas in patients with NITDM, 0.45% and 0.62% patients experienced late and very late stent thrombosis, respectively, which partly contributed to the results that were obtained.
Nevertheless, following the previously published research article  based on patients with ITDM and NITDM post PCI, and upon reader requests, this analysis has further shown a new outcome, whereby early stent thrombosis was significantly higher in ITDM patients compared with those with NITDM, whereas late and very late stent thromboses were not significantly different in patients with ITDM and NITDM. This scientific concept should be of significant clinical importance and definitely find a place in medical libraries.
Finally, while recent analyses have focused on different types of drug-eluting stents and the associated stent thrombosis [14, 15], future analysis should compare stent thrombosis in male versus female patients with diabetes mellitus , specifically in male and female patients with ITDM and NITDM. In addition, the SYNTAX score [17, 18] should be included in future studies with ITDM and NITDM patients, and stent thrombosis should be assessed in patients with a low versus a high SYNTAX score.
Although the total number of patients was sufficient to reach a conclusion based on patients who were treated with DES as a whole, the number of patients was not sufficient to reach a conclusion when each DES (EES, SES, PES, ZES) was individually assessed.
First- and second-generation DESs were combined and analyzed assuming that they are all DESs; this could also have influenced the results.
For those studies that had a follow-up period > 1 year, it was not known whether DAPT was continued or discontinued. This might also have influenced the results.