OrbusNeich (China)

Background: The aim of this subanalysis of the REDUCE (Short-term Dual Antiplatelet Therapy in Patients with ACS Treated with the COMBO Dual-therapy Stent) trial was to evaluate differences between non-ST-elevation MI/unstable angina (NSTEMI/UA) patients and ST-elevation MI (STEMI) patients in terms of patient characteristics, procedures and outcomes. Methods: In the REDUCE trial, 1,496 acute coronary syndrome patients undergoing successful COMBO stent implantation were randomised to 3 or 12 months of dual antiplatelet therapy (DAPT) treatment. In total, 789 (52.8%) patients had NSTEMI/UA and 706 (47.2%) had STEMI. For this analysis, NSTEMI/UA patients (n=789) were compared with STEMI patients (n=706). Results: In the analysis of the NSTEMI/UA and STEMI cohorts comparing 3-month DAPT (751 patients) and 12-month DAPT treatment (745 patients) there were no statistically significant differences in the primary endpoints of all-cause mortality, MI, stent thrombosis, stroke, target vessel revascularisation or bleeding (Bleeding Academic Research Consortium [BARC] II, III, V) at 360 and 720 days between the two cohorts. Comparing the overall primary endpoints in the NSTEMI/UA cohort, 3-month DAPT was better than 12-month DAPT (9.6% versus 10.0% at 360 days and 12.1% versus 15.0% at 720 days). In the STEMI cohort, 12-month DAPT was better than 3-month DAPT (8.4% versus 11.0% at 720 days). Conclusion: For NSTEMI/UA patients, a numerically lower occurrence of outcomes was observed with 3-month DAPT at 360 and 720 days, whereas for STEMI patients, 12-month DAPT appeared to be better at 720 days. NSTEMI patients seemed to have less favourable long-term outcomes than STEMI patients in this subanalysis. Further adequately powered randomised trials are needed to confirm the findings.

Drug-coated balloons (DCBs) have become an established therapy for the treatment of above-the-knee peripheral artery disease. The paclitaxel DCB has shown clinical benefit in terms of patency and freedom from re-intervention in multiple randomised trials. However, a recent meta-analysis has suggested an association between mortality and the use of paclitaxel-coated devices. Sirolimus is another potential choice of anti-proliferative agent for use in DCBs because of its wider therapeutic index and lower risk for dose-dependent toxicity. More recently, encapsulating sirolimus in micro-reservoirs or polymers has facilitated the development of effective sirolimus DCBs, some of which are available in Europe and Asia. In this review, the authors focus on paclitaxel and sirolimus DCB technologies from the standpoint of drug characteristics and clinical trials.

First-generation sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) have dramatically reduced restenosis, although concern still exists about the long-term safety of this technology since observational studies have shown a steady increase in the rate of late stent thrombosis (LST), an infrequent but catastrophic complication. Although the mechanisms of LST are multifactorial, our laboratory has demonstrated that delayed arterial healing accompanied by poor endothelialisation is the primary pathogical substrate underlying this event. Delayed arterial healing is associated with penetration of necrotic core, long/overlapping stents and bifurcation stenting, especially in flow divider (high shear) regions. Grade V stent fracture is also associated with adverse pathogical findings including LST and restenosis. Moreover, localised hypersensitivity reaction is exclusive to SES as an underlying mechanism of LST, while malapposition secondary to excessive fibrin deposition is associated with PES. Uncovered struts are still identified in both SES and PES with implant duration beyond 12 months, particularly in stents placed for ‘off-label’ indications. In conclusion, the first generation of drug-eluting stents (DES) certainly reduce neointimal growth but this comes at the price of delayed healing.