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A stent that combines a bioabsorbable polymer, sirolimus elution to prevent restenosis, and murine anti-CD34 antibodies to capture circulating endothelial progenitor cells (EPCs) with the aim of accelerating healing at the site of percutaneous coronary intervention (PCI) has shown noninferiority to everolimus-eluting stents (EES) for 1-year target-vessel failure, according to findings from the randomized, pivotal, registration trial, Japan–USA HARMONEE.

Despite improvements in the safety and efficacy of drug-eluting stents, safety concerns remain, in particular with respect to stent thrombosis. Delayed endothelialization after DES implantation might be a substrate of stent thrombosis, which prompted the development of stents coated with anti-CD34 antibodies to capture bone marrow-derived CD34+ EPCs. The hypothesis was that captured EPCs would differentiate into endothelial cells, thereby facilitating endothelial coverage of the stent and promoting early healing after stent implantation.

The primary clinical end point of the trial was noninferior 1-year target-vessel failure with the Combo stent compared with EES in patients undergoing PCI for ischaemic coronary disease and non-ST-segment elevation acute coronary syndromes. Superior strut coverage assessed by optical coherence tomography (OCT) was used as a surrogate marker of the EPC-capture technology (primary mechanistic end point).

At 1 year after PCI, the Combo stent met the noninferiority criteria for target-vessel failure, with a rate of 7.0% (20 of 287 patients) compared with 4.2% (12 of 285 patients) for EES (P = 0.02). No cardiac deaths occurred, one stent thrombosis was observed in the EES group, and angiographic late lumen loss was low and similar with both stent types. The mechanistic OCT analysis showed that strut coverage with healthy tissue (>40 μm) was significantly greater with the Combo stent (91.3%) than with EES (74.8%; P < 0.001), with homogeneous tissue in 81.2% versus 68.8% of the analysed lesions, respectively. Of note, almost all struts were covered with either the Combo stent or EES (99.2% versus 98.8%; P = 0.02), and neointimal hyperplasia thickness was significantly greater with the Combo stent than with EES (0.180 mm versus 0.107 mm; P < 0.001).

In summary, the Combo stent was noninferior to EES for 1-year target-vessel failure and late lumen loss, with superior strut coverage with more homogeneous tissue. Nevertheless, the trial investigators caution that the patient cohort had a less complex clinical history and anatomy than expected, which led to the observed 1-year target-vessel failure rate of 4.2% with EES being much lower than the protocol-assumed rate of 9.0%. Therefore, further studies are needed to confirm the noninferiority of the Combo stent to EES in patients with a more complex medical history and anatomy.