A Pilot Study Registry of the BioFreedom™ BA9™ Ultra Drug-Coated Coronary Stent for Patients With ST Elevation Myocardial Infarct (STEMI) Undergoing Percutaneous Coronary Intervention (PCI)

Coronary artery disease (CAD) is the leading cause of death and disability worldwide. One severe manifestation of CAD is acute ST elevation myocardial infarction (STEMI) which is commonly due to atherothrombosis of major epicardial coronary artery. The treatment aim of STEMI is emergent reperfusion of blocked coronary artery by mechanical or pharmacological means. Percutaneous coronary intervention (PCI) with stent implantation of obstructive coronary lesions has been shown to improve patients' survival and outcome.

Early generation drug-eluting stents (DES), namely, sirolimus-eluting stents and paclitaxel-eluting stents, have been compared with bare-metal stents (BMS) in the clinical setting of STEMI in several randomized controlled trials and consistently showed a reduction in major adverse cardiac events (MACE) mainly related to a lower risk of repeat revascularization procedures [1-6]. However, vessel healing is delayed with evidence of chronic inflammation related at least in part to the persistence of durable polymer components in patients with acute STEMI [7] after implantation of a DES compared to a BMS DES as opposed to BMS implanted into a pro-thrombotic, inflammatory milieu of ruptured plaques in STEMI patients may lead to aneurysmal changes of the adjacent vessel wall. Moreover, DES implanted into STEMI lesions have been associated with a higher frequency of incompletely apposed struts and uncovered struts as assessed by OCT compared with DES implanted into stable lesions [7]. These data suggest a significantly increased risk of late thrombotic complications related to DES. In recent years, newer-generation devices with drug release from durable or biodegradable polymer surface coating may provide the basis for improved biocompatibility and vascular healing [8]. The EXAMINATION (clinical Evaluation of the Xience-V stent in Acute Myocardial INfArcTION) and COMFORTABLE-AMI (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) trials have tested the efficacy of everolimus eluted from durable polymer (everolimus-eluting stent [EES]) and of biolimus A9 eluted from biodegradable polymer (biolimusA8-eluting stent [BES]) stents versus BMS, respectively, in an all-comer STEMI population [9-12]. Whereas the EXAMINATION trial showed a significant reduction in stent thrombosis with the EES (0.9% vs. 2.5%, p = 0.019), the COMFORTABLE-AMI trial demonstrated a significant reduction in MACE with the BES (4.3% vs. 8.7%, p = 0.004) compared with BMS at 1 year [12].

In view of concerns over long term safety of DES polymer, third generation of stents that still release drug but without polymer are being developed. The BioFreedom DCS Coronary Stent Delivery System is comprised of three key components including 1) a 316 L stainless steel bare metal stent platform which has been modified with a proprietary surface treatment resulting in a selectively micro-structured, abluminal surface. The selectively micro-structured surface allows 2) Biolimus A9 (drug) adhesion to the abluminal surface of the stent without the use of a polymer or binder.

The BioFreedom First In Man (FIM) trial was a prospective, single blinded, randomized clinical trial to evaluate the safety and effectiveness of a low and standard dose BioFreedom Biolimus A9 Drug-Eluting Coronary Stent Delivery System compared with a Taxus® Liberté® control arm for the treatment of stenotic lesions in native coronary arteries [13]. The BioFreedom FIM trial documented, that the BioFreedom (BFD) stent was non-inferior to the CE-mark approved Taxus Liberté Paclitaxel Eluting stent (PES) for the angiographic endpoint "in-stent late lumen loss" at 12 months (BFD 0.17mm vs. PES 0.35mm; p=0.001 for non-inferiority; p=0.11 for superiority). Despite a numerically better late lumen loss for the BFD, superiority was not reached. Both stents showed similar clinical outcomes at 12 months with MACE rates of 6.1% (BFD) vs. 5.5% (PES) (p=0.98), and of 23.8% (BFD) vs. 20.3% (PES) at 5 years (p=0.67). No ARC definite/probable stent thrombosis occurred in either arm. These results demonstrated that the BFD stent has comparable angiographic efficacy at 1 year and similar long-term safety outcomes as the PES out to 5 years.

Later on, The LEADERS FREE trial [14] was a prospective, randomized, double-blind trial to evaluate the safety and efficacy of the BioFreedom polymer-free and carrier-free drug-coated stent compared with a bare-metal stent (BMS) in patients with increased bleeding risk. 2,466 patients were enrolled at 68 sites in 20 countries from December 2012 through May 2014, with 1,239 randomly assigned to the BioFreedom stent, and 1,227 randomly assigned to the bare-metal stent. All patients were prescribed one month of dual antiplatelet therapy. Inclusion criteria were designed to create a patient population with high bleeding risk (or otherwise considered as candidates for a BMS as opposed to a DES, and not considered suitable for prolonged dual antiplatelet therapy). Patients with coronary artery disease and a clinical indication for PCI were eligible if they met one or more inclusion criteria. The trial was powered to determine whether the BioFreedom stent was non-inferior to the bare-metal stent in 2-years outcomes according to the primary safety endpoint. If non-inferiority was shown, the safety endpoint would then be tested for superiority. The primary safety endpoint was a composite of cardiac death, MI, and definite or probable stent thrombosis at two different time point: a 390 and a 790-days time point. The primary efficacy endpoint was incidence of clinically-driven target-vessel revascularization (CI-TLR) at 390 and 790 days. 2,432 patients underwent PCI, and 2,386 (98.1%) were followed until death or 730 days, with follow-up visits at 30 days and 1 year, and either on-site or telephone follow-up at 2 months, 4 months, and 2 years.