3rd Generation Resorbable Magnesium Scaffolds vs Biodegradable Polymer Drug Eluting Stents in Patients With Non ST-segment Elevation Acute Coronary Syndromes: the RESORB-ACS Randomized Clinical Trial

INTRODUCTION AND RATIONALE Scaffolding the coronary vessels while maintaining the physiological and rheological properties was an appealing idea resulting in the development of the bioresorbable scaffolds (BRS). The most thoroughly studied BRS - the poly-L-lactide acid based BRS ABSORB™ - evidenced increased rates of device-related adverse events in the randomized controlled trials (RCT) and was removed from market in 2017. ABSORB was an everolimus eluting BRS, characterized by limited radial force, thicker and wider struts, unfavorable crossing profile and unpredictable resorption.

In an effort to overcome these obstacles, metallic resorbable scaffolds were developed - with the main representative being the resorbable magnesium scaffolds (RMS). The absorbable metal stent (AMS) (BIOTRONIK AG, Bülach, Switzerland). was the first device tested in the PROGRESS-AMS trial showing feasibility but necessity for improvement. DREAMS 1G (BIOTRONIK AG, Bülach, Switzerland) was the first generation of the improved RMS, designed to improve radial force and coated with a paclitaxel-polymer matrix. It was studied in the BIOSOLVE-I and showed improved performance compared to the AMS with no probable or definite scaffold thrombosis, however late-lumen-loss (LLL) was relatively high compared to ABSORB scaffolds and contemporary drug eluting stents (DES).

The second generation was the DREAMS 2G (BIOTRONIK AG, Bülach, Switzerland), gaining CE-Mark in 2016 and marketed as Magmaris™. It is designed with more flexible and stronger scaffold backbone targeting in improved radial force with 150x140μm strut thickness. The drug-polymer coating was substituted by the sirolimus BIOlute™ matrix of the Orsiro™ DES, to decrease more effectively neointimal formation. Also, radiopaque markers were added for enhanced x-ray visibility. The outcomes of Magmaris™ have been investigated in the BIOSOLVE II, III, IV trials. In summary, BIOSOLVE II and III demonstrated no scaffold thrombosis with improved LLL improved to its precursor and BIOSOLVE IV exhibited low event rates in a large single-arm study.

The concept of protecting the vulnerable, eroded or ruptured plaque without a permanent metallic endoprosthesis finds ideal application in the acute coronary syndromes. Culprit lesions present as a ruptured plaque, plaque erosion or less frequently as a calcific nodule complicated by thrombotic burden and implantation of a BRS may adequately revascularize the vessel, protect the lesion and be resorbed after vessel healing restoring its elastic and hydraulic properties. However, the high thrombotic status of an acute coronary syndrome (ACS) was preventing BRS of being utilized in such situations. The TROFI-II RCT compared the ABSORB scaffold with DES in ST-segment elevation myocardial infarction (STEMI) and 6-month results were comparable. The Magmaris™ was tested in STEMI patients in the MAGSTEMI RCT and showed significantly higher vasodilatory response at 1-year compared to Orsiro™. Furthermore, Magmaris™ did not raise thrombotic concerns, but resulted in higher target lesion revascularization (TLR) rates although not powered for those endpoints. The BESTMAG trial was a small propensity-matching study providing hypothesis generating outcomes of numerically higher TLR rates with Magmaris™ compared to contemporary biodegradable polymer (BP) or durable polymer (DP)-DES in STEMI presentations. The BIOSOLVE IV registry (n=206) underwent PCI because of non ST-segment elevation (NSTE) myocardial infarction and target vessel failure (TVL) was calculated at 6.1% in 12 months. One death (0.5%) and 2 thrombotic complications were reported (1%). Smaller registries that included NSTE/ACS patients treated with Magmaris™ RMS demonstrated zero deaths and scaffold thrombosis, albeit these are hypothesis generating results limited by the small sample.

The BIOMAG-I first-in-human study investigated the third generation Freesolve™ RMS. The main characteristics are a refined magnesium alloy to enhance scaffolding properties, increased scaffold marker x-ray visibility, larger size range, thinner strut thickness and predictable full resorption in about 12 months. The 1-year results of the BIOMAG-I showed lower LLL (38% lower) than the BIOSOLVE II, low target lesion failure (TLF) rates and no death, target vessel myocardial infarction (MI) or scaffold thrombosis. Of note no struts ware visible in the 1-year optical coherence tomography (OCT). 20.7% of the patients presented with NSTE myocardial infarction lesions and were treated accordingly.