Prospective, ranDomized, Controlled, multicEnter Study for the Treatment of CALCIFied Coronary Artery Lesions With Rotational Atherectomy vs Intravascular LithotripsY

1. Introduction

Calcified coronary lesions are frequently observed and with increasing age and comorbidities of the patients they become even more prevalent (1,2). Calcified lesions are often difficult to dilate by conventional angioplasty leading to vessel perforation, dissection, or stent under-expansion, which impact survival, myocardial infarction rates, and target lesion revascularization (3 - 6). Lesion preparation before stent implantation has been strongly recommended using high-pressure dilatation, scoring/cutting balloons, or rotational atherectomy (RA) devices (7-12).

RA can effectively modify calcified plaques by differential cutting, facilitating balloon dilatation, plaque fracture, stent delivery, and expansion (11). Patients undergoing RA experienced various clinical and angiographic complications, including vasospasm, perforation, short term vessel closure, side branch loss, and slow-flow/no-reflow resulting in stroke, myocardial infarction, and death (12). In the PREPARE-CALC trial (The Comparison of Strategies to Prepare Severely Calcified Coronary Lesions Trial) comparing RA and scoring or cutting balloons before drug-eluting stent implantation achieved a higher procedural success in RA (98% versus 81%), complications including larger dissection, perforation, and pericardial effusion were seen in 3%, 4%, and 3% of cases, respectively, in-hospital MACE occurred in 2% of cases (13). In the ORBIT II trial (14) an alternative atherectomy device was used which is based on the same mechanism of action as RA. In this trial the primary effectiveness performance goal, defined as successful stent delivery with residual stenosis < 50% and without in-hospital MACE, was not achieved in 11.1 % and the in-hospital MACCE rate was at 9.8 %, the rate of periprocedural myocardial infarction (MI), defined as CK-MB level > 3x ULN at discharge was 9.3% (non-Q-wave MI of 8.6 % and Q-wave MI of 0.7 %). Peri-procedural MI based on the 4th Universal Definition (15) after RA or ORBIT atherectomy have not been reported so far.

Intravascular lithotripsy (IVL) disrupts subendothelial calcification by electrohydraulic-generated sonic pressure waves (16,17). In a recently published multicenter registry 78 patients were assigned to primary IVL therapy for patients with calcified de-novo lesions (n=39 lesions), secondary IVL therapy for patients with calcified lesions in which non-compliant balloon dilatation failed (n=22 lesions), and tertiary IVL therapy in patients with stent under expansion after previous stenting (n=17 lesions). The primary endpoint of strategy success (stent expansion with <20% in-stent residual stenosis) was reached in 84.6% with de-novo lesions with only 3 Type B dissections and no in-hospital MACCE (18). Recently Intravascular Lithotripsy for Treatment of Severely Calcified Coronary Artery Disease (Disrupt CAD III) Study (19) has been presented using the same in- and exclusion criteria as the ORBIT II study. The performance of IVL was compared with the performance of the ORBIT device, as being reported in the literature (14). The primary safety endpoint (cardiac death, or myocardial infarction, or target vessel revascularization) as well as the primary effectiveness endpoint (successful stent delivery with residual stenosis < 50 % and without in-hospital MACE) were 92.2 %, which were non-inferior to those reported in the ORBIT II study. Stent expansion was measured by QCA, data on OCT-based measurements of stent expansion in comparison to RA is not available. The rate of in-hospital peri-procedural MI, defined as CK-MB level > 3x ULN at discharge, was 6.8 %. Peri-procedural myocardial infarction and injury are associated with an increased rate of cardiovascular events at 30 days in patients undergoing elective coronary stenting (20).

In order to evaluate the effectiveness of IVL in comparison to RA based on OCT- measurements of stent expansion and to study the incidence of in-hospital MACCE following either RA or IVL, we aim to perform a randomized trial. 2. Device Description and Intended Use