One-Month Dual Antiplatelet Therapy After Bioresorbable Polymer Everolimus-Eluting Stents in High Bleeding Risk Patients

Carlo A Pivato, Bernhard Reimers, Luca Testa, Andrea Pacchioni, Carlo Briguori, Carmine Musto, Giovanni Esposito, Raffaele Piccolo, Luigi Lucisano, Leonardo De Luca, Federico Conrotto, Andrea De Marco, Anna Franzone, Patrizia Presbitero, Giuseppe Ferrante, Gerolama Condorelli, Valeria Paradies, Gennaro Sardella, Ciro Indolfi, Gianluigi Condorelli, Giulio G Stefanini, Carlo A Pivato, Bernhard Reimers, Luca Testa, Andrea Pacchioni, Carlo Briguori, Carmine Musto, Giovanni Esposito, Raffaele Piccolo, Luigi Lucisano, Leonardo De Luca, Federico Conrotto, Andrea De Marco, Anna Franzone, Patrizia Presbitero, Giuseppe Ferrante, Gerolama Condorelli, Valeria Paradies, Gennaro Sardella, Ciro Indolfi, Gianluigi Condorelli, Giulio G Stefanini

Abstract

Background It is unknown whether contemporary drug-eluting stents have a similar safety profile in high bleeding risk patients treated with 1-month dual antiplatelet therapy following percutaneous coronary interventions. Methods and Results We performed an interventional, prospective, multicenter, single-arm trial, powered for noninferiority with respect to an objective performance criterion to evaluate the safety of percutaneous coronary interventions with Synergy bioresorbable-polymer everolimus-eluting stent followed by 1-month dual antiplatelet therapy in patients with high bleeding risk. In case of need for an oral anticoagulant, patients received an oral anticoagulant in addition to a P2Y12 inhibitor for 1 month, followed by an oral anticoagulant only. The primary end point was the composite of cardiac death, myocardial infarction, or definite or probable stent thrombosis at 1-year follow-up. The study was prematurely interrupted because of slow recruitment. From April 2017 to October 2019, 443 patients (age, 74.8±9.2 years; women, 29.1%) at 10 Italian centers were included. The 1-year primary outcome occurred in 4.82% (95% CI, 3.17%-7.31%) of patients, meeting the noninferiority compared with the predefined objective performance criterion of 9.4% and the noninferiority margin of 3.85% (Pnoninferiority<0.001) notwithstanding the lower-than-expected sample size. The rates of cardiac death, myocardial infarction, and definite or probable stent thrombosis were 1.88% (95% CI, 0.36%-2.50%), 3.42% (95% CI, 2.08%-5.62%), and 0.94% (95% CI, 0.35%-2.49%), respectively. Conclusions Among high bleeding risk patients undergoing percutaneous coronary interventions with the Synergy bioresorbable-polymer everolimus-eluting stent, a 1-month dual antiplatelet therapy regimen is safe, with low rates of ischemic and bleeding events. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03112707.

Keywords: Synergy stent; bioresorbable polymer stent; coronary artery disease; high bleeding risk; percutaneous coronary intervention; short DAPT.

Figures

Figure 1. Study design and flowchart.
Figure 1. Study design and flowchart.
ASA indicates acetylsalicylic acid; CAD, coronary artery disease; def/prob ST, definite/probable stent thrombosis; EES, everolimus‐eluting stent; GFR, glomerular filtration rate; ICH, intracerebral hemorrhage; ITT, intention‐to‐treat; MI, myocardial infarction, NSAIDs, nonsteroidal anti‐inflammatory drugs; OAC, oral anticoagulant; PCI, percutaneous coronary intervention; and ST, stent thrombosis.
Figure 2. High bleeding risk inclusion criteria.
Figure 2. High bleeding risk inclusion criteria.
DAPT indicates dual antiplatelet therapy; NSAIDs, nonsteroidal anti‐inflammatory drugs; and PCI, percutaneous coronary intervention. *Anemia was defined as hemoglobin level †Chronic kidney disease was defined as creatinine clearance <40 mL/min. ‡Thrombocytopenia was defined as platelet count <100.000/mm3.
Figure 3. Primary end point analysis.
Figure 3. Primary end point analysis.
On the left, Kaplan‐Meier time to event curve for the primary outcome (composite of cardiac death, any myocardial infarction, or definite or probable stent thrombosis) with 95% CI. On the right, the difference between POEM primary outcome and objective performance criterion is represented by the rhombus with 1‐sided 97.5% upper confidence limit (UCL) indicated by the error bar.
Figure 4. Findings in perspectives.
Figure 4. Findings in perspectives.
Event rates observed in POEM as compared with those observed in contemporary DES trials that enrolled and treated HBR patients with a short DAPT regimen following PCI. The Synergy bioresorbable‐polymer everolimus‐eluting stent was used in the POEM, SENIOR and EVOLVE Short DAPT trials. The BioFreedom polymer‐free bioliomus‐eluting stent was used in LEADERS FREE, LF II, and ONYX ONE trials. The Resolute Onyx durable‐polymer zotarolimus‐eluting stent was used in the ONYX ONE trial. The Xience durable‐polymer was used in the XIENCE 28 trial. The Ultimaster bioresorbable‐polymer sirolimus‐eluting stent was used in the MASTER DAPT trial. Event rates are through 1 year follow‐up except for *the EVOLVE Short DAPT (events observed between 3 and 15 months), for †the XIENCE 28 (events observed at 6 months) and for ‡the MASTER DAPT (events observed between 1 and 12 months) trials. BARC indicates Bleeding Academic Research Consortium; DAPT, dual antiplatelet therapy; HBR, high bleeding risk; PCI, percutaneous coronary intervention; and ST, stent thrombosis.

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