Polymer Free Biolimus Eluting Stent Implantation In All Comers Population: Analysis Of Dapt Cessation And Clinical Outcome After Biofreedom Stent Implantation

AIM OF THE STUDY: The aim of the present registry is to investigate the procedural as well as the long-term clinical results in terms of safety and efficacy of the polymer-free DES technology in all comers patients with an indication to percutaneous coronary intervention.

PRIMARY SAFETY ENDPOINTS: the cumulative hierarchical incidence of major adverse cardiac events (MACCE) defined as: cardiac death, non-fatal myocardial infarction (MI), stroke and ARC-defined stent thrombosis (18) at any time point and bleeding defined according to BARC classification (19).

PRIMARY EFFICACY ENDPOINTS: clinically driven target lesion revascularization (TLR).

STUDY DESIGN: multicenter (presumably 10 centers across the Italian territory), prospective observational registry aiming to enroll a population of 1000 patients.

STUDY DURATION: We project 12 months for recruitment, 5 year follow-up duration after last patient in the registry.

CLINICAL FOLLOW-UP PLAN: 30 days, 3, 6, 9 months, 1 year, and then yearly up to 5 years after the index procedure.

PATIENTS SELECTION CRITERIA:

This is an "all comers" registry and patient who will be enrolled have to meet the sequent criteria:

• Patient must be at least 18 years of age at the time of signing the Informed Consent Form after Biofreedom placement.

• All "de novo" lesion subsets are included.

• Patient must agree to undergo all required follow-up visits and data collection.

• Patient must have indication to percutaneous coronary intervention following:

• Stable angina or evidence of myocardial ischemia with stress echocardiography/ myocardial SPECT/exercise test, or

• Unstable angina / non ST-elevation myocardial infarction

• ST-elevation myocardial infarction with de novo culprit lesion.

EXCLUSION CRITERIA:

The exclusion criteria must follow the most recent IFU which may include but are not limited to the following:

• Known intolerance to any of the device components
• In-stent restenosis
• Woman with childbearing potential
• Age < 18y/o
• Inability to provide written informed consent

EFFICACY PARAMETERS: TLR and TVR up to 5-year follow-up.

SAFETY "PATIENT ORIENTED" PARAMETERS: all cause mortality, any myocardial infarction, Stent thrombosis based on the ARC classification, up to 5-year follow-up and bleeding occurrence according to BARC classification. Data on dual antiplatelet therapy use will also be collected and analyzed according to duration and cessation modalities.

Sample size justification: Being this an observational registry aiming at quantifying effect estimates without direct comparisons to other devices for coronary angioplasty, we relied on confidence interval profiling for sample size justification, without proceeding with formal power analysis. The main analysis will be an overall and comprehensive analysis and it will be planned the primary analytical approach of all-comers patients with coronary artery disease and indication to PCI. Accordingly, we computed that a target sample of 1000 patients will enable the computation of reasonably precise 95% confidence intervals. Specifically, assuming a 8% MACE rate at 1 year (in keeping with RUDY study and LEADERS FREE trial design), confidence intervals computed with the adjusted Wald method would be 7.1% to 9.6% for a 1000-patient sample (point estimate 80/1000 [8.0%]). Given that the registry aims to reflect real-world patients and practice, no prevision to limit or restrict patient enrollment is considered.

Analytical plan: Continuous endpoints will be summarized by presenting the total number of patients, mean, standard deviation, median, minimum, and maximum. Tabulation of categorical parameters will include counts and percentages. The outcomes will be summarized as both a discrete and a continuous variable using the method described above. Survival analysis will be performed with the Kaplan-Meier method. Statistical inference will be based on the computation of 95% confidence intervals using the adjusted Wald method. Additional analyses will involve key subgroups defined according to baseline, lesion, and procedural features, with statistical significance set at the 5% 2-tailed level. Specifically, Student t, Fisher exact, and log-rank tests will be used for such bivariate analyses, whereas multivariable linear regression, logistic regression, and Cox proportional hazard analyses will be used to adjust for confounders.