Time-Varying Outcomes With the Absorb Bioresorbable Vascular Scaffold During 5-Year Follow-up: A Systematic Meta-analysis and Individual Patient Data Pooled Study

Abstract

Importance: Bioresorbable scaffolds were designed to provide clinical benefits after their complete bioresorption. Prior studies demonstrated early risks with the Absorb polymeric bioresorbable vascular scaffold (BVS). Whether this risk profile changes over time during the course of its bioresorption is unknown.

Objective: To examine outcomes of the first-generation BVS before and after 3 years, the point of its complete bioresorption in animals.

Data sources: We searched MEDLINE and the Cochrane database, conference proceedings, and public websites for relevant studies.

Study selection: Eligible studies were randomized clinical trials of BVS vs metallic drug-eluting stents in patients with coronary artery disease with at least 5-year follow-up. Four trials of BVS vs everolimus-eluting stents (EES) with 3384 patients met criteria.

Data extraction and synthesis: Individual patient data from the 4 trials were pooled, and summary-level meta-analysis was performed.

Main outcomes and measures: The major effectiveness and safety measures were target lesion failure (TLF; cardiac death, target vessel-related myocardial infarction, or ischemia-driven target lesion revascularization) and device thrombosis. Outcomes were examined through 5-year follow-up and between 0 to 3 and 3 to 5 years.

Results: Mean age for the 3384 patients was 62.8 years; 2452 patients were men (72.5%), and diabetes was present in 1020 patients (30.2%). Through 5-year follow-up, treatment with BVS compared with EES was associated with higher rates of TLF (14.9% vs 11.6%; HR, 1.26; 95% CI, 1.03-1.54; P = .03) and device thrombosis (2.5% vs 0.8%; HR, 2.87; 95% CI, 1.46-5.65; P = .002). Target lesion failure occurred in 11.6% of BVS-treated patients vs 7.9% of EES-treated patients between 0 to 3 years (HR, 1.42; 95% CI, 1.12-1.80), and 4.3% of BVS-treated patients vs 4.5% of EES-treated patients between 3 to 5 years (HR, 0.92; 95% CI, 0.64-1.31) (P for interaction = .046). Device thrombosis occurred in 2.4% of BVS-treated patients vs 0.6% of EES-treated patients between 0 to 3 years (HR, 3.86; 95% CI, 1.75-8.50) and 0.1% of BVS-treated patients vs 0.3% of EES-treated patients between 3 to 5 years (HR, 0.44; 95% CI, 0.07-2.70) (P for interaction = .03). These results were consistent by spline analysis and after multiple imputation and multivariable analysis.

Conclusions and relevance: The period of excess risk for the first-generation Absorb BVS ends at 3 years. These data provide mechanistic insights into the timing of adverse events after BVS and identify the hurdles to be overcome for bioresorbable technology to be accepted as a valid alternative for patients with coronary artery disease.

Trial registration: ClinicalTrials.gov identifiers: NCT01751906, NCT01844284, NCT01923740, and NCT01425281.

Conflict of interest statement

Conflict of Interest Disclosures: Within the last 3 years, Dr Stone has received speaker honoraria from Amaranth and Terumo; has served as a consultant to Shockwave, Valfix, Reva, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Matrizyme, Miracor, Neovasc, V-wave, Abiomed, Claret, Sirtex, MAIA Pharmaceuticals, SpectraWave, and Ancora; has equity in Ancora, Qool Therapeutics, Claret, Applied Therapeutics, the MedFocus and Biostar family of funds, SpectraWave, Aria, and Orchestra Biomed; and reports that Columbia University receives royalties from Abbott for sale of the MitraClip. Dr Kimura reports research grants from Abbott Vascular. Dr Gao reports grants from Abbott Vascular. Dr Kereiakes reported personal fees from Abbot Vascular, Boston Scientific, and Elixir Medical during the conduct of the study. Dr Ellis is a consultant for Abbott Vascular. Dr Onuma is a past member of an Abbott Vascular advisory board. Dr Chevalier is a consultant for Abbott Vascular, Biotronic, and Terumo, is a proctor for Medtronic, and is an employee and shareholder of CERC, a CRO involved in interventional cardiology. Dr Simonton is an employee of Abbott Vascular. Dr Ali reports grants from Cardiovascular Systems Inc and Abbott Vascular, personal fees from Boston Scientific, AstraZeneca, ACIST Medical, Opsens Medical, and Cardinal Health, and stock in Shockwave Medical. Dr Serruys reports personal consultancy fees from Abbott Laboratories, Biosensors, Cardialysis, Medtronic, Micell, Sino Medical Sciences Technology, Philips/Volcano, Xeltis, and Heartflow. No other disclosures were reported

Figures

Figure 1.. Study-Level Stratified Individual Patient Data Pooled Event Rates for 3884 Patients Randomized to Bioresorbable Vascular Scaffolds (BVS) vs Everolimus-Eluting Stents (EES) in 4 Randomized Clinical Trials

A, Target lesion failure cumulative through 5 years. B, Device thrombosis (definite or probable) cumulative through 5 years. C, Target lesion failure between 0 to 3 years and 3 to 5 years. D, Device thrombosis (definite or probable) between 0 to 3 years and 3 to 5 years. The P value for interaction (Pint) represents the likelihood of interaction between the periods and the relative treatment effect. HR indicates hazard ratio.

Figure 2.. Spline Analysis Demonstrating the Association of the Hazard for Target Lesion Failure After Treatment With Bioresorbable Vascular Scaffolds (BVS) vs Everolimus-Eluting Stents (EES) During the 5-Year Follow-up Period

The solid black line represents the hazard ratio while the gray shadow represents the 95% confidence interval. There were not enough events to perform a similar analysis for device thrombosis.