A Bioresorbable Everolimus-Eluting Scaffold Versus a Metallic Everolimus-Eluting Stent III - ABSORB III

Contribution To Literature:

The ABSORB III trial showed that Absorb BVS is noninferior to the cobalt–chromium-based Xience DES at 1 year for cardiovascular outcomes in noncomplex coronary lesions, with lower acute procedural success.

Description:

The goal of the trial was to assess the safety and efficacy of Absorb BVS, an everolimus-eluting bioresorbable vascular scaffold, compared with Xience, a cobalt–chromium drug-eluting stent (DES) at 1 year.


Study Design

Patients were randomized in a 2:1 ratio to either Absorb BVS (n = 1,322) or cobalt–chromium-based Xience DES (n = 686).

  • Total number of enrollees: 2,008
  • Duration of follow-up: 1 year
  • Mean patient age: 63.6 years
  • Percentage female: 30%

Other salient features/characteristics:

  • Diabetes: 32%
  • Prior percutaneous coronary intervention (PCI): 38%
  • Stable angina: 59%
  • Single-vessel disease: 68%
  • Lesion length: 13 mm
  • Reference vessel diameter (RVD): 2.65 mm
  • Post-dilatation required for BVS vs. Xience: 65.5% vs. 51.2%, p < 0.001
  • Intravascular imaging: 11%

Inclusion criteria:

  • >18 years old
  • Evidence of myocardial ischemia (stable/unstable/post-infarction angina or silent ischemia)
  • No elevation of creatine kinase-myocardial band
  • One or two de novo target lesions in up to two native coronary arteries (maximum one lesion per artery)
  • Diameter stenosis ≥50% and <100% with Thrombolysis in Myocardial Infarction (TIMI) flow ≥1
    • If <70%, abnormal functional test (including fractional flow reserve ≤0.80), unstable angina, or post-infarct angina
  • RVD ≥2.50 mm and ≤3.75 mm (site-determined)
  • Lesion length ≤24 mm (site-determined)

Exclusion criteria:

  • Known hypersensitivity or contraindication to aspirin, both heparin and bivalirudin, antiplatelet medication specified for use in the study (clopidogrel and prasugrel and ticlopidine, inclusive), everolimus, poly (L-lactide), poly (DL-lactide), cobalt, chromium, nickel, tungsten, acrylic, and fluoro polymers or contrast sensitivity that cannot be adequately premedicated
  • Subject has a known diagnosis of acute myocardial infarction (AMI) at any time preceding the index procedure and relevant cardiac enzymes have not returned within normal limits at the time of procedure
  • Evidence of ongoing AMI in electrocardiogram prior to procedure
  • Subject has current unstable arrhythmias
  • Left ventricular ejection fraction <30%
  • Prior PCI in target vessel within 12 months
  • Need for staged PCI within 30 days
  • Subject has received a heart transplant or any other organ transplant or is on a waiting list for any organ transplant
  • Subject is receiving immunosuppressant therapy and/or has known immunosuppressive or autoimmune disease
  • Subject has a platelet count <100,000 cells/mm3 or >700,000 cells/mm3, a white blood cell count of <3,000 cells/mm3, or documented or suspected liver disease
  • Known renal insufficiency (e.g., estimated glomerular filtration rate <60 ml/kg/1.73 m2 or serum creatinine level of >2.5 mg/dl, or subject on dialysis)
  • History of bleeding diathesis or coagulopathy or will refuse blood transfusions
  • Subject had a cerebrovascular accident or transient ischemic neurological attack within the past 6 months

Angiographic exclusion criteria:

  • Target lesion which prevents adequate (residual stenosis at target lesion/s is ≤40% by visual assessment) coronary predilatation
  • Target lesion in left main trunk
  • Aorto-ostial target lesion (within 3 mm of the aorta junction)
  • Target lesion located within 3 mm of the origin of the left anterior descending or left circumflex artery
  • Target lesion involving a bifurcation lesion with side branch ≥2 mm in diameter, or with a side branch <2 mm in diameter requiring guidewire protection or dilatation
  • Total occlusion (TIMI flow 0), prior to wire crossing
  • Excessive tortuosity (≥2, 45° angles), or extreme angulation (≥90°) proximal to or within the target lesion
  • Heavy calcification proximal to or within the target lesion
  • Target lesion located within an arterial or saphenous vein graft or distal to any arterial or saphenous vein graft
  • Vessel has been previously treated with a stent at any time prior to the index procedure such that the Absorb BVS or Xience stent would need to cross the stent to reach the target lesion

Principal Findings:

The primary outcome, target-lesion failure (cardiac death, target vessel MI [TV-MI], ischemia-driven target-vessel revascularization [ID-TLR]) for BVS vs. Xience, was 7.8% vs. 6.1% (p for noninferiority = 0.007, p for superiority = 0.16)

  • Cardiac death: 0.6% vs. 0.1%, p = 0.29
  • TV-MI: 6.0% vs. 4.6%, p = 0.18
  • ID-TLR: 3.0% vs. 2.5%, p = 0.5

Secondary outcomes:

  • Acute success: 94.3% vs. 99.3%, p < 0.0001
  • Immediately post-procedure quantitative coronary angiography: In-device minimum lumen diameter: 2.37 mm vs. 2.49 mm, p < 0.0001; acute gain: 1.45 vs. 1.59 mm, p < 0.0001
  • Device thrombosis: 1.5% vs. 0.7%, p = 0.13
  • All revascularization: 9.1% vs. 8.1%, p = 0.5

2-year results: Approximately two thirds of patients were on dual antiplatelet therapy at 2 years. For BVS vs. Xience: Target lesion failure (TLF): 11.0% vs. 7.9%, p = 0.03; cardiac death: 1.1% vs. 0.6%, p > 0.05; TV-MI: 7.3% vs. 4.9%, p = 0.04; ID-TLR: 5.3% vs. 4.3%; p > 0.05; device thrombosis: 1.9% vs. 0.8%; p > 0.05.

For outcomes between 1 and 2 years: TLF: 3.7% vs. 2.5%; cardiac death: 0.5% vs. 0.4%, TV-MI: 1.3% vs. 0.7%, ID-TLR:  2.6% vs. 1.8%; device thrombosis: 0.3% vs. 0%; p > 0.05

3-year results: Approximately 54% of patients were on DAPT at 3 years. For BVS vs. Xience: TLF: 13.4% vs. 10.4%, p = 0.06; TV-MI: 8.6% vs. 5.9%, p = 0.03; TLR: 7.3% vs. 5.9%, p = 0.25; device thrombosis: 2.3% vs. 0.7%, p = 0.01.

For outcomes between 1 and 3 years: TLF: 7% vs. 6%, p = 0.39; device thrombosis: 0.8% vs. 0%, p = 0.02. Pre-procedure RVD <2.25 mm was an independent predictor of 3-year TLF and device thrombosis in the BVS arm.

Interpretation:

The results of this trial indicate that Absorb BVS is noninferior to cobalt-chromium-based Xience DES at 1 year for cardiovascular outcomes in noncomplex coronary lesions. On follow-up up to 3 years, the results for Xience DES were statistically superior compared with BVS, including a lower risk of TV-MI and stent/scaffold thrombosis. Acute device and post-procedure success were both lower, and unfavorable trends were also observed for device thrombosis and TVF in smaller vessels (RVD <2.25 mm) with BVS; a RVD <2.25 mm was also a predictor of long-term poor outcomes with BVS.

ABSORB III was the pivotal trial towards US FDA approval of Absorb BVS, but the stent was recently commercially withdrawn in the US given poor sales. Physicians have also been concerned about many of the safety signals noted in the ABSORB trials. Longer-term data as well as trials with improved stent design and implementation techniques are awaited.

References:

Kereiakes DJ, Ellis SG, Metzger C, et al., on behalf of the ABSORB III Investigators. Three-Year Clinical Outcomes With Everolimus-Eluting Bioresorbable Scaffolds: Results From the Randomized ABSORB III Trial. J Am Coll Cardiol 2017;Oct 31:[Epub ahead of print].

Stone GW, Abizaid A, Onuma Y, et al. Impact of Technique on Outcomes Following Bioresorbable Vascular Scaffold Implantation: From the ABSORB trials. J Am Coll Cardiol 2017;Oct 31:[Epub ahead of print].

Editorial Comment: King SB III, Gogas BD. Can the Vanishing Stent Reappear? Fix the Technique, or Fix the Device? J Am Coll Cardiol 2017;Oct 31:[Epub ahead of print].

Presented by Dr. Stephen G. Ellis at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2017), Denver, CO, October 31, 2017.

Presented by Dr. Stephen G. Ellis at the American College of Cardiology Annual Scientific Session (ACC 2017), Washington, DC, March 18, 2017.

Ellis SG, Kereiakes DJ, Metzger C, et al., on behalf of the ABSORB III Investigators. Everolimus-Eluting Bioresorbable Scaffolds for Coronary Artery Disease. N Engl J Med 2015;373:1905-15.

Presented by Dr. Dean J. Kereiakes at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2015), San Francisco, CA, October 12, 2015.


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