JOURNAL CLUB

01/03/2016

Stent vs Scaffold

• Previously called Endovascular prosthesis

• Those which resorb completely= scaffolds

BACKGROUND

• Contemporary drug-eluting coronary stents have better clinical outcomes than have either bare-metal stents or first-generation drug-eluting stents.

• But ongoing risks of stent thrombosis and restenosis limit their long-term safety and efficacy.

• First revolution- balloon angioplasty

• Invention of balloon angioplasty as a percutaneous treatment for obstructive coronary disease by Andreas Gruntzig in 1977.

Plain Old Balloon Angioplasty (POBA)

Dissections – Focal to threatened dissectionAcute recoilChronic constrictive remodeling

• Second revolution – BMS

• The advent of BMS and the landmark Belgian-Netherlands Stent Study (BENESTENT) and Stent Restenosis Study (STRESS) trials have established BMS as the second revolution in interventional cardiology.

• A solution to acute vessel occlusion by– sealing the dissection flaps – preventing recoil – making emergency bypass surgery a rare occurrence.

– Serruys et al.A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease: Benestent Study Group. N Engl J Med. 1994;331:489–495.

Plain Old Balloon

Angioplasty(POBA)

Bare Metal Stent(BMS)

• Third revolution - DES

• The first 45 patients implanted with the sirolimus eluting Bx velocity stent (Cordis, Johnson & Johnson) were found to have negligible neointimal hyperplasia at follow-up.

• This was confirmed in the randomized comparison of sirolimus-eluting stent with a standard stent for coronary revascularization (RAVEL) study.

– Morice MC, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med. 2002.

• The development of late adverse events with permanent metallic stents may be related to:persistent inflammation, loss of normal vessel curvature, impaired vasomotion, strut fracture,ongoing tissue growth within the stent

frame,Neoatherosclerosis.

• Disadvantages• Increased risk of late and very late ST.• late ST rates of 0.53%/y, with a continued increase to 3% over 4

years. – Late thrombosis in DES after discontinuation of antiplatelet

therapy. Lancet. 2004

• In the (ARTS II) trial, the rate of combined definite, probable, and possible ST was as high as 9.4% at 5 years, accounting for 32% of MACE.

– J Am Coll Cardiol. 2009–

• Postmortem specimens of DES revealed significant numbers of uncovered struts with persistent inflammation around the stent struts.

• Vasomotion testing demonstrated vasoconstriction to Ach. – Vascular responses to drug eluting stents: importance of

delayed healing. Arterioscler Thromb Vasc Biol. 2007

• Fully Bioresorbable Scaffold: The Fourth Revolution in Interventional Cardiology?

Why Bioabsorbable stents??

Potential advantages of BRS

• On Premise that scaffolding & drug are only required on a temporary basis following coronary interventions.

• Several studies support this concept and indicate that there is no incremental clinical benefit of a permanent implant over time.

• Use of Absorbable scaffold eliminates the presence of a mechanical restraint and offers potential of restoring natural vessel reactivity.

– Incidence of restenosis after successful coronary angioplasty: a time-related phenomenon. A quantitative angiographic study in 342 consecutive patients at 1, 2, 3, and 4 months. Circulation, 1988.

Vascular Reparative therapy

What is the Minimum Duration of Radial Support?

Serruys PW, et al., Circulation 1988; 77: 361.

n = 342 patients (n = 93 at 30-day F/U; n = 79 at 60-day F/U; n = 82 at 90-day F/U; n = 88 at 120-day F/U)

The lumen appears to stabilize approximately three months after PTCA.

p < 0.00001

p < 0.00001

Quantitative angiographic study in 342 consecutive patients at 1, 2, 3, and 4 months

While stent performance is characterized by a single phase (Revascularization), the performance of Absorb is governed by three distinct phases: Revascularization Restoration Resorption.

Together, these phases of Absorb performance deliver VRT

What is Required of a Fully Bioresorbable Scaffold to Fulfill the Desire for ‘Vascular

Restoration Therapy’?Revascularization Restoration Resorption

0 to 3 months 3 to ~6-9 months + ~9 months +

Performance should mimic that of a standard DES

Transition from scaffolding to discontinuous structure

Implant is discontinuous and inert

• Good deliverability

• Minimum of acute recoil

• High acute radial strength

• Controlled delivery of drug to abluminal tissue

• Excellent conformability

• Gradually lose radial strength

• Struts must be incorporated into the vessel wall (strut coverage)

• Become structurally discontinuous

• Allow the vessel to respond naturally to physiological stimuli

• Resorb in a benign fashion

Types of Bioabsorbable stents

• The Absorb bioresorbable vascular scaffold (Abbott Vascular) consists of a 150-μm-thick bioresorbable poly(l-lactide) scaffold with a 7-μmthick bioresorbable poly(d,l-lactide) coating, which elutes everolimus.

• 100 ugm/cm2 rate of release, 80% by 28 days.• This bioresorbable vascular scaffold has been

studied in registries and in three modest-sized randomized trials.

• In these trials, there was no significant difference in the rate of adverse events between the Absorb bioresorbable scaffold and the Xience cobalt–chromium stent (Abbott Vascular) within 1 year.

• However, these studies were not adequately powered for clinical end points, and therefore the safety and effectiveness of the bioresorbable scaffold, as compared with drug-eluting stents, have not yet been established.

A large-scale, multicenter, randomized trial to determine the relative safety and effectiveness ofthe Absorb scaffold as compared with the Xience stent in patients with coronary artery disease.

ABSORB RCT OVERALL DESIGN

METHODS

• ABSORB III was a multicenter, single-blind, active-treatment, controlled clinical trial.

• Funded by Abbott Vascular

Study Patients• Patients 18 years of age or older with myocardial

ischemia who were undergoing percutaneous coronary intervention (PCI) for one or two new native coronary artery lesions in separate epicardial coronary vessels were eligible for enrollment.

• Each lesion was required to be no more than 24 mm in length with a reference-vessel diameter of 2.5 to 3.75 mm on visual assessment.

• Patients with acute myocardial infarction and specific complex lesion features were excluded.

Angiographic Exclusion Criteria• 1. Lesion prevents complete balloon predilatation viz. Heavily calcified lesion

• 2. Anatomy proximal to or within the lesion that prevents proper passage or placement of delivery system

Extreme angulation (≥ 90°) proximal to or within the target lesion Excessive tortuosity (≥ two 45° angles) proximal to or within the target lesion

• 3. Lesion located within or distal to a diseased (vessel irregularity per angiogram and > 20% stenosed lesion) arterial or saphenous vein graft.

• 4. Aorto-ostial lesion (within 3 mm of the aorta junction).

• 5. Lesion located in the left main.

• 6. Lesion located within 2 mm of the origin of the LAD or LCX.

• 7. Lesion involving a bifurcation with a:– side branch ≥ 2 mm in diameter and/or ostial lesion ≥ 50% stenosed– side branch requiring protection guide wire– side branch requiring predilatation.

Angiographic Exclusion Criteria• 8. Target vessel contains thrombus as indicated in the

angiographic images.

• 9. Lesion involves myocardial bridge.

• 10. Target vessel was previously treated with any type of PCI (e.g., balloon angioplasty, sent, cutting balloon, atherectomy) < 9 months prior to index procedure.

• 11. Non-target vessel or non-treated vessel was previously treated with any type of PCI < 90 days prior to the index procedure.

• 12. Additional clinically significant lesion(s) (e.g., %DS > 50%) in a target/non-target vessel or side branch for which PCI may be required < 90 days after the index procedure.

Treatments and Randomization• All the study patients received a loading dose of at least

300 mg of aspirin within 24 hours before the procedure. • A loading dose of a P2Y12 receptor antagonist was

administered before the procedure or within 1 hour after the procedure.

• Other medications were administered according to standard practice.

• Predilatation of the target lesion was required.• After successful predilatation, patients were randomly

assigned in a 2:1 ratio to receive one of the two study devices (the Absorb everolimus eluting bioresorbable scaffold or the Xience everolimus- eluting cobalt–chromium stent).

• After implantation, high-pressure postdilatation was recommended to achieve 10% residual stenosis or less for both devices.

• Expansion of the bioresorbable scaffold to more than 0.5 mm larger than the nominal scaffold diameter was not permitted in order to avoid strut fracture.

• Dual antiplatelet therapy was continued for at least 1 year, and aspirin (at a dose of at least 81 mg daily) was continued indefinitely.

• Clinical follow-up is to be performed through 5 years and is still ongoing.

• At each follow-up visit, patients are asked about interim clinical events, the presence and severity of anginal symptoms, and the use of cardiovascular medications.

• The Seattle Angina Questionnaire and other quality-of-life instruments were used to perform assessments at baseline, at 1 month, and at 12 months.

Study End PointsPrimary Endpoint Target Lesion Failure at 1 year, powered

for non-inferiority (NI) against the control.

TLF is defined as the composite of cardiac death, myocardial infarction attributable to the target vessel (TV-MI), or ischemia-driven target lesion revascularization (ID-TLR).

Major secondary end points were

• The 1-year rates of angina (excluding symptoms through the time of hospital discharge),

• All revascularization, • and ischemia-driven target-vessel

revascularization

RESULTS

• From March 19, 2013, to April 3, 2014.

• ABSORB III and ABSORB IV cohorts • 13,789 patients were assessed for

eligibility at 202 clinical sites in the United States and Australia.

Procedural outcome

Procedural outcome

LIMITATIONS

• Only stable patients• Non-complex lesions• Underpowered to assess low frequency

events• Underpowered subgroup analysis• Only 1 year follow up

TAKE HOME MESSAGES Bioabsorbable scaffold technology is still in infancy but

developing at fast pace.

Preliminary trials have shown quite hopeful results, especially in stable patients with non complex lesions.

Larger randomized trials are ongoing and their results will dictate the future of this novel technology.

Although promising in certain conditions at present but more randomised trials and technology advance is required to implement them in a wider perspective.

46

THANK YOU …

“In 10 years, we may look back and laugh at the time when we used to leave behind little pieces of metal inpatients’ vessels,”

Dr. Ron Waksman MD, FACCAssociate director at Washington Hospital

Center, Washington, D.C.

Sample size