Higher Scaffold Thrombosis Risk With Absorb BVS vs a Wide Range of Stents: Network Meta-Analysis

A large network meta-analysis comparing numerous stent types across different clinical trials has shown that treatment with an everolimus-eluting bioresorbable vascular scaffold (BVS) is associated with a higher rate of scaffold thrombosis when compared with modern drug-eluting stents.

Use of the Absorb BVS (Abbott Vascular) was associated with a risk of scaffold thrombosis two-to-three-fold higher than stent thrombosis rates seen in patients treated with the Xience cobalt-chromium everolimus-eluting stent (Abbott Vascular), Orsiro hybrid sirolimus-eluting stent (Biotronik), or Promus platinum-chromium everolimus-eluting stent (Boston Scientific). 

In addition, there were trends toward higher risk of scaffold thrombosis compared with other devices, such as the Resolute zotarolimus-eluting stent (Medtronic) and stents with a biodegradable polymer including Nobori (Terumo) and Synergy (Boston Scientific), among others, although these results were not statistically significant.

The researchers, including Si-Hyuck Kang, MD (Seoul National University, South Korea), who led the study, point out that complete degradation of Absorb BVS occurs between 1 and 4 years after device implantation. “Thus, the benefit of BVS may emerge after 1 year postimplantation,” they write in an article published online June 1, 2016, in JACC: Cardiovascular Interventions. “Considering that scaffold thrombosis occurs in 1% of patients during the first year and then in 0.5% per year thereafter, the benefit, if present, would be paramount.”

The group notes this is not the first study to show a higher risk of scaffold thrombosis with the Absorb stent. As reported by TCTMD, investigators conducting a meta-analysis of the major ABSORB studies showed definite or probable stent thrombosis after a median of 12 months was two-fold higher in BVS-treated patients when compared with those who received an everolimus-eluting metallic stent. Additional meta-analyses have yielded similar results, although in others the increased risk of scaffold thrombosis was not significant.

To TCTMD, Davide Capodanno, MD, PhD (University of Catania, Italy), who wrote an editorial accompanying the study, said the increased risk of scaffold thrombosis observed with Absorb compared with the other devices is expected given that most of the data in the network meta-analysis is derived from clinical trials comparing it with the everolimus-eluting stents. Those and other meta-analyses suggest “there is a cumulative signal of increase thrombosis” with BVS, Capodanno said in an email.

Comparisons Across Clinical Trials

The large network meta-analysis included 147 trials and 126,526 patients and is designed to compare the different stents using direct comparisons within randomized controlled trials and indirect comparisons across randomized trials based on a common comparator. The studies included prospective randomized trials testing bare-metal stents, Taxus/Taxus Liberté paclitaxel-eluting stents (Boston Scientific), Cypher sirolimus-eluting stents (Cordis), and polymer-free drug-eluting stents, as well as Absorb BVS, Xience, Orsiro, Promus, Nobori, Resolute, and the Endeavour zotarolimus-eluting stent (Medtronic).

Overall, the Promus, Xience, and Orsiro stents were associated with “excellent safety,” with the Xience stent having significantly lower rates of stent thrombosis compared with multiple devices, including Absorb BVS and the biodegradable polymer biolimus-eluting stent. The Orsiro stent performed as well as Xience in its head-to-head comparisons with other devices. All commercially available drug-eluting stents, including those with a biocompatible durable polymer, a biodegradable polymer, and without a polymer, were associated with a significantly lower risk of probable or definite stent thrombosis compared with bare-metal stents or first-generation devices, report investigators.  

The contemporary stents, including the Absorb BVS, were also associated with a low rate of coronary revascularization.

Regarding the network design, Capodanno said some of the comparisons are obsolete given that they refer to bare-metal stents of drug-eluting stents no longer on the market. Eliminating these from the comparison, though, would significantly reduce the statistical power of the analysis. While a network meta-analysis has limitations, such as a reliance on indirect comparisons, they can “provide useful data in data-free zones,” he said.

On the whole, Capodanno agreed with the researchers, saying the benefits of the Absorb stent would be expected long-term after the stent disappears. Although purely hypothetical at this stage, he said there are potential advantages of freeing the coronary arteries from the metallic cage. In addition, using the BVS properly—avoiding small vessels, following good implantation techniques—might eliminate the “disturbing signal of stent thrombosis” noted to date.

“The problem for BVS, as shown by this meta-analysis, is that the bar is very high: modern drug-eluting stents are very good,” stated Capodanno.

Symmetry and Risk of Device-Related Events

In a second study, also published June 1, 2016, in JACC: Cardiovascular Interventions, Pannipa Suwannasom, MD (Erasmus University Medical Center, Rotterdam, the Netherlands), and colleagues address the implantation of the Absorb stent, particularly the impact of asymmetrical stent expansion occurring afterward.

In an analysis of 470 patients in the ABSORB II study who underwent intravascular ultrasound (IVUS) after device implantation, researchers reported that the metallic Xience stent expanded more symmetrically and concentrically than the Absorb BVS. Optimal stent expansion was achieved in 20% of patients who received the Xience stent and 8% of those treated with Absorb.

In the analysis, asymmetrical expansion, which was quantified using an IVUS-derived asymmetry index (AI > 0.3), was an independent predictor of device-oriented cardiovascular outcomes (defined as cardiac death, MI, and ischemia-driven target lesion revascularization). Among the BVS-treated patients, asymmetric expansion of the Absorb stent was associated with a nine-fold higher risk of adverse clinical outcomes—mainly periprocedural MI—but asymmetric expansion of the Xience stent was not linked with adverse outcomes.

The researchers caution that the results should be considered hypothesis-generating given the low event rates, however.

To TCTMD, Hiram Bezerra, MD (UH Case Medical Center, Cleveland, OH), who was not involved in the study, said that historic IVUS studies in drug-eluting stents have failed to correlate lumen asymmetry with clinical outcomes, leading to a decline in interest in the metric. Bezerra added that asymmetry/eccentricity is related to the underlying plaque, with an eccentric fibrotic/calcified plaque, where the plaque is not distributed evenly around the coronary artery circumference, resulting in an eccentric final lumen.

“I personally don’t believe eccentricity per se has a significant clinical impact [but instead think that it] can be an epiphenomenon of an underlying eccentric calcified plaque which is an accepted predictor of suboptimal results, specifically suboptimal expansion,” he noted.

Myeong-Ki Hong, MD, and Jung-Sun Kim, MD (Yonsei University College of Medicine, South Korea), who wrote an editorial accompanying the analysis by Suwannasom et al, state that the clinical implications of asymmetric expansion are unclear in metallic drug-eluting stents, but appear to play a role with BVS. They agree that symmetric expansion is usually affected by plaque characteristics and suggest that proper lesion preparation could increase the likelihood of optimal symmetric stent expansion and ultimately reduce the frequency of post-stent balloon dilation, which can lead to higher risks of periprocedural MI.   

• Kang SH, Chae IH, Park JJ, et al. Stent thrombosis with drug-eluting stents and bioresorbable scaffolds: evidence from a network meta-analysis of 147 trials. J Am Coll Cardiol Intv. 2016;Epub ahead of print.
• Capodanno D. Revisiting the network of drug-eluting stent trials: bioresorbable scaffolds enter the arena. J Am Coll Cardiol Intv. 2016;Epub ahead of print.
• Suwannasom P, Sotomi Y, Ishibashi Y, et al. The impact of post-procedural asymmetry, expansion, and eccentricity of bioresorbable everolimus-eluting scaffold and metallic everolimus-eluting stent on clinical outcomes in the ABSORB II trial. J Am Coll Cardiol Intv. 2016;Epub ahead of print.
• Hong MK, Kim JS. Does asymmetric expansion of bioresorbable vascular scaffolds cause stent failure. J Am Coll Cardiol Intv. 2016;Epub ahead of print.

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