Bioabsorbable Stents – Where Are We Now?

The perfect human prosthetic implant is one that is easily put in, does its job, and then disappears with no residual effects. That would be ideal for a coronary or other vascular stent. When I think about bioabsorbable stents, this is the image that comes to mind. Unfortunately, reality has a way of disturbing our dreams. In the case of bioabsorbable vascular stents (BVS) replacing metal stents, we still have a way to go before it becomes the ideal ‘disappearing’ stent, a proposition that is scientifically irresistible. For example, if the BVS absorbed into the vessel wall over the next year, we would expect a number of great things: that the vessel might resume some or most of its normal function. There would be no need for dual antiplatelet drugs, remodeling of the vessel would not be inhibited by a metal cage, and normal vasomotion might be restored. With no metal left in the vessel, should the time come for a bypass surgery, there would be no interference with the bypass graft implant. 

In addition to the scientific benefits, there may be some significant psychological benefits. No one wants a metal stent (or any metal prosthesis) permanently left in their body. Just walk through the airport metal detector and ask that question again. The promise of a bioabsorbable stent to treat obstructive coronary artery disease (CAD) and then disappear, while tremendously appealing, has not yet been fulfilled. Let’s see where we are now.

History of bioabsorbable stents

To briefly review stent history, recall that the first metallic stents were available in 1988 and were initially indicated to treat only dissections and abrupt vessel closure. They required intense anticoagulation with coumadin. We learned that full stent strut expansion and vessel wall apposition (by intravascular ultrasound [IVUS] documentation) made coumadin unnecessary, and permitted the use of dual antiplatelet therapy (aspirin and ticlopidine, now clopidogrel). First-generation metal stents had thick struts and limited flexibility. Restenosis was reduced to 20-30%, down from the 50% noted with plain old balloon angioplasty. Over time, second- and third-generation metal stent designs further reduced restenosis. In the mid 1990’s, drug-eluting metallic stents brought restenosis into the single digits, i.e., <10%. 

Downside of metallic stents

Despite the big benefits of stent-related reductions in restenosis, metal stents had their downside as well. Metal stents are associated with acute and late thrombosis, need for long-term dual antiplatelet therapy and lasting impact of a metal scaffold in the artery interfering with adequate computed tomography (CT) or magnetic resonance imaging (MRI), vascular remodeling, and coronary vasomotion (including endothelial function). Extensive stenting also makes future coronary artery bypass graft (CABG) procedures difficult, if not impossible. 

Advent of bioabsorbable stents

For the last decade, initial experiences with various types of bioabsorbable stents to replace metal stents have been under intense study. It is hoped that the bioabsorbable stent would avoid or overcome the above-mentioned downsides of metal in the artery. Bioabsorbable stents would avoid the loss of (and perhaps restore) normal vasomotion (ability to constrict and relax), improve persistently abnormal endothelial function, and permit vessel remodeling not possible within the metallic stent cage. Additional advantages include a parole from side branch stent jail as the stent struts absorb over time. 

Characteristics and properties of four bioabsorbable stent types are summarized in Table 1. Clinical characteristics are summarized in Table 2.

Recent outcomes of the ABSORB study

Positive long-term data from the two-stage ABSORB trial, using the Abbott Laboratories’ drug-eluting vascular scaffold (the Absorb^™ Bioresorbable Vascular Scaffold [BVS]), was presented at the American Heart Association meeting in November 2011 by the Rotterdam group. The Absorb BVS is made of poly-L-lactide and coated with everolimus. It possesses unique challenges. For example, it has thicker stent struts, with less tolerance for overexpansion than metal stents, and its rate of absorption varies.

At five years, in the 30 patients receiving the Absorb BVS, there were no reports of cardiac deaths, stent thrombosis or ischemia-driven target lesion revascularization. The major adverse cardiac event (MACE) rate at five years was 3.4 percent, with no new events reported between six months and five years.

In the stage 2 part of the trial examining mechanisms of bioresorption in 44 patients, the MACE rate was 7%. Using angiography, the lumen late loss was only 0.27 mm, meaning minimal endothelial proliferation. Interestingly, testing of vasomotor function at two years showed signs of it returning (constriction or dilation of the vessel). The return of vasomotion indicates that the vessels were not tightly constrained, as is the case with a permanent metallic implant. 

After a number of years, the Absorb BVS, a fully bioabsorbable everolimus-eluting stent, shows much promise and is furthest along in clinical development. However, given the lag in time to resorb and the patient’s continued need for dual antiplatelet therapy until full endothelialization, expert opinion varies on how frequently these stents will be used. Is the cost worth the benefit, given the downsides of manufacturing and the fact that these stents have thicker struts than current stents on the market? Is 3 or 4 years before absorption (the current estimation for the general class of bioabsorbable stents) too long? Should the stents be used for vulnerable arteries that are not yet significantly narrowed, with the intention of making an unhealthy vessel healthy again? Some interventionalists posit that implanting bioabsorbable stents will be necessary in only in a minority of patients. Dr. Renu Virmani (CVPath Institute, Gaithersburg, MD) believes there will probably be 10% to 20% of the population in whom such stents will not work, probably in those with severe amounts of lesion calcification. The Absorb, with its thick stent struts, dissolves fully in about two years. However, at two years, even bare-metal stents have healed and the benefit of using such stents becomes less evident.

On the other hand, other investigators feel that if the scaffold degrades and is no longer in the artery, there will be no stimulus to cause inflammation, believed to be associated with late lesion progression and late stent thrombosis. Unfortunately, it is reported that new and next-generation bioabsorbable stent designs would likely take 3 or 4 years to disappear, without further reduction of restenosis (<4% at one year).  

The bottom line

The benefits of a bioabsorbable stent are evident, and if most or all of these features come to pass, the bioabsorbable stent will replace bare-metal and drug-eluting stents over time.  However, it appears that the current research, both clinically and mechanistically, put the bioabsorbable stent 4 to 5 years away from availability in United States cath labs. Until then, we will just have to continue our superlative jobs with drug-eluting stents, IVUS, and fractional flow reserve as the best stent decisions for our patients.

Dr. Kern reports that he is a speaker for Volcano Therapeutics and St. Jude Medical, and is a consultant for Merit Medical.

Reference

1. Ormiston JA, Serruys PW.  Contemporary reviews in interventional cardiology: bioabsorbable coronary stents. Circ Cardiovasc Interv 2009; 2: 255-260.