COMMENTARY: Is the “Bioabsorbable Stent” an Answer for Late Stent Thrombosis?

Acute coronary syndrome is one of the leading causes of morbidity and mortality in the United States, and afflicts 879,000 Americans each year.¹ Percutaneous treatment of acute coronary syndrome is a well-accepted remedy for relief of symptoms and reducing the extent of ischemic damage, but fails to alter the mortality rate.² Percutaneous stent placement has proven to be an effective modality to reduce obstructive coronary lesions.³ The Achilles’ heel of percutaneous stent placement is in-stent restenosis.
Restenosis is exaggerated intravascular neointimal proliferation inside the stent and results in increased target vessel revascularization. The rate of restenosis in clinical trials ranged from 8–80%, depending on patient characteristics and the coronary anatomy⁴ with bare-metal stents. In-stent restenosis leads to an increased incidence of revascularization procedures. The first human study by Sousa et al⁵ utilized sirolimus-eluting stents in obstructive coronary artery lesions. Among the 45 patients treated, no in-stent restenosis occurred at 2 years, and 1 patient had target vessel thrombosis. Several major studies have reinforced the benefits of using drug-eluting stents. SIRIUS⁶ and TAXUS IV⁷ were two large, prospective, randomized clinical trials that demonstrated a decrease in restenosis rates to less than 10%, and also decreased repeat revascularization rates with sirolimus- and paclitaxel-coated bare-metal stents. Since 2002, drug-eluting stents have revolutionized treatment strategies in interventional cardiology. Recently, however, the initial enthusiasm of drug-eluting stents was dampened due to the adverse effects of hypersensitivity,8 allergic reaction,⁹ and late stent thrombosis.^10,11 Still, an independent analysis¹² by the U.S. Food and Drug Administration on late stent thrombosis concluded that drug-eluting stents do not carry any increased risk compared to bare-metal stents.¹³ Despite the package labeling directing the use of drug-eluting stents in a specific patient profile and anatomy, clinicians adopted widespread use of drug-eluting stents initially and reduced their use of bare-metal stents.
Late stent thrombosis has continued to plague cardiologists in the past few years and persists as a topic of intense debate. Although the precise mechanism of late stent thrombosis is not well understood, some factors include delayed endothelialization, noncompliance with dual antiplatelet therapy, reaction to the delivery polymer, poor technique during insertion, and use of drug-eluting stents in inappropriate settings (outside the indication guidelines).¹⁴
In the past year, there have been extensive debates, meetings, expert consensus, and changes in guidelines. The new recommendations conclude that dual-platelet therapy (consisting of aspirin and clopidogrel for at least 1 year) should be adopted along with limitations on the use of drug-eluting stents to certain groups of patients.
In the search for better remedies to this new problem, bioabsorbable polymer or biodegradable stents have surfaced. Bioabsorbable polymer-coated, and bioabsorbable metal stents are being studied and seem to have many beneficial effects. The advantages appear to be that they leave no metal behind, have a reduced risk of neointimal hyperplasia, and less risk of late in-stent thrombosis.¹⁵
The CURAMI (Sirolimus-eluting, bioabsorbable polymer-coated constant stent [Cura™] in acute ST-elevation myocardial infarction) registry by Lee et al is a pivotal study in interventional cardiology.¹⁶ The registry evaluates the use of bioabsorbable polymer in the treatment of ST-elevation myocardial infarction. The study is based on the assumption that a bioabsorbable drug-eluting polymer will help reduce intimal hyperplasia and prevent late thrombosis as it gets absorbed, in addition to the perceived benefit of leaving no polymer behind.
The CURAMI registry, however, revealed that the restenosis rate was 22%, and thus comparable to bare-metal stent restenosis. Angiographic follow up was performed in only 56% of patients. We are unaware of the restenosis status in the remaining 42%. Hence, the actual rate of restenosis could be higher if all patients had undergone angiographic follow up.
On follow up, 1 patient was symptomatic; he had ST-elevation myocardial infarction in a new artery. Coronary angiography showed restenosis in the stented artery, and the patient went on to have restenosis of the new Cura stent at 9 months. Can this mean the pathophysiology of restenosis is independent of bioabsorbable polymers?
Another patient, upon follow up for restenosis, underwent intravascular ultrasound evaluation, which showed aneurysmal dilatation of the mid portion of the stent. Aneurysmal dilatation is similar to microaneurysmal dilatation in patients with late stent thrombosis with drug-eluting stents, as described by Virmani et al. Thus, further study may reveal that many of the same problems that we have seen with drug-eluting stents will appear with this new technology. The study group was followed for only 9 months, which may be insufficient time to draw conclusions regarding late stent thrombosis, since recent drug-eluting stent trials are beginning to reveal late stent thrombosis as late as 4 years postimplantation.
Subacute thrombosis occurs at a higher rate in patients who receive stents on an emergent basis compared to use in elective cases.¹⁵ The CURAMI registry was tested in a high-risk population of ST-elevation myocardial infarction, however, thus the results may not be inappropriate.
The biodegradable polymer and bioabsorbable metal stents are still in their evolutionary stages. Thus far, these stents have not been shown to prevent late stent thrombosis. These stents may show their full potential if studied in a more controlled setting with a large, randomized, controlled trial with enough power to reinforce their benefit. Studying their benefit against bare-metal and drug-eluting stents in stable patients may show their advantages to a greater extent.
Patient selection based on lesion characteristics and anatomy of the coronary lesions may play an important role in future outcomes. Understanding that high-risk subgroups, including those with diabetes mellitus, ST-elevation myocardial infarction, left ventricular dysfunction, and renal failure will have poor outcomes irrespective of the stent and polymer used, may be helpful in analyzing the study data.
Bioabsorbable and biodegradable stents may have another role in peripheral vascular arteries. Superficial femoral artery, common femoral artery, and popliteal artery stenting carry a high risk of restenosis and vessel occlusion. Restenosis in peripheral vasculature is due to shortening, lengthening, twisting, and compression of the artery with limb movement. Bioabsorbable self-expanding stents may be ideal in this vascular bed to reduce the plaque burden acutely and prevent late thrombosis as the stents disappear and leave no metal behind.

References

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