Intracoronary Stents

September 16, 1977, in Zurich Germany, Andreas Grunzig performed the first balloon angioplasty in a coronary artery on Andreas Bachman. Grunzig used the first known balloon, a DG 20-30. This method of treating a coronary artery was effective 10 to 20 years after Bachman performed this first procedure. Follow-up studies revealed excellent vessel patency. Unfortunately, this is not the typical result for most patients receiving balloon angioplasty as the Achilles heel of balloon angioplasty is a 5% to 10% acute vessel closure after the procedure. Balloon angioplasty creates vessel dissection at the edges of plaques, and these are nidus points for thrombus and subsequent occlusion. This problem with balloon angioplasty led to the development of bare metal coronary stents that could act as scaffolds to uphold and outwardly compress the vascular epithelial bed. These original stents were thick stainless steel devices with poor radial force. They were effective in solving the mechanical problem of acute vessel closure from balloon angioplasty but introduced a new problem, stent thrombosis. Stent thrombosis caused by these new devices was remedied with dual antiplatelet therapy. As time passed, a new problem with the bare metal stents became evident, and this was in-stent stenosis. Bare metal stents have a restenosis rate anywhere between 20% to 50%. The pathology for this occurrence is neo-intimal hyperplasia due to inflammation and injury to the intima and media of the vessel. Given this response of the vessel to the bare metal stent, the next step in the development of intracoronary stents was to develop a stent that would limit or minimize this neo-intimal hyperplastic response. The development of first-generation, drug-eluting stents ensued. Drug-eluting stents are composed of 3 components: the metal base, a polymer to control the release of the antiproliferative medication, and antiproliferative medications. The first generation of drug-eluting stents was made of stainless steel with a closed-cell design. These first generation stents were relatively thick in diameter making them difficult to maneuver through significantly diseased and calcified vessels. The first drugs utilized with these stents were paclitaxel and sirolimus. Sirolimus is an analog of rapamycin an mTOR inhibitor, and paclitaxel targets tubulin in mitotic cells and inhibits the spindle apparatus during cell division.[1][2][3][4]

In the TAXUS study, the use of first-generation, drug-eluting stents (when compared to bare metal stents) reduced the rate of target vessel revascularization by 50% over a 5-year period. The problems with first-generation, drug-eluting stents were in the very late stent thrombosis events. Accordingly, long-term evaluation of those patients in the TAXUS study noted in an increase in myocardial infarction rates over the period of 5 years due to this very late stent thrombosis event. This was suspected to be due in part to the polymer of drug delivery of these first-generation stents but also as up to 60% of the surface area of the first-generation, drug-eluting stents deployed never fully endothelialized. The drug and polymer combination within these first stents was powerful enough to stop neointimal hyperplasia but also powerful to the point of arresting endothelialization of the vessel where the stent was deployed, hence the very late stent thrombosis events. [5][6]

Second-generation, drug-eluting stents sought to remedy the problems of first-generation, drug-eluting stents. This next generation of stents was developed with thinner strut thickness therapy allowing for faster healing and endothelialization of the coronaries with less inflammation and injury to the media. Instead of stainless steel metal base, second-generation, drug-eluting stents are made of cobalt-chromium thereby making them more malleable and deliverable. The polymers within the second-generation stents were fluorinated polymers making them biocompatible with thromboresistant properties. The drugs utilized to inhibit neointimal hyperplasia in these stents were everolimus and zotarolimus. In the SPIRIT II, III, IV, and Compare trials, head-to-head comparison of everolimus-eluting stents as compared to paclitaxel-eluting stents were shown to significantly reduce major adverse cardiovascular event rates (MACE) defined as cardiac death, myocardial infarction, and ischemic target vessel revascularization over a period of 24 months by 30% to 40%. In these trials, the second-generation, drug-eluting stents reduced very late stent thrombosis by about 70%.[7][8]

3rd generation stents that are currently still being developed make the stent struts thinner and have either bioabsorbable polymers, no polymer at all, and some eliminate the stent with a scaffold that degrades over time. In the BIOFlOW V trial, a thin strut 60-micron, bioabsorbable, third-generation, drug-eluting stent was compared to a current drug-eluting stent with stent struts of 82 microns and durable fluoropolymer. There was a significant reduction of target lesion failure and event rates in the thinner strut group likely secondary to the lower profile of the thinner stent. A meta-analysis performed by Bangalore and Stone comparing ultra-thin, less than 70-micron stents to thicker strut second-generation stents showed a trend toward better outcomes in the thinner stent group driven by less target lesion failure and less stent thrombosis. In a meta-analysis by Palmerini comparing bioabsorbable polymer-based, drug-eluting stents to durable, polymer, drug-eluting stents, there was a small trend toward lower cardiac death and myocardial infarction when compared to bare metal stents. Furthermore, there was less target vessel revascularization when compared to bare metal stents, but they did not show any significant benefit over the current durable, polymer, drug-eluting stents currently deployed. In the EVOLVE II trial comparing a bioabsorbable stent to a durable, polymer, drug-eluting stent after 36 months, there was no significant difference between the 2 stents in terms of target lesion failure.[9][10][11][12]

Another possible evolving front in third-generation stents is polymer-free, drug-coated stents. These are 120-micron-thick, stainless steel stents with microstructured surfaces that hold the antiproliferative drug in an abluminal surface structure. These polymer-free stents offer possible shorter, dual, antiplatelet duration and also do away with possible issues of non-uniformity of drug elution from the polymer coating. This one stent in particular releases biolimus that is 10-times more lipophilic than sirolimus, everolimus, and zotarolimus, allowing it to stay in the surface layers of the cells and self-elute over time. In the Leaders Free trial, the drug-coated stent significantly decreased in target lesion failure as compared to a bare-metal stent, as well as lowered myocardial infarction and cardiac death; although, stent thrombosis rates were about the same. The stent thrombosis rates are likely attributable to the large stent structure of this stent (120-micron) and newer version of this product with more malleable thinner struts will be forthcoming. Another concept for the future is thin strut drug filled stents with an outer cobalt alloy layer, middle tantalum layer and inner layer core material removed becoming a lumen filled with an antiproliferative medication. This concept was tested in the RevElution trial and showed less in-stent late loss over 9 months.[13][14][15][16][17][18]

During deployment of an intracoronary stent, the vessel anatomy in which the stent is deployed is of utmost importance. The stent is sized to the maximal diameter of the distal aspect of the vessel where it will be placed. If the vessel appears significantly calcified, a further assessment with intracoronary imaging with ultrasound or optical coherence tomography may need to be performed to better assess plaque morphology and the possible need to perform rotational, orbital, or laser atherectomy. Another consideration when deploying a stent is possible side-branch impingement and plaque shift during the procedure.[1]

Placement of an intracoronary stent is indicated after successful balloon angioplasty of a significant lesion and during treatment of acute myocardial infarction [19]. It has been well documented that balloon angioplasty causes significant epithelial damage, including small edge dissections of intracoronary plaque, and these dissections ultimately can lead to acute vessel thrombosis. Balloon angioplasty without stent placement, although successful, has significantly elevated restenosis rates approaching 50%. When comparing balloon angioplasty to the placement of bare-metal or drug-eluting stents, all stents groups display significantly lower long-term, target vessel failure, and future revascularization is needed.[20]

Contraindications to intracoronary stent placement tend to be due to systemic conditions that place patients at prohibitive risk to receive the necessary medications that are needed to be given during the procedure or after a stent has been deployed. Contraindications to the procedure are an inability to consume anti-platelet medications, significant anemia, and significant thrombocytopenia. Another contraindication, or relative contraindication, to the procedure is sepsis with active bacteremia and significant renal dysfunction and any significant comorbid condition where the possible harm of the procedure outweighs the possible benefit.

During preparation, to place an intracoronary stent, a 6F or larger guiding catheter must be utilized to engage the coronary ostia. Anticoagulation in the form of heparin, enoxaparin, or bivalirudin may be given to obtain an anticoagulation time greater than 250 seconds. Next, a coronary wire is utilized to provide a rail to be able to deliver balloons and stents to the lesions being treated. Once at the appropriate site in the vessel the stent delivery balloon is insufflated to high atmospheric pressures via an insufflator device that is manually inflated by the technician or the head operator.