In an effort to combat the shortcomings of balloon angioplasty, the use of synthetic devices was considered to maintain the lumen patency of the diseased artery.
Pioneering work to implant the first coronary stent in a human was performed by Sigwart et al in 1986 (Sigwart, Puel et al. 1987). This stent was described as the first self-expanding bare-mental stent (BMS) following balloon angioplasty, and it was approved in the United States for coronary patients who had high risk of acute vessel closure after failed PTCA (Ruygrok and Serruys 1996, Sousa, Serruys et al. 2003).
The advances of this new technology in reducing early elastic recoil and could be considered as an alternative way to avoid emergency CABG after failed PTCA were
confirmed in subsequent studies (Newsome, Kutcher et al. 2008). In two landmark trials conducted in 1993, the STRESS and the BENESTENT trials indicated that BMS implantations were superior to balloon angioplasty alone. Restenosis rates reduced from 42% to 32% (p = 0.04) in the STRESS trial, and from 32% to 22% (p = 0.02) in the BENESTENT trial. The prevalence of target vessel revascularization went down from 25% -35% in the balloon angioplasty alone group to 10-15% with stenting group in the STRESS trial (Fischman, Leon et al. 1994, Serruys, de Jaegere et al. 1994).
These results promoted BMS implantation to be the accepted standard of care and by 1999, approximately 85% of all PTCA involved stent implantation (Newsome, Kutcher et al. 2008).
Despite these advances and encouraging success, follow-up studies found that the BMS insertion only reduced but did not eliminate in-stent restenosis. Re-stenosis was still persistent at the rate of 20-30% in medium and long-term follow-up studies (Newsome, Kutcher et al. 2008, Canfield and Totary-Jain 2018). The reason was attributed to the combination of proliferation and migration of vascular smooth muscle cells inside the stents. The other challenge in the early application of BMS was the early occurrence of stent thrombosis, which might lead to dangerous complications such as STEMI in 90% and mortality in 20% of cases. Clinical trials of BMS reported the prevalence of stent thrombosis varied from 16-24% in the first 30-days after stent implantation (Newsome, Kutcher et al. 2008).
In attempts to enhance the safety of BMS stenting, the techniques of stent deployment were much improved and the use of anticoagulation was replaced with dual- antiplatelet therapy in optimal medical therapy following PCI. Initially,
anticoagulation was used together with aspirin as the main therapeutic modality for the reduction of early thrombotic events. Further studies confirmed the superior combination of aspirin with a thienopyridine in comparison with uses of anticoagulation and aspirin, which promoted a new cornerstone of antithrombotic prophylaxis (Newsome, Kutcher et al. 2008). Among current thienopyridine, clopidogrel showed advances in safety profiles including lower incidences of skin rash, neutropenia, and thrombotic thrombocytopenic purpura. Then the dual antiplatelet therapy including aspirin and clopidogrel become the medical standard therapy to reduce the incidence of early thrombotic events. Advances in stenting deployment techniques and dual antiplatelet therapies have reduced the incidence of stent thrombosis to the rate of 1.2% (Wenaweser, Rey et al. 2005).
Another revolution in interventional cardiology was the development of drug-eluting stent (DES) in an attempt to inhibit the restenosis process. DES had been developed by coating the surface of BMS with a layer of polymer containing anti-proliferative material which has the advantage to eliminate the neo-intimal proliferation, which reduced the restenosis incidence and the requirement for reintervention (Newsome, Kutcher et al. 2008). This manufactured structure of DES allows the release of drug directly at the diseased lesions, which maximizes the effect of drug in preventing local intimal proliferation after the procedure. Initially, the first generation of DES was coated with either sirolimus or paclitaxel, two agents were found to effectively inhibit the migration of vascular smooth cell and proliferation by various mechanisms. The superior advances in reducing restenosis of new DES compared with BMS at 6-12 months were confirmed by several randomized controlled trials with careful patient recruitment (Moses, Leon et al. 2003, Stone, Ellis et al. 2004). At initial follow-ups,
both types of DES were shown to continually ensure the clinical safety and efficacy in preventing restenosis at 74% reduction after initial deployment (Sousa, Costa et al.
2003, Grube and Buellesfeld 2004). These advanced findings led to the approval of public use of DES in Europe in 2002. In the United States, the Food and Drug Administration gave the approval for sirolimus-eluting stents use in 2003 while paclitaxel-eluting stents were approved in 2004. In 2005, approximately 85% of implanted stents in the United States and Europe were DES (Newsome, Kutcher et al.
2008). However, later clinical registries reported the increasing risk of MI and mortality due to late thrombosis in patients implanted with DES, mostly with those who discontinued dual anti-platelet therapy (Stone, Moses et al. 2007).
To enhance the safety of the first DES generation with regard to incidence of thrombosis, second-generation DES with durable polymers were invented. The platform was improved with material of cobalt-chromium or platinum-chromium, making it thinner than the predecessors. The newer derivatives of sirolimus, namely everolimus and zotarolimus, were used with the aim of improving lipophilicity and cellular uptake (Canfield and Totary-Jain 2018). The advances of second-generation DES were reducing thrombosis and target lesion revascularization rates, confirmed in large randomized controlled trials with thousands of participants (Toyota, Shiomi et al. 2015, Jensen, Thayssen et al. 2016).
The third-generation DES with biodegradable polymers was designed to ensure the proper time of drug release and avoid the hypersensitivity reaction to the durable polymer as well as improve the stent integrity and healing of the arteries. Similar safety and efficacy outcomes were shown in reliable studies for these biodegradable polymer-
based DES and they received the food and drug administration approval for use in 2015 (Canfield and Totary-Jain 2018).