Version May 2024
INTRODUCTION — For most patients undergoing percutaneous coronary intervention with stenting, current-generation drug-eluting stents (DES) are preferred to bare metal stents due to a significantly lower risk of the need for target vessel revascularization. (See "Intracoronary stent restenosis", section on 'Incidence of restenosis' and "Percutaneous coronary intervention with intracoronary stents: Overview", section on 'Role for bare metal stents'.)
While all DES have the same general components, they differ with respect to the stent platform, the polymer used, and antirestenotic drug type (table 1). Clinical differences are observed with respect to deliverability (ease of placement), efficacy (prevention of restenosis), and safety (rates of stent thrombosis and myocardial infarction [MI]). This topic will review the studies that compared one DES with another and provide broad guidance regarding which DES to choose. The approach to stenting in subgroups of patients with coronary artery stenoses is discussed elsewhere. (See "Percutaneous coronary intervention of specific coronary lesions", section on 'Small coronary arteries' and "Coronary artery revascularization in stable patients with diabetes mellitus", section on 'Stent type' and "Intracoronary stent restenosis", section on 'Choice of device'.)
OUR APPROACH — For most patients undergoing percutaneous coronary artery intervention with stent placement, we place a current-generation DES rather than a bare metal stent to reduce the risk of target-vessel revascularization. Current-generation DES include everolimus-eluting stents (EES), zotarolimus-eluting stents (R-ZES]), ridaforolimus-eluting stents (RES), and two bioresorbable polymer DES (SYNERGY and Orsiro). We do not prefer one type of stent over another; each as a similar safety and efficacy profile. (See "Coronary artery stent thrombosis: Incidence and risk factors", section on 'Comparison of differing DES'.)
There is insufficient evidence to suggest that bioresorbable polymer or polymer-free stents are superior to current-generation DES. (See 'Bioresorbable polymer drug-eluting stents' below and 'Polymer-free drug-eluting stents' below.)
Bioresorbable scaffold stents are not clearly better than the bioresorbable polymer stents covered in this topic. Bioresorbable scaffold stents are discussed in detail elsewhere. (See "Bioresorbable scaffold coronary artery stents".)
EXPLANATION OF STENT TYPES — Most DES have the following components: a metal stent platform, a durable polymer, and an antirestenotic drug that is embedded within the polymer and released slowly (table 1). The durable polymer remains permanently on the stent after the drug is eluted from the polymer.
This topic groups DES according to polymer characteristics and then further subdivides based on strut thickness. This categorization is somewhat arbitrary but is a reasonable framework from which the reader can understand stent design. Not all newer stents for which results have been published are included in this topic.
Newer stents attempt to further lower the already low long-term risks of stent thrombosis and restenosis seen with current-generation DES (see 'Everolimus- versus zotarolimus-eluting stents' below). Stents that have been evaluated include those that have a bioresorbable (also referred to as "biodegradable") polymer or those that are polymer free. In addition, stents that have thinner metal struts are being evaluated. Some stent designs include changes to both the polymer and the strut thickness. Finally, bioresorbable scaffolds have been evaluated and are discussed separately. (See "Bioresorbable scaffold coronary artery stents".)
Bioresorbable polymer — The durable polymers on current-generation (second-generation) DES produce minimal inflammatory response and have more rapid vessel endothelialization or healing compared with first-generation DES. This biocompatibility and associated reduced inflammatory response are likely due to improvements in polymer technology and may translate into lower rates of MI and stent thrombosis.
Despite the low long-term risks of stent thrombosis and restenosis seen with current-generation DES (see 'Everolimus- versus zotarolimus-eluting stents' below), it might be possible to further lower the risk by allowing for polymer reabsorption. The theoretical advantage of a bioabsorbable (biodegradable) polymer DES over a durable polymer DES is the removal of the polymer as a potential chronic stimulus for inflammation, thereby effectively becoming a bare metal stent (BMS), further reducing thrombotic risk, and potentially shortening duration of dual antiplatelet therapy (DAPT). Despite this potential improvement in biocompatibility, the ability to reduce the duration of DAPT, which might be particularly useful in patients at high bleeding risk, is unproven. (See "Coronary artery stent thrombosis: Incidence and risk factors" and "Coronary artery stent thrombosis: Clinical presentation and management".)
Polymer-free drug-eluting stents — In polymer-free DES, the drug, which is coated to the stent, is released into the vessel wall for about one month.
A polymer-free stent, similar to a bioresorbable polymer stent, may be associated with less chronic inflammation and improved vascular healing. The difficulty in designing a polymer-free stent is achieving adequate levels of antiproliferative drugs over time to effectively inhibit neointimal hyperplasia and restenosis. Currently, there are no FDA-approved DES that are polymer free.
The potential utility of polymer-free DES is discussed below. (See 'Polymer-free drug-eluting stents' below.)
Variation in strut thickness — As will be discussed below, decreasing stent strut diameter may be associated with lower risks of restenosis and thrombotic complications [1,2]. Current-generation (second-generation) DES have diameters in the 70 to 100 micrometer range and have been referred to as "thin stents." Thick strut (greater than 100 micrometers) and ultra-thin diameter (less than 70 micrometers) stents are under investigation. Some studies have used struts that are between 60 and 81 micrometers; these have been referred to as "very thin struts" by some investigators. (See 'Ultra-thin-strut bioresorbable drug-eluting stents' below.)
Bioresorbable scaffold — Bioresorbable or biodegradable scaffold stents are discussed separately. (See "Bioresorbable scaffold coronary artery stents".)
EARLY-GENERATION DRUG-ELUTING STENTS — Sirolimus- and paclitaxel-eluting stents (SES and PES, respectively) were the first commercially available intracoronary drug-eluting stents (DES) and are referred to as "first-generation" stents. Neither is used with any regularity in most of the United States, Europe, and Canada due to advances in stent platforms and polymer biocompatibility found in newer DES, as discussed below. (See '2012 comparison of drug-eluting stents' below.)
The studies of the SES and PES are relevant to the extent that they helped to establish the rates of clinically important outcomes against which newer stents are compared.
Two 2007 meta-analyses evaluated short-term outcomes with SES or PES [3,4]. SES reduced the primary endpoints of the risk of reintervention and stent thrombosis compared with PES, and the risks of death and MI were similar between the two stents. Longer-term outcomes after SES or PES in patients with more complex lesions come from five-year follow-up of patients enrolled in the SIRTAX trial [5]. Comparing SES with PES, there was no significant difference in the rates of a composite primary endpoint, which included cardiac death, MI, and ischemia-driven target lesion revascularization (19.7 versus 21.4 percent), ischemia-driven target lesion revascularization (13.1 versus 15.1 percent), or definite or probable stent thrombosis (4.8 versus 4.9 percent). (See "Coronary artery stent thrombosis: Incidence and risk factors", section on 'Definitions'.)
DURABLE POLYMER DRUG-ELUTING STENTS — Most commercially available, current-generation stents available in the United States contain a metal stent platform (the supporting structure), a durable polymer, and an antirestenotic drug embedded within the polymer. These include zotarolimus-eluting, everolimus-eluting, and ridaforolimus-eluting stents (everolimus-eluting stents [EES], ZES, and RES).
In these DES, the stent platform is made of a cobalt or platinum chromium alloy. They are thinner and more deliverable than the first-generation DES. In addition, these current-generation DES are more biocompatible than first-generation DES, as they generate less inflammatory response and have more rapid vessel endothelialization or healing. This biocompatibility and the associated reduced inflammatory response are likely due to improvements in polymer technology and may translate into lower rates of MI and stent thrombosis [6]. (See "Coronary artery stent thrombosis: Incidence and risk factors".)
Everolimus-eluting stents — Two versions of the EES with a durable polymer are available: one with cobalt chromium and one with platinum chromium stent material (table 1). With regard to EES:
●EES are superior to first-generation paclitaxel-eluting stents (PES) [7-13] and comparable to sirolimus-eluting first-generation stents [14-20].
●The two versions of the EES were found to have similar efficacy and safety in the PLATINUM trial, which randomly assigned 1530 patients with one or two de novo native lesions to a platinum chromium or a cobalt chromium stent [21]. The 12-month rates of target lesion failure (a composite of target vessel-related cardiac death, target vessel-related MI, or ischemia-driven target lesion revascularization) were 2.9 and 3.4 percent, respectively. At five years, target lesion failure was similar for the platinum and cobalt chromium EES (9.1 percent versus 9.3 percent, p = 0.87) as was stent thrombosis (0.8 percent versus 0.7 percent) [22].
Zotarolimus-eluting stents — The first ZES, the Endeavor (E-ZES), was used in several important clinical trials that led to the US Food and Drug Administration approval of ZES. The Endeavor was replaced by the Resolute (R-ZES), due to its improved drug release characteristics [23].
The Endeavor used a polymer that mimics the cell membrane phospholipid phosphorylcholine. Zotarolimus was eluted within a few weeks from the polymer, with 95 percent of the drug released within about two weeks. To improve upon drug release kinetics and achieve a greater degree of inhibition of intimal hyperplasia, the ZES was redesigned as the R-ZES with an alternative polymer, the proprietary BioLinx polymer. The R-ZES has extended delivery of zotarolimus (85 percent within 60 days and the remainder by 180 days). Late lumen loss, a surrogate measure of restenosis, is lower with R-ZES [23]. More recently, the stent platform of R-ZES was updated to the Onyx ZES.
The following are the major findings of studies comparing E-ZES with first-generation DES:
●E-ZES are inferior to sirolimus-eluting stents (SES) and PES with respect to the angiographic finding of in-stent late loss [24-31].
●Long-term studies evaluating clinical outcomes comparing E-ZES with SES come to no firm conclusions [25-28,31].
●Studies comparing E-ZES with PES suggest similar [29,30] or better long-term clinical outcomes [31], depending on the patient population.
The relatively high late lumen loss observed in the above studies of E-ZES drove the development of the R-ZES, which has longer drug elution. Although the E-ZES and the R-ZES have not been directly compared, results from a study that examined in-stent late lumen loss in 139 patients with single de novo coronary lesions suggest benefit from the polymer in the R-ZES. At nine-month follow-up, in-stent late lumen loss was 0.22±0.27 mm with the R-ZES, which was lower than previously observed in E-ZES [32].
Everolimus- versus zotarolimus-eluting stents — As EES and R-ZES have better clinical outcomes compared with PES, and as SES are no longer available, comparisons between EES and ZES are central to the formulation of recommendations for the choice of DES. Multiple randomized trials and one registry have found that EES and R-ZES are comparable in terms of efficacy and safety [33-40].
A 2015 meta-analysis evaluated outcomes in the five largest randomized trials (n = 9899) comparing R-ZES with EES: RESOLUTE All Comers, TWENTE, ISAR-LEFT MAIN, DUTCH PEERS, and HOST-ASSURE [41]. The studies included a wide range of patient and lesion characteristics. The following findings (with follow-up at five years) were noted comparing these two stents, respectively:
●No difference in the primary efficacy endpoint of target vessel revascularization (6.34 versus 5.05 percent; risk ratio [RR] 1.06, 95% CI 0.90-1.24).
●No difference in the primary safety point of definite or probable stent thrombosis (1.27 versus 0.88 percent; RR 1.26, 95% CI 0.86-1.85).
●No difference in the secondary endpoints of cardiac death or target vessel MI (RR 1.01 and 1.10, respectively).
2012 comparison of drug-eluting stents — A 2012 mixed-treatment comparison meta-analysis of 76 randomized trials with over 100,000 patient-years of follow-up supports the conclusions of the individual studies (and their meta-analyses) presented above [42]. The meta-analysis, performed prior to approval of RES, came to the following conclusions:
●With regard to the risk of target vessel revascularization at one year or less and long term, SES, EES, and R-ZES were similar and had lower rates than PES or E-ZES.
●With regard to the risk of death at one year or less, as well as long term, there was no significant difference between any pair of DES.
●With regard to the risk of definite or probable stent thrombosis, EES had the lowest risk of any DES.
Ridaforolimus-eluting stent — The EluNIR stent is an RES that has been less well studied than EES or R-ZES. In the BIONICS trial, 1919 patients with broad inclusion criteria, including those with recent MI, total occlusions, and bifurcation lesions, were randomly assigned to RES or R-ZES [43]. At 12 months, the primary endpoint of target lesion failure (composite of cardiac death, target vessel-related MI, and target lesion revascularization) was 5.4 percent for both devices (upper bound of one-sided 95% CI 1.8 percent, p for noninferiority = 0.001). Definite/probable stent thrombosis rates were low in both groups (0.4 percent RES versus 0.6 percent ZES, p = 0.75). Thirteen-month angiographic in-stent late lumen loss was 0.22±0.41 mm and 0.23±0.39 mm (p for noninferiority = 0.004) for the RES and ZES groups, respectively.
BIORESORBABLE POLYMER DRUG-ELUTING STENTS — Several studies have tested whether the risk of stent-related adverse outcomes (such as stent thrombosis) can be reduced by allowing for resorption (or elimination) of the polymer. (See 'Explanation of stent types' above.)
The evidence from randomized clinical trials presented below suggests that bioresorbable (biodegradable) polymer DES are comparable to current-generation DES with durable polymers in terms of efficacy and safety at two years (table 1) and perhaps longer. Similar outcomes between the two stent types have been observed in large, all-comer observational studies [44,45].
We believe the evidence is not strong enough to recommend bioresorbable polymer in preference to durable polymer DES, particularly if the goal is to shorten the recommended duration of dual antiplatelet therapy (DAPT). (See "High bleeding risk patients undergoing percutaneous coronary intervention", section on 'Our approach'.)
In a 2017 meta-analysis that included 16 randomized trials comparing second-generation DES with biodegradable polymer DES (n = 19,886) (table 1), there were no significant differences in target vessel revascularization (p = 0.62), cardiac death (p = 0.46), MI (p = 0.98), or stent thrombosis (risk ratio [RR] 0.83, 95% CI 0.64-1.09) [46]. A landmark analysis within this study found that bioresorbable polymer DES were not associated with a reduction in the risk of very late stent thrombosis (RR 0.87, 95% CI 0.49-1.53). Similar outcomes were seen regardless of the drug coating (biolimus versus sirolimus), the stent platform (stainless steel versus alloy), the strut thickness of the bioresorbable polymer DES, or the DAPT duration (≥6 versus ≥12 months). (See 'Our approach' above.)
However, we are reluctant to use the results of these network meta-analyses to formulate recommendations, as multiple comparisons were performed on widely different stent technologies. Some of these have never been directly compared.
The SYNERGY (see 'Thin-strut bioresorbable polymer drug-eluting stents' below) and Orsiro (see 'Ultra-thin-strut bioresorbable drug-eluting stents' below) stents are the first bioresorbable polymer DES approved by the US Food and Drug Administration. Other bioresorbable polymer DES discussed below are either investigational or not available in the United States. These polymers degrade over approximately 3 to 18 months. The studies presented below are similar in that the polymer was bioresorbable. However, as different stent designs and antiproliferative drugs were used, caution needs to be exerted when making any conclusions from indirect comparisons.
Thin-strut bioresorbable polymer drug-eluting stents — The SYNERGY stent is a bioresorbable polymer, everolimus-eluting stent (EES), with thin struts (comparable to that of durable polymer DES). SYNERGY was evaluated in the following studies, which generally found similar efficacy and safety to durable polymer DES:
●The EVOLVE trial compared two dose formulations of the SYNERGY stent, and the durable polymer, platinum chromium EES. Two hundred and ninety-one patients with de novo coronary lesions were randomized 1:1:1. At 30 days, target lesion failure occurred in 0, 1.1, and 3.1 percent of patients in the durable polymer EES, SYNERGY, and SYNERGY half-dose groups, respectively. At six months, no difference was observed in the three groups in in-stent late loss. No stent thromboses occurred through six-month follow-up [19].
●The EVOLVE II trial randomized 1684 patients with stable angina or non-ST elevation acute coronary syndrome to the SYNERGY stent or durable polymer platinum chromium EES. The primary endpoint of 12-month target lesion failure was observed in 6.7 percent of SYNERGY and 6.5 percent durable polymer EES-treated subjects (p = 0.83 for difference; p = 0.0005 for noninferiority). Clinically indicated target lesion revascularization or stent thrombosis was observed in 2.6 versus 1.7 percent (p = 0.21) and 0.4 versus 0.6 percent (p = 0.50) of the two stents, respectively [20]. Outcomes were similar in the two groups at five years [47].
●The SORT OUT VIII trial randomly assigned 1385 patients to a thin-strut biodegradable polymer EES (SYNERGY) with a thick-strut biodegradable polymer biolimus-eluting stent (NeoFlex) [48]. The primary composite endpoint (cardiac death and MI not clearly attributable to a nontarget lesion, as well as target lesion revascularization at 12 months) occurred at a similar rate (4.0 versus 4.4 percent, respectively).
The SYNERGY stent has also been evaluated in subjects with high bleeding risk to assess shorter DAPT strategies. (See "High bleeding risk patients undergoing percutaneous coronary intervention", section on 'Definition of high bleeding risk'.)
●The SENIOR trial randomly assigned 1200 patients 75 years or older 1:1 to the SYNERGY stent or bare metal stent (BMS; rather than a current-generation DES), with one month of DAPT for stable presentation and six months for unstable presentation. The primary endpoint of major adverse cardiac and cerebrovascular events at one year was 12 percent in the DES group and 16 percent in the BMS group (RR 0.71, 95% CI 0.52-0.94) [49]. In both groups, the rate of stent thrombosis was 1 percent.
●The EVOLVE Short DAPT study enrolled 1487 patients who had a SYNERGY stent and a high risk of bleeding to evaluate the effect of 3 or 12 months of DAPT on the rate of cardiovascular and bleeding events [50]. Patients enrolled in this study were matched to historic controls using a propensity score. The study found that three months of DAPT was noninferior to 12 months of DAPT for the risk of the composite of death or myocardial infarction (5.6 versus 5.7 percent in the 12-month group) and for risk of significant bleeding (6.3 versus 4.2 percent in the 12-month group). The rate of stent thrombosis with three months of DAPT was 0.2 percent.
Ultra-thin-strut bioresorbable drug-eluting stents — Decreasing the stent strut diameter may decrease the risk of restenosis and thrombotic complications [1,2]. Ultra-thin stents have strut diameters of 70 micrometers or less; current-generation (second-generation) DES (ie, "thin-strut" stents) have diameters in the 70 to 100 micrometer range. The available evidence suggests that ultra-thin stents have a lower risk of target lesion failure and target lesion revascularization, but no decrease in cardiovascular death.
●In a meta-analysis of trials comparing long-term (mean 2.5 years) outcomes with ultra-thin stents versus thin stents, there was a lower rate of clinically driven target lesion revascularization with ultra-thin stents (3.9 versus 5 percent in the thin-stent group; RR 0.75; 95% CI 0.62-0.92) [51].
Trials in the meta-analyses that evaluated specific ultra-thin stents include the following:
•In the BIO-RESORT trial, 3514 patients with either stable disease or an acute coronary syndrome were randomly assigned to treatment with a thin-strut biodegradeable polymer EES (SYNERGY), ultra-thin SES (Orsiro), or thin-strut durable polymer zotarolimus-eluting stents (ZES) [52]. At 12 months, there was not a significant difference in the rate (5 percent) of the primary endpoint (a composite of safety [cardiac death or target vessel-related MI] and efficacy [target vessel revascularization]). There were no significant between-stent differences at three years.
•In the DESSOLVE III trial, 1398 patients were randomly assigned to a sirolimus-eluting bioresorbable polymer, ultra-thin-strut stent (MiStent), or an everolimus-eluting durable polymer thin stent [53]. With the MiStent, the polymer fully disappears in three months, but the sirolimus persists in the vessel wall for up to nine months. Nearly 60 percent of patients enrolled had an acute coronary syndrome. At 12 months, the primary combined endpoint (cardiac death, target–vessel MI, or clinically indicated target lesion revascularization) occurred with similar frequency in both groups (5.8 versus 6.5 percent, respectively; absolute difference -0.8 percent, 95% CI -3.3 to 1.8). The rate of stent thrombosis was low and did not differ between the two groups.
•In the TALENT trial, 1435 patients were randomly assigned to implantation of either an SES with a biodegradable polymer coating and ultra-thin struts (60 micrometers) (Supraflex) or an EES with a durable polymer coating and thin struts (81 micrometers; Xience) [54]. At 12 months, there was no significant difference in the rate of the primary composite endpoint (cardiac death, target-vessel MI, or clinically indicated target lesion revascularization) between the two groups (4.9 versus 5.3 percent, respectively). The rate of definite or probable stent thrombosis was low and similar in the two groups (0.8 versus 0.9 percent, respectively).
●In a separate meta-analysis of individual participant data that compared a sirolimus-coated, ultra-thin-strut stent with an everolimus-coated, durable polymer, thin-strut stent, there was a lower but nonsignificant decrease in the risk of target vessel revascularization with sirolimus-coated, ultra-thin-strut stents (10.3 versus 12.2 percent in the everolimus-coated stent group; hazard ratio [HR] 0.86, 95% CI 0.71-1.06) [55]. There were no significant differences between the two stent types in cardiac death, target-vessel MI, or clinically driven target vessel revascularization.
●A meta-analysis of nine randomized controlled trials of over 11,000 patients compared the efficacy of Orsiro bioresorbable SES with durable polymer DES (n = 11,302) on reducing total lesion failure (composite of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularization). After 2.8 years, patients assigned to the bioresorbable SES had less total lesion failure (odds ratio [OR] 0.82; 95% CI 0.69-0.98) [56]. This was driven by a reduction in target vessel myocardial infarction (OR 0.8; 95% CI 0.65-0.98).
Other studies with bioresorbable polymer — Among other bioresorbable polymer stents, those that contain biolimus are the best studied. There have been multiple trials evaluating biolimus-eluting, bioresorbable polymer stents, which are available in Europe and parts of Asia, but not in the United States [57-62]. The following studies suggest similar efficacy and safety to first-generation durable polymer stents:
●In the LEADERS trial, 1707 patients with both stable and unstable coronary artery disease were randomly assigned to either a biolimus-eluting (a sirolimus analog), thick-strut stent with a bioresorbable polymer applied only to the abluminal (outer) surface or to a first-generation sirolimus-eluting permanent polymer stent [57,58]. The primary composite endpoint of cardiac death, MI, or clinically indicated target vessel revascularization at nine months (9 versus 11 percent, respectively) and at five years (22.3 versus 26.1, respectively; RR 0.83, 95% CI 0.68-1.02) was similar in the two groups. In LEADERS, differences in favor of biolimus, including a lower rate of very late stent thrombosis for as long as five years (0.7 versus 2.5 percent, RR 0.26, 95% CI 0.10-0.68), may reflect a late safety advantage of bioabsorbable polymer.
●The SORT OUT V trial also compared a biolimus-eluting biodegradable polymer stent (Nobori) with a first-generation SES [59]. In SORT OUT V, 1229 patients with stable and unstable disease were randomly assigned to one stent or the other. At one-year follow-up, the biolimus stent was not shown to be noninferior to the SES for the primary composite safety and efficacy endpoint (4.1 versus 3.1 percent, respectively). While there appear to be some differences between the LEADERS and SORT OUT V trials, including lower event rates in the latter, the two studies are of different designs.
●The NEXT trial randomly assigned 3235 patients to a biodegradable polymer biolimus-eluting stent (Nobori) or an EES [62]. At one year, there was no significant difference in the primary efficacy endpoint of target lesion revascularization (4.2 percent in both groups).
●The COMPARE II trial randomly assigned 2707 patients to a biolimus-eluting stent or a second-generation EES in a 2:1 manner [61]. At 12 months, there was no significant difference in the rates of the primary endpoint (5.2 versus 4.8 percent, respectively), which was a composite of safety and efficacy outcomes.
●The BASKET-PROVE II noninferiority trial randomly assigned 2291 patients with acute or stable disease to biodegradable polymer biolimus-A9-eluting, second-generation EES, or BMS [63]. The primary endpoint of cardiac death, MI, and clinically indicated target vessel revascularization within two years occurred in 7.6 and 6.8 percent of the first two groups, respectively, with the criteria for noninferiority being met. There was no significant difference in the combined safety endpoint of very late stent thrombosis, MI, or cardiac death.
Studies that have evaluated other unapproved, thin-strut biodegradable stents include:
●The TARGET All Comers trial randomly assigned 1653 patients to a DES with a fully biodegradable sirolimus-containing polymer coating (Firehawk cobalt chromium coronary stent) or to a durable polymer, EES [64]. The primary composite endpoint of target lesion failure at 12 months (cardiac death, target vessel MI, or ischemia-driven target lesion revascularization) occurred with similar frequency in the two groups (6.1 versus 5.9 percent, respectively; difference 0.2 percent, 90% CI -1.9 to 2.2). Safety and efficacy were similar at two years [65].
●The ISAR-TEST 4 trial randomly assigned 2603 patients to either biodegradable polymer SES (Yukon Choice PC) or permanent polymer (durable) stents (with either an EES or an SES [66]). At three years, there was no significant difference between the biodegradable polymer and the two permanent polymer stents with regard to the primary composite endpoint of cardiac death, target vessel-related MI, or target lesion revascularization (20 versus 20.9 percent; hazard ratio [HR] 0.95, 95% CI 0.80-1.13). At 10 year follow-up, the rate of the primary endpoint was similar between the biodegradable polymer-based SES and the EES (47.7 versus 46.0 percent, respectively; HR 1.04, 95% CI 0.87-1.24) [67]. Similarly, there was no difference in the rate of stent thrombosis.
●The PIONEER II trial randomly assigned 170 patients to the BuMA Supreme thin-strut, biodegradable polymer SES or durable polymer ZES. At nine-month angiographic follow-up, in-stent late lumen loss was greater in the SES group (0.29±0.33 versus 0.14±0.37 mm; p for noninferiority = 0.45). At 12-month clinical follow-up, there was no difference between treatment arms with regard to the device-oriented composite clinical endpoint (4.9 percent versus 5.7 percent; p = 0.72) [68].
POLYMER-FREE DRUG-ELUTING STENTS — Polymer-free drug-eluting stents have a few theoretical advantages compared with current durable-polymer DES [69-73] (see 'Polymer-free drug-eluting stents' above). However, randomized trials have not demonstrated a clinical advantage. Our contributors do not use these stents where available (some European Union countries) and would not use them if available in the United States. Additional study may reveal clinical situations in which these newer stents are advantageous to durable-polymer DES.
The following are important studies of polymer-free DES:
●In the LEADERS FREE trial, 2466 patients who were candidates for a bare metal stent (BMS) rather than a DES were randomly assigned to a polymer- and carrier-free drug-coated stent that transfers umirolimus (biolimus A9) into the vessel wall over one month or a similar BMS [69]. All patients received DAPT for one month followed by aspirin alone. The primary safety endpoint, a composite of cardiac death, MI, or stent thrombosis, occurred less often in the drug-coated group at 390 days (9.4 versus 12.9 percent; p = 0.005 for superiority), owing to a difference in spontaneous and type 4C (restenosis-related) MI during follow-up. The primary efficacy endpoint of target lesion revascularization occurred less often in the drug-coated stent group (5.1 versus 9.8 percent; p<0.001). The safety and efficacy endpoints were maintained at two years [70].
Limitations of LEADERS FREE include the higher-than-expected rates of early and late stent thrombosis in both arms, the BMS used (thick struts, stainless steel) was not consistent with contemporary best-of-class BMS (which have thin struts), and there was not a comparison to contemporary DES.
●In the ONYX ONE trial, 1996 patients at high bleeding risk were randomly assigned to receive ZES or polymer-free DES [73]. More than 50 percent of patients presented with an acute coronary syndrome. All patients received dual antiplatelet therapy for one month followed by single antiplatelet therapy. There was no significant difference in the primary outcome, a composite of cardiac death, myocardial infarction, or stent thrombosis at one year, between the two groups (17.1 and 16.9 percent, respectively).
●In the ReCre8 study, 1502 patients were randomly assigned to a permanent polymer zotarolimus-eluting stent or a polymer-free amphilimus-eluting stent [71]. Troponin-positive patients received DAPT for 12 months while troponin-negative patients were planned to receive one month of DAPT. There was no significant difference in the rate of the primary end point of target lesion failure, a combination of cardiac death, target-vessel MI, or target lesion revascularization, at 12 months (5.6 versus 6.2 percent of the two groups, respectively). The rate of definite or probable stent thrombosis was approximately 1.0 percent in both groups.
●The ISAR-TEST 5 trial, which randomly assigned 3002 patients to treatment with either polymer-free sirolimus- and probucol-eluting stents or durable polymer zotarolimus-eluting stents in a 2:1 manner, found no difference in a combined cardiovascular outcome at 10 years [74].
●The SORT OUT IX trial randomly assigned 3151 patients to treatment with a stainless steel, drug-coated stent without polymer or to an ultra-thin strut, biodegradable polymer, cobalt-chromium sirolimus-eluting stent [75]. At one year, the composite endpoint (cardiac death, MI, or target lesion revascularization) occurred more often with the polymer-free stent (5.0 versus 3.7 percent [Pnoninferiority =0.14]), and the rate of target lesion revascularization was greater with the polymer-free stent (3.5 versus 1.3 percent; rate ratio 2.77, 95% CI 1.66-4.62).
The LEADERS FREE and ONYX ONE trials enrolled high-bleeding-risk patients and treated them with dual antiplatelet therapy for one month. These studies do not directly address the question of whether dual antiplatelet therapy (DAPT) can be safely and effectively shortened to one month in high-bleeding-risk patients, particularly if they have had a recent acute coronary syndrome. (See "High bleeding risk patients undergoing percutaneous coronary intervention", section on 'BMS versus DES'.)
Other — The Combo stent combines sirolimus elution from an abluminal biodegradable polymer matrix with a CD34 antibody layer. The CD34 antibody is directed toward circulating endothelial progenitor cells with a goal of increasing the rate of cellular coverage and thus decreasing the rate of stent thrombosis. In the first-in-man trial, the Combo stent was noninferior to a paclitaxel-eluting stent for outcomes of nine-month angiographic in-stent late lumen loss and 12-month major adverse cardiovascular events [76,77].
BARE METAL STENTS — We believe the evidence supports the use of a second-generation DES, rather than a bare metal stent (BMS), in patients who are likely to receive short-duration dual antiplatelet therapy. There are decreasing circumstances in which implantation of a BMS may be reasonable, but the following is considered by some of our experts:
●Patients who require noncardiac surgery within four to six weeks of percutaneous coronary intervention.
●Patients with active bleeding at the time of percutaneous coronary intervention or those at very high risk of bleeding while taking dual antiplatelet therapy.
●Patients unlikely to adhere with antiplatelet therapy for at least one month.
In patients who need to stop DAPT before the recommended duration of therapy, the likelihood of stent thrombosis significantly increases.
However, there is uncertainty regarding the relative rates of stent thrombosis with BMS and DES in patients who stop DAPT prematurely for any reason. Some experts have suggested the earlier endothelialization seen with BMS compared with DES might lead to a relatively decreased risk of stent thrombosis in patients treated with BMS who prematurely discontinue DAPT. There is no high-quality evidence that demonstrates the use of BMS is superior to second-generation DES in this setting.
Prior to 2015, patients at high risk of bleeding were often considered for BMS; however, there are now several randomized trials in this cohort comparing BMS with DES with a short DAPT duration.
●In the ZEUS trial, 1606 patients (with stable or unstable symptoms) for whom it was not clear whether DES or BMS was a superior choice (eg, high bleeding risk, low restenosis risk, or high stent thrombosis risk) were randomly assigned to Endeavor-zotarolimus-eluting stent (E-ZES) or BMS and treated with DAPT for at least 30 days, after which they received either aspirin or P2Y12 monotherapy [78]. The total duration of DAPT was prespecified based on the reason for inclusion, and the mean duration was 32 days. The primary endpoint of 12-month major adverse cardiovascular events (including death, myocardial infarction [MI], or target vessel revascularization) occurred less often with E-ZES (17.5 versus 22.1 percent; hazard ratio [HR] 0.76, 95% CI 0.61-0.95). This was driven by lower rates of MI and target vessel revascularization. The rates of definite or probable stent thrombosis were significantly reduced in E-ZES patients (2 versus 4.1 percent).
A prespecified analysis evaluated outcomes in 828 patients at high bleeding risk who had at least one of the following: age older than 80 years, clinical indication for treatment with oral anticoagulant agents, recent bleeding episodes that required medical attention or hospitalization, systemic conditions associated with increased bleeding risk, known anemia, and the need for long-term treatment with steroids or nonsteroidal anti-inflammatory drugs [79]. The primary endpoint occurred less often with E-ZES (22.6 versus 29 percent; HR 0.75, 95% CI 0.57-0.98).
●In the LEADERS FREE trial, 2466 patients who were candidates for a BMS rather than a DES were randomly assigned to a polymer- and carrier-free drug-coated stent that transfers umirolimus (biolimus A9) into the vessel wall over one month or a similar BMS [69]. All patients received DAPT for one month followed by aspirin alone. The primary safety endpoint, a composite of cardiac death, MI, or stent thrombosis, occurred less often in the drug-coated group at 390 days (9.4 versus 12.9 percent), owing to a difference in spontaneous and type 4C (restenosis-related) MI during follow-up. The primary efficacy endpoint of target lesion revascularization occurred less often in the drug-coated stent group (5.1 versus 9.8 percent).
●The Onyx-One trial demonstrated noninferiority for the durable polymer Resolute-Onyx zotarolimus-eluting stent compared with the biolimus-eluting stent used in LEADERS-FREE (discussed directly above) [73].
The ZEUS and LEADERS FREE trials suggest that even in patients who receive DAPT for as short as 30 days, outcomes are better with second-generation DES compared with BMS. Thus, we believe it may be reasonable to consider a second-generation DES or a BMS for patients who can receive 30 days of uninterrupted DAPT, but not the recommended longer duration of DAPT. However, the DES used in the LEADERS-FREE trial is not available for clinical use in the United States, and the E-ZES used in ZEUS is no longer available.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Percutaneous coronary intervention".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: Angina treatment — medical versus interventional therapy (Beyond the Basics)" and "Patient education: Stenting for the heart (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Background – Thick strut, durable polymer sirolimus- and paclitaxel-eluting stents are referred to as first-generation drug-eluting stents (DES). Neither of the first-generation devices is marketed for use in the United States, Europe, or Canada (table 1). (See 'Early-generation drug-eluting stents' above.)
●Durable polymer stents – Everolimus-, zotarolimus-, ridaforolimus-eluting stents (EES, ZES, and RES), with durable polymer and some bioresorbable polymer DES are commercially available, current-generation (second-generation) DES. These stents have significantly lower rates of restenosis and stent thrombosis compared with first-generation DES. (See 'Durable polymer drug-eluting stents' above.)
●Our approach – For patients undergoing intracoronary stenting, we use mostly EES, either with a durable or bioresorbable polymer, Resolute ZES with durable polymer (R-ZES or RES), RES, or the ultra-thin-strut sirolimus-eluting stent (SES) with bioresorbable polymer. The choice between these current-generation devices should be guided by issues such as cost, practitioner familiarity, and availability. (See 'Our approach' above and 'Everolimus- versus zotarolimus-eluting stents' above and 'Ridaforolimus-eluting stent' above and '2012 comparison of drug-eluting stents' above.)
Circumstances in which implantation of a BMS may be reasonable include (see 'Bare metal stents' above):
•Patients in whom a DES cannot be implanted due to large vessel size (>5 mm).
•Patients who cannot take 30 days of dual antiplatelet therapy, such as those requiring urgent surgery or have active bleeding. However, the evidence for safety of BMS or benefit over DES in these settings is lacking.
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