Risk Of Late Stent Thrombosis Research Articles

Evolution of drug-eluting coronary stents: a back-and-forth journey from the bench to bedside.

Coronary stents have revolutionized the treatment of coronary artery disease. Compared with balloon angioplasty, bare-metal stents (BMSs) effectively prevented abrupt vessel closure but were limited by in-stent restenosis (ISR) due to smooth muscle cell proliferation and neointimal hyperplasia. The first-generation drug-eluting stent (DES), with its antiproliferative drug coating, offered substantial advantages over BMSs as it mitigated the risk of ISR. Nonetheless, they had several design limitations that increased the risk of late stent thrombosis. Significant advances in stent design, including thinner struts, enhanced polymers' formulation, and more potent antiproliferative agents, have led to the introduction of new-generation DES with a superior safety profile. Cardiologists have over 20 different DES types to choose from, each with its unique features and characteristics. This review highlights the evolution of stent design and summarizes the clinical data on the different stent types. We conclude by discussing the clinical implications of stent design in high-risk subsets of patients.

Antiplatelet Therapy After Percutaneous Coronary Intervention - Past, Current and Future Perspectives.

Optimal antiplatelet therapy after percutaneous coronary intervention (PCI) has been changed in parallel with the improvements of coronary stent and antiplatelet therapy. Over the past 25 years, dual antiplatelet therapy (DAPT) with aspirin plus P2Y12inhibitor has been the standard of care used after coronary stent implantation. First-generation drug-eluting stent (DES) appeared to increase the risk of late stent thrombosis, and duration of DAPT was prolonged to 12 months. DAPT duration up to 12 months was the dominant strategy after DES implantation in the subsequent >10 years, although there was no dedicated randomized controlled trial supporting this recommendation. The current recommendation of DAPT duration is getting shorter due to the development of new-generation DES, use of a P2Y12inhibitor as a monotherapy, and the increasing prevalence of high-bleeding risk patients. Furthermore, an aspirin-free strategy is now emerging as one of the novel strategies of antiplatelet therapy after PCI. This review gives an overview of the history of antiplatelet therapy and provides current and future perspectives on antiplatelet therapy after PCI.

Impact of stent malapposition on intracoronary flow dynamics: An optical coherence tomography-based patient-specific study

Percutaneous coronary intervention with stent implantation has emerged as a popular approach to treat coronary artery stenosis. Stent malapposition (SM), also referred as incomplete stent apposition, could reduce stent tissue coverage and hence increase the risk of late stent thrombosis. The objective of this study was to investigate the impact of SM on intracoronary flow dynamics by combining optical coherence tomography (OCT) image-based model reconstruction and computational analysis. Firstly, a stenosed coronary artery model was reconstructed from OCT and angiography imaging data of a patient. Two structural analyses were carried out to simulate two types of coronary artery stent implantations: a fully-apposed (FA) case and a SM case. Then, based on the two deformed coronary geometries, two computational fluid dynamics (CFD) analyses were performed to evaluate the differences of hemodynamic metrics between the FA and the SM cases, including wall shear stress (WSS), time-averaged WSS (TWSS), oscillatory shear index (OSI), WSS gradient (WSSG), time-averaged WSSG (TWSSG), and relative residence time (RRT). The results indicated that maximum flow velocity was higher in the SM case than that of the FA case, due to the incomplete expansion of the stent and artery. Moreover, the SM case had a lower percentage of areas of adverse WSS (< 0.5 Pa) and RRT (> 10/Pa) but a higher percentage of areas of adverse OSI (> 0.1) and WSSG (> 5000 Pa/m). Specifically, the differences of OSI, WSSG, and RRT between the two cases were relatively small. It was suggested that SM might not be responsible for negative hemodynamic metrics which would further result in stent thrombosis on the basis of the present specific model.

Methotrexate Therapy Promotes Cell Coverage and Stability in in-Stent Neointima

Anti-proliferative drugs released from drug-eluting stents delay cell coverage and vascular healing, which increases the risk of late stent thrombosis. We assessed the potential effects of systemic methotrexate (MTX) on cell coverage, vascular healing and inflammation activation in vivo and in vitro. We applied MTX in the right common carotid artery in a rabbit stenting model to determine the impact on cell coverage and inflammation activation using a serial optical coherence tomography (OCT) analysis and elucidated the molecular mechanism of MTX in human umbilical vein endothelial cells (HUVECs). Low-dose MTX promoted the development of cell coverage and vascular healing, which was associated with fewer uncovered struts (%) and cross-sections with any uncovered struts (%) at 4 weeks of stenting. The MTX group also exhibited lower rates of heterogeneity, microvessels and per-strut low-signal-intensity layers, indicating neointimal instability at 12 weeks of stenting. In vitro, low-dose MTX strongly inhibited HUVEC apoptosis, promoted proliferation and inhibited inflammatory activation by targeting the phosphoinositide 3-kinase (PI3K)/AKT signalling pathway. Low-dose MTX may be a key means of promoting early cell coverage via the inhibition of the inflammatory response and stability of neointima by targeting inflammatory pathways after stent implantation.

OCT analysis of early endothelialization of the Synergy stent in young non-ST segment elevation acute coronary syndrome. The OCT EROS study

Early healing of the struts is a major challenge to reduce the risk of late stent thrombosis (LST), and for decreasing the duration of dual antiplatelet therapy (1 or 3 months), in patients high risk of bleeding. The bioresorbable polymer everolimus eluting stent (EES) SYNERGY, new generation of stent, has biocompatibility and mechanical properties, allowing complete strut coverage throughout the entire length of the stent at 3 months, in humans, resulting in a low rate of LST. Optical Coherence tomography analysis (OCT), which provide the best spatial resolution, is the method of choice to evaluate early healing of the strut. To estimate the early healing of the strut at 1 month after implantation of the EES, using OCT analysis, in patients admitted for acute coronary syndrome without ST segment elevation. This was a prospective and mono-centric study performed at the university hospital the North of Marseille. The patients eligible had to benefit from complementary angioplasty at 1 month after implantation of the EES for the culprit lesion of the acute coronary syndrome. An OCT of EES implanted was performed. OCT analysis and proofreading of coronary angiography were achieved by 2 physicians practicing these tests on daily basis. The primary study endpoint was the percentage of uncovered struts in OCT imaging, at 1 month ( Fig. 1 ). Twenty-four patients were included between December 2016 and February 2018. The percentage of uncovered struts was 21,48 ± 10% of 3849 struts analyzed. The neointimal thickness facing covered struts was 0,0508 ± 0,016mm. At follow-up, no ischemic event was reported, however, one death by hemorrhagic stroke was identified. The percentage of uncovered struts of the SYNERGY stent was 21,48% at 1 month post angioplasty in the context of ACS. This result provides a logical rationale for decreasing the duration of dual antiplatelet therapy at 1 month in patients at high risk of bleeding.

TCTAP A-134 Biodegradable Polymer vs. Durable Polymer Drug-eluting Stents in Patients with Acute Myocardial Infarction Patients

Drug-eluting stents (DESs) have improved the outcomes of acute myocardial infarction patients (AMI) patients, however, the risk of late stent thrombosis with DES due to delayed healing of vessel wall is still considerable. The aim of this study was to compare the safety and efficacy of biodegradable

Evaluation of Magnesium-based Medical Devices in Preclinical Studies: Challenges and Points to Consider.

Absorbable metallic implants have been under investigation for more than a century. Animal and human studies have shown that magnesium (Mg) alloys can be safely used in bioresorbable scaffolds. Several cardiovascular and orthopedic biodegradable metallic devices have recently been approved for use in humans. Bioresorbable Mg implants present many advantages when compared to bioabsorbable polymer or nonabsorbable metallic implants, including similar strength and mechanical properties as existing implant-grade metals without the drawbacks of permanence or need for implant removal. Imaging visibility is also improved compared to polymeric devices. Additionally, with Mg-based cardiovascular stents, the risk of late stent thrombosis and need for long-term anti-platelet therapy may be reduced as the host tissue absorbs the Mg degradation products and the morphology of the vessel returns to a near-normal state. Absorbable Mg implants present challenges in the conduct of preclinical animal studies and interpretation of pathology data due to their particular degradation process associated with gas production and release of by-products. This article will review the different uses of Mg implants, the Mg alloys, the distinctive degradation features of Mg, and the challenges confronting pathologists at tissue collection, fixation, imaging, slide preparation, evaluation, and interpretation of Mg implants.

100.22 Biodegradable-Polymer vs. Durable-Polymer Drug-Eluting Stents in Patients With Acute Myocardial Infarction

Drug-eluting stents (DES) have improved the outcomes of acute myocardial infarction patients (AMI) patients; however, the risk of late stent thrombosis with DES due to delayed healing of the vessel wall is still considerable. The aim of this study was to compare the safety and efficacy of

Methotrexate Therapy to Promote Endothelialization and Stability of Neointima by Reducing Inflammation Activation in a Rabbit Stenting Model

Background: Anti-proliferative drugs released from drug-eluting stents delay re-endothelialization and vascular healing, which increases the risk of late stent thrombosis. We assessed the potential effects of systemic methotrexate (MTX) on endothelialization, vascular healing and inflammation activation in vivo and in vitro. Methods: We used MTX in a rabbit stenting model in the right common carotid artery to determine the impact on endothelialization and inflammation activation using serial optical coherence tomography (OCT) analysis and elucidated the molecular mechanism of MTX in human umbilical vein endothelial cells (HUVECs). Findings: Low-dose MTX promoted the development of endothelialization and vascular healing, which was associated with fewer uncovered struts (%) and cross-sections with any uncovered struts (%) at 4 weeks of stenting. The MTX group also exhibited lower rates of heterogeneity, microvessels and per-strut low-signal-intensity layers, indicating neointimal instability at 12 weeks of stenting. Low-dose MTX in vitro strongly inhibited HUVEC apoptosis, promoted proliferation and inhibited inflammatory activation via targeting of the phosphoinositide 3-kinase (PI3K)/AKT signalling pathway. Interpretation: Low-dose MTX may be a key means of promoting early endothelialization via inhibition of the inflammatory response and stability of neointima via targeting of inflammatory pathways after stent implantation. Funding Statement: This work was supported by the National Natural Science Foundation of China (Grant Nos. 81330033, 81771946, 81670373, and 81670459). This study was also supported by the Graduate Student Innovation Foundation of Heilongjiang Province (YJSCX2017-39HYD). Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: The Hospital Scientific Affairs Committee on Animal Research and Ethics approved the study protocol, and the methods were performed in accordance with ARRIVE guidelines.

Incidence and predictors of target lesion failure in a multiethnic Asian population receiving the SYNERGY coronary stent: A prospective all-comers registry.

To evaluate the target lesion failure (TLF) rate of the SYNERGY stent in all-comers, multiethnic Asian population. Currently, most drug eluting stents deliver anti-proliferative drugs from a durable polymer which is associated with a risk of late stent thrombosis. The novel everolimus-eluting, platinum chromium SYNERGY stent is coated with a bioabsorbable abluminal polymer that resolves within 4 months. This was a prospective, single center registry of consecutive patients treated with the SYNERGY stent between December 2012 and April 2015. The primary outcome was the incidence of TLF, defined as the combination of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization (TLR) at 1 year. A total of 807 patients received the SYNERGY stent during the study period. One-year clinical outcome data was available for 765 patients (94.8%) and were considered for statistical analysis. The mean age was 60.7 ± 10.8 years, and 83.4% were males. Patients with acute myocardial infarction consisted of 50.3% (ST-segment elevation myocardial infarction: 23.0%, Non-ST-segment elevation myocardial infarction: 27.3%) of the study population. The treated lesions were complex (ACC/AHA type B2/C: 72.7%). The primary end point of TLF at 1 year was 5.8%. Rates of cardiac mortality, target vessel myocardial infarction, and TLR were 4.2, 1.0, and 1.3%, respectively, at 1 year. Predictors of the incidence and time to early TLF were female gender, Malay ethnicity, diabetes mellitus, acute myocardial infarction at presentation, a prior history of coronary artery bypass surgery and the presence of lesion calcification. The incidence of definite stent thrombosis was 0.4% at 1 year. In this registry, the use of the SYNERGY stent was associated with low rates of TLF at 1 year.

Thirty days only double antiplatelet therapy after drug-eluting stenting: could a 'short-term' treatment be advantageous?

Thirty days only double antiplatelet therapy after drug-eluting stenting: could a 'short-term' treatment be advantageous?

Evaluation of promoting effect of a novel Cu-bearing metal stent on endothelialization process from in vitro and in vivo studies

Drug eluting stents (DES) have been extensively applied nowadays and reduce the incidence of in-stent restenosis (ISR) greatly as compared with bare metal stents (BMS). However, the development of DES is hindered by the risk of late stent thrombosis (LST) due to delayed re-endothelialization, while endothelialization is an important process related to ISR and LST after implantation. 316L is a traditional stent material without bioactivity and have a high risk of ISR. Cu is recognized for angiogenesis stimulation in these years. Hence a copper bearing 316L stainless steel (316L-Cu) was prepared and evaluated about its effect on endothelialization in this paper. Compared with traditional 316L, it was proved that 316L-Cu increased the proliferation of co-cultured human umbilical vein endothelial cells (HUVECs) at first day. Moreover, HUVECs stretched better on the surface of 316L-Cu. It also improved the expression of angiogenesis related genes and tube formation ability in vitro. 316L-Cu-BMS, DES and 316L-BMS were implanted in swine to evaluate the re-endothelialization ability in vivo. And 316L-Cu-BMS showed the best effect on endothelialization with good biosafety. Consequently, 316L-Cu is a kind of promising BMS material for coronary field.

Contemporary Drug-Eluting Stents and Vascular Response

Cardiovascular disease is a leading cause of death and disability worldwide. Current treatment strategies aimed at treating the consequences of coronary artery disease have embraced both optimal medical therapy and catheter based percutaneous coronary intervention with drug-eluting stents (DES). Current-generation DES elute predominantly mammalian target of rapamycin (mTOR) inhibitors, which act primarily as a cytostatic agent that retards vascular smooth muscle cell proliferation and migration; this occurs in response to injury and thus prevents restenosis. While DES have reduced restenosis, the use of first-generation DES was associated with an increased risk of late stent thrombosis and accelerated neointimal atherosclerosis (i.e. neoatherosclerosis), both major contributors to late stent failure. The underlying substrate of late DES failure is likely related to vascular endothelial dysfunction, which occurs after DES implantation. Initial concerns with first-generation DES have led to improvements in stent design, polymer load and biocompatibility, and pharmacologic agents, all of which have helped to improve healing responses, lessen late stent failure, and result in an overall improved safety profile. The armamentarium of DES has expanded from the current-generation durable polymer DES to bioresorbable polymer DES, polymer-free DES, and lastly totally bioresorbable vascular scaffolds with a goal of improving vascular responses and endothelial function while preserving anti-restenotic efficacy. We will review these contemporary DES in relation to their short and long-term effects on vascular biocompatibility and healing responses.

Development of Novel Drug-Eluting Stents for Acute Myocardial Infarction.

Delayed arterial healing at culprit sites after drug-eluting stent (DES) placement for acute myocardial infarction (AMI) is associated with increased risk of late stent thrombosis. The Korea Acute Myocardial Infarction Registry was established in commemoration of the 50th anniversary of Korea Circulation Society. Between November 2005 and December 2016, more than 62,000 patients were registered from 50 primary percutaneous coronary intervention (PCI) centers in Korea. DES in AMI may be safe and effective, however, there is concern about increased stent thrombosis after DES implantation in AMI patients, requiring longer-term dual anti-platelet therapy to reduce the risk of late stent thrombosis. Device innovation is needed to overcome issues such as stent thrombosis and restenosis by using new coating materials with biocompatible polymers, different coating methods using non-polymer techniques, bioabsorbable stents and pro-healing stents. In this review article, we describe the current usage of DES in AMI in Korea and introduce novel DES uses in development for patients with AMI. We have developed many types of DES in our research laboratory. Abciximab-coated stents inhibited platelet thrombi and restenosis. Furthermore, anti-oxidants (carvedilol, probucol and alpha-lipoic acid) were used for stent coating. Currently we are developing novel DESs using polymer-free and natural binding techniques, peptide coating stents, gene-and-drug delivery, bioabsorbable stents using 3D printing, endothelial progenitor cell capturing stents to promote reendothelialization and reduce stent thrombosis. New DESs in development may be safe and effective in preventing late stent thrombosis and restenosis in patients with AMI.

Late and Very Late Stent Thrombosis in the Era of Second-Generation Drug-Eluding Stents

Stent thrombosis is a life-threatening complication of percutaneous coronary intervention that often results in ST-segment myocardial infarction or sudden cardiac death. First-generation drug-eluting stents (DESs) are associated with an increased risk of late and very late stent thrombosis compared with bare- metal stents due to delayed endothelialisation of the stent struts. The second-generation DES design includes a number of improved features (thinner stent struts, fluorinated copolymers, and different anti-proliferative agents) to decrease the risk of late stent thrombosis. Currently, the cobalt-chromium everolimus-eluting stent, a second-generation stent, has the lowest risk of stent thrombosis when compared with the available alternatives. Given the improved design of second-generation stents, a shorter duration of dual antiplatelet therapy of 6 months may be enough to reduce the rate of bleeding complications without increasing the risk of adverse cardiovascular events. Future large-scale randomised trials are required to evaluate the safety and efficacy of third-generation DESs which feature bioresorbable polymers and scaffolds.

Curcumin Attenuates Rapamycin-induced Cell Injury of Vascular Endothelial Cells.

Although drug-eluting stents (DES) effectively improve the clinical efficacy of percutaneous coronary intervention, a high risk of late stent thrombosis and in-stent restenosis also exists after DES implantation. Anti-smooth muscle proliferation drugs, such as rapamycin, coating stents, not only inhibit the growth of vascular smooth muscle cells but also inhibit vascular endothelial cells and delay the reendothelialization. Therefore, the development of an ideal agent that protects vascular endothelial cells from rapamycin-eluting stents is of great importance for the next generation of DES. In this study, we demonstrated that rapamycin significantly inhibited the growth of rat aortic endothelial cells in both dose- and time-dependent manner in vitro. Cell apoptosis was increased and migration was decreased by rapamycin treatments in rat aortic endothelial cells in vitro. Surprisingly, treatment with curcumin, an active ingredient of turmeric, significantly reversed these detrimental effects of rapamycin. Moreover, curcumin increased the expression of vascular nitric oxide synthases (eNOS), which was decreased by rapamycin. Furthermore, caveolin-1, the inhibitor of eNOS, was decreased by curcumin. Knockdown of eNOS by small interfering RNA significantly abrogated the protective effects of curcumin. Taken together, our results suggest that curcumin antagonizes the detrimental effect of rapamycin on aortic endothelial cells in vitro through upregulating eNOS. Therefore, curcumin is a promising combined agent for the rescue of DES-induced reendothelialization delay.

Abstract 561: A Novel Integrin Modulating Arg-Gly-Asp(RGD)-Peptide-Coated Stent Reduces Neoatherosclerosis in a Rabbit Model

Objective: While drug-eluting stents have dramatically reduced restenosis, they are often associated with increased risk of late stent thrombosis and neointimal atherosclerosis (“neoatherosclerosis”). In-stent neoatherosclerosis represents a further accelerated and possibly more unstable manifestation of atherosclerotic progression in nascent neointimal tissue after stent implantation. We hypothesized that poor arterial re-endothelialization accompanied by leaky endothelial junctions is a primary mechanism contributing to neoatherosclerosis. In the present study, we tested the ability of a RGD-peptidomimetic-coating of bare metal stents to reduce the formation of in-stent neoatherosclerosis by promoting integrin-mediated adhesion of endothelial cells, and improving their functional integrity. Approach and Results: Established iliofemoral plaques were created in male New Zealand white rabbits (n=10) by balloon injury and feeding a high cholesterol (1.0%) diet for 5 wks, which was then switched to a low cholesterol diet (0.025%) for the remainder of the study. At 3 wks after diet switch, an RGD-coated stent was implanted together with a drug-eluting stent in the contralateral iliac artery, and animals were continued on the low cholesterol diet for 7 wks (serum cholesterol between 400-1,000 mg/dl). Endothelial permeability was assessed by FITC-dextran (250/500 kDa, approx. LDL radius) injected intravenously 1 h before termination. Oil red O and Filipin staining demonstrated neutral lipid and free cholesterol accumulation in the developing neointimal of stented arteries. En face confocal microscopy of the luminal surface following immunostaining against endothelial markers followed by scanning electron microscopy showed greater endothelial coverage of luminal surfaces for RGD-coated stents. Stents were further quantified by histomorphometric analysis for vascular healing, thrombus formation and inflammation. Conclusion: A rabbit neoatherosclerosis model was established to study the formation and progression of this novel disease manifestation. RGD-coated stents showed reduced formation of neoatherosclerosis in association with improved vessel healing and re-endothelialization compared to drug-eluting stents.

How long should dual antiplatelet therapy be continued following implantation of drug eluting stents?

Drug eluting stents (DES) are now established in the treatment of coronary artery disease (1) and their development promised to improve upon limitations associated with original bare metal stents in particular that of late restenosis. Whilst restenosis rates have improved, DES have been claimed to be associated with a higher risk of late stent thrombosis (2). The administration of dual antiplatelet therapy (DAPT), consisting of aspirin and a P2Y12-receptor inhibitor following implantation of DES significantly reduces the likelihood of coronary stent thrombosis (ST) due to inflammation of the stented segmented during healing (3) and for this reason is deemed mandatory in all patients following DES implantation. DAPT is also associated with additional benefits (unrelated to the stented coronary artery segment) and has been associated with a reduction in ischemic events and an improvement of clinical outcomes (4). However, these benefits are limited by a significant increase in bleeding and therefore current guidelines recommend that DAPT should be administered for 6-12 months following DES (1) with recent studies investigating the feasibility of further reducing the length of DAPT in a bid to further improve safety without exposing patients to unnecessary risks (5-7). However, the current reality is that the most effective duration of DAPT to prevent both stent thrombosis and further ischemic events (e.g., myocardial infarction) remains to be determined and the effects of prolonged DAPT beyond the currently recommended 12 months are poorly characterised.

Nine-month angiographic and two-year clinical follow-up of novel biodegradable-polymer arsenic trioxide-eluting stent versus durable-polymer sirolimus-eluting stent for coronary artery disease.

Background:Despite great reduction of in-stent restenosis, first-generation drug-eluting stents (DESs) have increased the risk of late stent thrombosis due to delayed endothelialization. Arsenic trioxide, a natural substance that could inhibit cell proliferation and induce cell apoptosis, seems to be a promising surrogate of sirolimus to improve DES performance. This randomized controlled trial was to evaluate the efficacy and safety of a novel arsenic trioxide-eluting stent (AES), compared with traditional sirolimus-eluting stent (SES).Methods:Patients with symptoms of angina pectoris were enrolled and randomized to AES or SES group. The primary endpoint was target vessel failure (TVF), and the second endpoint includes rates of all-cause death, cardiac death or myocardial infarction, target lesion revascularization (TLR) by telephone visit and late luminal loss (LLL) at 9-month by angiographic follow-up.Results:From July 2007 to 2009, 212 patients were enrolled and randomized 1:1 to receive either AES or SES. At 2 years of follow-up, TVF rate was similar between AES and SES group (6.67% vs. 5.83%, P = 0.980). Frequency of all-cause death was significantly lower in AES group (0 vs. 4.85%, P = 0.028). There was no significant difference between AES and SES in frequency of TLR and in-stent restenosis, but greater in-stent LLL was observed for AES group (0.29 ± 0.52 mm vs. 0.10 ± 0.25 mm, P = 0.008).Conclusions:After 2 years of follow-up, AES demonstrated comparable efficacy and safety to SES for the treatment of de novo coronary artery lesions.

Abstract 20233: Does Evidence Influence Practice in the Real World? Secular Trends in Indication for PCI and Use of Drug-Eluting vs. Bare-Metal Stents From 2006-2012

Introduction: In this study, we examined the real-world impact of research evidence on the use of and indications for percutaneous coronary intervention (PCI) (before and after COURAGE Trial publication) and the choice of drug eluting stents (DES) vs. bare metal stents (BMS) (before and after FDA warnings about risk of DES thrombosis). Methods: We used hospital discharge data from Florida to calculate the distribution of primary indication for PCI and the % of PCI patients who received DES, BMS, or no stent on a quarterly basis from Jan 2006 - Jun 2012. We plotted stent trends separately for patients with principal diagnosis of STEMI (n=66,054), NSTEMI/ICS (n=140,886), and stable CHD (n=117,307). Results: Since 2006, the % of PCIs with a primary indication of either STEMI or NSTEMI has steadily increased, while the % with an indication of stable CHD declined from 45% to 28%. In early 2006, DES were used in 86.9% of NSTEMI patients, 87.5% of stable CHD patients, and 81.4% of STEMI patients. DES use first declined in all diagnosis groups in Q3 2006, coinciding with the release of meta-analysis results showing higher risk of late stent thrombosis for DES vs. BMS. The lowest rate of DES usage was reached in Q1 2008 (45% for STEMI, 63% for NSTEMI, 67% for stable CHD). However, by Q2 2012, DES use had increased to 60% in STEMI cases, 75% in NSTEMI cases, and 76% in stable CHD cases. The percent of PCI patients who received no stent has remained stable at &lt; 9% since 2006, regardless of diagnosis. Conclusions: The COURAGE Trial showed no benefit of PCI over medical treatment in stable coronary heart disease (CHD). From 2006-2012, the proportion of PCIs with an indication of stable CHD declined from 45% to 28%, indicating a real-world response to evidence. Similarly, following controversy about long-term effects of DES, off-label use, and patient compliance with thienopyridines which began in late 2006, there was an immediate resurgence in use of BMS, especially for STEMI. However, the proportion of patients receiving DES has steadily increased since early 2008, regardless of primary indication. More research on the influence of provider and hospital characteristics on response to evidence is needed.