The risks and benefits of drug-eluting stents in the setting of STEMI

Primary percutaneous coronary intervention (PCI) represents the treatment of choice in patients with ST-segment elevation myocardial infarction (STEMI). In randomized trials excluding STEMI patients, using drug-eluting stents (DES) significantly reduced angiographic restenosis and target vessel revascularization compared with bare metal stents (BMS); however, concerns exist regarding an increased follow-up incidence of stent thrombosis after DES implantation. This complication, which is associated with higher mortality and morbidity rates, may be more frequent among STEMI patients receiving DES versus BMS. Various registries, randomized trials, and two recent meta-analyses on patients undergoing primary PCI have shown that using DES is safe and is associated with significantly reduced rates of restenosis and repeat intervention without an increased risk of myocardial infarction or stent thrombosis at intermediate-term follow-up. However, large trials with hard clinical end points and longer follow-up are needed before routine DES use can be recommended in patients undergoing primary PCI.     

Drug-eluting stents are associated with similar cardiovascular outcomes when compared to bare metal stents in the setting of acute myocardial infarction

BACKGROUND: Recent randomized trials have demonstrated conflicting results regarding the use of drug-eluting stents (DESs) as compared to bare metal stents (BMSs) in primary percutaneous coronary intervention (PCI). We compared outcomes among patients presenting with acute ST-elevation myocardial infarction (STEMI) who received DES with those who received BMS. METHODS: In-hospital, 30-day, 6-month, and 1-year outcomes of a cohort of 122 patients who underwent primary or facilitated PCI and received a BMS were compared to 122 propensity-matched patients who received a DES. Seventy-two patients received sirolimus-eluting stents, and 50 received paclitaxel-eluting stents. RESULTS: Baseline demographics were similar among groups. One-, 6-, and 12-month outcomes, including reinfarction, death, stent thrombosis, and target vessel revascularization (TVR), were similar among groups. At 1 year, all-cause mortality was 13.3% in the BMS group and 9.2% in the DES group [P=not significant (ns)], recurrent MI was 5.3% in the BMS group vs. 4.4% in the DES group (P=ns), and TVR was 7% in the BMS group vs. 8.7% in the DES group (P=ns). CONCLUSIONS: Our data do not support the general use of DES in the setting of STEMI given similar cardiovascular outcomes among patients receiving BMS or DES, the need for long-term dual antiplatelet therapy with DES, and the possible repercussions of very late stent thrombosis.     

Stent thrombosis and drug-eluting stents

Coronary stents have been used for the treatment of patients with coronary artery disease (CAD), and significantly improved procedural safety and are associated with a lower rate of restenosis compared with balloon angioplasty alone. Drug-eluting stents (DES) have been dominant for the treatment of CAD with efficacy in significantly reducing both restenosis and target lesion revascularization. However, late and very late stent thrombosis have become a major concern in DES-implanted arteries compared with those treated with bare-metal stents (BMS). This review focuses on the feature of DES thrombosis and pathological examination and dual antiplatelet therapy for prevention of stent thrombosis.Currently, the incidence of stent thrombosis associated with first-generation and second-generation DES remains unclear in data from real-world cohort registry studies. Further studies of larger multicenter trials would give us insight into the specific mechanisms of stent thrombosis among different generations of DES.     

Vascular responses to drug eluting stents: importance of delayed healing

Polymer-based sirolimus- (Cypher) and paclitaxel-eluting (Taxus) drug eluting stents have become the treatment of choice for patients with symptomatic coronary artery disease undergoing percutaneous coronary intervention (PCI). Although these stents reduce rates of restenosis compared with bare metal stents (BMS), late thrombosis, a life threatening complication, has emerged as a major safety concern. Our understanding of the pathophysiology of late DES thrombosis is derived from animal and human pathologic samples taken after implantation of these devices. These data indicate that both DES cause substantial impairment in arterial healing characterized by lack of complete reendothelialization and persistence of fibrin when compared with BMS. This delayed healing is the primary substrate underlying all cases of late DES thrombosis at autopsy. Several additional risk factors for late stent thrombosis such as penetration of necrotic core, malapposition, overlapping stent placement, excessive stent length, and bifurcation lesions represent additional barriers to healing and should be avoided if DES are to be used to minimize the risk of late thrombosis. Because the time course of complete healing with DES in man is unknown, the optimal duration of antiplatelet treatment remains to be determined.     

Antiplatelet therapy following drug-eluting stent implantation: new clinical data and recommendations

Technological developments in percutaneous coronary interventions (PCI) allow the possibility for less invasive revascularization in an increasing number of patients with atherosclerotic coronary artery disease. Bare-metal stents (BMS) have considerably improved the efficacy of PCI in addition to greatly reducing restenosis. However, even with standard stents, restenosis has remained a significant limitation of this revascularization technique. The advent of drug-eluting stents (DES) has dramatically reduced in-stent restenosis and, as a result, the need for repeat revascularization. However, their potential thrombogenicity has raised concerns about their clinical utility and long-term safety. Indeed, there is a possible higher rate of late stent thrombosis (LST) with DES compared with BMS. Antiplatelet therapy has been shown to be efficient in preventing DES thrombosis. Nevertheless, in the future, significant improvement will occur to improve the safety and efficacy of this therapy. This article will summarize the pathophysiology and the epidemiology of stent thrombosis (ST). Definitions of definite, probable and possible ST will be described. Furthermore, clinical risk factors for ST will be clearly enumerated. Then, the various antiplatelet therapeutic strategies used to prevent ST will be taken in consideration. Finally, a summary of the major recommendations about antiplatelet therapy made by some of the most prestigious learned societies will be presented.     

Late and very late thrombosis of drug-eluting stents: evolving concepts and perspectives

Coronary stents are the mainstay of percutaneous coronary revascularization procedures and have significantly decreased the rates of acute vessel closure and restenosis. Stent thrombosis (ST) after percutaneous coronary intervention is an uncommon and potentially catastrophic event that might manifest as myocardial infarction and sudden death. Optimization of stent implantation and dual antiplatelet therapy have markedly reduced the occurrence of this complication. Bare-metal stent (BMS) thrombosis occurs in <1% of the cases, usually within the first month after implantation. The advent of drug-eluting stents (DES) has raised concerns regarding later occurrence of ST, beyond the traditional 1-month timeframe, especially in complex lesion subsets that were excluded from randomized trials that compared BMS to DES. There is widespread controversy regarding the actual incremental risk associated with DES. Recent studies suggest a 0.5% increased long-term thrombosis risk with DES; however, the clinical significance of these events remains under debate. The degree of protection achieved by dual antiplatelet therapy and optimal duration of treatment are under investigation. Novel stent designs might potentially decrease the incidence of this event. In this review, we will describe the current knowledge of the pathophysiology of late DES thrombosis, although many aspects remain incompletely understood.     

Late and very late thrombosis of drug-eluting stents: evolving concepts and perspectives.

Coronary stents are the mainstay of percutaneous coronary revascularization procedures and have significantly decreased the rates of acute vessel closure and restenosis. Stent thrombosis (ST) after percutaneous coronary intervention is an uncommon and potentially catastrophic event that might manifest as myocardial infarction and sudden death. Optimization of stent implantation and dual antiplatelet therapy have markedly reduced the occurrence of this complication. Bare-metal stent (BMS) thrombosis occurs in <1% of the cases, usually within the first month after implantation. The advent of drug-eluting stents (DES) has raised concerns regarding later occurrence of ST, beyond the traditional 1-month timeframe, especially in complex lesion subsets that were excluded from randomized trials that compared BMS to DES. There is widespread controversy regarding the actual incremental risk associated with DES. Recent studies suggest a 0.5% increased long-term thrombosis risk with DES; however, the clinical significance of these events remains under debate. The degree of protection achieved by dual antiplatelet therapy and optimal duration of treatment are under investigation. Novel stent designs might potentially decrease the incidence of this event. In this review, we will describe the current knowledge of the pathophysiology of late DES thrombosis, although many aspects remain incompletely understood.     

Another view of personalized medicine: optimizing stent selection on the basis of predicted benefit in percutaneous coronary intervention

Drug-eluting stents (DES) decrease the risk of restenosis compared to bare metal stents (BMS) for percutaneous coronary intervention (PCI). However, their use requires patients to take prolonged dual antiplatelet therapy that increases bleeding risk and without which, patients have an increased risk of developing stent thrombosis. In light of these competing risks, understanding which patients derive the greatest benefit of DES compared to BMS is essential for guiding therapy. We review recent efforts to predict the magnitude of the restenosis benefit of DES compared to BMS for individual patients. Understanding and predicting the likelihood of benefit for individual patients is essential to rational decision making with regard to the type of stent to use during PCI and will serve to increase the value of the health care that clinicians deliver.     

Safety and Effectiveness of Firebird Sirolimus-Eluting Stent in Patients With Multi-Vessel Coronary Artery Disease

Objective:This study sought to evaluate the long-term safety and efficacy of the Firebird sirolimus-eluting stent in patients with multi-vessel coronary artery disease.The main limitation of percutaneous coronary intervention(PCI)with bare metal stents(BMS)was the increased incidence of instent restenosis.Recently,DES are frequently implanted in patients with off-label indications such as multi-vessel coronary artery disease.However,the long-term safety and effectiveness of DES among patients with multi-vessel coronary artery disease are not well understood.Methods:From January to December 2006,a total of 392 patients with multi-vessel coronary artery disease,exclusively treated with Firedird stents at 12 centers from China,were enrolled in this prospective,multicenter registry.They were followed up clinically at 6,12,18 and 24 months after the procedure.Results:A core laboratory analyzed quantitative coronary angiography data immediately after stenting and at 6-month follow-up.Acute angiographic success was 100%.Angiographic restenosis rate was 2.80% at the sixth month.The percentage of acute major adverse cardiac events(MACE)was 4.86%,4.37% and 6.91%,and the percentage of secondary cardiac events was 5.62%,5.88% and 6.39% at 12,18 and 24 months,respectively.The incidence of death,myocardial infarction,or stent thrombosis during 24 month was 3.84%(15 of 392),1.02%(4 of 392)or 2.05%(8 of 392).Conclusion:This study indicates that Firebird sirolimus-eluting stent is safe and effective for patients with multi-vessel coronary artery disease.     

Predictors and variability of drug‐eluting vs bare‐metal stent selection in contemporary percutaneous coronary intervention: Insights from the PRISM study

Drug‐eluting stents (DES ) reduce risk of in‐stent restenosis after percutaneous coronary intervention (PCI ) but require dual antiplatelet therapy (DAPT ) for a longer term than bare‐metal stents (BMS ). Few studies have examined clinical predictors of DES vs BMS , and variability in provider selection between DES and BMS in clinical practice has not been well described. These insights can inform our understanding of current practice and may identify opportunities to improve decision‐making stent selection decinsion‐making. In a multicenter registry, 3295 consecutive patients underwent PCI by 158 interventional cardiologists across 10 US sites. Eighty percent of patients with treated with DES. Using hierarchical regression, diabetes mellitus, multivessel disease, health insurance, and white race were independently associated with greater DES use, whereas increasing age, history of hypertension, anticipated surgery, use of warfarin, lower hemoglobin, prior history of bleeding, and treatment of right coronary and left circumflex artery lesions as compared with PCI of left anterior descending artery were associated with lower likelihood of receiving DES . Adjusted rates of DES use across providers varied from 52.3% to 94.6%, and adjusted median odds ratio for DES selection was 1.69. DES selection appeared to reflect physicians’ attempts to balance benefits of DES against risks of prolonged DAPT . Nevertheless, marked residual variability in DES selection across providers persisted after adjusting for predictors of restenosis, bleeding, and other factors. Further studies are needed to better understand drivers of this variability and identify the impact of patient and provider preferences on stent selection at the time of PCI .     

Safety and efficacy of drug-eluting stents and bare metal stents in acute coronary syndrome

Compared with medical therapy, percutaneous coronary intervention has been shown to reduce the rates of death and recurrent ischemia in patients presenting with acute coronary syndromes (ACS). In the current interventional era, both drug-eluting stents (DES) and bare-metal stents (BMS) have been widely used, despite the fact that the use of DES in the context of ACS was initially an “off-label” indication and that ACS has been associated with stent thrombosis (ST). In contrast to the wealth of data available for the use of DES in patients with ST-elevation myocardial infarction, data regarding the performance of DES in non–ST-elevation ACS is restricted to a handful of registries with conflicting data. The aim of this review was to summarize the safety and efficacy of DES in the entire spectrum of ACS.     

Second- and third-generation drug-eluting coronary stents

Drug-eluting stents (DES) have revolutionized the treatment of coronary artery disease by reducing the rate of in-stent restenosis from 20?C40% with bare-metal stent (BMS) to 6?C8% with DES. However, with widespread use of DES, safety concerns have risen due to the observation of late stent thrombosis. With this in mind and better understanding of mechanism and pathophysiology of stent thrombosis, the technological platform, especially innovative anti-restenotic agents, polymeric coatings, and stent platforms, improved with newer DES. Two second-generation DES, the Endeavor zotarolimus-eluting stent (ZES) and the Xience-V everolimus-eluting stent (EES), have provided promising results in both randomized controlled trials (SPIRIT and ENDEAVOR) and registries (E-Five, COMPARE) compared with bare-metal stents (BMS) and first-generation DES. Newer third-generation stent technology, especially biodegradable polymers, polymer-free stents, and biodegradable stents on the basis of poly-L-lactide (PLLA) or magnesium, has been evaluated in preclinical and initial clinical trials. However, despite encouraging initial results, long-term data of large-scale randomized trials as well as registries comparing them to currently approved first- and second-generation DES are still lacking.     

Second- and third-generation drug-eluting coronary stents: progress and safety

Drug-eluting stents (DES) have revolutionized the treatment of coronary artery disease by reducing the rate of in-stent restenosis from 20-40% with bare-metal stent (BMS) to 6-8% with DES. However, with widespread use of DES, safety concerns have risen due to the observation of late stent thrombosis. With this in mind and better understanding of mechanism and pathophysiology of stent thrombosis, the technological platform, especially innovative anti-restenotic agents, polymeric coatings, and stent platforms, improved with newer DES. Two second-generation DES, the Endeavor zotarolimus-eluting stent (ZES) and the Xience-V everolimus-eluting stent (EES), have provided promising results in both randomized controlled trials (SPIRIT and ENDEAVOR) and registries (E-Five, COMPARE) compared with bare-metal stents (BMS) and first-generation DES. Newer third-generation stent technology, especially biodegradable polymers, polymer-free stents, and biodegradable stents on the basis of poly-L-lactide (PLLA) or magnesium, has been evaluated in preclinical and initial clinical trials. However, despite encouraging initial results, long-term data of large-scale randomized trials as well as registries comparing them to currently approved first- and second-generation DES are still lacking.     

Antiplatelet therapy in the era of late stent thrombosis

Opinion statement Drug-eluting stents (DES) are the treatment of choice for obstructive coronary artery disease when percutaneous intervention is feasible. Although there are concerns regarding increased incidence of stent thrombosis, subsequent myocardial infarction, and death in patients receiving DES, careful analysis of large randomized trials has shown that risk of stent thrombosis with both bare metal stents (BMS) and DES is small. However, late stent thrombosis seems to occur more frequently with DES and seems to be closely associated with the discontinuation of dual antiplatelet therapy with aspirin and a thienopyridine derivative (usually clopidogrel). Before placing a DES in a patient, the interventional cardiologist must ensure that there are no conditions under which a patient or physician may have to discontinue dual antiplatelet therapy within a year after stent placement. If the cardiologist anticipates premature discontinuation of thienopyridine and aspirin therapy, his or her alternative is to place a BMS or recommend bypass surgery. If a situation arises in which dual antiplatelet therapy may have to be interrupted (eg, emergency or semi-elective surgery), it is strongly recommended that the treating physician consult a cardiologist and follow published guidelines.     

Drug-Eluting Versus Bare-Metal Stents in Older Patients: A Meta-Analysis of Randomized Controlled Trials

BackgroundDespite the high prevalence of ischemic heart disease in older patients, there is a substantial lack of evidence to guide clinical decision-making in this population. Hence, we performed a meta-analysis to determine the safety and efficacy of percutaneous coronary intervention (PCI) with drug-eluting stents (DES) versus bare-metal stents (BMS).MethodsElectronic databases were searched for randomized trials comparing DES with BMS in patients ≥70 years-old. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes included different ischemic and bleeding events. Subgroup analyses for dual-antiplatelet therapy (DAPT) duration were conducted.ResultsWe included 7 trials with a total of 5449 patients. The use of DES compared with BMS was associated with a significant reduction in MACE (odds ratio [OR]:0.76; 95% confidence interval [CI]:0.62–0.93; P = 0.007) with no increased risk of bleeding events (OR: 1.07; 95% CI: 0.89–1.27; P = 0.48). However, longer duration of DAPT (>6 months) for the DES group increased bleeding events (OR: 1.52; 95% CI: 1.05–2.20; P = 0.03). In contrast, shorter DAPT showed persistent efficacy in reducing MACE in DES-treated patients with no increased bleeding events (OR: 0.72; 95% CI: 0.60–0.87; P < 0.01 and OR: 1.01; 95% CI: 0.84–1.22; P = 0.89, respectively).ConclusionsIn older patients who had undergone PCI, DES showed superior efficacy in reducing MACE with no increased risk of bleeding compared with BMS. Persistent MACE reduction was evident with shorter DAPT durations in DES-treated patients.SummaryThis meta-analysis of randomized clinical trials demonstrated that drug-eluting stents were associated with a significant reduction in major adverse cardiovascular events with no increased risk of bleeding compared with bare-metal stents. The risk of bleeding was high with longer dual antiplatelet therapy duration for patients who underwent DES placement. However, short duration of dual antiplatelet therapy substantially reduced major adverse cardiovascular events with no increased bleeding risk.     

Drug-eluting stents: from the results of clinical studies to economic simulation models in the Italian reality]

Several studies with drug-eluting stents (DES) have demonstrated dramatic reductions in restenosis rates compared with bare metal stents (BMS). Although the clinical benefits of DES are increasingly evident, important concerns about their costs have been raised. Most data regarding the impact of restenosis on long-term costs after percutaneous coronary intervention (PCI) are derived from clinical trials. These studies demonstrate that there is no single cost or economic burden of restenosis; these values vary substantially according to the specific patient population under investigation and to the healthcare system reality where they are applied. In the present study we propose an economic interactive decision model which was applied to the Italian healthcare system, considering the different reimbursement rates of the Italian regions for DES and for both PCI and coronary artery bypass surgical interventions (CABG). The aim of this model was to simulate the impact of DES introduction after potential complete reimbursement by the national healthcare system, hypothesizing the usage of 1.4 stent per patient in case of single vessel disease and 2.4 stents in case of multivessel disease, and utilizing the TAXUS IV rate of revascularization for reintervention costs calculation and the ARTS-I study for CABG costs. For a low risk patients' population, the mean cost of a procedure with DES was 6% greater than utilizing BMS (xi 8125 for DES vs xi 7651 for BMS). However, this percentage was reduced in case of diabetic patients (+4%), long lesions (+2%) and was favourable for small vessels (-3%). In addition, in case of multivessel disease with conversion from CABG to DES, the 12 months cost per patients was reduced of around 30% (xi 10 170 for PCI vs xi 14 584 for CABG). This model suggests that national healthcare system may save 2.1% of the total costs (xi 18.60 millions) if 60% of revascularization procedures converts to total DES utilization and 15% from CABG to PCI with DES.     

Medikamente freisetzende Koronarstents und mit Medikamenten beschichtete Ballonkatheter

The Position Paper of the German Cardiac Society on drug-eluting stents (DES) and drug-coated balloon catheters (DCB) focuses on products which are approved for use and are available in Germany after successful investigation in clinical trials. Randomized, controlled clinical trials with the primary angiographic endpoint of providing evidence for antirestenotic efficacy should be required for all products as well as subsequent clinical endpoint trials. The use of DES in comparison to bare metal stents (BMS) leads to reduction of repeat revascularizations, while the clinical endpoints such as death or myocardial infarction remain unchanged. DES should be preferred in cases of increased risk for in-stent stenosis (ISR). In cases of elevated risk for stent thrombosis or expected problems of prolonged dual antiplatelet therapy, preference should be given to the use of BMS. The duration of dual antiplatelet therapy should be 1 month after BMS implantation, 1 month after treatment of BMS ISR with DCB, and 6–12 months after DES implantation in all patients and as a matter of principle 12 months after acute coronary syndrome (ACS) irrespective of the type of intervention.     

Drug-eluting stents versus bare metal stents in ST elevation myocardial infarction: from evidence to practice

In 2001, drug-eluting stents (DES) were introduced as a strategy to decrease restenosis and need for re-intervention. As the utilization of DES grew in general practice, there was considerable use of DES in "off-label" patients not evaluated in the initial randomized clinical trials. Single-center and large registry studies were able to demonstrate that the clinical efficacy of DES persisted even in patient subgroups not included in the initial clinical trials. These observations provided support for evaluating DES in STEMI patients. We will consider the evidence that evaluates the relative safety and efficacy of DES compared to BMS in STEMI patients, as well as address practical issues faced in the routine clinical care of these patients.     

Novel drug-eluting stents for coronary revascularization

Over the past decades, there has been significant evolution in coronary stents used in percutaneous coronary intervention. The current novel drug-eluting stents available in the United States represent significant advancements compared to angioplasty, bare-metal stents, and the first generation of drug-eluting stents (DES). The Xience everolimus-eluting stents, Promus everolimus-eluting stents, and Resolute zotarolimus-eluting stents currently demonstrate the optimal balance of safety and efficacy. Endeavor zotarolimus-eluting stents have shorter drug-elution courses, and recent evidence suggests that 3 months of dual antiplatelet therapy appears safe, making Endeavor preferred when early discontinuation of dual antiplatelet therapy is warranted. Despite these advances in stent design, the permanent polymer and metallic stent remain in the vessel wall and may precipitate sustained inflammation, persistent vasomotor dysfunction, and in-stent neo-atherosclerosis. Bioresorbable platforms with biodegradable polymers have been developed to overcome the aforementioned limitations, and the outcomes of ongoing clinical trials are eagerly anticipated to determine if these novel stents will further improve clinical outcomes.