Late Stent Thrombosis In Patients Research Articles

The Association Between S100A8/A9 and the Development of Very Late Stent Thrombosis in Patients With Acute Myocardial Infarction

Very late stent thrombosis (VLST) is a rare but serious complication following percutaneous coronary intervention (PCI). S100A8/A9 plays an important role in thrombosis through modulating the inflammatory response. This observational study aimed to reveal the association between S100A8/A9 and VLST. Continuous blood samples were collected from patients at both the time of index PCI for acute myocardial infarction (AMI) and the time of PCI for VLST (VLST group) or follow-up coronary angiography (AMI group). In all, 56 patients were selected in each group from a cohort of 8476 patients and other 112 individuals who underwent health checkups (normal control [NC] group) were selected as controls. Serum levels of S100A8/A9 and high sensitivity C-reactive protein (hs-CRP) were tested and compared. The mean level of S100A8/A9 was 3754.4 ± 1688.9 ng/mL during index PCI and increased to 5517.8 ± 2650.9 ng/mL at the time of VLST; in the AMI group, S100A8/A9 level was 2434.9 ± 1243.4 ng/mL during index PCI and decreased to 1568.2 ± 772.1 ng/mL during follow-up, similar to that detected in the NC group (1618.2 ± 641.4 ng/mL). Of note, S100A8/A9 levels showed significant increases during VLST when compared to its own levels during index PCI, which was different from the changes of hs-CRP. Higher serum levels of S100A8/A9 are associated with the development of VLST.

Early and Late Stent Thrombosis in Patients with Versus Without Diabetes Mellitus Following Percutaneous Coronary Intervention with Drug-Eluting Stents: A Systematic Review and Meta-Analysis.

Nowadays, drug-eluting stents (DES) are most commonly used compared with bare metal stents (BMS) since the former are associated with significantly lower rates of revascularization following percutaneous coronary intervention (PCI). However, unpredictable in-stent thrombosis is a major concern with DES, especially in patients with diabetes mellitus. In this analysis, we aimed to systematically compare early and late stent thrombosis in patients with versus without diabetes mellitus following PCI with DES. Studies were included if they were randomized controlled trials or observational studies comparing patients with diabetes mellitus versus those without it following PCI with DES and they reported acute and sub-acute/early and late stent thrombosis among their clinical outcomes. Early stent thrombosis was defined as stent thrombosis that occurred before 30days and late stent thrombosis was defined as stent thrombosis that occurred after 30days following PCI. The statistical analysis was carried out by the new version of the RevMan software (version 5.3), and odds ratios (ORs) and 95% confidence intervals (CIs) were considered as the statistical parameters. A total number of 18,910 patients were included in this analysis comparing early and late stent thrombosis in patients with diabetes mellitus (5123 patients) and in patients without diabetes mellitus (13,787 patients). Both groups of patients had similar rates of early stent thrombosis, with an OR of 1.30 (95% CI 0.89-1.91; P = 0.18, I2 = 9%) (4962 patients with diabetes mellitus were compared with 13,392 patients without diabetes mellitus). However, late stent thrombosis was significantly higher in patients with diabetes mellitus, with an OR of 1.95 (95% CI 1.35- 2.81; P = 0.0004, I2 = 0%) (5113 patients with diabetes mellitus and 13,775 patients without diabetes mellitus were compared). Both patients with and without diabetes mellitus had a similar rate of early stent thrombosis following PCI with DES. However, diabetes mellitus was associated with a significantly higher rate of late stent thrombosis.

Very late stent thrombosis in patients with first-generation drug-eluting stents: A systematic review of reported cases

Age, mean ± SD, years 59.1 ± 12.2 Not reported, n (%) 19 (11.1) Sex, n (%) Female 22 (12.8) Not reported 20 (11.6) DES type, n (%) PES 70 (40.7) SES 102 (59.3) Occluded artery, n (%) LAD 97 (56.4) RCA 35 (20.4) LCx 12 (7.0) LM 2 (1.2) Multiple arteries 6 (3.5) Not reported 20 (11.6) Clinical presentation, n (%) MI 106 (61.6) Angina 7 (4.1) Unstable angina 28 (16.3) Sudden death 1 (0.6) Other 6 (3.5) Not reported 24 (13.9) In-hospital mortality, n (%) 17 (9.9) Not reported 29 (16.9) Time from index PCI to VLST, days Mean ± SD 849.4 ± 411.8 Median (IQR) 752 (517, 1020) Time from ASA discontinuation to VLST, days Mean ± SD 112.6 ± 300 Median (IQR) 8.5 (7, 33) Time from thienopyridine discontinuation to VLST, days Mean ± SD 405.9 ± 434.2 Median (IQR) 304 (30, 609)

Long-term risk of late and very late stent thrombosis in patients treated with everolimus against paclitaxel-eluting stents: an updated meta-analysis.

Everolimus-eluting stent (EES) reduces the risk of late and very late stent thrombosis (ST) in a number of randomized controlled trials (RCTs). However, the benefits have been variable. We evaluated the effect of EES and paclitaxel-eluting stent (PES) on the risk of late and very late ST in patients with coronary artery disease. We identified RCTs by a systematic search of MEDLINE, EMBASE, and Cochrane Database. Seven RCTs (8162 patients) were included. Overall, EES therapy lowered the risk of very late ST significantly [relative risk (RR), 0.40; 95% confidence interval (CI), 0.20-0.80; I(2)=0.0%; P=0.009] compared with PES. Meanwhile, EES was associated with a significantly lower incidence of major adverse cardiac events (RR, 0.76; 95% CI, 0.67-0.86; I(2)=34.2%; P=0.00) driven by a markedly lower rate of myocardial infarction and target-vessel revascularization in the EES group. However, there was no significant difference in the risk of late ST (RR, 0.45; 95% CI, 0.15-1.39; I(2)=30.7%; P=0.166) between the two groups. A subgroup analysis showed that EES might not decrease the risk of very late ST significantly in patients older than 63.5 years or in patients with diabetes, those presenting with acute coronary syndrome, or those with a longer follow-up. Compared with PES, EES treatment decreased risk of very late ST significantly. However, the risk of late ST was similar between the two groups. More studies are needed to confirm the subgroup findings.

Very Late Stent Thrombosis in Patients With First Generation Drug-Eluting Stents Following the Discontinuation of Dual Antiplatelet Therapy: a Systematic Review of Reported Cases

Very Late Stent Thrombosis in Patients With First Generation Drug-Eluting Stents Following the Discontinuation of Dual Antiplatelet Therapy: a Systematic Review of Reported Cases

Clinical Outcomes from Unselected Real-World Patients with Acute Myocardial Infarction Receiving Biodegradable Polymer Coated Sirolimus-Eluting Stents

Objectives: To investigate clinical outcomes of acute myocardial infarction population in a real-life setting when treated with Indolimus® biodegradable polymer coated sirolimus-eluting coronary stent. Background: Drug-eluting stents in acute myocardial infarction are still feared for possible late and very late stent thrombosis. Newer antiproliferative drugs and more biodegradable polymers have shown promise in reducing further the rate of late stent thrombosis in patients with stable angina. However, limited data is available on the safety and efficacy of biodegradable polymer coated drug-eluting stent in acute myocardial infarction patients. Methods: We studied patients undergoing cardiac catheterization with acute myocardial infarction (n=239) and without acute myocardial infarction (n=291) who had been implanted with Indolimus® sirolimus-eluting stents. The outcomes were reported for 1 and 6-months. The primary endpoint was the composite of major adverse cardiac events at 1 and 6-months after discharge from hospital. The secondary endpoint was stent thrombosis. Results: A higher proportion of patients in the acute myocardial infarction group had renal insufficiency at screening (p=0.02), but there was a higher proportion of patients with a history of myocardial infarction (p<0.001), previous percutaneous coronary intervention (p=0.01) in the non- myocardial infarction group. The frequency of type B2/C lesions (p<0.001) and chronic total occlusion (p<0.001) was higher in the myocardial infarction group. There was no significant difference in parameters related to target vessel distribution and severity of disease. The six months follow-up was completed for 516 (97.4%) enrolled patients. The incidence of any major adverse cardiac events at 6-months was 2.1% and 4.2% for non-myocardial infarction and myocardial infarction population, respectively. There was no stent thrombosis up to 6-months in both groups. Conclusions: In this all-comer, real-world Indolimus acute myocardial infarction study, major adverse cardiac events rates did not differ between acute myocardial infarction and non-acute myocardial infarction population. Six-month observation of acute myocardial infarction treatment using Indolimus® stent compared with non- acute myocardial infarction has no clinical disadvantage. Keywords: Acute myocardial infarction, Percutaneous Coronary Intervention, Sirolmus-eluting stent, biodegradable polymer. Read more →

Coronary stent thrombosis in patients undergoing multidigit replantation

The development of drug-eluting stents has decreased the rate of in-stent restenosis. However, there have been reports of late stent thrombosis in patients with drug-eluting stents, especially when dual antiplatelet therapy is interrupted. The high mortality rate associated with cardiac stent thrombosis has led to recent recommendations regarding duration of antiplatelet therapy as well as timing of elective surgery in patients with both drug-eluting stents and bare metal stents. However, in patients requiring emergency operations, delaying surgery is not an option. In a retrospective review of 65 patients undergoing replantation from 2005 to 2010, only two patients with coronary stents presented, both with drug-eluting stents. Both of these patients developed acute in-stent thrombosis postoperatively (days 5 and 2) despite continuing dual antiplatelet therapy while undergoing multidigit replantation. Several factors including large transfusion requirements and the complex pharmacogenetics of clopidogrel may have played a role. These cases bring to light the increasing number of patients with indwelling drug-eluting stents in whom the need for massive surgical or trauma type management will become more frequent.

Long-Term Outcomes of Intravascular Ultrasound-Guided Stenting in Coronary Bifurcation Lesions

Stenting for bifurcation lesions is still challenging, and the effect of intravascular ultrasound (IVUS) guidance on long-term outcomes has not been evaluated. We assessed the long-term outcomes of IVUS-guided stenting in bifurcation lesions. We evaluated 758 patients with de novo nonleft main coronary bifurcation lesions who underwent stent implantation from January 1998 to February 2006. We compared the adverse outcomes (i.e., death, stent thrombosis, and target lesion revascularization) within 4 years, after adjustment using a multivariate Cox proportional hazard model and propensity scoring. IVUS-guided stenting significantly reduced the long-term all-cause mortality (hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.13 to 0.74, p = 0.008) in the total population and in the patients receiving drug-eluting stents (DESs) (HR 0.24, 95% CI 0.06 to 0.86, p = 0.03), but not in the patients receiving bare metal stents (HR 0.41, 95% CI 0.13 to 1.26, p = 0.12). IVUS-guided stenting had no effect on the rate of stent thrombosis (HR 0.48, 95% CI 0.16 to 1.43, p = 0.19) or target lesion revascularization (HR 1.47, 95% CI 0.79 to 2.71, p = 0.21). In patients receiving DESs, however, IVUS guidance reduced the development of very late stent thrombosis (0.4% vs 2.8%, p = 0.03, log-rank test). In conclusion, in patients receiving DESs, IVUS-guided stenting for treatment of bifurcation lesions significantly reduced the 4-year mortality compared to conventional angiographically guided stenting. In addition, IVUS guidance reduced the development of very late stent thrombosis in patients receiving DESs.

Temporal Trends in the Use of Drug‐eluting Stents for Approved and Off‐label Indications: A Longitudinal Analysis of a Large Multicenter Percutaneous Coronary Intervention Registry

We sought to examine the temporal variations in the rate of both bare-metal stent (BMS) and drug-eluting stent (DES) use for off-label indications after the reports of an increased risk of very late stent thrombosis in patients with DES at the 2006 meeting of the European Society of Cardiology (ESC). To determine whether the decrease in use of DES has affected both on and off-label indications. The study cohort included patients undergoing coronary intervention in a large regional registry, the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2). Patient demographic and clinical characteristics for patients with DES in the third quarter of 2006 (pre-ESC) were compared to those from the fourth quarter of 2008 (post-guideline changes). Use of DES for off-label indications, such as ST-segment elevation myocardial infarction (STEMI), in-stent restenosis (ISR), and saphenous vein graft (SVG) interventions, were evaluated. The overall deployment of DES fell sharply from 83% pre-ESC to a plateau of 58% in the first quarter of 2008. This corresponded to a rise in BMS use, while angioplasty procedures stayed the same. The STEMI subgroup showed the most dramatic change, from 78% to only 36%. Off-label use in SVGs showed a similar trend, from 74% to 43%. Drug-eluting stent deployment for ISR was less affected, though it also fell 25% (from 79%-56%). The use of DES has fallen dramatically from June 2006 to December 2008, particularly for nonapproved indications. Our study provides a real-world assessment of contemporary change in DES use in response to the presentation of negative observational studies.

A Case Against Low-Volume Percutaneous Coronary Intervention Centers

Since the publication of the Clinical Outcomes Utiliz- ing Revascularization and Aggressive Drug Evaluation (COURAGE) trial1 in April 2007, percutaneous coronary intervention (PCI) has received harsh scrutiny in both the scientific and lay press.2,3 The COURAGE investigators concluded that PCI did not reduce chances of death or myocardial infarction (MI) in patients with stable coronary artery disease and mild symptoms. At the same time, enormous controversy and media attention turned to a concern about late stent thrombosis in patients treated with drug-eluting stents. Studies suggested that an excess of deaths occurred 1 to 3 years after drug-eluting stent implantation.4,5 More recently, Tonino et al6 demonstrated in the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) trial that the risk of MI could be reduced by use of fractional flow reserve measurements during PCI. The FAME trial suggested that patients were benefited by deployment of fewer stents. In 2008, Hannan et al7 found that risk-adjusted mortality was less for coronary artery bypass grafting (CABG) than PCI with drug-eluting stents in the New York State registry. In March 2009, the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) trial was published, and Serruys et al8 concluded that PCI with drug-eluting stents was inferior to CABG in patients with multivessel or left main coronary disease. In June 2009, the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) investigators reported that patients with treated diabetes mellitus had no improvement in survival when they were revascularized with PCI; however, an improvement in survival occurred when patients were treated with CABG.9 Article see p 600 In the aggregate, these studies combined with the dramatic decrease of interventions for in-stent restenosis have significantly decreased the growth of PCI use in the United States. Patients and referring …

Safety of Drug-Eluting Stents in Patients With Left Ventricular Dysfunction Undergoing Percutaneous Coronary Intervention

Recent studies have reported a higher incidence of late stent thrombosis in patients undergoing drug-eluting stent (DES). Reduced left ventricular (LV) ejection fraction (EF) is considered a risk factor for this complication after both bare-metal stent (BMS) and DES implantation. Therefore, the aim of this study was to evaluate the safety of DES on long-term follow-up in patients with LV dysfunction undergoing percutaneous coronary intervention. We retrospectively selected all patients with an EF <45% undergoing percutaneous coronary intervention with implantation of > or =1 sirolimus- or paclitaxel-eluting stent at our institution. The primary endpoint of the study was all-cause mortality, retrieved using both Social Security Database and hospital records. We also compared the results of this group with a historical cohort of patients with LV dysfunction undergoing BMS implantation; 121 patients who received > or =1 DES were enrolled. The mean LVEF was 36 +/- 8%, with 20 patients (16%) with a LVEF < or =25%; 36 patients (30%) had diabetes mellitus, and DES implantation was considered off-label in 100 patients (83%). Survival at 1-, 2-, and 3-year follow-up was 94% (95% confidence interval [CI] 88 to 100), 90% (95% CI 82 to 98) and 88% (95% CI 80 to 96), respectively. In conclusion, the favorable results of this study demonstrate the safety of DES in patients with LV dysfunction.

Drug-eluting stents: a critique

Despite advances in the design of balloons and stents, restenosis remains a major drawback of coronary angioplasty. Multiple randomised trials have demonstrated that drug-eluting stents (DES) can significantly reduce rates...

Late Stent Thrombosis in Patients Receiving Ticlopidine and Aspirin After Sirolimus-Eluting Stent Implantation

There is little information about the efficacy of ticlopidine plus aspirin after sirolimus-eluting stent (SES) implantation. The incidence of stent thrombosis was evaluated in 1,029 patients receiving ticlopidine and aspirin after SES deployment. Clinical follow-up was obtained in 98.9% (mean follow-up 17.0+/-7.9 months). Early stent thrombosis was observed in 5 patients (0.49%). There was 1 case each of late (0.1%) and very late stent thrombosis (0.1%). Late and very late stent thrombosis in Japanese patients receiving ticlopidine and aspirin after SES deployment occurs infrequently.

Clinical Considerations with the Use of Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention

Despite the proven benefits of using antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI), a number of key questions remain to be answered. In recent years, clopidogrel dosing strategies among such patients have evolved considerably, with newer approaches involving loading doses prior to PCI and increases in the time interval and loading dosage in an effort to overcome variable responsiveness/hyporesponsiveness to platelet inhibition. Further, the role of glycoprotein (GP) IIb/IIIa antagonists in elective stenting continues to be defined, with recent evidence suggesting that most appropriate use of these agents is in high-risk patients with elevated troponin levels. There appears to be a relationship between the use of GP IIb/IIIa antagonists with clopidogrel loading and attenuation of early inflammatory and cardiac marker release. Strategies to minimize the chance of late stent thrombosis in patients who receive drug-eluting stents (DES) are also under intense investigation. Among some patients receiving sirolimus and paclitaxel DES, current standard long-term antiplatelet strategies may be insufficient. Patient nonadherence to treatment and premature discontinuation and underutilization of antiplatelet therapies by physicians remain important clinical problems with potentially dire consequences.

Response to the letter “Granulocyte-colony stimulating factor and hypercoagulability” by Kaptan et al.

The effects of a therapy with granulocyte-colony stimulating factor (G-CSF) on coagulation are fairly unknown and may exert a reasonable thrombotic risk especially in patients with atherosclerosis. However, it is difficult to assess the role of G-CSF in the development of late stent thrombosis in patients treated with G-CSF and subsequent transcoronary transplantation of autologous stem cells following stent implantation for acute myocardial infarction, as both, G-CSF therapy and transcoronary transplantation of stem cells, contain risk factors for intravascular thrombosis.

Late stent thrombosis: Considerations and practical advice for the use of drug‐eluting stents: A report from the Society for Cardiovascular Angiography and Interventions drug‐eluting stent task force

Recent analyses have suggested that implantation of drug-eluting stents (DES) is associated with a higher rate of very late stent thrombosis when compared with bare metal stents. This complication is evident with both sirolimus-eluting stents as well as polymer-based paclitaxel-eluting stents, but the precise magnitude of this risk and whether this applies to all patients or only a subset of those who have received DES is incompletely characterized. This alert is designed to provide the practicing interventional cardiologist with practical advice in light of this new information. It is not the purpose of this document to provide an exhaustive review of the literature on DES and the risk of stent thrombosis; however a brief summary is appropriate. While exact definitions have been variable in different trials, late stent thrombosis generally refers to stent thrombosis occurring at least 1 month following stent implantation, while very late stent thrombosis refers to events occurring more than 12 months following stent placement. Following bare metal stent implantation, stent thrombosis is rare after 2 weeks, and dual antiplatelet therapy (aspirin and a thienopyridine) was typically prescribed for 3–6 weeks. In contrast, sporadic reports of late stent thrombosis in patients receiving DES have occurred over the past few years. These events often (but not always) occurred in the setting of premature discontinuation of dual antiplatelet therapy. In March 2006, the BASKET-LATE trial was reported, describing a significantly greater composite occurrence of cardiac death and non-fatal myocardial infarction in patients treated with DES when compared with bare-metal stents after clopidogrel had been discontinued at 6 months [1]. Other meta-analyses of the existing DES trials also showed an increase in late events in the DES cohort although these analyses were limited by incomplete data in publications, abstracts, and Internet sources [2,3]. In October 2006, an independent patient-level meta analysis of the four pivotal randomized Cypher stent trials and the five pivotal randomized Taxus stent trials was publicly presented. These analyses demonstrated an increased rate of stent thrombosis with both sirolimus-eluting and paclitaxelJ_ID: Z7V Customer A_ID: 06-0418 Cadmus Art: CCI 21093 Date: 5-JANUARY-07 Stage: I Page: 1

Late Clinical Events After Clopidogrel Discontinuation May Limit the Benefit of Drug-Eluting Stents: An Observational Study of Drug-Eluting Versus Bare-Metal Stents

We sought to define the incidence of late clinical events and late stent thrombosis in patients treated with drug-eluting (DES) versus bare-metal stents (BMS) after the discontinuation of clopidogrel as well as their timing and outcome. There is growing concern that delayed endothelialization after DES implantation may lead to late stent thrombosis and related myocardial infarction (MI) or death. However, event rates and outcomes after clopidogrel discontinuation versus BMS are unknown. A consecutive series of 746 nonselected patients with 1,133 stented lesions surviving 6 months without major events were followed for 1 year after the discontinuation of clopidogrel. Patients were assigned randomly 2:1 to DES versus BMS in BASKET (Basel Stent Kosten Effektivitäts Trial). The primary focus of this observation was cardiac death/MI. Rates of 18-month cardiac death/MI were not different between DES and BMS patients. However, after the discontinuation of clopidogrel (between months 7 and 18), these events occurred in 4.9% after DES versus 1.3% after BMS implantation. Target vessel revascularization remained lower after DES, resulting in similar rates of all clinical events for this time period (DES 9.3%, BMS 7.9%). Documented late stent thrombosis and related death/target vessel MI were twice as frequent after DES versus BMS (2.6% vs. 1.3%). Thrombosis-related events occurred between 15 and 362 days after the discontinuation of clopidogrel, presenting as MI or death in 88%. After the discontinuation of clopidogrel, the benefit of DES in reducing target vessel revascularization is maintained but has to be balanced against an increase in late cardiac death or nonfatal MI, possibly related to late stent thrombosis.

Comparison of ticlopidine vs. clopidogrel in addition to aspirin after paclitaxel-eluting stent implantation: Insights from the TRUE (Taxus™ in Real-life Usage Evaluation) Study

Thienopyridines and aspirin are beneficial in patients undergoing bare-metal stent implantation, and aspirin and clopidogrel treatment have also been proved effective after drug-eluting stent (DES) implantation. However, despite the common substitution of clopidogrel with ticlopidine because of cost or patient intolerance, there are no data on the comparison of ticlopidine vs. clopidogrel after DES implantation. We hereby compare ticlopidine vs. clopidogrel after paclitaxel-eluting stent implantation in subjects enrolled in the prospective multicenter Taxus in Real-life Usage Evaluation (TRUE) Study. Across the 505 analyzed patients (112 treated with ticlopidine and 393 with clopidogrel), similar rates of early and mid-term (7 months) adverse thrombotic events were found with either antiplatelet regimen, with the notable exception of 2 cases of late stent thrombosis in patients who had prematurely withdrawn ticlopidine treatment just 3 months after the procedure. These findings thus support the overall safety and effectiveness of ticlopidine after DES implantation, and also confirm the increased risk of late thrombosis when premature withdrawal of thienopyridines occurs.