Sirolimus-eluting Stent Implantation Research Articles

Abstract 11911: Comparison of Late Catch-Up Phenomenon Between Sirolimus-Eluting Stent and Everolimus-Eluting Stent During 3 Years Follow-Up - a Propensity Matched Study -

Background: Recent studies have suggested the possibility of late catch-up phenomenon after implantation of sirolimus-eluting stent (SES) for coronary artery disease (CAD) compared to bare metal stent. However, little is known about the incidence of late catch-up phenomenon after implantation of everolimus-eluting stent (EES). Methods: Between April 2007 and May 2011, 1234 patients with CAD were treated with SES and 502 patients were treated with EES in our institution. We used a propensity score matching method with 1:1 matching, including 495 patients treated with SES and 495 patients treated with EES. Late catch-up phenomenon which was defined as target lesion restenosis (1 year to 3 years) were compared between the 2 groups. Results: After the propensity matching, no difference was seen in baseline characteristics between the 2 groups. Cumulative incidence of TLR at 3 years was 7.1% in EES group and 13.5% in SES group (P=0.001, log-rank test). Incidence of late catch-up phenomenon was 4.2% in EES group and 7.8% in SES group (P=0.020, log-rank test). Multivariate Cox’s proportional hazard analysis revealed that sirolimus eluting stent usage (HR 4.7, 95%CI 2.8-7.9, P<0.001), hemodialysis (HR 2.7, 95%CI 1.5-4.9, P=0.001), 2 stent use for bifurcation (HR 2.1, 95%CI 1.1-4.1, P=0.028), IVUS usage (HR 0.41, 95%CI 0.27-0.62, P<0.001), and ACS (HR 1.9, 95%CI 1.0-3.4, P=0.038) were independent predictors of late catch up phenomenon. Conclusions: EES was significantly superior to SES in the incidence of late catch-up phenomenon.

Abstract 12022: Long-Term Clinical Outcomes of Everolimus-Eluting Stents versus Sirolimus-Eluting Stents: Systematic Review and a Meta-Analysis of 14 Randomized Control Trials, Focused on Stent Thrombosis

Background: We sought to compare the long-term clinical outcomes between everolimus-eluting stent (EES) and sirolimus-eluting stents (SES) with a meta-analysis method. The long-term clinical outcomes, especially stent thrombosis (ST), after EES versus SES implantation has not been clearly defined among trials directly comparing the 2 types of stents. Methods: We searched PubMed, Cochrane database, and ClinicalTrials.gov. for trials comparing outcomes between EES (Xience V/Promus) and SES (Cypher select/Cypher select plus) in patients with native coronary artery disease using randomized controlled trial (RCT) design. We selected the article reporting the longest follow-up outcomes from each RCT. The outcome measure was all-cause death, myocardial infarction (MI), definite ST, and target-lesion revascularization (TLR). ST was further classified as those occurring early (<=30 days), late (30-365 days), or very late (<365 days). Results: We identified 14 RCT comparing EES and SES including 2 trials reporting the longest follow-up outcomes as a pooled analysis. We analyzed 13,434 randomly assigned patients with the weighted follow-up period of 2.1 years (Follow-up <=1-year: 7 trials, and 3191 patients; >1-year: 7 trials, and 10243 patients). EES as compared to SES was associated with significantly lower risks for overall ST, and early ST (pooled odds ratio (OR) 0.49, 95% confidence interval (CI) 0.30-0.81, P=0.01, and OR 0.42, 95% CI 0.18-0.99, P=0.046, respectively), while there was no significant difference in the risk for late ST and very late ST (OR 0.49, 95% CI 0.17-1.43, P=0.19, and OR 0.66, 95% CI 0.23-1.85, P=0.43, respectively). EES as compared to SES was also associated with significantly lower risks for TLR (OR 0.84, 95% CI 0.71-0.99, P=0.04). There was no significant difference in the risk for all-cause death, and MI between EES and SES. (OR 0.91, 95% CI 0.78-1.07, P=0.11, and OR 0.92, 95% CI 0.75-1.13, P=0.44, respectively). Conclusions: In the current meta-analysis of 14 RCT directly comparing EES with SES, implantation of EES as compared to SES implantation was associated with significantly lower risk for definite ST and TLR.

Long-Term Outcome of Sirolimus-Eluting and Zotarolimus-Eluting Coronary Stent Implantation in Patients With and Without Diabetes Mellitus (A Danish Organization for Randomized Trials on Clinical Outcome III Substudy)

We compared 5-year clinical outcomes in diabetic and nondiabetic patients treated with Endeavor zotarolimus-eluting stents (ZESs; Endeavor Sprint, Medtronic, Santa Rosa, California) or Cypher sirolimus-eluting stents (SESs; Cordis, Johnson & Johnson, Warren, New Jersey) coronary implantation. We randomized 2,332 patients to either ZESs (n = 1,162, n = 169 diabetic patients) or SESs (n = 1,170, n = 168 diabetic patients) stratified according to presence or absence of diabetes mellitus. End points included major adverse cardiac event (MACE), a composite of cardiac death, myocardial infarction, target vessel revascularization (TVR), and definite stent thrombosis. Among diabetic patients, MACE occurred more frequently in patients treated with ZESs than SESs (48 [28.4%] vs 31 [18.5%]; odds ratio [OR] 1.75, 95% confidence interval [CI] 1.05 to 2.93, p = 0.032) because of a higher rate of TVR (32 [18.9%] vs 14 [8.3%]; OR 2.57, 95% CI 1.32 to 5.02, p = 0.006). Among nondiabetic patients, ZES and SES had similar MACE rates at 5-year follow-up but SES was associated with a significantly higher risk of definite stent thrombosis (10 [1.0%] vs 23 [2.3%]; OR 0.43, 95% CI 0.20 to 0.91, p = 0.028). Moreover, during the last 4 years, ZES had fewer MACE, TVR, and stent thrombosis events among nondiabetic patients. In conclusion, SES remains superior to ZES in patients with diabetes throughout the 5-year follow-up, however, among nondiabetic patients, SES demonstrated a highly dynamic performance with favorable initial results followed by a late catch-up that included an overall higher risk of stent thrombosis.

Mechanisms explaining the late “catch-up” phenomenon after sirolimus-eluting stent implantation

Drug-eluting stents (DES) have a significantly reduced in-stent restenosis (ISR). However, there is concern about the durability of the efficacy, i.e., late “catch-up” phenomenon [1,2]. In the bare-metal stent (BMS) era, the ISR occurred predominantly within the first year, which was clinically much more important than late restenosis. However, in the first generation DES era, late ISR leading to late target-lesion revascularization (TLR) beyond 1year has emerged as a new problem. The mechanisms of the late restenosis after the first-generation DES implantation are not fully understood.

Long-term clinical outcomes after sirolimus-eluting stent implantation for unprotected left main coronary artery disease.

Previous studies reporting long-term (≥5year) clinical outcome in patients with unprotected left main coronary artery (LMCA) disease undergoing drug-eluting stent (DES) implantation are currently limited, although late adverse events beyond 1year are one of the major concerns of DES. We evaluated long-term clinical outcomes in 134 consecutive patients who underwent sirolimus-eluting stents (SES) for unprotected LMCA lesion in a single center from 2004 to 2009. The median follow-up duration was 3.8 (range: 0.5-7.9) years. Eight patients suffered from serious cardiovascular events potentially related to LMCA lesion (primary outcome measure) (sudden cardiac death: N=5, emergent coronary revascularization for the LMCA lesion: N=2, and acute congestive heart failure related to LMCA lesion: N=1) with the cumulative 5-year incidence of only 4.4%. The cumulative 5-year incidence of all-cause death, cardiac death, target vessel myocardial infarction, definite stent thrombosis, and target-lesion revascularization was 26.5, 8.1, 0, 0, and 12.9%, respectively. In a subgroup analysis, the cumulative incidence of the primary outcome measure was significantly higher in patients with 2-stenting (N=27) than in patients with 1-stenting (N=107) (14.0 and 2.2%, P<0.001). All 8 patients with serious adverse events had a true bifurcation lesion and 5 patients received 2-stenting for the LMCA lesion. SES implantation in patients with unprotected LMCA lesion was associated with a favorable long-term outcome with acceptably low rate of serious adverse event potentially related to LMCA lesion. However, complex LMCA lesions necessitating 2-stenting strategy might be associated with higher risk for serious adverse events.

TCT-660 Nine-year Clinical Outcomes After The First Sirolimus-eluting Stent Implantation: Impact Of In-stent Restenosis Lesion

TCT-660 Nine-year Clinical Outcomes After The First Sirolimus-eluting Stent Implantation: Impact Of In-stent Restenosis Lesion

TCT-373 Temporal course of neointimal maturity after implantation of biodegradable polymer sirolimus-eluting stents as assessed by optical coherence tomography gray-scale signal intensity at 3, 6 and 9 months

We previously reported that in patients undergoing follow-up after stenting optical coherence tomography (OCT) gray-scale signal intensity (GSI) analysis can differentiate between stent coverage with mature (smooth muscle cell-rich) versus immature tissue (hypocellular fibrin-rich) using

TCT-262 Comparison of Target Lesion Revascularization in Patients with Renal Insufficiency after Sirolimus-eluting Stent and Everolimus-eluting Stent Implantation: Three-year Outcomes from Single-center Retrospective Study

TCT-262 Comparison of Target Lesion Revascularization in Patients with Renal Insufficiency after Sirolimus-eluting Stent and Everolimus-eluting Stent Implantation: Three-year Outcomes from Single-center Retrospective Study

TCT-649 Outcomes After Repeat Intervention With Everolimus-eluting Stent For Sirolimus-eluting Stent Restenosis Lesion With Stent Fracture

Presence of stent fracture (SF) after sirolimus-eluting stent (SES) implantation has reported to be associated with an increased risk of adverse events and those are previously reported. But little is known about the outcomes after re-intervention for SES restenosis lesion with SF. From April 2007

TCT-228 Long-term Safety and Efficacy of Sirolimus Eluting Stent Implantation for Unprotected Left Main Trunk Bifurcation Lesion with Single Stent Strategy Versus Left Anterior Descending Artery Lesion

TCT-228 Long-term Safety and Efficacy of Sirolimus Eluting Stent Implantation for Unprotected Left Main Trunk Bifurcation Lesion with Single Stent Strategy Versus Left Anterior Descending Artery Lesion

Safety and Long-Term Efficacy of Sirolimus-Eluting Stents

Sirolimus was isolated in 1975 and was initially approved for the treatment of renal transplant rejection. The main mechanism of action is mTOR inhibition, which prevents cell cycle progression. The first-in-human study of the sirolimus-eluting stent (SES) was initiated in 1999 in Sao Paulo Brazil and Rotterdam. The study demonstrated a reduction in restenosis after SES implantation when compared with bare-metal stents. The first approved drug-eluting stent was the SES Cypher®. Several modifications in stent platform and polymer coating have been made, in an effort to improve deliverability and to reduce inflammatory response secondary to nonbiocompatible polymers. Bioabsorbable polymer and polymer-free technologies are the main characteristic of the second- and third-generation SES. Larger studies with longer follow-up are needed to prove the efficacy of those stents when compared with previous platforms.

Long-Term Clinical Outcomes After Everolimus- and Sirolimus-Eluting Coronary Stent Implantation

Long-term clinical outcomes of everolimus-eluting stent (EES) compared with sirolimus-eluting stent (SES) have not been evaluated fully yet, especially whether EES implantation could positively affect late adverse events reported after SES implantation occurring >1 year. In this all-comer prospective multicenter randomized open-label trial, 3196 patients were assigned randomly to implant either EES (n=1596) or SES (n=1600). At 3 years, EES was noninferior to SES on the primary safety end point (all-cause death or myocardial infarction; 10.1% versus 11.5%; noninferiority P <0.001; and superiority P=0.19). Cumulative incidence of definite stent thrombosis was low and was not significantly different between the 2 groups (0.5% versus 0.6%; P=0.81). There was no significant difference in the efficacy end point of target-lesion revascularization between the EES and SES groups (6.6% versus 7.9%; P=0.16). However, the cumulative incidence of target-lesion failure (cardiac death/target-vessel myocardial infarction/ischemia-driven target-lesion revascularization) was significantly lower in the EES group than in the SES group (8.8% versus 11.4%; P=0.01). By a landmark analysis at 1 year, the cumulative incidence of very late stent thrombosis and late target-lesion revascularization was not significantly different between the 2 groups (0.2% versus 0.2%; P=0.99 and 2.2% versus 2.9%; P=0.21, respectively). The efficacy and safety outcomes for this trial after EES implantation remained comparable with those after SES implantation through 3-year follow-up. However, improvement of clinical outcome after EES implantation compared with SES implantation was suggested by the significantly lower cumulative incidences of target-lesion failure, which has been the most widely used primary end point in the stent-versus-stent trials. http://www.clinicaltrials.gov. Unique identifier: NCT01035450.

Recurrent restenosis in saphenous vein graft. What is the next step?

The long-term outcome after percutaneous treatment of saphenous vein graft (SVG) is worse than of native coronaries. We present a patient with degenerated SVG, which had been treated with several interventions. Despite this, there was multiple recurrence of SVG-restenosis. A 76-year-old patient after implantation of a cardiac pacemaker, with arterial hypertension, atrial fibrillation, and chronic kidney disease, underwent coronary artery bypass grafting in 1993. Left internal mammary artery to left anterior descending artery, jump-SVG to marginal (Marg) and diagonal branches and SVG to right coronary artery (RCA) were inserted. Control angiography carried out 18 years later revealed occluded native coronary arteries and occluded SVG segment to Marg. Additionally, there was tight stenosis in RCA-SVG (Fig. 1A). Immediate intravascular ultrasound-guided percutaneous coronary intervention (PCI) of RCA-SVG was done with a 2.5 × 12 mm paclitaxel-eluting stent implantation and postdilatation. Seven months later, tight in-stent restenosis was diagnosed (Fig. 1B). After predilatation, a 2.5 × 18 mm zotarolimus-eluting stent was implanted. Subsequent two in-stent restenoses a few months later were treated twice with 3.0 × 25 mm paclitaxel-eluting balloons (Figs. 1C, D). The last in-stent restenosis (Fig. 1E) was treated with a 3.0 × 15 mm everolimus-eluting stent. There is no convincing proof of better long-term outcomes after SVG-PCI with drug-eluting stents (DES) compared to bare metal stents (BMS). DES significantly reduces the target vessel revascularisation (TVR) in SVG. However, there is no clear benefit on mortality and myocardial infarction. Histological examination of SVG-lesions shows a different pattern of restenosis compared to native coronaries, with enhanced inflammatory and thrombotic response. A Japanese restenosis registry in native coronaries indicated that if the original restenosis developed in a sirolimus-eluting stent (SES), it would more likely occur again after the next in-stent SES implantation. However, the need for TVR for second restenosis was rarer, if the original restenosis developed in BMS (and not in SES) and was subsequently treated with in-BMS SES implantation. Both first and second generation DES failed in our case. There have been no direct comparisons from randomised trials of different DES types for SVG. Chatani et al. (J Interv Cadiol, 2009; 22: 354–361) suggested that the only independent predictive factor of re-restenosis after SES-in-SES implantation in native coronaries was the reference diameter. In our case, we implanted two second generation DESs into a first generation DES. Additionally, two PCIs with drug-eluting balloons, postponed further metal jacket insertion. After careful lesion preparation, implantation of the last (third) DES with larger diameter than the previous stents was possible. DESs have the advantage over BMSs in terms of SVG-TVR reduction, but in rare cases both DESs of first and second generation and drug-eluting balloon fail to prevent it. If a sixth restenosis were to occur, implantation of bioabsorbable vessel scaffolding or rotablation might be the treatment option.

OUTCOMES AFTER REPEAT PERCUTANEOUS CORONARY INTERVENTION WITH EVEROLIMUS-ELUTING STENT FOR SIROLIMUS-ELUTING STENT RESTENOSIS LESION WITH STENT FRACTURE

Presence of stent fracture (SF) after sirolimus-eluting stent (SES) implantation has reported to be associated with an increased risk of adverse events and those are previously reported. But little is known about the outcomes after re-intervention for SES restenosis lesion with SF. From April 2007

Worsening late-acquired incomplete stent apposition after sirolimus-eluting stent implantation for a chronic total occlusion lesion

A 70-year-old man underwent percutaneous coronary intervention (PCI) using sirolimus-eluting stent (SES) at the just proximal site of left anterior descending coronary artery. Six months after SES implantation, he suffered from late stent thrombosis. Intravascular ultrasound (IVUS) images demonstrated positive remodeling of the vessel, indicating late-acquired incomplete stent apposition (ISA). An angioplasty with a bigger balloon was performed to obtain sufficient stent struts apposition. Twenty-six months after the second PCI, he developed ST-elevation myocardial infarction and his CAG showed re-occlusion of the SES. Optical coherence tomography showed ISA and IVUS revealed further enlargement of the coronary artery around the SES.

Impact of sirolimus-eluting stent fractures without early cardiac events on long-term clinical outcomes: A multislice computed tomography study

This study sought to evaluate the impact of sirolimus-eluting stent (SES) fractures on long-term clinical outcomes using multislice computed tomography (MSCT). In this study, 528 patients undergoing 6- to 18-month follow-up 64-slice MSCT after SES implantation without early clinical events were followed clinically (the median follow-up interval was 4.6 years). A CT-detected stent fracture was defined as a complete gap with Hounsfield units (HU) <300 at the site of separation. The major adverse cardiac events (MACEs), including cardiac death, stent thrombosis, and target lesion revascularisation, were compared according to the presence of stent fracture. Stent fractures were observed in 39 patients (7.4 %). MACEs were more common in patients with CT-detected stent fractures than in those without (46 % vs. 7 %, p < 0.01). Univariate Cox regression analysis indicated a significant relationship between MACE and stent fracture [hazard ratio (HR) 7.65; p < 0.01], age (HR 1.03; p = 0.04), stent length (HR 1.03; p < 0.01), diabetes mellitus (HR 1.77; p = 0.04), and chronic total occlusion (HR 2.54; p = 0.01). In the multivariate model, stent fracture (HR 5.36; p < 0.01) and age (HR 1.03; p = 0.04) remained significant predictors of MACE. An SES fracture detected by MSCT without early clinical events was associated with long-term clinical adverse events. • Long-term outcomes of sirolimus-eluting stent fracture have not been fully clarified. • MSCT could detect stent fracture with high accuracy. • Sirolimus-eluting stent fracture detected by MSCT was associated with long-term adverse events.

Late Adverse Events After Implantation of Sirolimus-Eluting Stent and Bare-Metal Stent

Late adverse events such as very late stent thrombosis (VLST) or late target-lesion revascularization (TLR) after first-generation sirolimus-eluting stents (SES) implantation have not been yet fully characterized at long term in comparison with those after bare-metal stent (BMS) implantation. Among 13 058 consecutive patients undergoing first percutaneous coronary intervention in the Coronary REvascularization Demonstrating Outcome study-Kyoto registry Cohort-2, 5078 patients were treated with SES only, and 5392 patients were treated with BMS only. During 7-year follow-up, VLST and late TLR beyond 1 year after SES implantation occurred constantly and without attenuation at 0.24% per year and at 2.0% per year, respectively. Cumulative 7-year incidence of VLST was significantly higher in the SES group than that in the BMS group (1.43% versus 0.68%, P<0.0001). However, there was no excess of all-cause death beyond 1 year in the SES group as compared with that in the BMS group (20.8% versus 19.6%, P=0.91). Cumulative incidences of late TLR (both overall and clinically driven) were also significantly higher in the SES group than in the BMS group (12.0% versus 4.1%, P<0.0001 and 8.5% versus 2.6%, P<0.0001, respectively), leading to late catch-up of the SES group to the BMS group regarding TLR through the entire 7-year follow-up (18.8% versus 25.2%, and 10.6% versus 10.2%, respectively). Clinical presentation as acute coronary syndrome was more common at the time of late SES TLR compared with early SES TLR (21.2% and 10.0%). Late catch-up phenomenon regarding stent thrombosis and TLR was significantly more pronounced with SES than that with BMS. This limitation should remain the target for improvements of DES technology.

Impact of angiographic peri-stent contrast staining (PSS) on late adverse events after sirolimus-eluting stent implantation: an observation from the multicenter j-Cypher registry PSS substudy

This study sought to assess clinical significance of angiographic peri-stent contrast staining (PSS) after sirolimus-eluting stent (SES) implantation in a large multicenter study with 5-year follow-up. The j-Cypher PSS substudy is a multicenter study including 5712 patients (7838 lesions) who underwent follow-up angiographic study within 12months after SES implantation. Late acquired PSS was observed in 184 patients (3.2%) or 194 lesions (2.5%). Independent risk factors of PSS were chronic total occlusion and left anterior descending artery lesion, while negative risk factors were in-stent restenosis, diabetes mellitus, ≥70years of age, and left circumflex coronary artery lesion. Cumulative incidence of definite very late stent thrombosis (VLST) at 4years after the index follow-up angiography in lesions with PSS was significantly higher than that in lesions without PSS (5.3 versus 0.7%, P<0.0001). Late target-lesion revascularization (TLR) was also more frequently observed in the PSS group (13 versus 6.9%, P=0.01), while late TLR for restenosis excluding those TLR procedures for VLST tended to be higher in the PSS group (9.9 versus 6.3%; P=0.15). PSS found in 2.5% of lesions within 12months after SES implantation was associated with higher risk for subsequent VLST.

Repeated occurrence of slow flow phenomenon during and late after sirolimus-eluting stent implantation

A 78-year-old man with unstable angina showed 90% stenosis in the proximal left anterior descending artery. Pre-procedural intravascular ultrasound revealed ruptured plaque and attenuated plaque in the lesion. Under these conditions, two overlapping sirolimus-eluting stent (SES) implantation in this lesion resulted in slow flow which was recovered by intracoronary nitrates, nicorandil, and nitroprusside without further complications. When the patient showed up again 5 years later with recurrence of angina pectoris, angiography revealed a hazy ulcerated in-stent restenosis (ISR) at the site of the SES. Pre-procedural optical coherence tomography (OCT) imaging revealed multiple intimal ruptures, cavity formation behind the stent struts, a thin-cap fibroatheroma containing neointima surrounded by signal-poor, lipid-rich area in the proximal SES, suggesting the progression of neoatherosclerosis within SES. Importantly, there occurred slow flow again after balloon angioplasty for this lesion. We would suggest careful OCT examination is warranted to confirm development of neoatherosclerosis within the stent, and distal protection device should be considered to prevent slow flow phenomenon even in a patient with very late ISR.

Two peri-stent contrast stainings and one late restenosis in the late phase after sirolimus-eluting stent implantation

Both peri-stent contrast staining (PSS) and late restenosis are abnormal findings after drug-eluting stent implantation and they occur with low incidence. We describe a case with two PSSs and one late restenosis after sirolimus-eluting stent implantation. Persistent high value of C-reactive protein in this patient suggested chronic systematic inflammation as a contributing factor of these abnormal findings.<Learning objective: The advent of drug-eluting stents has dramatically reduced in-stent restenosis. However, there are still some concerns about long-term safety. We show a case with multiple sirolimus-eluting stent-related complications, taking into account the underlying pathogenesis.>