Thrombotic Complications Associated With Early and Late Nonadherence to Dual Antiplatelet Therapy

ObjectivesThis study sought to assess the frequency and clinical impact of dual antiplatelet therapy (DAPT) nonadherence.BackgroundThere are limited data on the impact of DAPT nonadherence during the first year after a second-generation drug-eluting stent placement.MethodsAfter successful Endeavor zotarolimus-eluting stent implantation, 2,265 patients were enrolled in a registry with limited exclusions and monitored during 12 months of prescribed DAPT. Predictors of any nonadherence (ANA) at 6 months were analyzed by multivariable analysis, and the association between ANA at 6 or 12 months with the endpoints of death, myocardial infarction, and stent thrombosis was assessed.ResultsThe study population included 30% female patients, 34% with diabetes and 36% with acute coronary syndromes. ANA occurred in 208 patients (9.6%) before 6 months and 378 patients (18.5%) before 1 year. Major bleeding (odds ratio [OR]: 12.83, 95% confidence interval [CI]: 7.55 to 21.80, p < 0.001) was the only predictor of ANA at 6 months. In time-dependent analyses, ANA before 6 months was associated with an increased risk of death or myocardial infarction (7.6% vs. 3.0%, p < 0.001) and a numerical increase in stent thrombosis (2.0% vs. 0.9%, p = 0.12). After adjustment for baseline differences, ANA within 6 months remained associated with death or MI (OR: 1.95, 95% CI: 1.02 to 3.75). ANA occurring after 6 months did not increase the risk of subsequent ischemic events.ConclusionsDAPT ANA occurs frequently and is associated with increased risk for thrombotic complications if it occurs within the first 6 months. Major bleeding was a significant correlate of DAPT ANA within 6 months. (EDUCATE: The MEDTRONIC Endeavor Drug Eluting Stenting: Understanding Care, Antiplatelet Agents and Thrombotic Events; NCT01069003)     

Comparison of Stent Expansion Guided by Optical Coherence Tomography Versus Intravascular Ultrasound: The ILUMIEN II Study (Observational Study of Optical Coherence Tomography [OCT] in Patients Undergoing Fractional Flow Reserve [FFR] and Percutaneous Coronary Intervention)

ObjectivesThe present study sought to determine whether optical coherence tomography (OCT) guidance results in a degree of stent expansion comparable to that with intravascular ultrasound (IVUS) guidance.BackgroundThe most important predictor of adverse outcomes (thrombosis and restenosis) after stent implantation with IVUS guidance is the degree of stent expansion achieved.MethodsWe compared the relative degree of stent expansion (defined as the minimal stent area divided by the mean of the proximal and distal reference lumen areas) after OCT-guided stenting in patients in the ILUMIEN (Observational Study of Optical Coherence Tomography [OCT] in Patients Undergoing Fractional Flow Reserve [FFR] and Percutaneous Coronary Intervention) (N = 354) and IVUS-guided stenting in patients in the ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) study (N = 586). Stent expansion was examined in all 940 patients in a covariate-adjusted analysis as well as in 286 propensity-matched pairs (total N = 572).ResultsIn the matched-pair analysis, the degree of stent expansion was not significantly different between OCT and IVUS guidance (median [first, third quartiles] = 72.8% [63.3, 81.3] vs. 70.6% [62.3, 78.8], respectively, p = 0.29). Similarly, after adjustment for baseline differences in the entire population, the degree of stent expansion was also not different between the 2 imaging modalities (p = 0.84). Although a higher prevalence of post-PCI stent malapposition, tissue protrusion, and edge dissections was detected by OCT, the rates of major malapposition, tissue protrusion, and dissections were similar after OCT- and IVUS-guided stenting.ConclusionsIn the present post-hoc analysis of 2 prospective studies, OCT and IVUS guidance resulted in a comparable degree of stent expansion. Randomized trials are warranted to compare the outcomes of OCT- and IVUS-guided coronary stent implantation.     

A Randomized Comparison of Novel Biodegradable Polymer- and Durable Polymer–Coated Cobalt-Chromium Sirolimus-Eluting Stents

ObjectivesThe aim of this study was to investigate the hypothesis that a novel biodegradable polymer–coated, cobalt-chromium (CoCr), sirolimus-eluting stent (BP-SES) is noninferior in safety and efficacy outcomes compared with a durable polymer (DP)-SES.BackgroundNo randomized trials have the compared safety and efficacy of BP-SES versus DP-SES on similar CoCr platforms, thereby isolating the effect of the polymer type.MethodsIn this prospective, single-blind, randomized trial conducted at 32 Chinese sites, 2,737 patients eligible for coronary stenting were treated with BP- or DP-SES in a 2:1 ratio. The primary endpoint was 12-month target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction, or clinically indicated target lesion revascularization. Secondary endpoints included TLF components, and definite/probable stent thrombosis.ResultsAt 12 months, the difference in the primary endpoint of TLF between BP-SES (6.3%) and DP-SES (6.1%) groups was 0.25% (95% confidence interval: −1.67% to 2.17%, p for noninferiority = 0.0002), demonstrating noninferiority of BP-SES to DP-SES. Individual TLF components of cardiac death (0.7% vs. 0.6%, p = 0.62), target vessel myocardial infarction (3.6% vs. 4.3%, p = 0.39), and clinically indicated target lesion revascularization (2.6% vs. 2.2%, p = 0.50) were similar, as were low definite/probable stent thrombosis rates (0.4% vs. 0.6%, p = 0.55).ConclusionsIn this large-scale real-world trial, BP-SES was noninferior to DP-SES for 1-year TLF. (Evaluate Safety and Effectiveness of the Tivoli ® DES and the Firebird ® DES for Treatment of Coronary Revascularization; NCT01681381)     

Outcomes After Percutaneous Coronary Intervention With Stents in Patients Treated With Thoracic External Beam Radiation for Cancer

ObjectivesThe aim of this study was to assess outcomes after percutaneous coronary intervention (PCI) with stents in patients treated with thoracic external beam radiation therapy (EBRT).BackgroundThoracic EBRT for cancer is associated with long-term cardiotoxic sequelae. The impact of EBRT on patients requiring coronary stents is unclear.MethodsWe analyzed outcomes after PCI in cancer survivors treated with curative thoracic EBRT before and after stenting between 1998 and 2012. Reference groups were propensity-matched cohorts with stenting but no EBRT. Primary endpoint was target lesion revascularization (TLR), a clinical surrogate for restenosis. Secondary endpoints included myocardial infarction (MI) and cardiac and overall mortality.ResultsWe identified 115 patients treated with EBRT a median 3.6 years after stenting (group A) and 45 patients treated with EBRT a median 2.2 years before stenting (group B). Long-term mean TLR rates in group A (3.2 vs. 6.6%; hazard ratio: 0.6; 95% confidence interval: 0.2 to 1.6; p = 0.31) and group B (9.2 vs. 9.7%; hazard ratio: 1.2; 95% confidence interval: 0.4 to 3.4; p = 0.79) were similar to rates in corresponding control patients (group A: 1,390 control patients; group B: 439 control patients). Three years post-PCI, group A had higher overall mortality (48.6% vs. 13.9%; p < 0.001) but not MI (4.8% vs. 4.3%; p = 0.93) or cardiac mortality (2.3% vs. 3.6%; p = 0.66) rates versus control patients. There were no significant differences in MI, cardiac, or overall mortality rates in group B.ConclusionsThoracic EBRT is not associated with increased stent failure rates when used before or after PCI. A history of PCI should not preclude the use of curative thoracic EBRT in cancer patients or vice versa. Optimal treatment of cancer should be the goal.     

Drug-Coated Balloons Versus Second-Generation Drug-Eluting Stents for the Management of Recurrent Multimetal-Layered In-Stent Restenosis

ObjectivesThis study aimed to investigate the clinical outcomes of patients presenting with recurrent drug-eluting stent (DES) in-stent restenosis (ISR) treated with a second-generation DES or with a drug-coated balloon (DCB).BackgroundTo date, there are no reports of DCB treatment and limited data with regard to the efficacy of further DES implantation for recurrent ISR.MethodsBetween January 2008 and December 2013, 171 lesions were assessed for eligibility (82 lesions in the second-generation DES group and 89 lesions in the DCB group).ResultsAcute gain was greater in the second-generation DES group (second-generation DES, 2.09 ± 0.53 mm vs. DCBs, 1.60 ± 0.62 mm, p < 0.001). The rates of major adverse cardiac events were comparable (at 1 year, DES 14.0% vs. DCBs 12.3%; at 2 years, DES 28.8% vs. DCBs 43.5%, p = 0.21). Major adverse cardiac event rates were mainly driven by target lesion revascularization (at 1 year, DES 12.5% vs. DCBs 10.9%; at 2 years, DES 27.7% vs. DCBs 38.3%; p = 0.40). Definite scaffold thrombosis occurred in 2 patients (1 patient in each group). Multivariable analysis revealed ISR recurrence within 1 year (hazard ratio: 2.43, 95% confidence interval: 1.14 to 5.18, p = 0.02) and lesion length (per 10-mm increase) (hazard ratio: 1.15, 95% confidence interval: 1.00 to 1.32, p = 0.049) to be independent predictors of TLR.ConclusionsThe results after both treatments were equivalent. ISR recurrence within 1 year of the first reintervention and lesion length were independent predictors of future target lesion revascularization. Larger studies are required to confirm the late (>1 year) differences with regard to clinical outcomes.     

Acute Thrombogenicity of a Durable Polymer Everolimus-Eluting Stent Relative to Contemporary Drug-Eluting Stents With Biodegradable Polymer Coatings Assessed Ex Vivo in a Swine Shunt Model

ObjectivesThis study sought to evaluate whether the permanent fluoropolymer-coated Xience Xpedition everolimus-eluting stent (Xience-EES) exhibits lower acute thrombogenicity compared with contemporary drug-eluting stents (DES) with biodegradable polymer coatings in an acute swine shunt model.BackgroundPrevious pre-clinical and clinical experience suggests that several factors may influence the predisposition for acute thrombus formation of polymer-coated DES, including stent design and the polymer coating technology. It remains unclear whether relevant differences exist with respect to acute thrombogenicity, particularly between current commercial stent designs using permanent polymers and those using biodegradable polymers.MethodsAn ex vivo carotid to jugular arteriovenous porcine shunt model involving a test circuit of 3 in-line stents, was used to test acute thrombogenicity, where Xience-EES (n = 24) was compared with 4 CE-marked DES with biodegradable polymer coatings (BioMatrix Flex, Synergy, Nobori, and Orsiro [n = 6 each]). After 1 h of circulation, platelet aggregation in whole mount stents was evaluated by confocal microscopy with immunofluorescent staining against dual platelet markers (CD61/CD42b) along with scanning electron microscopy.ResultsXience-EES showed the least percentage of thrombus-occupied area as compared with the biodegradable polymer-coated DES, with a significant difference compared with BioMatrix Flex and Synergy (mean differences: [BioMatrix Flex: 15.54, 95% confidence interval [CI]: 11.34 to 19.75, p < 0.001; Synergy: 8.64, 95% CI: 4.43 to 12.84, p < 0.001; Nobori: 4.22, 95% CI: -0.06 to 8.49, p = 0.055; Orsiro: 2.95, 95% CI: -1.26 to 7.15, p = 0.286). The number of cell nuclei on strut surfaces was also the least in Xience-EES, with a significant difference relative to BioMatrix Flex, Nobori, and Orsiro (mean ratios: BioMatrix Flex: 4.73, 95% CI: 2.46 to 9.08, p < 0.001; Synergy: 1.44, 95% CI: 0.75 to 2.76, p = 0.51; Nobori: 5.97, 95% CI: 3.11 to 11.44, p < 0.001; Orsiro: 5.16, 95% CI: 2.69 to 9.91, p < 0.001).ConclusionsXience-EES’s overall design confers acute thromboresistance relative to contemporary DES with biodegradable coatings, with less platelet aggregation versus BioMatrix Flex and Synergy, and less inflammatory cell attachment versus BioMatrix Flex, Nobori, and Orsiro, in an ex vivo swine shunt model, which lends support to reported clinical findings of lower early stent thrombosis.     

Randomized Comparison of FFR-Guided and Angiography-Guided Provisional Stenting of True Coronary Bifurcation Lesions: The DKCRUSH-VI Trial (Double Kissing Crush Versus Provisional Stenting Technique for Treatment of Coronary Bifurcation Lesions VI)

ObjectivesThis study sought to compare the outcomes of fractional flow reserve (FFR)–guided and angiography (Angio)–guided provisional side-branch (SB) stenting for true coronary bifurcation lesions.BackgroundAngio-guided provisional SB stenting after stenting of the main vessel provides favorable outcomes for the majority of coronary bifurcation lesions. Whether an FFR-guided provisional stenting approach is superior has not been studied.MethodsA total of 320 patients with single Medina 1,1,1 and 0,1,1 coronary bifurcation lesions undergoing stenting with a provisional SB approach were randomly assigned 1:1 to Angio-guided and FFR-guided groups. SB stenting was performed for Thrombolysis In Myocardial Infarction flow grade <3, ostial SB stenosis >70%, or greater than type A dissection after main vessel stenting in the Angio-guided group and for SB-FFR <0.80 in the FFR-guided group. The primary endpoint was the 1-year composite rate of major adverse cardiac events (cardiac death, myocardial infarction, and clinically driven target vessel revascularization).ResultsComparing the Angio-guided and FFR-guided groups, treatment of the SB (balloon or stenting) was performed in 63.1% and 56.3% of lesions respectively (p = 0.07); stenting of the SB was attempted in 38.1% and 25.9%, respectively (p = 0.01); and, when attempted, stenting was successful in 83.6% and 73.3% of SBs, respectively (p = 0.01). The 1-year composite major adverse cardiac event rate was 18.1% in both groups (hazard ratio: 0.91, 95% confidence interval: 0.48 to 1.88; p = 1.00). The 1-year target vessel revascularization and stent thrombosis rates were 6.9% and 5.6% (p = 0.82) and 1.3% and 0.6% (p = 0.56) in the Angio-guided and FFR-guided groups, respectively.ConclusionsIn this multicenter, randomized trial, angiographic and FFR guidance of provisional SB stenting of true coronary bifurcation lesions provided similar 1-year clinical outcomes. (Randomized Study on DK Crush Technique Versus Provisional Stenting Technique for Coronary Artery Bifurcation Lesions; ChiCTR-TRC-07000015)     

In-Stent Yellow Plaque at 1 Year After Implantation Is Associated With Future Event of Very Late Stent Failure: The DESNOTE Study (Detect the Event of Very late Stent Failure From the Drug-Eluting Stent Not Well Covered by Neointima Determined by Angioscopy)

ObjectivesThis study examined whether coronary angioscopy-verified in-stent yellow plaque at 1 year after drug-eluting stent (DES) implantation is associated with future event of very late stent failure (VLSF).BackgroundAtherosclerosis detected as yellow plaque by angioscopy has been associated with future events of acute coronary syndrome. Development of in-stent neoatherosclerosis is a probable mechanism of VLSF.MethodsThis study included 360 consecutive patients who received successful angioscopic examination at 1 year after implantation of a DES. They were clinically followed up for VLSF defined as cardiac death, acute myocardial infarction or unstable angina, or need for revascularization associated with the stent site.ResultsThe follow-up interval was 1,558 ± 890 days (4.3 ± 2.4 years). The incidence of VLSF was significantly higher in the patients with yellow plaque than in those without (8.1% vs. 1.6%; log rank p = 0.02). Multivariable analysis revealed the presence of yellow plaque (hazard ratio [HR]: 5.38; p = 0.02) and absence of statin therapy (HR: 3.25; p = 0.02) as risks of VLSF.ConclusionsIn-stent atherosclerosis evaluated by yellow plaque at 1 year after the implantation of DES and the absence of statin therapy were risks of VLSF. The underlying mechanism of VLSF appeared to be the progression of atherosclerosis as demonstrated by the yellow plaque.     

Randomized Comparison of Everolimus-Eluting Stents and Sirolimus-Eluting Stents in Patients With ST Elevation Myocardial Infarction: RACES-MI Trial

ObjectivesThe aim of the current study was to compare everolimus-eluting stents (EES) with sirolimus-eluting stents (SES) in patients undergoing primary angioplasty.BackgroundDrug-eluting stents may offer benefits in terms of repeat revascularization. However, as shown for first-generation drug-eluting stents, they may be counterbalanced by a potential higher risk of stent thrombosis, especially among patients with ST-segment elevation myocardial infarction (STEMI). No data have been reported so far on the long-term benefits and safety of the new generation of drug-eluting stents in STEMI.MethodsConsecutive STEMI patients admitted within 12 h of symptom onset and undergoing primary angioplasty and stent implantation at a tertiary center with 24-h primary percutaneous coronary intervention capability were randomly assigned to SES or EES. The primary endpoint was a major adverse cardiac event at 3-year follow-up. The secondary endpoints were death, reinfarction, definite or probable stent thrombosis, and target vessel revascularization at 3-year follow-up. No patient was lost to follow-up.ResultsFrom April 2007 to May 2009, 500 patients with STEMI were randomized to EES (n = 250) or SES (n = 250). No difference was observed in terms of baseline demographic and clinical characteristics between the groups. No difference was observed between the groups in terms of number of implanted stents per patient or total stent length. However, a larger reference diameter was observed with SES (3.35 ± 0.51 mm vs. 3.25 ± 0.51 mm, p = 0.001), whereas patients randomized to EES more often received glycoprotein IIb/IIIa inhibitors (54.4% vs. 42.4%, p = 0.006). Follow-up data were available in all patients (1,095 ± 159 days). No significant difference was observed between EES and SES in major adverse cardiac events (16% vs. 20.8%, adjusted hazard ratio [HR]: 0.75 [95% confidence interval (CI): 0.5 to 1.13], p = 0.17), cardiac death (4.4% vs. 5.6%, adjusted HR: 0.77 [95% CI: 0.35 to 1.71], p = 0.53), recurrent MI (6.4% vs. 10%, adjusted HR: 0.62 [95% CI: 0.33 to 1.16], p = 0.13), and target vessel revascularization (4.8% vs. 4.8%, adjusted HR: 1.00 [95% CI: 0.45 to 2.32], p = 0.99). However, EES was associated with a significant reduction in stent thrombosis (1.6% vs. 5.2%, adjusted HR: 0.3 [95% CI: 0.1 to 0.92], p = 0.035).ConclusionsThis study shows that among STEMI patients undergoing primary angioplasty, EES has similar efficacy as SES, but is associated with a significant reduction in stent thrombosis. (Randomized Comparison of Everolimus Eluting Stents and Sirolimus Eluting Stent in Patients With ST Elevation Myocardial Infarction [RACES-MI]; NCT01684982)     

Incidence and Clinical Impact of Stent Fracture After PROMUS Element Platinum Chromium Everolimus-Eluting Stent Implantation

ObjectivesThis study sought to assess the incidence and clinical impact of stent fracture (SF) after the PROMUS Element platinum-chromium everolimus-eluting stent (PtCr-EES).BackgroundSF remains an unresolved, clinically relevant issue, even in the newer-generation drug-eluting stent era.MethodsFrom March 2012 to August 2013, 816 patients with 1,094 lesions were treated only with PtCr-EES and 700 patients (85.7%) with 898 lesions undergoing follow-up angiography within 9 months after the index procedure were analyzed. SF was defined as complete or partial separation of the stent, as assessed by plain fluoroscopy, intravascular ultrasound, or optical coherence tomography during the follow-up. We assessed the rate of SF and the cumulative incidence of clinically driven target lesion revascularization and definite stent thrombosis within 9 months after the index procedure.ResultsSF was observed in 16 of 898 lesions (1.7%) and 16 of 700 patients (2.2%). Lesions with in-stent restenosis at baseline (odds ratio [OR]: 14.2, 95% confidence intervals [CI]: 5.09 to 39.7; p < 0.001) or hinge motion (OR: 4.31, 95% CI: 1.12 to 16.5; p = 0.03), and total stent length (per 10-mm increase; OR: 1.32, 95% CI: 1.12 to 1.57; p = 0.001) were predictors of SF. Cumulative incidence of clinically driven target lesion revascularization within 9-months was numerically higher in the SF group than that in the non-SF group (18.7% vs. 2.3%). Cumulative incidence of definite stent thrombosis within 9 months after the index procedure was similar between the SF and non-SF groups (0.0% vs. 0.23%).ConclusionsSF after PtCr-EES occurs in 1.7% of lesions and appears to be associated with clinically driven target lesion revascularization.     

Clinical Events and Patient-Reported Chest Pain in All-Comers Treated With Resolute Integrity and Promus Element Stents: 2-Year Follow-Up of the DUTCH PEERS (DUrable Polymer-Based STent CHallenge of Promus ElemEnt Versus ReSolute Integrity) Randomized Trial (TWENTE II)

ObjectivesThis study assessed clinical events and patient-reported chest pain 2 years after treatment of all-comers with Resolute Integrity zotarolimus-eluting stents (Medtronic Vascular, Santa Rosa, California) and Promus Element everolimus-eluting stents (Boston Scientific, Natick, Massachusetts).BackgroundFor both drug-eluting stents (DES), no all-comer outcome data from >12 months of follow-up have been published. Although there is increasing interest in patient-reported chest pain following stenting, data with novel DES are scarce.MethodsThe DUTCH PEERS multicenter trial (TWENTE II) (DUrable Polymer-Based STent CHallenge of Promus ElemEnt Versus ReSolute Integrity) Randomized Trial [TWENTE II]) randomized 1,811 all-comer patients to treatment with 1 type of DES. Monitoring and event adjudication were performed by independent contract research organizations.ResultsThe 2-year follow-up of 1,810 patients (99.9%) was available. The primary composite endpoint target vessel failure occurred in 8.6% and 7.8% of patients treated with zotarolimus- and everolimus-eluting stents, respectively (p = 0.55). Rates of components of target vessel failure were: cardiac death (2.4% vs. 1.9%, p = 0.42); target vessel–related myocardial infarction (2.4% vs. 1.8%, p = 0.33); clinically-indicated target vessel revascularization (4.6% vs. 4.9%, p = 0.83). At 1- and 2-year follow-up, >80% of patients were free from chest pain (no between-stent difference). In addition, >87% of patients were either free from chest pain or experienced pain only at maximal physical exertion, but not during normal daily activities. Patients with chest pain after 12 months at no more than moderate physical effort had a higher risk of target vessel revascularization during the following year (hazard ratio: 1.89 [95% confidence interval: 1.05 to 3.39], p = 0.03).ConclusionsDuring the second year of follow-up, the incidence of adverse clinical endpoints remained similar and low for both DES. The vast majority of patients were free from chest pain.     

Randomized Comparisons Between Different Stenting Approaches for Bifurcation Coronary Lesions With or Without Side Branch Stenosis

ObjectivesThis study sought to evaluate the optimal percutaneous coronary intervention techniques using drug-eluting stents for bifurcation coronary lesions.BackgroundThe optimal bifurcation stenting technique needs to be evaluated.MethodsThe trial included 2 randomization studies separated by the presence of side branch (SB) stenosis for patients having non–left main bifurcation lesions. For 306 patients without SB stenosis, the routine final kissing balloon or leave-alone approaches were compared. Another randomization study compared the crush or single-stent approaches for 419 patients with SB stenosis.ResultsBetween the routine final kissing balloon and leave-alone groups for nondiseased SB lesions, angiographic restenosis occurred in 17.9% versus 9.3% (p = 0.064), comprising 15.1% versus 3.7% for the main branch (p = 0.004) and 2.8% versus 5.6% for the SB (p = 0.50) from 214 patients (69.9%) receiving 8-month angiographic follow-up. Incidence of major adverse cardiac events including death, myocardial infarction, or target vessel revascularization over 1 year was 14.0% versus 11.6% between the routine final kissing balloon and leave-alone groups (p = 0.57). In another randomization study for diseased SB lesions, 28.2% in the single-stent group received SB stents. From 300 patients (71.6%) receiving angiographic follow-up, between the crush and single-stent groups, angiographic restenosis rate was 8.4% versus 11.0% (p = 0.44), comprising 5.2% versus 4.8% for the main branch (p = 0.90) and 3.9% versus 8.3% for the SB (p = 0.12). One-year major adverse cardiac events rate between the crush and single-stent groups was 17.9% versus 18.5% (p = 0.84).ConclusionsAngiographic and clinical outcomes were excellent after percutaneous coronary intervention using drug-eluting stents with any stent technique for non–left main bifurcation lesions once the procedure was performed successfully.     

Comparative Effectiveness and Safety of New-Generation Versus Early-Generation Drug-Eluting Stents According to Complexity of Coronary Artery Disease: A Patient-Level Pooled Analysis of 6,081 Patients

ObjectivesThe purpose of this study was to compare the 2-year safety and effectiveness of new- versus early-generation drug-eluting stents (DES) according to the severity of coronary artery disease (CAD) as assessed by the SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score.BackgroundNew-generation DES are considered the standard-of-care in patients with CAD undergoing percutaneous coronary intervention. However, there are few data investigating the effects of new- over early-generation DES according to the anatomic complexity of CAD.MethodsPatient-level data from 4 contemporary, all-comers trials were pooled. The primary device-oriented clinical endpoint was the composite of cardiac death, myocardial infarction, or ischemia-driven target-lesion revascularization (TLR). The principal effectiveness and safety endpoints were TLR and definite stent thrombosis (ST), respectively. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated at 2 years for overall comparisons, as well as stratified for patients with lower (SYNTAX score ≤11) and higher complexity (SYNTAX score >11).ResultsA total of 6,081 patients were included in the study. New-generation DES (n = 4,554) compared with early-generation DES (n = 1,527) reduced the primary endpoint (HR: 0.75 [95% CI: 0.63 to 0.89]; p = 0.001) without interaction (p = 0.219) between patients with lower (HR: 0.86 [95% CI: 0.64 to 1.16]; p = 0.322) versus higher CAD complexity (HR: 0.68 [95% CI: 0.54 to 0.85]; p = 0.001). In patients with SYNTAX score >11, new-generation DES significantly reduced TLR (HR: 0.36 [95% CI: 0.26 to 0.51]; p < 0.001) and definite ST (HR: 0.28 [95% CI: 0.15 to 0.55]; p < 0.001) to a greater extent than in the low-complexity group (TLR p_int = 0.059; ST p_int = 0.013). New-generation DES decreased the risk of cardiac mortality in patients with SYNTAX score >11 (HR: 0.45 [95% CI: 0.27 to 0.76]; p = 0.003) but not in patients with SYNTAX score ≤11 (p_int = 0.042).ConclusionsNew-generation DES improve clinical outcomes compared with early-generation DES, with a greater safety and effectiveness in patients with SYNTAX score >11.     

Final 5-Year Follow-Up of a Randomized Controlled Trial of Everolimus- and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice: The COMPARE Trial (A Trial of Everolimus-Eluting Stents and Paclitaxel Stents for Coronary Revascularization in Daily Practice)

ObjectivesThis study sought to report the 5-year outcomes of everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES) in an all-comers population undergoing percutaneous coronary intervention (PCI).BackgroundThe medium-term 1 and 2-year results of the prospective randomized COMPARE trial (A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice) showed superior clinical outcomes with EES compared with PES in an all-comers PCI population. Whether this benefit is sustained over longer-term follow-up is unknown. Furthermore, systematic long-term follow-up data on these metallic drug eluting stents with durable polymers are scarce.MethodsWe randomly assigned 1,800 patients undergoing PCI to EES or PES. The pre-specified composite primary endpoint was death, myocardial infarction (MI), or target vessel revascularization (TVR).ResultsFollow-up at 5 years was completed in 1,791 (99.5%) patients. Treatment with EES compared with PES led to a relative risk reduction of the primary endpoint by 27% (18.4% vs. 25.1%, p = 0.0005), driven by lower rates of MI (7.0% vs. 11.5%, p = 0.001) and TVR (7.4% vs. 11.4%, p = 0.003), but not with mortality (9.0% vs. 10.3%, relative risk 0.88, p = 0.36). Moreover, patients treated with EES compared with PES had lower rates of definite/probable stent thrombosis at 5 years (3.1% vs. 5.9%, p = 0.005). The hazard curves for TVR, MI, and stent thrombosis diverge over the first 3 years and, subsequently, progress in parallel.ConclusionsThe early- and medium-term superiority of EES over PES measured both by safety and efficacy endpoints is sustained at 5 years in this all-comer population. (A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice [COMPARE]; NCT01016041)     

Long-Term Outcomes After Treatment With a Paclitaxel-Coated Balloon Versus Balloon Angioplasty: Insights From the PEPCAD-DES Study (Treatment of Drug-eluting Stent [DES] In-Stent Restenosis With SeQuent Please Paclitaxel-Coated Percutaneous Transluminal Coronary Angioplasty [PTCA] Catheter)

ObjectivesThe intention this PEPCAD-DES (Treatment of Drug-eluting Stent [DES] In-Stent Restenosis With SeQuent Please Paclitaxel Eluting Percutaneous Transluminal Coronary Angioplasty [PTCA] Catheter) study update was to demonstrate the safety and efficacy of paclitaxel-coated balloon (PCB) angioplasty in patients with DES-ISR at 3 years.BackgroundIn the PEPCAD-DES trial late lumen loss and the need for repeat target lesion revascularization (TLR) was significantly reduced with PCB angioplasty compared with plain old balloon angioplasty (POBA) in patients with drug-eluting stent in-stent restenosis (DES-ISR) at 6 months. We evaluated whether the clinical benefit of reduced TLR and major adverse cardiac events (MACE) was maintained up to 3 years.MethodsA total of 110 patients with DES-ISR in native coronary arteries with reference diameters ranging from 2.5 mm to 3.5 mm and lesion lengths ≤22 mm were randomized to treatment with either PCB or POBA in a multicenter, randomized, single-blind clinical study. With a 2:1 randomization, 72 patients were randomized to the PCB group and 38 patients to the POBA group. At baseline, there were lesions with at least 2 stent layers in PCB (52.8%, 38 of 72) and POBA (55.3%, 21 of 38) patients.ResultsAt 36 months, the TLR rates were significantly lower in the PCB group compared with the POBA control group (19.4% vs. 36.8%; p = 0.046). Multiple TLRs in individual patients were more frequent in the POBA group compared with the PCB group (more than 1 TLR: POBA, 13.2%; PCB, 1.4%; p = 0.021). The 36-month MACE rate was significantly reduced in the PCB group compared with the POBA group (20.8% vs. 52.6%, log-rank p = 0.001).ConclusionsPCB angioplasty was superior to POBA for the treatment of DES-ISR patients in terms of MACE and TLR for up to 36 months. There was no late catch-up phenomenon. (Treatment of Drug-eluting Stent [DES] In-Stent Restenosis With SeQuent® Please Paclitaxel Eluting Percutaneous Transluminal Coronary Angioplasty [PTCA] Catheter [PEPCAD-DES]; NCT00998439)     

Comparison of Neoatherosclerosis and Neovascularization Between Patients With and Without Diabetes: An Optical Coherence Tomography Study

ObjectivesThis study aimed to investigate the characteristics of neoatherosclerosis (NA) in patients with diabetes mellitus (DM) after drug-eluting stent (DES) implantation using optical coherence tomography.BackgroundNA is an important substrate for stent failure. In vivo NA characteristics in DM patients have not been investigated.MethodsA total of 397 patients with 452 DES who underwent follow-up optical coherence tomography examination after DES implantation were enrolled. Characteristics of NA were compared between DM and non-DM patients. Neovascularization was defined as signal-poor holes or tubular structures with a diameter of 50 to 300 μm.ResultsA total of 123 DES with NA lesions in 115 patients were identified. The incidence of NA was similar between DM and non-DM patients (29.6% vs. 28.6%; p = 0.825). Compared with the non-DM group, neovascularization was more frequently observed in the DM group (55.1% vs. 32.4%; p = 0.012). The multivariate logistic model demonstrated that DM (odds ratio: 3.00; 95% confidence interval: 1.31 to 6.81; p = 0.009) and follow-up duration (odds ratio: 1.03; 95% confidence interval: 1.02 to 1.05; p < 0.001) were the independent predictors for neovascularization in NA lesions. DM patients with glycated hemoglobin ≥7.0% had a higher prevalence of thin-cap fibroatheroma compared with those with glycated hemoglobin <7.0% (40.0% vs. 8.3%; p = 0.01).ConclusionsThe incidence of NA was similar between patients with and without DM. Neovascularization in NA lesions was more frequent in those with DM. Poorly controlled DM patients had a higher incidence of thin-cap fibroatheroma, compared with those with well-controlled DM.     

Correlates and Outcomes of Late and Very Late Drug-Eluting Stent Thrombosis: Results From DESERT (International Drug-Eluting Stent Event Registry of Thrombosis)

ObjectivesThe aim of this study was to identify clinical, procedural, and angiographic correlates of late/very late drug-eluting stent (DES) thrombosis as well as to determine the clinical outcomes of these events.BackgroundLate/very late DES thromboses are a poorly studied phenomenon, partly due to the relative infrequency of these events, even in large cohort studies.MethodsIn the DESERT (International Drug-Eluting Stent Event Registry of Thrombosis), a retrospective, case-control registry, 492 cases of late/very late definite DES thrombosis from 21 international sites were matched in a 1:1 fashion with controls without stent thrombosis (ST). Controls were matched according to 2 criteria: same enrolling institution and date of initial DES implantation. Baseline and procedural variables were collected, and clinical follow-up was obtained for patients with ST as long as 1 year after the event. Offline quantitative coronary angiography was performed for a subset of 378 case-control pairs.ResultsThe majority of ST events occurred after 1 year (75%) and continued to occur for as long as 7.3 years. The clinical presentation of late/very late ST events was mainly myocardial infarction (66.7% ST-segment elevation myocardial infarction and 22.0% non–ST-segment elevation myocardial infarction); in-hospital mortality was 3.8%. A minority of patients (30%) with ST were receiving dual-antiplatelet therapy at the time of the event. Independent clinical correlates of late/very late ST were younger age, African-American race, current smoking, multivessel disease, longer stented length, overlapping stents, and percutaneous coronary intervention of vein graft lesions. Independent angiographic correlates for late/very late ST were lesions within the left anterior descending artery or a bypass graft, thrombus, and a larger residual diameter stenosis after the initial DES implantation. Despite the large sample of ST cases, all identified correlates of late/very late ST had weak associations with subsequent ST (all odds ratios <2.5).ConclusionsDespite a large sample of ST cases and use of limited matching to maximize the identification of predictive factors associated with late/very late ST, the variables associated with the development of late/very late ST were only weakly predictive of subsequent events. Additionally, a relatively low observed mortality rate of ST in this series may reflect a different pathophysiology of these late/very late events compared with acute/subacute ST. (Drug Eluting Stent Registry of Thrombosis [DESERT]; NCT00812552).     

Safety and Effectiveness of Everolimus-Eluting Stents in Chronic Total Coronary Occlusion Revascularization: Results From the EXPERT CTO Multicenter Trial (Evaluation of the XIENCE Coronary Stent,Performance, and Technique in Chronic Total Occlusions)

ObjectivesThis study sought to evaluate procedural and clinical outcomes among patients undergoing chronic total occlusion (CTO) percutaneous coronary intervention (PCI) using contemporary methods and everolimus-eluting stents (EES).BackgroundLimited studies have detailed the procedural and late-term safety and efficacy of CTO revascularization among multiple centers applying modern techniques and with newer-generation drug-eluting stents.MethodsAmong 20 centers, 250 consecutive patients were enrolled for attempted CTO PCI. Procedural and in-hospital clinical outcomes were examined in addition to the 1-year primary endpoint of death, myocardial infarction, and target lesion revascularization (major adverse cardiac events [MACE]).ResultsDemographic, lesion, and procedural characteristics included prior bypass surgery: 9.9%; diabetes: 40.1%; lesion length: 36.1 ± 18.5 mm; and stent length: 51.7 ± 27.2 mm. Procedural success, defined as guidewire recanalization with no in-hospital MACE, was 96.4%. Success with antegrade-only methods was 97.9% and 86.2% by retrograde/combined methods, respectively. Compared with a pre-specified performance goal derived from 6 prior CTO drug-eluting stent trials (1-year MACE: 24.4%), treatment with EES was associated with significantly lower composite adverse events for both intent-to-treat (18.5%, 1-sided upper confidence interval: 23.4%, p = 0.025) and per-protocol populations (8.2%, 1-sided upper confidence interval: 12.3%, p < 0.0001). Target lesion revascularization at 1 year was 6.3%. Dual antiplatelet therapy adherence was 53.9% at 1 year, yet subacute definite stent thrombosis occurred in only 2 patients (0.9%), and late probable stent thrombosis occurred in 1 patient (0.5%).ConclusionsIn a multicenter registration trial representing contemporary technique and EES, favorable procedural success and late-term clinical outcomes support CTO PCI in a patient population with high lesion complexity. (EXPERT CTO: Evaluation of the XIENCE PRIME LL and XIENCE Nano Everolimus Eluting Coronary Stent Coronary Stents, Performance, and Technique in Chronic Total Occlusions; NCT01435031)     

Outcomes With Cangrelor Versus Clopidogrel on a Background of Bivalirudin: Insights From the CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI])

ObjectivesThe aim of this study was to examine the efficacy and bleeding outcomes of cangrelor in patients in the CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI]) who underwent percutaneous coronary intervention with bivalirudin.BackgroundCangrelor is a potent intravenous P2Y₁₂ inhibitor with rapid onset and offset. In the CHAMPION PHOENIX, cangrelor compared with clopidogrel significantly reduced 48-h ischemic events including stent thrombosis, without increasing major bleeding. Bivalirudin has demonstrated ischemic outcomes similar to those with heparin plus glycoprotein IIb/IIIa inhibition, with reduced bleeding but increased early stent thrombosis.MethodsIn the modified intent-to-treat population, 2,059 patients (18.8%) received bivalirudin, with 1,014 patients in the cangrelor treatment arm and 1,045 in the clopidogrel treatment arm.ResultsAt 48 h, the primary endpoint of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis was lower with cangrelor versus clopidogrel (48 [4.7%] vs. 70 [6.7%]; odds ratio [OR]: 0.68, p = 0.047). Death was similar in both arms (2 [0.2%] vs. 2 [0.2%]). Myocardial infarction was reduced by cangrelor (37 [3.6%] vs. 59 [5.6%]; OR: 0.63, p = 0.03), as was death/myocardial infarction (39 [3.8%] vs. 61 [5.8%]; OR: 0.65, p = 0.04). Cangrelor was associated with a nonsignificant trend toward less stent thrombosis (7 [0.7%] vs. 15 [1.4%]; OR: 0.48, p = 0.10), which was evident within 2 h after percutaneous coronary intervention (p = 0.057). GUSTO (Global Use of Strategies to Open Occluded Arteries) severe bleeding was similar in both arms (2 of 1,021 [0.2%] vs. 2 of 1,055 [0.2%]) as were other bleeding definitions and transfusions. Efficacy and safety results were consistent in patients with stable angina, non–ST-segment elevation acute coronary syndrome, and ST-segment elevation myocardial infarction (p for interaction: 0.62 and 0.29).ConclusionsCangrelor may offer an attractive benefit risk profile when used in combination with bivalirudin.     

Paclitaxel-Coated Balloon Angioplasty Versus Drug-Eluting Stenting for the Treatment of Infrapopliteal Long-Segment Arterial Occlusive Disease: The IDEAS Randomized Controlled Trial

ObjectivesThis study sought to report the results of a prospective randomized controlled trial comparing paclitaxel-coated balloons (PCB) versus drug-eluting stents (DES) in long infrapopliteal lesions.BackgroundDES have an established role in the treatment of short infrapopliteal lesions, whereas there is increasing evidence for the use of PCB in longer below-the-knee lesions.MethodsInclusion criteria were patients with Rutherford classes 3 to 6 and angiographically documented infrapopliteal disease with a minimum lesion length of 70 mm. The primary endpoint was target lesion restenosis >50% assessed by digital angiography at 6 months. Secondary endpoints included immediate post-procedure stenosis and target lesion revascularization.ResultsFifty patients were randomized to undergo infrapopliteal PCB angioplasty (25 arteries in 25 limbs; PCB group) or primary DES placement (30 arteries in 27 limbs; DES group). Immediate residual post-procedure stenosis was significantly lower in DES (9.6 ± 2.2% vs. 24.8 ± 3.5% in PCB; p < 0.0001). At 6 months, 5 patients died (2 in PCB vs. 3 in DES; p = 1.00) and 3 suffered a major amputation (1 in PCB vs. 2 in DES; p = 1.00). In total, 44 angiograms were evaluable with quantitative vessel analysis. Binary (>50%) angiographic restenosis rate was significantly lower in DES (7 of 25 [28%] vs. 11 of 19 [57.9%] in PCB; p = 0.0457). There were no significant differences with regard to target lesion revascularization (2 of 26 [7.7%] in DES vs. 3 of 22 [13.6%] in PCB; p = 0.65). Positive vessel wall remodeling was observed in 3 cases in the PCB arm (3 of 19 [(15.8%)] vs. 0 of 19 [0%] in DES; p = 0.07).ConclusionsCompared with PCB in long infrapopliteal lesions, DES are related with significantly lower residual immediate post-procedure stenosis and have shown significantly reduced vessel restenosis at 6 months. PCB may produce positive vessel remodeling. (Infrapopliteal Drug-Eluting Angioplasty Versus Stenting [IDEAS-I]; NCT01517997)