Long-Term Efficacy and Safety of Paclitaxel-Eluting Balloon for the Treatment of Drug-Eluting Stent Restenosis: 3-Year Results of a Randomized Controlled Trial

ObjectivesThis study sought to investigate the long-term comparative efficacy and safety of paclitaxel-eluting balloon (PEB), paclitaxel-eluting stent (PES), or balloon angioplasty (BA) for the treatment of drug-eluting stent restenosis.BackgroundThe optimal treatment of drug-eluting stent restenosis remains unknown. Although PEB has shown encouraging results, the long-term clinical efficacy and safety of PEB remains poorly defined.MethodsA total of 402 patients with clinically significant restenosis in limus-eluting stents were randomly assigned to receive PEB (n = 137), PES (n = 131), or BA (n = 134). For this analysis, PEB versus PES and PEB versus BA were compared. The primary efficacy and safety endpoints were target lesion revascularization and the composite of death or myocardial infarction.ResultsAt a median follow-up of 3 years, the risk of target lesion revascularization was comparable with PEB versus PES (hazard ratio [HR]: 1.46, 95% confidence interval [CI]: 0.91 to 2.33; p = 0.11) and lower with PEB versus BA (HR: 0.51, 95% CI: 0.34 to 0.74; p < 0.001). The risk of death/myocardial infarction tended to be lower with PEB versus PES (HR: 0.55, 95% CI: 0.28 to 1.07; p = 0.08), due to a lower risk of death (HR: 0.38, 95% CI: 0.17 to 0.87; p = 0.02). The risk of death/myocardial infarction was similar with PEB versus BA (HR: 0.96, 95% CI: 0.46 to 2.0; p = 0.91).ConclusionsAt 3 years, the use of PEB as compared with PES to treat patients with limus-eluting stent restenosis has similar efficacy and safety. PEB remains superior to BA. The sustained efficacy without trade-off in safety supports the role of PEB as treatment option for patients with drug-eluting stent restenosis. (Intracoronary Stenting and Angiographic Results: Drug Eluting Stent In-Stent Restenosis: 3 Treatment Approaches [ISAR-DESIRE 3]; NCT00987324)     

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)     

Three-Year Outcomes After Revascularization With Everolimus- and Sirolimus-Eluting Stents From the SORT OUT IV Trial

ObjectivesThe study sought to compare the risk of late outcome with a focus on very late definite stent thrombosis of the everolimus-eluting stent (EES) with that of the sirolimus-eluting stent (SES) at 3-year follow-up.BackgroundIn the SORT OUT IV (SORT OUT IV Trial), comparing the EES with the SES in patients with coronary artery disease, the EES was noninferior to the SES at 9 months. The SORT OUT IV trial provides long-term head-to-head randomized comparison of the EES with the SES.MethodsWe prospectively randomized 2,774 patients in the SORT OUT IV trial. Follow-up through 3 years was complete in 2,771 patients (99.9%). The 3-year pre-specified endpoints were composites of safety and efficacy (major adverse cardiac events [MACE]: cardiac death, myocardial infarction, target vessel revascularization, and definite stent thrombosis).ResultsAt 3 years, the composite endpoint MACE occurred in 9.8% of the EES group and in 11.1% of the SES group (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.70 to 1.12). Overall rate of definite stent thrombosis was lower in the EES group (0.2% vs. 1.4%; HR: 0.15, 95% CI: 0.04 to 0.50), which was largely attributable to a lower risk of very late definite stent thrombosis: 0.1% versus 0.8% (HR: 0.09, 95% CI: 0.01 to 0.70).ConclusionsAt 3-year follow-up, the MACE rate did not differ significantly between EES- and SES-treated patients. A significant reduction of overall and very late definite stent thrombosis was found in the EES group. (The SORT OUT IV TRIAL [SORT OUT IV]; NCT00552877).     

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.     

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.     

Long-Term Clinical Outcomes of Final Kissing Ballooning in Coronary Bifurcation Lesions Treated With the 1-Stent Technique: Results From the COBIS II Registry (Korean Coronary Bifurcation Stenting Registry)

ObjectivesThis study investigated the impact of final kissing ballooning (FKB) after main vessel (MV) stenting on outcomes in patients with coronary bifurcation lesions after application of the 1-stent technique.BackgroundAlthough FKB has been established as the standard method for bifurcation lesions treated with a 2-stent strategy, its efficacy in a 1-stent approach is highly controversial.MethodsThis study enrolled 1,901 patients with a bifurcation lesion with a side branch diameter ≥2.3 mm, treated solely with the 1-stent technique using a drug-eluting stent from 18 centers in Korea between January 1, 2003 and December 31, 2009. The primary outcome was major adverse cardiac events (MACE)—cardiac death, myocardial infarction, or target lesion revascularization. Propensity score-matching analysis was also performed.ResultsFKB was performed in 620 patients and the post minimal lumen diameter of the MV and side branch was larger in the FKB group than in the non-FKB group. During follow-up (median 36 months), the incidence of MACE (adjusted hazard ratio [HR]: 0.68, 95% confidence interval [CI]: 0.46 to 0.99; p = 0.048) was lower in the FKB group than the non-FKB group. After propensity score matching (545 pairs), the FKB group had a lower incidence of MACE (adjusted HR: 0.50, 95% CI: 0.30 to 0.85; p = 0.01), and target lesion revascularization in the MV (adjusted HR: 0.51, 95% CI: 0.28 to 0.93; p = 0.03) and both vessels (adjusted HR: 0.47, 95% CI: 0.25 to 0.90; p = 0.02) than in the non-FKB group.ConclusionsIn coronary bifurcation lesions, we demonstrated that the 1-stent technique with FKB was associated with a favorable long-term clinical outcome, mainly driven by the reduction of target lesion revascularization in the MV or both vessels as a result of an increase in minimal lumen diameter. (Korean Coronary Bifurcation Stenting Registry II [COBIS II]: NCT01642992)     

Acute Kidney Injury in Patients With Chronic Kidney Disease Undergoing Internal Carotid Artery Stent Implantation

ObjectivesThis study sought to investigate acute kidney injury (AKI) following carotid artery stenting (CAS).BackgroundFew data exist on AKI following CAS.MethodsThis study evaluated 126 chronic kidney disease (CKD) patients who underwent CAS. The risk for contrast-induced AKI was defined by the Mehran score. Hemodynamic depression (i.e., periprocedural systolic blood pressure <90 mm Hg or heart rate <60 beats/min), AKI (i.e., an increase of ≥0.3 mg/dl in the serum creatinine concentration at 48 h), and 30-day major adverse events (including death, stroke, and acute myocardial infarction) were assessed.ResultsAKI occurred in 26 patients (21%). Although baseline kidney function and contrast volume were similar in the AKI group and the non-AKI group, the risk score was higher (10 ± 3 vs. 8 ± 3; p = 0.032), and hemodynamic depression (mostly due to hypotension) (65.5% vs. 35%; p = 0.005) was more common in the AKI group. The threshold of hemodynamic depression duration for AKI development was 2.5 min (sensitivity 54%, specificity 82%). Independent predictors of AKI were hemodynamic depression (odds ratio [OR]: 4.01; 95% confidence interval [CI]: 1.07 to 15.03; p = 0.009), risk score (OR: 1.29; 95% CI: 1.03 to 1.60; p = 0.024), and male sex (OR: 6.07; 95% CI: 1.18 to 31.08; p = 0.021). Independent predictors of 30-day major adverse events that occurred more often in the AKI group (19.5% vs. 7%; p = 0.058) were AKI (HR: 4.83; 95% CI: 1.10 to 21.24; p = 0.037) and hemodynamic depression (HR: 5.58; 95% CI: 1.10 to 28.31; p = 0.038).ConclusionsAKI in CKD patients undergoing CAS is mostly due to hemodynamic depression and is associated with a higher 30-day major adverse events rate.     

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).     

Impact of Balloon Post-Dilation on Clinical Outcomes After Transcatheter Aortic Valve Replacement With the Self-Expanding CoreValve Prosthesis

ObjectivesThe aim of this study was to assess the incidence and clinical impact of balloon post-dilation (BPD) after transcatheter aortic valve replacement (TAVR) with the CoreValve prosthesis (Medtronic Inc., Minneapolis, Minnesota).BackgroundBPD is a widely adopted strategy to reduce the degree of paraprosthetic regurgitation in case of transcatheter heart valve underexpansion. However, controversies still remain regarding its real effectiveness and safety.MethodsThe ClinicalService (a nation-based data repository and medical care project) dataset was analyzed. All patients were dichotomized according to the need for BPD during the index procedure.ResultsAmong 1,376 patients, BPD of the transcatheter heart valve was performed in 272 (19.8%). In 37% of cases, it was unsuccessful at reducing the paravalvular regurgitation to mild or less. No case of valve embolization, new intravalvular regurgitation, coronary occlusion, and aortic root injury occurred during BPD. There were no statistically significant differences between the 2 groups in the incidence of in-hospital all-cause and cardiovascular mortality, neurological events, myocardial infarction, bleeding, conversion to open-chest surgery, and the need for a permanent pacemaker. The need for BPD did not emerge as an independent risk factor for all-cause (adjusted hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 0.81 to 2.19, p = 0.264) and cardiovascular (adjusted HR: 1.48, 95% CI: 0.74 to 2.97, p = 0.265) mortality at 1 year after the procedure. In addition, BPD did not predispose to higher odds of neurological events during 12 months after TAVR (HR: 0.92, 95% CI: 0.45 to 1.88, p = 0.815).ConclusionsThis large study showed that BPD after TAVR was safe and not associated with increased rates of cerebrovascular events, mortality, myocardial infarction, and aortic root injury.     

Predictors of Recurrent Events in Patients With Cryptogenic Stroke and Patent Foramen Ovale Within the CLOSURE I (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale) Trial

ObjectivesThis study sought to identify predictors of recurrent ischemic neurologic events within the CLOSURE I (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale) trial.BackgroundThe CLOSURE I trial found that transcatheter patent foramen ovale (PFO) closure using the STARFlex device was not superior to medical therapy in patients with cryptogenic stroke or transient ischemic attack (TIA) and PFO.MethodsThe CLOSURE I trial is a multicenter, randomized trial of transcatheter PFO closure compared with medical therapy in patients who presented with cryptogenic stroke or TIA and had a PFO. We identified clinical predictors of recurrent ischemic stroke or TIA during 2 years of follow-up using Cox proportional hazards regression within the pooled intention-to-treat cohort.ResultsIn 909 patients, the incidence of recurrent events was 5.7% with 25 patients suffering a recurrent stroke and 30 a TIA. Patients who had a recurrent event had higher body mass index (30.2 ± 6.2 vs. 28.3 ± 5.8%; p = 0.03) and more frequently had diabetes (19.2% vs. 7.1%; p = 0.0016), hypertension (46.2% vs. 30.1%; p = 0.015), and ischemic heart disease (3.8% vs. 0.9%; p = 0.05). Diabetes (hazard ratio [HR]: 3.39; 95% confidence interval [CI]: 1.69 to 6.84; p = 0.0007), index TIA (HR vs. stroke: 2.13; 95% CI: 1.20 to 3.80; p = 0.01), and the detection of atrial fibrillation after study enrollment (HR: 4.85; 95% CI: 2.05 to 11.47; p = 0.0003) independently predicted recurrent ischemic neurologic events. Recurrent neurologic events were more frequent in subjects with RoPE (Risk of Paradoxical Embolism) score ≤5 than those with >5 (14.5% vs. 4.2%; p < 0.0001).ConclusionsThese findings suggest an alternative etiology to paradoxical embolism was frequently responsible for recurrent events within the CLOSURE I trial. (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke or TIA Due to the Possible Passage of a Clot of Unknown Origin Through a Patent Foramen Ovale (PFO) [CLOSURE I]; NCT00201461)     

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.     

Safety and Efficacy of Stent Retrievers for the Management of Acute Ischemic Stroke: Comprehensive Review and Meta-Analysis

ObjectivesThis study sought to evaluate the safety and efficacy of stent retriever for the management of acute ischemic stroke.BackgroundStroke is the third leading cause of death and the most common cause of disability in the United States. Early reperfusion has been associated with favorable outcomes. Stent retrievers are novel endovascular devices that provide vessel recanalization via thrombus retrieval mechanical thrombectomy.MethodsThe authors performed a literature search using PubMed, EMBASE, and Cochrane Central Register of Controlled Trials from May 2005 to May 2015. Randomized controlled trails (RCTs) comparing endovascular therapy (ET) with the use of retrievable stents against standard therapy (ST) for the management of acute stroke were included.ResultsFive RCTs (the MR CLEAN, ESCAPE, EXTEND-IA, SWIFT-PRIME, and REVASCAT studies) with 634 patients in the ET group and 653 patients in the ST group met inclusion criteria. The frequency of a low 90-day modified Rankin Score (0 to 2) in the intervention group was 42.6% compared with 26.1% in the control group (odds ratio: 2.43; 95% confidence interval [CI]: 1.9 to 3.09; p < 0.0001). The frequency of intracranial bleeding was 4.2% in the ET group compared with 4.3% in the ST group (risk ratio: 1.08; 95% CI: 0.64 to 1.82; p = 0.78). 90-day mortality was 15.1% in the ET group compared with 18.7% in the ST group (risk ratio: 0.81; 95% CI: 0.58 to 1.12; p = 0.19). There was no evidence of significant heterogeneity or publication bias for any of the endpoints.ConclusionsOn the basis of the results of this meta-analysis of RCTs, ET with stent retrievers appears as a safe and effective therapeutic option for acute ischemic stroke due to large vessel occlusion.     

Manual Thrombus Aspiration Is Not Associated With Reduced Mortality in Patients Treated With Primary Percutaneous Coronary Intervention: An Observational Study of 10,929 Patients With ST-Segment Elevation Myocardial Infarction From the London Heart Attack Group

ObjectivesThis study aimed to assess the impact of thrombus aspiration on mortality in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention (PCI).BackgroundThe clinical effect of routine intracoronary thrombus aspiration before primary PCI in patients with ST-segment elevation myocardial infarction is uncertain.MethodsWe undertook an observational cohort study of 10,929 ST-segment elevation myocardial infarction patients from January 2005 to July 2011 at 8 centers across London, United Kingdom. Patients’ details were recorded at the time of the procedure into local databases using the British Cardiac Intervention Society PCI dataset. Primary outcome was all-cause mortality at a median follow-up of 3.0 years (interquartile range: 1.2 to 4.6 years).ResultsIn our cohort, 3,572 patients (32.7%) underwent thrombus aspiration during primary PCI. Patients who had thrombus aspiration were younger, had lower rates of previous myocardial infarction but were more likely to have poor left ventricular function. Procedural success rates were higher (90.9% vs. 89.2%; p = 0.005) and in-hospital major adverse cardiac event rates were lower (4.4% vs. 5.5%; p = 0.012) in patients undergoing thrombus aspiration. However, Kaplan-Meier analysis demonstrated no significant difference in mortality rates between patients with and without thrombus aspiration (14.8% aspiration vs. 15.3% PCI only; p = 0.737) during the follow-up period. After multivariate Cox analysis (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.65 to 1.23) and the addition of propensity matching (HR: 0.85 95% CI: 0.60 to 1.20) thrombus aspiration was still not associated with decreased mortality.ConclusionsIn this cohort of nearly 11,000 patients, routine thrombus aspiration was not associated with a reduction in long-term mortality in patients undergoing primary PCI, although procedural success and in-hospital major adverse cardiac event rates were improved.     

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)     

Is There an Ideal Level of Platelet P2Y12-Receptor Inhibition in Patients Undergoing Percutaneous Coronary Intervention?: “Window” Analysis From the ADAPT-DES Study (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents)

ObjectivesThis study sought to determine whether there is an ideal level of platelet reactivity (PR) to optimize safety and efficacy within the large multicenter ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents) study of 8,582 patients receiving successful drug-eluting stent implantation.BackgroundPatients with high PR on clopidogrel have a greater incidence of adverse ischemic events after stent implantation, whereas low PR may increase bleeding. Due to limited sample size, previous studies have not been able to adjust for differences in baseline characteristics that may confound the relationship of PR and outcomes.MethodsIn the ADAPT-DES study, routine platelet function testing (VerifyNow) was performed following clopidogrel loading. To characterize the independent association between PR and clinical events, patients were stratified into quintiles of P2Y₁₂ reaction units (PRU).ResultsThe PRU medians of the 5 quintiles were 57, 130, 187, 244, and 317 (most to least inhibited). There was a monotonic association between successively higher PRU quintiles and stent thrombosis, whereas for clinically relevant bleeding, the greatest risk occurred in the lowest PRU quintile, with similar risks across the 4 higher quintiles. These relationships remained significant in fully adjusted multivariable analyses (adjusted hazard ratio [HR] for stent thrombosis in Q5 versus Q1: 2.32; 95% confidence interval [CI]: 1.17 to 4.59; p = 0.02; adjusted HR for clinically relevant bleeding in Q5 versus Q1: 0.61; 95% CI: 0.47 to 0.77; p < 0.001). However, there were no significant independent associations between the level of PRU and mortality.ConclusionsIn this large observational study, increasing PRU was associated with a monotonic increase in stent thrombosis, whereas bleeding risk was confined to the lowest PRU quintile, suggesting an optimal therapeutic window of platelet inhibition at moderately inhibited PRU. However, there was no demonstrable threshold effect for PRU and mortality in adjusted analyses, perhaps due to the offsetting impact of bleeding and ischemia across the spectrum of platelet inhibition. (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents [ADAPT-DES]; NCT00638794)     

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)     

Tricuspid Regurgitation Is Associated With Increased Risk of Mortality in Patients With Low-Flow Low-Gradient Aortic Stenosis and Reduced Ejection Fraction: Results of the Multicenter TOPAS Study (True or Pseudo-Severe Aortic Stenosis)

ObjectivesThis study sought to examine the impact of tricuspid regurgitation (TR) on mortality in patients with low-flow, low-gradient (LF-LG) aortic stenosis (AS) and reduced left ventricular ejection fraction (LVEF).BackgroundTR is often observed in patients with LF-LG AS and low LVEF, but its impact on prognosis remains unknown.MethodsA total of 211 patients (73 ± 10 years of age; 77% men) with LF-LG AS (mean gradient <40 mm Hg and indexed aortic valve area [AVA] ≤0.6 cm²/m²) and reduced LVEF (≤40%) were prospectively enrolled in the TOPAS (True or Pseudo-Severe Aortic Stenosis) study and 125 (59%) of them underwent aortic valve replacement (AVR) within 3 months following inclusion. The severity of AS was assessed by the projected AVA (AVA_proj) at normal flow rate (250 ml/s), as previously described and validated. The severity of TR was graded according to current guidelines.ResultsAmong the 211 patients included in the study, 22 (10%) had no TR, 113 (54%) had mild (grade 1), 50 (24%) mild-to-moderate (grade 2), and 26 (12%) moderate-to-severe (grade 3) or severe (grade 4) TR. During a mean follow-up of 2.4 ± 2.2 years, 104 patients (49%) died. Univariable analysis showed that TR ≥2 was associated with increased risk of all-cause mortality (hazard ratio [HR]: 1.82, 95% confidence interval [CI]: 1.22 to 2.71; p = 0.004) and cardiovascular mortality (HR: 1.85, 95% CI: 1.20 to 2.83; p = 0.005). After adjustment for age, sex, coronary artery disease, AVA_proj, LVEF, stroke volume index, right ventricular dysfunction, mitral regurgitation, and type of treatment (AVR vs. conservative), the presence of TR ≥2 was an independent predictor of all-cause mortality (HR: 1.88, 95% CI: 1.08 to 3.23; p = 0.02) and cardiovascular mortality (HR: 1.92, 95% CI: 1.05 to 3.51; p = 0.03). Furthermore, in patients undergoing AVR, TR ≥3 was an independent predictor of 30-day mortality compared with TR = 0/1 (odds ratio [OR]: 7.24, 95% CI: 1.56 to 38.2; p = 0.01) and TR = 2 (OR: 4.70, 95% CI: 1.00 to 25.90; p = 0.05).ConclusionsIn patients with LF-LG AS and reduced LVEF, TR is independently associated with increased risk of cumulative all-cause mortality and cardiovascular mortality regardless of the type of treatment. In patients undergoing AVR, moderate/severe TR is associated with increased 30-day mortality. Further studies are needed to determine whether TR is a risk marker or a risk factor of mortality and whether concomitant surgical correction of TR at the time of AVR might improve outcomes for this high-risk population.     

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.     

Impact of the Complexity of Bifurcation Lesions Treated With Drug-Eluting Stents: The DEFINITION Study (Definitions and impact of complEx biFurcation lesIons on clinical outcomes after percutaNeous coronary IntervenTIOn using drug-eluting steNts)

ObjectivesThe present study established criteria to differentiate simple from complex bifurcation lesions and compared 1-year outcomes stratified by lesion complexity after provisional stenting (PS) and 2-stent techniques using drug-eluting stents.BackgroundCurrently, no criterion can distinguish between simple and complex coronary bifurcation lesions. Comparisons of PS and 2-stent strategies stratified by lesion complexity have also not been reported previously.MethodsCriteria of bifurcation complexity in 1,500 patients were externally tested in another 3,660 true bifurcation lesions after placement of drug-eluting stents. The primary endpoint was the occurrence of a major adverse cardiac event (MACE) at 12 months. The secondary endpoint was the rate of stent thrombosis (ST).ResultsComplex (n = 1,108) bifurcation lesions were associated with a higher 1-year rate of MACE (16.8%) compared with simple (n = 2,552) bifurcation lesions (8.9%) (p < 0.001). The in-hospital ST and 1-year target lesion revascularization rates after 2-stent techniques in the simple group (1.0% and 5.6%, respectively) were significantly different from those after PS (0.2% [p = 0.007] and 3.2% [p = 0.009], respectively); however, 1-year MACE rates were not significantly different between the 2 groups. For complex bifurcation lesions, 2-stent techniques had lower rates of 1-year cardiac death (2.8%) and in-hospital MACE (5.0%) compared with PS (5.3%, p = 0.047; 8.4%, p = 0.031).ConclusionsComplex bifurcation lesions had higher rates of 1-year MACE and ST. The 2-stent and PS techniques were overall equivalent in 1-year MACE. However, 2-stent techniques for complex lesions elicited a lower rate of cardiac death and in-hospital MACE but higher rates of in-hospital ST and revascularization at 1 year for simple lesions.     

The Benefits Conferred by Radial Access for Cardiac Catheterization Are Offset by a Paradoxical Increase in the Rate of Vascular Access Site Complications With Femoral Access: The Campeau Radial Paradox

ObjectivesThe purpose of this study was to assess whether the benefits conferred by radial access (RA) at an individual level are offset by a proportionally greater incidence of vascular access site complications (VASC) at a population level when femoral access (FA) is performed.BackgroundThe recent widespread adoption of RA for cardiac catheterization has been associated with increased rates of VASCs when FA is attempted.MethodsLogistic regression was used to calculate the adjusted VASC rate in a contemporary cohort of consecutive patients (2006 to 2008) where both RA and FA were used, and compared it with the adjusted VASC rate observed in a historical control cohort (1996 to 1998) where only FA was used. We calculated the adjusted attributable risk to estimate the proportion of VASC attributable to the introduction of RA in FA patients of the contemporary cohort.ResultsA total of 17,059 patients were included. At a population level, the VASC rate was higher in the overall contemporary cohort compared with the historical cohort (adjusted rates: 2.91% vs. 1.98%; odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.17 to 1.89; p = 0.001). In the contemporary cohort, RA patients experienced fewer VASC than FA patients (adjusted rates: 1.44% vs. 4.19%; OR: 0.33, 95% CI: 0.23 to 0.48; p < 0.001). We observed a higher VASC rate in FA patients in the contemporary cohort compared with the historical cohort (adjusted rates: 4.19% vs. 1.98%; OR: 2.16, 95% CI: 1.67 to 2.81; p < 0.001). This finding was consistent for both diagnostic and therapeutic catheterizations separately. The proportion of VASCs attributable to RA in the contemporary FA patients was estimated at 52.7%.ConclusionsIn a contemporary population where both RA and FA were used, the safety benefit associated with RA is offset by a paradoxical increase in VASCs among FA patients. The existence of this radial paradox should be taken into consideration, especially among trainees and default radial operators.