Outcomes after transcatheter mitral valve implantation in valve-in-valve, valve-in-ring, and valve-in-mitral annular calcification.

AIMS: We aimed to evaluate transcatheter mitral valve implantation (TMVI) using predominantly balloon-expandable transcatheter heart valves (THV) in patients with a landing zone for a percutaneously delivered prosthesis. BACKGROUND: Patients with a degenerated mitral valve bioprosthesis, annuloplasty ring, and mitral annulus calcification (MAC) considered at high surgical risk currently represent a treatment challenge. TMVI is an alternative treatment option. METHODS: Retrospective analysis of patients with symptomatic degenerated mitral valve bioprosthesis, or annuloplasty ring, and MAC treated with TMVI between November 2011 and April 2021. Endpoints were defined according to Mitral Valve Academic Research Consortium (MVARC) criteria and included device and procedure success at 30 days as well as mortality at 30 days and 1 year after the procedure. RESULTS: A total of 77 patients underwent TMVI (valve in valve [ViV = 56], valve in ring [ViR = 11], and valve in MAC [ViMAC = 10]). There was a trend toward higher technical success (all = 93.5%, ViV = 96.4%, ViR = 90.9%, ViMAC = 80%, p = 0.06) and lower 30-day (all = 11.7%, ViV = 10.7%, ViR = 9.1%, ViMAC = 20%, p = 0.49) and 1-year mortality (all = 26%, ViV = 23.2%, ViR = 27.3%, ViMAC= 40%, p = 0.36) after ViV and ViR compared to ViMAC. CONCLUSION: TMVI represents a reasonable treatment option in selected patients with MAC or who are poor candidates for redo mitral valve surgery. Technical success and survival up to 1 year were not significantly dependent on the subgroup in which TMVI was performed.

Aspirin loading and coronary no-reflow after percutaneous coronary intervention in patients with acute myocardial infarction.

BACKGROUND: The association of aspirin loading with the risk of coronary no-reflow (CNR) after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) has not been investigated. We assessed the association of aspirin loading before PCI with CNR in patients with AMI. MATERIALS AND METHODS: This study included 3100 patients with AMI undergoing PCI. Of them, 2812 patients received aspirin loading (a single oral [or chewed] or intravenous dose of 150-300 mg) and 288 patients did not receive aspirin loading before PCI. The primary endpoint was CNR, defined as Thrombolysis in Myocardial Infarction blood flow grade of <3 after the PCI. RESULTS: CNR occurred in 130 patients: 127 patients in the group with aspirin loading and 3 patients in the group without aspirin loading before PCI (4.5% vs. 1.0%; odds ratio [OR] = 4.50, 95% confidence interval, [1.42-14.21], p = 0.005). After adjustment, the association between aspirin loading and CNR was significant (adjusted OR = 4.49 [1.56-12.92]; p < 0.001). There was no aspirin loading-by-P2Y12 inhibitor (ticagrelor or prasugrel) interaction (pint = 0.465) or aspirin loading-by-chronic aspirin therapy on admission (pint = 0.977) interaction with respect to the occurrence of CNR after PCI. Chronic low-dose aspirin therapy on admission was not independently associated with higher risk of CNR after PCI (adjusted OR = 1.06 [0.65-1.72]; p = 0.824). CONCLUSION: In patients with AMI undergoing PCI, aspirin loading before the PCI procedure at the guideline-recommended doses was associated with higher odds of developing CNR. However, due to the limited number of events, the findings should be considered as hypothesis generating.

Ten-year clinical outcomes of drug-eluting stents with different polymer coating strategies by degree of coronary calcification: a pooled analysis of the ISAR-TEST 4 and 5 randomised trials.

BACKGROUND: Long-term data concerning the efficacy of different polymer-coating strategies of new-generation drug-eluting stents (DES) in patients with coronary artery calcification (CAC) are scant. AIMS: We aimed to investigate 10-year outcomes by degree of CAC after new-generation DES implantation with different polymer-coating strategies. METHODS: We analysed individual patient and lesion characteristics of patients randomised to treatment with polymer-free sirolimus-eluting, biodegradable-polymer sirolimus-eluting and permanent-polymer zotarolimus- or everolimus-eluting stents. Endpoints of interest at 10 years were all-cause mortality, myocardial infarction (MI), target lesion revascularisation (TLR) and definite or probable stent thrombosis (ST) according to the degree of CAC (no, mild, moderate or severe) and coating strategy (polymer-free vs biodegradable-polymer vs permanent-polymer). RESULTS: A total of 4,953 patients with 6,924 lesions were included. No, mild, moderate or severe CAC was present in 24.5%, 41.8%, 25.8% and 8.0% of patients, respectively. At 10-year follow-up, overall event rates were high, with an incremental increase according to the degree of CAC (all-cause mortality: no 25.3%, mild 32.1%, moderate 41.7%, severe CAC 46.5%; adjusted [adj.] p=0.004; TLR: no 17.4%, mild 16.5%, moderate 19.8%, severe CAC 28.7%; adj. p=0.001; MI: no 4.9%, mild 5.9%, moderate 6.0%, severe CAC 10.5%; adj. p=0.02; and ST: no 1.3%, mild 1.4%, moderate 1.8%, severe CAC 3.6%; adj. p=0.57). In patients with moderate-severe CAC, event rates were comparable, regardless of the DES polymer-coating strategy. CONCLUSIONS: At 10 years after PCI with new-generation DES, there was an incremental increase in adverse events by degree of coronary calcification. These detrimental effects do not seem to be impacted by different polymer-coating strategies.

Prognostic value of glomerular function estimated by Cockcroft-Gault creatinine clearance, MDRD-4, CKD-EPI and European Kidney Function Consortium equations in patients with acute coronary syndromes.

BACKGROUND: It remains unknown which equation used to assess the glomerular function is better for risk stratification in patients with acute coronary syndrome (ACS). METHODS: This study included 3985 patients with ACS. Glomerular function was assessed using 4 equations: the Cockcroft-Gault creatinine clearance (C-GCrCl), Modification of Diet in Renal Disease-4 (MDRD-4), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and European Kidney Function Consortium (EKFC) equations. The primary outcome was one-year all-cause mortality. RESULTS: For each 30 ml/min decrement, the adjusted hazard ratio [HR] with 95% confidence interval [CI] for one-year mortality was 1.67 [1.27-2.25] for C-GCrCl, 1.45 [1.16-1.81] for MDRD-4, 1.76 [1.35-2.30] for CKD-EPI and 1.94 [1.44-2.63] for EKFC equation. Area under the receiver operating characteristic curve (AUC) for one-year mortality was 0.748 [0.709-0.788] for C-GCrCl, 0.670 [0.621-0.718] for estimated glomerular filtration rate (eGFR) calculated by MDRD-4 equation, 0.725 [0.684-0.765] for eGFR calculated by CKD-EPI equation and 0.741 [0.703-0.779] for eGFR calculated by EKFC equation (P = 0.342 for C-GCrCl, vs. EKFC equation and P ≤ 0.009 for all other AUC comparisons). CONCLUSIONS: In patients with ACS, C-GCrCl and EKFC equations showed a similar discriminatory power regarding prediction of one-year mortality. Both equations were better than MDRD-4 and CKD-EPI equations for risk discrimination for mortality. CLINICAL TRIAL REGISTRATION: NCT01944800.

Ticagrelor or Prasugrel in Patients With Acute Coronary Syndrome in Relation to Estimated Glomerular Filtration Rate.

OBJECTIVES: The aim of this study was to assess the safety and efficacy of ticagrelor versus prasugrel for patients with acute coronary syndrome (ACS) according to their estimated glomerular filtration rates (eGFRs). BACKGROUND: The outcomes of ticagrelor versus prasugrel in patients with ACS according to eGFR have not been defined. METHODS: Patients (n = 4,012) were categorized into 3 groups: low eGFR (<60 mL/min/1.73 m2), intermediate eGFR (≥60 and <90 mL/min/1.73 m2), and high eGFR (≥90 mL/min/1.73 m2). The primary endpoint was a composite of all-cause death, myocardial infarction, and stroke; the secondary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding, both at 1 year. RESULTS: Patients with low eGFRs had a higher risk for the primary endpoint compared with patients with intermediate eGFRs (adjusted HR: 1.89; 95% CI: 1.46-2.46]) and those with high eGFRs (adjusted HR: 2.33; 95% CI: 1.57-3.46). A risk excess for low eGFR was also observed for bleeding (adjusted HR: 1.55 [95% CI: 1.12-2.13] vs intermediate eGFR; adjusted HR: 1.59 [95% CI: 1.01-2.50] vs high eGFR). However, eGFR did not affect the relative efficacy and safety of ticagrelor versus prasugrel. In patients with low eGFR, the primary endpoint occurred in 20.5% with ticagrelor and in 14.7% with prasugrel (HR: 1.47; 95% CI: 1.04-2.08; P = 0.029); there was no significant difference in bleeding. CONCLUSIONS: These results show that among patients with ACS, reduction of eGFR is associated with increased risk for ischemic and bleeding events but has no significant impact on the relative efficacy and safety of ticagrelor versus prasugrel. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome [ISAR-REACT 5]; NCT01944800).

Efficacy and safety of ticagrelor versus prasugrel in smokers and nonsmokers with acute coronary syndromes.

BACKGROUND: The efficacy and safety of ticagrelor versus prasugrel according to smoking status in patients with acute coronary syndromes (ACS) are not known. We assessed the efficacy and safety of ticagrelor versus prasugrel according to smoking status in patients with ACS undergoing invasive management. METHODS: This pre-specified analysis of the ISAR-REACT 5 trial included 1349 smokers and 2652 nonsmokers randomized to receive ticagrelor or prasugrel. The primary endpoint was the incidence of death, myocardial infarction, or stroke; the secondary endpoint was the incidence of Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding (both endpoints assessed at 12 months). RESULTS: There was no significant treatment arm-by-smoking status interaction regarding the efficacy outcome. The primary endpoint occurred in 47 patients (7.0%) in the ticagrelor group and 41 patients (6.2%) in the prasugrel group in smokers (hazard ratio [HR] = 1.15; 95% confidence interval [CI] 0.76-1.75; P = 0.510) and in 133 patients (10.2%) in the ticagrelor group and 94 patients (7.2%) in the prasugrel group in nonsmokers (HR = 1.44 [1.10-1.87]; P = 0.007; P for interaction = 0.378). The secondary endpoint occurred in 27 patients (4.6%) in the ticagrelor group and 33 patients (5.6%) in the prasugrel group in smokers (HR = 0.81 [0.49-1.35]; P = 0.412) and in 66 patients (6.0%) in the ticagrelor group and 46 patients (4.4%) in the prasugrel group in nonsmokers (HR = 1.38 [0.94-2.01]; P = 0.097). CONCLUSIONS: In patients with ACS undergoing an invasive management strategy, the smoking status did not significantly interact with the relative treatment effect of ticagrelor vs. prasugrel. CLINICAL TRIAL REGISTRATION: NCT01944800.

Ticagrelor or Prasugrel in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

BACKGROUND: Current guidelines recommend intensified platelet inhibition by prasugrel or ticagrelor in patients with unstable angina (UA) or non-ST-segment elevation (NSTE) myocardial infarction (MI). OBJECTIVES: This study sought to investigate the benefits and risks of ticagrelor as compared with prasugrel in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and planned invasive management. METHODS: This post hoc analysis combines the pre-specified subgroups of UA and NSTEMI of the randomized ISAR-REACT 5 trial. It included 1,179 patients assigned to ticagrelor and 1,186 assigned to prasugrel. Ticagrelor was started immediately after randomization and prasugrel after coronary angiography. The primary endpoint was a composite of death, MI, or stroke during 1-year follow-up, and the safety endpoint was Bleeding Academic Research Consortium class 3-5. RESULTS: The primary endpoint was reached in 101 (8.7%) patients in the ticagrelor and in 73 (6.3%) patients in the prasugrel group (hazard ratio [HR]: 1.41; 95% confidence interval [CI]: 1.04 to 1.90). The HR for all-cause death was 1.43 (95% CI: 0.93 to 2.21) and that for MI 1.43 (95% CI: 0.94 to 2.19). The safety endpoint occurred in 49 (5.2%) patients in the ticagrelor and in 41 (4.7%) patients in the prasugrel group (HR: 1.09; 95% CI: 0.72 to 1.65). Landmark analysis revealed persistence of the efficacy advantage with prasugrel after the first month. CONCLUSIONS: In patients with NSTE-ACS, we found that prasugrel was superior to ticagrelor in reducing the combined 1-year risk of death, MI, and stroke without increasing the risk of bleeding. Due to the post hoc nature of the analysis, these findings need confirmation by further studies. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome; NCT01944800).

Ticagrelor or Prasugrel in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

BACKGROUND: Data on the comparative efficacy and safety of ticagrelor versus prasugrel in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention are limited. We assessed the efficacy and safety of ticagrelor versus prasugrel in a head-to-head comparison in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. METHODS: In this prespecified subgroup analysis, we included 1653 patients with ST-segment-elevation myocardial infarction randomized to receive ticagrelor or prasugrel in the setting of the ISAR REACT-5 trial (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5). The primary end point was the incidence of death, myocardial infarction, or stroke at 1 year after randomization. The secondary end point was the incidence of bleeding defined as BARC (Bleeding Academic Research Consortium) type 3 to 5 bleeding at 1 year after randomization. RESULTS: The primary end point occurred in 83 patients (10.1%) in the ticagrelor group and in 64 patients (7.9%) in the prasugrel group (hazard ratio, 1.31 [95% CI, 0.95-1.82]; P=0.10). One-year incidence of all-cause death (4.9% versus 4.7%; P=0.83), stroke (1.3% versus 1.0%; P=0.46), and definite stent thrombosis (1.8% versus 1.0%; P=0.15) did not differ significantly in patients assigned to ticagrelor or prasugrel. One-year incidence of myocardial infarction (5.3% versus 2.8%; hazard ratio, 1.95 [95% CI, 1.18-3.23]; P=0.010) was higher with ticagrelor than with prasugrel. BARC type 3 to 5 bleeding occurred in 46 patients (6.1%) in the ticagrelor group and in 39 patients (5.1%) in the prasugrel group (hazard ratio, 1.22 [95% CI, 0.80-1.87]; P=0.36). CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, there was no significant difference in the primary end point between prasugrel and ticagrelor. Ticagrelor was associated with a significant increase in the risk for recurrent myocardial infarction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800.

Long-Term Prognostic Impact of Restenosis of the Unprotected Left Main Coronary Artery Requiring Repeat Revascularization.

OBJECTIVES: The aim of this study was to evaluate the prognostic impact of target lesion revascularization (TLR) of the unprotected left main coronary artery (ULMCA) after stent failure. BACKGROUND: Although drug-eluting stents are safe and effective for treatment of the ULMCA, increased rates of repeat revascularization have been observed. METHODS: This is a patient-level pooled analysis of the randomized ISAR-LEFT-MAIN (Drug-Eluting-Stents for Unprotected Left Main Stem Disease) and ISAR-LEFT-MAIN-2 (Drug-Eluting Stents to Treat Unprotected Coronary Left Main Disease) trials, in which patients underwent stenting of the ULMCA. The present analysis includes patients who underwent angiography during follow-up. Patients with TLR were compared with those without. Additional long-term clinical follow-up after TLR was conducted, and its influence on mortality was evaluated. Mortality was calculated using the Kaplan-Meier method. Predictors of mortality were assessed in a multivariate analysis. RESULTS: A total of 1,001 patients were eligible, of whom 166 experienced TLR. The 5-year mortality rate was 30.2% in patients with TLR compared with 17.3% in those without TLR (p < 0.001). In the multivariate analysis, glomerular filtration rate (-30 ml/min; hazard ratio [HR]: 2.25; 95% confidence interval [CI]: 1.54 to 3.27; p < 0.001), chronic obstructive pulmonary disease (HR: 4.95; 95% CI: 1.33 to 18.42; p = 0.02), and body mass index (+5 kg/m2; HR: 1.61; 95% CI: 1.12 to 2.32; p = 0.01) were independent predictors of mortality after TLR due to left main stent failure. The type of repeat revascularization and the underlying stent did not influence the mortality after TLR of the ULMCA. CONCLUSIONS: Mortality after TLR for left main stent failure is high. Patient-related factors seem to have a greater impact on mortality after TLR than other variables.

Predicting factors for long-term survival in patients with out-of-hospital cardiac arrest - A propensity score-matched analysis.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is one of the leading causes of death worldwide, with acute coronary syndromes accounting for most of the cases. While the benefit of early revascularization has been clearly demonstrated in patients with ST-segment-elevation myocardial infarction (STEMI), diagnostic pathways remain unclear in the absence of STEMI. We aimed to characterize OHCA patients presenting to 2 tertiary cardiology centers and identify predicting factors associated with survival. METHODS: We retrospectively analyzed 519 patients after OHCA from February 2003 to December 2017 at 2 centers in Munich, Germany. Patients undergoing immediate coronary angiography (CAG) were compared to those without. Multivariate regression analysis and inverse probability treatment weighting (IPTW) were performed to identify predictors for improved outcome in a matched population. RESULTS: Immediate CAG was performed in 385 (74.1%) patients after OHCA with presumed cardiac cause of arrest. As a result of multivariate analysis after propensity score matching, we found that immediate CAG, return of spontaneous circulation (ROSC) at admission, witnessed arrest and former smoking were associated with improved 30-days-survival [(OR, 0.46; 95% CI, 0.26-0.84), (OR, 0.21; 95% CI, 0.10-0.45), (OR, 0.50; 95% CI, 0.26-0.97), (OR, 0.43; 95% CI, 0.23-0.81)], and 1-year-survival [(OR, 0.39; 95% CI, 0.19-0.82), (OR, 0.29; 95% CI, 0.12-0.7), (OR, 0.43; 95% CI, 0.2-1.00), (OR, 0.3; 95% CI, 0.14-0.63)]. CONCLUSIONS: In our study, immediate CAG, ROSC at admission, witnessed arrest and former smoking were independent predictors of survival in cardiac arrest survivors. Improvement in prehospital management including bystander CPR and best practice post-resuscitation care with optimized triage of patients to an early invasive strategy may help ameliorate overall outcome of this critically-ill patient population.

Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes.

BACKGROUND: The relative merits of ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned are uncertain. METHODS: In this multicenter, randomized, open-label trial, we randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. A major secondary end point (the safety end point) was bleeding. RESULTS: A total of 4018 patients underwent randomization. A primary end-point event occurred in 184 of 2012 patients (9.3%) in the ticagrelor group and in 137 of 2006 patients (6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P = 0.006). The respective incidences of the individual components of the primary end point in the ticagrelor group and the prasugrel group were as follows: death, 4.5% and 3.7%; myocardial infarction, 4.8% and 3.0%; and stroke, 1.1% and 1.0%. Definite or probable stent thrombosis occurred in 1.3% of patients assigned to ticagrelor and 1.0% of patients assigned to prasugrel, and definite stent thrombosis occurred in 1.1% and 0.6%, respectively. Major bleeding (as defined by the Bleeding Academic Research Consortium scale) was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P = 0.46). CONCLUSIONS: Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups. (Funded by the German Center for Cardiovascular Research and Deutsches Herzzentrum München; ISAR-REACT 5 ClinicalTrials.gov number, NCT01944800.).

ISAR-PEBIS (Paclitaxel-Eluting Balloon Versus Conventional Balloon Angioplasty for In-Stent Restenosis of Superficial Femoral Artery): A Randomized Trial.

BACKGROUND: Paclitaxel-eluting balloon (PEB) angioplasty has superior efficacy compared with conventional balloon angioplasty (BA) for de novo lesions of superficial femoral artery (SFA). Studies investigating the angiographic and clinical performance of PEB angioplasty versus BA for in-stent restenosis of SFA are limited. We performed a randomized trial to investigate angiographic and clinical performance of PEB versus BA for in-stent restenosis of SFA. METHODS AND RESULTS: Patients with symptomatic in-stent restenosis of SFA were randomly assigned to either PEB or BA at 2 centers in Munich, Germany. The primary end point was the percentage diameter stenosis at 6- to 8-month follow-up angiography. Secondary end points were the rate of binary restenosis at follow-up angiography and target lesion revascularization, target vessel thrombosis, ipsilateral amputation, bypass surgery of the affected limb, and all-cause mortality at 24-month follow-up. Seventy patients were assigned to PEB (n=36) or BA (n=34). Mean lesion length was 139±67 mm, and roughly one third of lesions were completely occluded at the time of the index procedure. At control angiography, the percentage diameter stenosis (44±33% versus 65±33%, P=0.01) and binary restenosis were significantly reduced with PEB versus BA (30% versus 59%, P=0.03). At 24-month follow-up, PEB was associated with a significant reduction of target lesion revascularization in comparison to BA (19% versus 50%, P=0.007). There was no difference with respect to other outcomes of interest. CONCLUSIONS: In patients with in-stent restenosis of SFA, a percutaneous therapy with PEB compared with BA has superior angiographic performance at 6 to 8 months and improved clinical efficacy up to 24-month follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01083394.

Everolimus-eluting bioresorbable vascular scaffolds versus everolimus-eluting metallic stents: a meta-analysis of randomised controlled trials.

BACKGROUND: Bioresorbable coronary stents might improve outcomes of patients treated with percutaneous coronary interventions. The everolimus-eluting bioresorbable vascular scaffold is the most studied of these stent platforms; however, its performance versus everolimus-eluting metallic stents remains poorly defined. We aimed to assess the efficacy and safety of everolimus-eluting bioresorbable vascular scaffolds versus everolimus-eluting metallic stents in patients with ischaemic heart disease treated with percutaneous revascularisation. METHODS: We searched Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), scientific sessions abstracts, and relevant websites for randomised trials investigating everolimus-eluting bioresorbable vascular scaffolds versus everolimus-eluting metallic stents published or posted between Nov 30, 2006, and Oct 12, 2015. The primary efficacy outcome was target lesion revascularisation and the primary safety outcome was definite or probable stent (scaffold) thrombosis. Secondary outcomes were target lesion failure (the composite of cardiac death, target-vessel myocardial infarction, or ischaemia-driven target lesion revascularisation), myocardial infarction, death, and in-device late lumen loss. We derived odds ratios (ORs) and weighted mean differences with 95% CIs, and calculated the risk estimates for the main outcomes according to a random-effects model. This study is registered with PROSPERO, number CRD42015026374. FINDINGS: We included six trials, comprising data for 3738 patients randomised to receive percutaneous coronary intervention with either an everolimus-eluting bioresorbable vascular scaffold (n=2337) or an everolimus-eluting metallic stent (n=1401). Median follow-up was 12 months (IQR 9-12). Patients treated with bioresorbable vascular scaffolds had a similar risk of target lesion revascularisation (OR 0.97 [95% CI 0.66-1.43]; p=0.87), target lesion failure (1.20 [0.90-1.60]; p=0.21), myocardial infarction (1.36 [0.98-1.89]; p=0.06), and death (0.95 [0.45-2.00]; p=0.89) as those treated with metallic stents. Patients treated with a bioresorbable vascular scaffold had a higher risk of definite or probable stent thrombosis than those treated with a metallic stent (OR 1.99 [95% CI 1.00-3.98]; p=0.05), with the highest risk between 1 and 30 days after implantation (3.11 [1.24-7.82]; p=0.02). Lesions treated with a bioresorbable vascular scaffold had greater in-device late lumen loss than those treated with a metallic stent (weighted mean difference 0.08 [95% CI 0.05-0.12]; p<0.0001). INTERPRETATION: Compared with everolimus-eluting metallic stents, everolimus-eluting bioresorbable vascular scaffolds had similar rates of repeat revascularisation at 1 year of follow-up, despite inferior mid-term angiographic performance. However, patients treated with a bioresorbable vascular scaffold had an increased risk of subacute stent thrombosis. Studies with extended follow-up in a larger number of patients are needed to fully assess the long-term advantages of everolimus-eluting bioresorbable vascular scaffolds. FUNDING: None.

Covered stents for endovascular repair of iatrogenic injuries of iliac and femoral arteries.

BACKGROUND: The growing number of complex endovascular procedures is expected to increase the risk of iatrogenic injuries of peripheral arteries. A strategy of percutaneous transluminal angioplasty (PTA) with covered stent (CS) may represent a valuable alternative to open surgery. However, systematic evaluations of CS in this setting represent a scientific gap. In the present study, we investigate the procedural and clinical outcomes associated with PTA and CS implantation to repair iatrogenic injuries of peripheral arteries. METHODS: All patients undergoing PTA with CS for endovascular repair of iatrogenic injuries of peripheral arteries between August 2010 and July 2013 at our Institution were retrospectively analyzed. The primary endpoint was the technical success. Secondary endpoints were in-hospital mortality and cumulative death, target lesion revascularization (TLR), amputation and major stroke at 12-month follow-up. RESULTS: During the period of observation, a total of 30 patients underwent PTA with either self-expandable (43.3%) or balloon-expandable CS (56.7%) for iatrogenic injuries of peripheral arteries. Injuries consisted of perforation/rupture (76.7%), arteriovenous fistula (16.7%) and pseudoaneurysm (6.7%) of iliac-femoral arteries. Technical success was achieved in all cases. Median follow-up was 409days [210-907]. The incidence of in-hospital mortality was 10.0%. At 12-month follow-up, the incidence of death, TLR, amputation and major stroke was 20.0%, 17.0%, 3.3% and 6.7%, respectively. CONCLUSION: The use of covered stents for endovascular repair of iatrogenic injuries of peripheral arteries shows a high technical success and may be alternative to surgery. Further studies with larger populations are needed to confirm these preliminary findings.

Influence of abciximab on evolution of left ventricular function in patients with non-ST-segment elevation acute coronary syndromes undergoing PCI after clopidogrel pretreatment: lessons from the ISAR-REACT 2 trial.

BACKGROUND: Abciximab reduced the combined endpoint of death, myocardial infarction (MI) and target vessel revascularization in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) undergoing percutaneous coronary intervention (PCI) with stent implantation after a 600-mg loading dose of clopidogrel. The aim of the present study was to investigate the impact of abciximab on the evolution of left ventricular ejection fraction (LVEF) in these patients. METHODS: The current study included 1,158 patients enrolled in the randomized, double-blind ISAR-REACT 2 (the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment) trial who had paired angiograms obtained at baseline and 6-8 months after randomization. Of them, 586 patients received abciximab and 572 patients received placebo. The primary outcome analysis was LVEF at 6-8-month follow-up. RESULTS: Baseline LVEF was comparable in patients assigned to abciximab or placebo (53.2 ± 12.6 vs. 53.7 ± 12.1%; P = 0.393). At 6-8-month follow-up angiography, there was no difference in LVEF between the abciximab and placebo groups (55.4 ± 11.5 vs. 55.8 ± 11.2%; P = 0.743). Subgroup analysis of patients with elevated baseline troponin (>0.03 µg/L) also revealed comparable LVEF at follow-up in both treatment groups (P = 0.527). The multivariate analysis identified age, arterial hypertension, prior MI, prior coronary artery bypass graft surgery, baseline LVEF, MI at 30 days and repeat PCI as independent correlates of follow-up LVEF. CONCLUSION: Although abciximab reduced the 30-day and 1-year incidence of major adverse cardiac events in patients with NSTE-ACS undergoing primary PCI after pre-treatment with a 600-mg loading dose of clopidogrel, the agent did not improve or impact on the evolution of LVEF over 6-8 months of follow-up.

Randomized trial of paclitaxel- versus sirolimus-eluting stents for treatment of coronary restenosis in sirolimus-eluting stents: the ISAR-DESIRE 2 (Intracoronary Stenting and Angiographic Results: Drug Eluting Stents for In-Stent Restenosis 2) study.

OBJECTIVES: For patients with sirolimus-eluting stent (SES) restenosis requiring reintervention, we compared a strategy of repeat SES (Cypher, Cordis, Miami Lakes, Florida) implantation with paclitaxel-eluting stent (PES) (Taxus, Boston Scientific, Natick, Massachusetts) implantation. BACKGROUND: Despite their high anti-restenotic efficacy, the widespread utilization of SES therapy has led to a significant absolute number of patients presenting with SES treatment failure. The optimal treatment strategy for such patients remains unclear. METHODS: The ISAR-DESIRE 2 (Intracoronary Stenting and Angiographic Results: Drug Eluting Stents for In-Stent Restenosis 2) study was a randomized, open-label, active-controlled trial conducted among 450 patients with clinically significant in-SES restenosis at 2 centers in Munich, Germany. After pre-treatment with 600 mg clopidogrel, all patients were randomly assigned to either SES or PES implantation. The primary end point was late lumen loss, based on in-stent analysis, at 6- to 8-month follow-up angiography. Secondary end points were binary angiographic restenosis (diameter stenosis >50%) at 6- to 8-month follow-up, target lesion revascularization, the composite of death or myocardial infarction, and definite stent thrombosis at 12 months. RESULTS: Regarding anti-restenotic efficacy, there were no differences between SES and PES in late loss (0.40 +/- 0.65 mm vs. 0.38 +/- 0.59 mm; p = 0.85), binary restenosis (19.6% vs. 20.6%; p = 0.69), or target lesion revascularization (16.6% vs. 14.6%; p = 0.52). In terms of safety outcomes, the rates of death/myocardial infarction (6.1% vs. 5.8%; p = 0.86) and stent thrombosis (0.4% vs. 0.4%; p > 0.99) were also similar. CONCLUSIONS: In cases of SES restenosis, treatment with either repeat SES or switch to PES was associated with a comparable degree of efficacy and safety. Drug resistance at an individual patient level may play a contributory role to the somewhat higher than expected late loss observed with the SES in the current study. (Intracoronary Stenting and Angiographic Results: Drug-Eluting Stents for In-Stent Restenosis 2 [ISAR-DESIRE 2]; NCT00598715).

Long-term risk of adverse outcomes and new malignancies in patients treated with oral sirolimus for prevention of restenosis.

OBJECTIVES: We sought to investigate the long-term efficacy of oral sirolimus therapy and its impact on the incidence of de novo malignancies in the OSIRIS (Oral Sirolimus to Inhibit Recurrent In-Stent Stenosis) trial population. BACKGROUND: The OSIRIS trial showed a significant reduction of angiographic restenosis with an oral adjunctive sirolimus treatment for in-stent restenosis. The long-term efficacy of oral sirolimus therapy is unknown. METHODS: Three hundred patients with in-stent restenosis were randomly assigned to receive placebo, a cumulative loading dose of 8 mg (usual-dose), or 24 mg (high-dose) of sirolimus over 3 days (2 days before and the day of intervention) followed by maintenance therapy of 2 mg/day for 7 days. The primary outcome of this analysis was the incidence of composite of death, myocardial infarction, and target vessel revascularization at 4-year follow-up. Secondary outcome was the incidence of newly diagnosed malignancies. RESULTS: No significant differences were observed between placebo, usual-, and high-dose sirolimus treatment groups regarding primary outcome (33.3%, 39.4%, and 31.3%, respectively; p = 0.46), death (5.9%, 9.1%, and 11.1%, respectively; p = 0.41), target vessel revascularization (30.4%, 30.3%, and 22.2%, respectively; p = 0.33), and rate of newly diagnosed malignancies (7.8%, 3.0%, and 11.1%, respectively; p = 0.09). CONCLUSIONS: The benefit in the reduced need for repeat intervention observed at 1 year with high-dose oral sirolimus therapy was attenuated over 4 years. Moreover, this regimen was associated with numerical yet not a significant increase in newly diagnosed malignancies without augmenting the malignancy-induced risk of death. (Oral Sirolimus for In-Stent Restenosis [OSIRUS] trial; NCT00859183).