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OBJECTIVES We investigated the clinical efficacy of a paclitaxel-coated balloon (PCB) with a novel matrix coating and reduced drug concentration in comparison with a widely used PCB with iopromide excipient. METHODS We prospectively enrolled patients with restenosis in drug-eluting stents. All patients were treated with a novel low-dose PCB with citrate-based excipient (Agent PCB). Angiographic follow-up was scheduled at 6-8 months. Outcomes were compared against those of patients treated with iopromide excipient PCB (SeQuent Please PCB) enrolled in a trial with identical inclusion and exclusion criteria. The primary endpoint was percent diameter stenosis (%DS) at follow-up angiography. The primary hypothesis was that the investigational device would be non-inferior to the control device (ClinicalTrials.gov Identifier: NCT02367495). RESULTS One hundred twenty-five patients with 151 lesions were enrolled. Mean age was 68.1 ± 10.2 years, 40.8% had diabetes mellitus and 80.1% had focal morphology in-stent restenosis. Follow-up angiography data at 6-8 months was available for 102 (81.6%) patients. The Agent PCB was non-inferior to the SeQuent Please PCB in terms of the primary endpoint (38.9 ± 17.5 vs. 38.1 ± 21.5%; p non-inferiority = 0.0056). Late lumen loss was also comparable between the groups (0.35 ± 0.55 vs. 0.37 ± 0.59; p = 0.71). There was no difference between the groups in the incidence of TLR (27.7% vs. 22.1%; p = 0.31), death or myocardial infarction (4.2% vs. 4.4%; p = 0.92) or target lesion thrombosis (1.0% vs. 0.7%; p = 0.93). CONCLUSION In patients with DES restenosis, angioplasty with a novel PCB with citrate-based excipient was non-inferior to PCB with iopromide excipient in terms of angiographic outcome.

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 ( 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 )

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

Die perkutane Revaskularisation von chronisch verschlossenen Koronarien stellt seit jeher eine grose Herausforderung fur die interventionelle Kardiologie dar. In den letzten Jahrzenten wurde eine Vielzahl an Anstrengungen unternommen, um die Revaskularisationsstrategien fur chronisch verschlossene Koronarien zu standardisieren. Diese Bestrebungen sind v. a. in dem steigenden Interesse der verschiedenen kardiologischen Fachgesellschaften an dieser Patientengruppe, in der zunehmenden Erfahrung der Interventionalisten und in der fortwahrenden Entwicklung des technischen Instrumentariums und von endovaskularen Unterstutzungstechnologien begrundet. Diese Ubersichtsarbeit beleuchtet die aktuell zur Verfugung stehenden Hilfsmittel sowie Technologien, Techniken und Strategien zur perkutanen Rekanalisation von chronisch verschlossenen Koronarien.

BACKGROUND: The comparative efficacy of balloon-based techniques to prepare severely calcified coronary lesions before stenting remains poorly studied. AIMS: We sought to compare stent expansion following preparation of severely calcified coronary lesions with either a super high-pressure balloon or a scoring balloon. METHODS: In this randomised, open-label trial, patients with severely calcified coronary lesions were enrolled at five centres in Germany and Switzerland. After unsuccessful lesion preparation with a standard non-compliant balloon (0.99). Strategy success (91.9% vs 83.8%; p=0.48) and procedural success (100% vs 89.2%; p=0.12) were numerically more frequent with the super high-pressure balloon versus the scoring balloon. CONCLUSIONS: In patients with severely calcified coronary artery lesions, preparation with a super high-pressure balloon versus a scoring balloon was associated with comparable stent expansion on intravascular imaging and a trend towards improved angiographic performance. VISUAL SUMMARY: A ComparIson of Strategies to PrepAre SeveRely CALCified Coronary Lesions: the ISAR-CALC randomised trial.

BACKGROUND: Drug-coated balloons (DCB) and drug-eluting stents (DES) represent the currently recommended treatments for in-stent restenosis (ISR). Optical coherence tomography (OCT) allows detailed neointimal characterisation which can guide treatment strategies. AIMS: The aims of this study were first, to assess the relation between neointimal pattern and clinical outcomes following in-stent restenosis (ISR) treatment, and second, to explore a potential interaction between neointimal pattern and treatment modality relative to clinical outcomes. METHODS: Patients undergoing OCT-guided treatment (DCB or DES) of ISR in three European centres were included. Based on the median of distribution of non-homogeneous neointima quadrants, patients were categorised into low and high inhomogeneity groups. RESULTS: A total of 197 patients (low inhomogeneity=100 and high inhomogeneity=97) were included. There were no significant differences in terms of major adverse cardiac events (MACE) (p=0.939) or target lesion revascularisation (TLR) (p=0.732) between the two groups. The exploratory analysis showed a significant interaction between neointimal pattern and treatment modality regarding MACE (pint=0.006) and TLR (pint=0.022). DES showed a significant advantage over DCB in the high (MACE: HR 0.26 [0.10-0.65], p=0.004; TLR: HR 0.28 [0.11-0.69], p=0.006), but not in the low inhomogeneity group (MACE: p=0.917; TLR: p=0.797). CONCLUSIONS: In patients with ISR treated with DCB or DES, there were no significant differences in terms of MACE or TLR between the low and high inhomogeneity groups. A significant interaction was observed between treatment modality and neointimal pattern with an advantage of DES over DCB in the high and no difference in the low inhomogeneity group. This warrants confirmation from prospective dedicated studies.

Background Very long-term outcomes according to diabetic status of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) with new-generation drug-eluting stents (DES) are scant. Both, the durable polymer zotarolimus-eluting stent (DP-ZES), the first DES to gain FDA-approval for specific use in patients with diabetes mellitus, and the polymer-free sirolimus- and probucol-eluting stent (PF-SES), with a unique design that enables effective drug release without the need of a polymer offer the potential to enhance clinical long-term outcomes especially in patients with diabetes mellitus. Methods We investigate 10-year clinical outcomes of the prespecified subgroups of patients with and without diabetes mellitus, randomly assigned to treatment with PF-SES versus DP-ZES in the ISAR-TEST 5 trial. The primary endpoint of interest was major adverse cardiac events (MACE), defined as the composite of all-cause death, any myocardial infarction or any revascularization. Further endpoints of interest were cardiac death, myocardial infarction related to the target vessel and target lesion revascularization as well as the individual components of the primary composite endpoint and the incidence of definite or probable stent thrombosis at 10 years. Results This analysis includes a total of 3002 patients randomly assigned to PF-SES (n = 2002) or DP-ZES (n = 1000). Prevalence of diabetes mellitus was high and comparable, 575 Patients (28.7%) in PF-SES group and 295 patients (29.5%) in DP-ZES group (P = 0.66). At 10 years 53.5% of patients with diabetes mellitus and 68.5% of patients without diabetes mellitus were alive. Regarding major adverse cardiac events, PF-SES as compared to DP-ZES showed comparable event rates in patients with diabetes mellitus (74.8% vs. 79.6%; hazard ratio 0.86; 95% CI 0.73–1.02; P = 0.08) and in patients without diabetes (PF-SES 62.5% vs. DP-ZES 62.2%; hazard ratio 0.99; 95% CI 0.88–1.11; P = 0.88). Conclusion At 10 years, both new-generation DES show comparable clinical outcome irrespective of diabetic status or polymer strategy. Event rates after PCI in patients with diabetes mellitus are considerable higher than in patients without diabetes mellitus and continue to accrue over time. Trial registration ClinicalTrials.gov, NCT00598533, Registered 10 January 2008, https://clinicaltrials.gov/ct2/show/NCT00598533?term=NCT00598533 Graphic abstract Kaplan-Meier estimates of endpoints of interest for patients with vs. without diabetes mellitus treated with PF-SES vs. DP-ZES. Bar graphs: Kaplan-Meier estimates as percentages. PF-SES: polymer-free sirolimus-eluting stent; DP-ZES: durable polymer zotarolimus-eluting stent; DM: diabetes mellitus. Comparison of event rates of individual endpoints in patients with and without diabetes mellitus treated with PF-SES vs. DP-ZES all without statistically significant differences. Comparison of event rates of individual endpoints in overall patients with vs. without diabetes mellitus significantly different (P ≤ 0.01 for all comparisons).

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.

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 )

Resumen Introduccion y objetivos Los resultados de los pacientes con reestenosis de stents farmacoactivos (SFA) son peores que los de pacientes con reestenosis de stents metalicos. No se sabe si esta relacionado o no con la presencia de recubrimiento de polimero. Se compararon los resultados tras la intervencion sobre la reestenosis del stent (RS) de SFA sin polimero y SFA recubiertos de polimero duradero. Metodos Se incluyo a los pacientes del estudio aleatorizado ISAR-TEST 5 sometidos a un nuevo intervencionismo percutaneo por RS durante el seguimiento. Se analizaron los resultados angiograficos a los 6 y a los 8 meses y los eventos clinicos a los 2 anos, y se compararon los 2 grupos en funcion del tipo de stent. Las diferencias entre uno y otro grupo se ajustaron mediante analisis multivariable. Resultados Se incluyo a 326 pacientes con RS: 220 de SFA sin polimero y 106 de SFA con polimero. Se dispuso de angiografia de control del 83,4% de los pacientes. No se observaron diferencias entre los grupos en cuanto a reestenosis binaria recurrente (el 31,7 y el 27,0%; p = 0,38; pajustada = 0,29). A los 2 anos, el objetivo compuesto de muerte, infarto de miocardio o nueva revascularizacion de la lesion diana fue similar en los 2 grupos (el 35,7 frente al 34,0%; HR = 1,04; IC95%, 0,70-1,55; p = 0,83; pajustada = 0,79). Las tasas de nueva revascularizacion de la lesion diana de ambos grupos tambien fueron comparables (el 29,8 y el 31,5%; HR = 0,91; IC95%, 0,60-1,39; p = 0,68; pajustada = 0,62). Conclusiones No se encontraron diferencias entre los pacientes sometidos a reintervencion por RS de SFA en cuanto a eventos clinicos o angiograficos en funcion del tipo de stent, con o sin polimero.

BACKGROUND Whether there are differences in the risk profile and treatment effect in patients recruited in a low recruitment center (LRC) versus patients recruited in a high recruitment center (HRC) in a randomized multicenter trial remains unknown. METHODS AND RESULTS This study included 4018 patients with acute coronary syndrome recruited in the ISAR‐REACT 5 (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5) trial. The primary end point was a composite of all‐cause death, myocardial infarction, or stroke. Overall, 3011 patients (75%) were recruited in the HRCs (7 centers recruiting 258 to 628 patients; median, 413 patients) and 1007 patients (25%) were recruited in the LRCs (16 centers recruiting 5 to 201 patients; median, 52 patients). Patients recruited in the LRCs had more favorable cardiovascular risk profiles than patients recruited in the HRCs. The primary end point occurred in 72 patients in the LRCs and 249 patients in the HRCs (cumulative incidence, 7.3% and 8.4%; P =0.267). All‐cause mortality was lower among patients recruited in the LRCs (n=29) than among patients recruited in the HRCs (n=134; cumulative incidence 2.9% versus 4.5%; P =0.031). There was no significant interaction between the treatment effect of ticagrelor versus prasugrel and patient recruitment category (LRC versus HRC) regarding the primary efficacy end point (LRC: hazard ratio [HR], 1.42 [95% CI, 0.89–2.28]; HRC: HR, 1.33 [95% CI, 1.04−1.72]; P for interaction=0.800). CONCLUSIONS Patients with acute coronary syndrome recruited in a LRC appear to have more favorable cardiovascular risk profiles and lower 1‐year mortality rates compared with patients recruited in a HRC. The recruitment volume did not interact with the treatment effect of ticagrelor versus prasugrel. REGISTRATION URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01944800.

BACKGROUND The prognostic value of in-hospital haemoglobin drop in patients with acute coronary syndrome (ACS) undergoing invasive therapy remains insufficiently investigated. MATERIALS AND METHODS This observational study included 3838 patients with ACS with admission and in-hospital nadir haemoglobin values available. Haemoglobin drop was defined as a positive difference between admission and nadir haemoglobin values. The primary endpoint was one-year all-cause mortality. RESULTS In-hospital haemoglobin drop occurred in 3142 patients (82%). Patients were categorized into 4 groups: no haemoglobin drop (n = 696 patients)

OBJECTIVE The aim of this study was to investigate the impact of drug eluting stent (DES) overlap on clinical outcomes after percutaneous coronary intervention (PCI). BACKGROUND While the use of overlapping bare metal stent has been associated with an increased risk of adverse clinical events, the long-term impact of DES overlap on clinical outcomes is not certain at present. Similarly, the effect of different DES generations and polymer types on DES overlap associated clinical outcomes has not previously been comprehensively elucidated. METHODS We analyzed the angiographic and clinical outcomes of 5605 patients treated with DES in the setting of the ISAR-TEST 4 and ISAR-TEST 5 randomized control trials according to the presence or absence of stent overlap. The clinical endpoints assessed in this study were all-cause death, myocardial infarction (MI), target lesion revascularization (TLR), and definite or probable stent thrombosis at 10-years. We also compared rates of binary angiographic restenosis (BAR) at 6-8 months. RESULTS At 10 years, all-cause mortality (Hazard ratios [HR] = 1.05 [0.95-1.16]; p = 0.348) did not differ between the stent overlap and no stent overlap groups. MI (8.4% vs. 5.2%; HR = 1.67 [1.35-2.07], p

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.

Importance It is unclear whether ticagrelor or prasugrel hydrochloride is superior for patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). Objective To assess the safety and efficacy of ticagrelor vs prasugrel for patients with ACS treated with PCI. Design, Setting, and Participants A prespecified analysis was performed of a postrandomization subgroup of 3377 patients who presented with ACS and were treated with PCI in the investigator-initiated, multicenter, phase 4, open-label Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5 randomized clinical trial, conducted from September 1, 2013, to February 28, 2018. Statistical analysis was performed from September 1, 2020, to January 30, 2021. Analysis was performed according to the intention-to-treat principle. Interventions Patients were randomly assigned to a ticagrelor-based or prasugrel-based strategy. This analysis focuses on the subgroup of patients who underwent PCI that was formed after randomization. Main Outcomes and Measures The primary end point was a composite consisting of all-cause death, myocardial infarction, or stroke at 12 months. The safety end point was Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding. Results The ticagrelor group comprised 1676 patients (1323 men [78.9%]; mean [SD] age, 64.4 [12.0] years), and the prasugrel group comprised 1701 patients (1341 men [78.8%]; mean [SD] age, 64.7 [12.0] years). The primary end point occurred for 162 patients (9.8%) in the ticagrelor group and 120 patients (7.1%) in the prasugrel group (hazard ratio [HR], 1.41; 95% CI, 1.11-1.78;P = .005). Myocardial infarction occurred in 88 patients (5.3%) in the ticagrelor group compared with 55 patients (3.8%) in the prasugrel group (HR, 1.67; 95% CI, 1.19-2.34;P = .003). The safety end point, BARC type 3 to 5 bleeding, occurred in 84 of 1672 patients (5.3%) in the ticagrelor group and 78 of 1680 patients (4.9%) in the prasugrel group (HR; 1.10; 95% CI, 0.81-1.50;P = .54). Conclusions and Relevance Among patients presenting with ACS who were treated with PCI, the incidence of the primary composite end point occurred less frequently for patients who received prasugrel compared with those who received ticagrelor. The incidence of bleeding events was comparable between the 2 groups. These results suggest that, for patients presenting with ACS who undergo PCI, a prasugrel-based strategy is superior to a ticagrelor-based strategy. However, because these observations are based on a postrandomization subgroup, these findings should be regarded as hypothesis generating and dedicated randomized clinical trials may be warranted to confirm these findings. Trial Registration ClinicalTrials.gov Identifier:NCT01944800

Background: The comparative efficacy and safety of ticagrelor and prasugrel in patients with acute coronary syndrome undergoing complex percutaneous coronary intervention (PCI) has not been defined. Methods: This post hoc analysis included all patients with acute coronary syndrome treated with PCI and randomized to either ticagrelor or prasugrel in the ISAR-REACT 5 trial (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment). Complex PCI was defined as at least one of the following: multivessel PCI, ≥3 stents implanted, ≥3 lesions treated, and total stented length >60 mm. The primary efficacy end point was the composite of all-cause death, myocardial infarction, or stroke; the safety end point was Bleeding Academic Research Consortium types 3 to 5 bleeding. Outcomes were assessed out to 12 months after randomization. Results: Among the 3377 patients treated with PCI in the ISAR-REACT 5 trial, 1429 underwent complex PCI (ticagrelor, N=696 and prasugrel, N=733) and 1948 underwent noncomplex PCI (ticagrelor, N=980 and prasugrel, N=968). There was no interaction between PCI complexity, assignment to either ticagrelor or prasugrel, and the primary efficacy or safety end points ( P for interaction: ≥0.13). In the complex PCI group, the primary efficacy end point (11.0% versus 9.2%, hazard ratio: 1.19 [0.85–1.66], P =0.303) and the safety end point (5.2% versus 6.1%, hazard ratio: 0.83 [0.53–1.31], P =0.419) were not statistically different in patients receiving either ticagrelor or prasugrel. In the noncomplex PCI group, the primary efficacy end point occurred more frequently in patients assigned to ticagrelor as compared to prasugrel (8.9% versus 5.5%, hazard ratio: 1.66 [1.18–2.34], P =0.004) without significant difference in terms of the safety end point (5.4% versus 4.1%, hazard ratio: 1.41 [0.92–2.17], P =0.110). Conclusions: In patients with acute coronary syndrome, PCI complexity does not influence the comparative efficacy and safety of ticagrelor and prasugrel. The observed comparable performance of ticagrelor and prasugrel in patients with acute coronary syndrome undergoing complex PCI requires further confirmation. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01944800.

Background Extended long‐term follow‐up data of new‐generation drug‐eluting stents in patients with diabetes mellitus is scant. The aim of this study is to assess the 10‐year clinical outcome of new‐generation biodegradable polymer‐based sirolimus‐eluting stents (Yukon Choice PC) versus permanent polymer‐based everolimus‐eluting stents (XIENCE) in patients with and without diabetes mellitus. Methods and Results In a prespecified subgroup analysis, outcomes of patients with or without diabetes mellitus treated with drug‐eluting stents were compared. The primary end point of this analysis was major adverse cardiac event, the composite of death, myocardial infarction, or target lesion revascularization. The analysis includes a total of 1951 patients (560 patients with and 1391 patients without diabetes mellitus) randomized to treatment with Yukon Choice PC (n=1299) or Xience (n=652). Regarding the primary end point, at 10 years patients with diabetes mellitus showed significantly higher major adverse cardiac event rates than patients without diabetes mellitus ( P P =0.91; HR, 1.01; 95% CI, 0.79–1.30) nor without diabetes mellitus ( P =0.50; HR, 0.94; 95% CI, 0.79–1.21). Rates of definite/probable stent thrombosis were 2.3% in patients with and 1.9% in patients without diabetes mellitus (HR, 1.27; 95% CI, 0.34–2.60; P =0.52), without significant differences between study devices. Conclusions The clinical outcome of patients with diabetes after percutaneous coronary intervention with different new‐generation drug‐eluting stents is considerably worse than that of patients without diabetes mellitus, with event rates constantly increasing out to 10 years. Registration URL: https://clinicaltrials.gov . Unique Identifier: NCT00598676.

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 mul...

Aims Women and men suffering from coronary artery disease differ in their risk profiles. We sought to investigate the impact of sex on two-year outcomes after BVS implantation in routine clinical practice. Methods and results Sex-based analysis of clinical outcomes was carried out by pooling the individual patient data of the ISAR-ABSORB and KUM-ABSORB registries performed in four high-volume tertiary centres in Munich. Of the total of 1,032 patients, 259 (25.1%) were women. The primary composite endpoint of death, target vessel myocardial infarction (TV-MI) and target lesion revascularisation (TLR) up to two years occurred in 13.2% of women and 17.9% of men (p=0.12). Compared to men, women experienced numerically lower rates of TLR and definite or probable BVS thrombosis - 7.5% vs 12.4% (p=0.051) and 1.2% and 2.7% (p=0.20), respectively. Independent predictors of increased risk for TLR were use of smaller size BVS (HR 1.28, 95% CI: 1.02-1.62), while being a woman was a protective factor (HR 0.59, 95% CI: 0.35-1.00). Conclusions BVS used in a routine setting tend to perform better among women compared to men, which might be partially related to the lower complexity of their coronary artery disease.

OBJECTIVES: We sought to compare the procedural and clinical performance of dual- versus single-catheter strategy for transradial coronary angiography. BACKGROUND: The radial artery (RA) is recommended as the vascular access of choice in patients undergoing coronary angiography and intervention. The procedural and clinical performance of dual- versus single-catheter strategy in patients undergoing transradial coronary angiography remains a matter of debate. METHODS: This is a study-level meta-analysis of randomized trials. The primary outcome was procedure time. The main secondary outcome was fluoroscopy time. Other outcomes of interest were contrast volume, crossover to other catheter strategy and RA spasm. RESULTS: A total of 2,062 patients (978 randomly assigned to dual-catheter and 1,084 to single-catheter strategy) included in seven trials were available for the quantitative synthesis. A dual-catheter strategy was associated with procedure time (standardized mean difference [95% confidence intervals (CI)], 0.55 [-0.69, 1.78]; p = .32), fluoroscopy time (-0.36 [-2.39, 1.67]; p = .68) and contrast volume (-0.93 [-3.79, 1.94]; p = .44) comparable to a single-catheter strategy. The risk for crossover was lower (risk ratio [95% CI], 0.14 [0.03, 0.70]; p = .025) while the risk for RA spasm was higher (1.81 [1.54, 2.12]; p

Ziel einer Myokardrevaskularisation bei Patienten mit KHK ist die Verbesserung persistierender Symptome und der Prognose. Der Erfolg hangt stark von der Vollstandigkeit der Revaskularisation ab. Die anatomische Komplexitat und das Vorliegen von Komorbiditaten wie Diabetes mellitus bestimmen masgeblich die relativen Vorteile von PCI und Bypass-Operation. Im Fall einer PCI sollte diese uber einen transradialen Zugangsweg mit Implantation eines DES der neuen Generation erfolgen.

BACKGROUND Whether there are sex differences in the outcome of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains controversial. We undertook this study to assess whether there are sex-related differences in the long-term mortality in a large series of patients with CAD after PCI. METHODS The study included 18,334 patients (4735 women and 13,599 men) with CAD treated with PCI. Propensity matching was performed to obtain a group of patients (3000 women and 3000 men) matched for all characteristics available in database. The primary outcome was a composite of cardiac mortality, myocardial infarction or stroke at 3 years of follow-up. RESULTS The primary outcome occurred in 660 women and 1440 men (Kaplan-Meier [KM] estimates, 15.2% in women and 11.6% in men, unadjusted hazard ratio [HR] = 1.35, 95% confidence interval [CI] 1.24 to 1.49; P

OBJECTIVES We aimed to assess the association of left ventricular end-diastolic pressure (LVEDP) with myocardial salvage and long-term mortality in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). BACKGROUND The association of LVEDP with myocardial salvage or long-term mortality in patients with STEMI has not been investigated. METHODS This study included 1,312 patients with STEMI undergoing primary PCI between 2002 and 2007. LVEDP was measured at the time of intervention. Patients were divided into three groups: a group with LVEDP in the 1st tertile (LVEDP, 4-19 mmHg; n = 496), a group with LVEDP in the 2nd tertile (LVEDP >19-24 mmHg; n = 410) and a group with LVEDP in the 3rd tertile (LVEDP >24-45 mmHg; n = 406). The primary outcome was 8-year cardiac mortality. RESULTS The primary outcome (cardiac deaths) occurred in 114 patients. Deaths occurred in 26 (7.9%), 36 (11.5%), and 52 (16.4%) patients with LVEDP in the 1st to 3rd tertiles, respectively (adjusted hazard ratio = 1.18, 95% confidence interval 1.02-1.36, P = 0.022, for 5 mmHg increment in the LVEDP values). LVEDP correlated with the extent of myocardial ischemia (R = 0.351; P

The relationship between central pulse pressure (CPP) measured at the time of primary percutaneous coronary intervention (PPCI) and long-term prognosis after ST-segment elevation myocardial infarction (STEMI) has not been investigated. CPP measurements were performed in 1348 patients with STEMI (327 women; mean age 62.5 ± 12.1 years) undergoing PPCI. Aortic systolic and diastolic blood pressure was measured before intervention. The primary outcome was 8-year all-cause mortality. The median [25–75th percentile] CPP value was 55.0 [43.0–70.0] mmHg. CPP correlated negatively with heart rate (P

Background: New-generation drug-eluting stents offer the potential for enhanced late outcomes in comparison with early generation drug-eluting stents. However, assessment of extended long-term outcomes for these devices is lacking, especially regarding the comparison between new-generation drug-eluting stents with biodegradable or permanent polymers. The aim of this study is to compare the efficacy and safety of biodegradable polymer-based sirolimus-eluting stents (BP-SES; Yukon Choice PC) versus permanent polymer-based everolimus-eluting stents (PP-EES; Xience) versus early generation permanent polymer-based sirolimus-eluting stents (PP-SES; Cypher) at 10-year follow-up. Methods: Overall, 2603 patients were randomized to treatment with BP-SES (n=1299), PP-EES (n=652), or PP-SES (n=652). The primary end point of this analysis was major adverse cardiac event, the composite of death, myocardial infarction, or target lesion revascularization. The main secondary end point of interest was definite/probable stent thrombosis. Follow-up at 10 years was available in 83% of the study patients. Results: The 10-year incidence of major adverse cardiac event (BP-SES 47.7% versus PP-EES 46.0% versus PP-SES 54.9%, P =0.003) and mortality (BP-SES 31.8% versus PP-EES 30.3% versus PP-SES 37.2%, P =0.02) was different among the groups. Definite/probable stent thrombosis was not significantly different among the groups (BP-SES 1.8% versus PP-EES 2.5% versus PP-SES 3.7%, P =0.09). Definite stent thrombosis was significantly different among the groups (BP-SES 1.1% versus PP-EES 0.8% versus PP-SES 2.4%, P =0.03). There were no significant differences between BP-SES and PP-EES. Conclusions: In this unique long-term outcome analysis, BP-SES and PP-EES showed comparable clinical outcomes out to 10 years. PP-SES had higher rates of major adverse cardiac events and definite stent thrombosis. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00598676.

BACKGROUND: Clinical and angiographic outcomes following recanalisation of coronary chronic total occlusions (CTO) through contemporary dissection and re-entry techniques (DART) as opposed to intraplaque techniques remain controversial. AIMS: The aim of this study was to compare clinical and angiographic outcomes following subintimal and intraplaque CTO recanalisation. METHODS: A total of 454 consecutive patients undergoing successful CTO recanalisation (473 vessels) were included. Intraplaque techniques were used in 403 (85.2%) and DART in 70 (14.8%) vessels. Surveillance angiography was scheduled at 6-9 months and clinical follow-up was performed up to 12 months. RESULTS: There were no significant differences in terms of the cumulative incidence of MACE (p=0.908) or binary restenosis (p=0.320) between the two groups. There was no independent correlation between recanalisation technique and MACE occurrence or in-segment binary restenosis. Target lesion revascularisation (TLR) was performed in 60 (17.5%) and 12 (18.1%) (p=0.719) lesions, respectively. The occurrence of occlusive restenosis was low (7 [2.3%] vs 1 [1.6%]; p=0.824) and comparable between groups. CONCLUSIONS: Contemporary DART are associated with similar midterm clinical and angiographic outcomes compared to intraplaque recanalisation. The rate of occlusive restenosis was low and comparable in both groups. Regardless of recanalisation technique, the overall incidences of binary restenosis and TLR following CTO recanalisation remain higher than those reported for non-CTO PCI.

Background The clinical impact of early aspirin discontinuation compared with dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention with stenting remains poorly studied. We investigated the clinical outcomes of patients assigned to either early aspirin discontinuation or DAPT after percutaneous coronary intervention with stenting. Methods and Results We performed a meta‐analysis of aggregate data from randomized clinical trials enrolling participants receiving a percutaneous coronary intervention with stenting and assigned to either early aspirin discontinuation or DAPT. Scientific databases were searched from inception through March 30, 2020. Trial‐level hazard ratios (HRs) and 95% CIs were pooled using a random effects model with inverse variance weighting. The primary outcome was all‐cause death. Secondary outcomes were myocardial infarction, stent thrombosis, stroke, and major bleeding. Overall, 36 206 participants were allocated to either early aspirin discontinuation (experimental therapy, n=18 088) or DAPT (control therapy, n=18 118) in 7 trials. Median follow‐up was 12 months. All‐cause death occurred in 2.5% of patients assigned to experimental and 2.9% of patients assigned control therapy (hazard ratio [HR], 0.91, 95% CI, 0.75–1.11; P =0.37). Overall, patients treated with experimental versus control therapy showed no significant difference in terms of myocardial infarction (HR, 1.02 [0.85–1.22], P =0.81), stent thrombosis (HR, 1.02 [0.87–1.20], P =0.83), or stroke (HR, 1.01 [0.68–1.49], P =0.96). However, the risk for major bleeding (HR, 0.58 [0.43–0.77], P Conclusions In patients treated with percutaneous coronary intervention and stenting, assigned to a strategy of early aspirin discontinuation versus DAPT, the risk of death and ischemic events is not significantly different but the risk of bleeding is lower.

Background In-stent restenosis (ISR) represents the more frequent modality of stent failure. The currently recommended treatment strategies are represented by repeat drug-eluting stent (DES) implantation or drug-coated balloon (DCB) angioplasty. Optical coherence tomography can display important information regarding mechanisms of stent failure as well as neointimal characterization. Purpose Aim of the present study was to determine the impact of treatment modality (DES vs. DCB) as well as neointimal characteristics (homogeneous vs. non-homogeneous) as determined by intravascular OCT, on clinical outcomes and explore whether there is an interaction between neointimal pattern of ISR and treatment modality. Methods Patients presenting with ischemic symptoms and/or evidence of myocardial ischemia in three European centers and undergoing intravascular OCT prior to percutaneous coronary intervention (PCI) for ISR, were retrospectively included in this study. Characterization of neointimal tissue was performed at the frame displaying the maximal %AS as well as the 5 preceding and following analyzed frames. Each frame was subdivided in 4 quadrants (90°) and the neointimal characteristics separately characterized for each of them. Based on its optical characteristics, neointimal tissue was categorized as homogeneous, heterogeneous, layered or neoatherosclerosis. Based on the dominant neointimal type, the study population was divided in two groups, (predominantly homogeneous and non-homogeneous). Primary endpoints of the study were represented by major adverse cardiac events (MACE) and its idividual components (death, cardiac death, myocardial infarction and target lesion revascularization (TLR)) at 2 years follow-up. Results A total of 197 patients undergoing OCT prior to PCI for ISR were included in this study. 100 patients were classified as having predominantly homogeneous and 97 as having predominantly non-homogeneous neointima. No association was found between predominant OCT pattern (homogenous vs. non-homogenous) and MACE at 2 years follow-up (HR=1.01, 95% CI: 0.59–1.75; p=0.94), or the individual MACE components. Analogously, no significant differences in terms of MACE at 2 years were found between predominantly homogeneous vs. non-homogeneous neointima in the patient subgroup receiving a DES (p=0.10) and in that undergoing DCB treatment (p=0.11). However, a significant interaction was found between neointimal tissue pattern and treatment modality in terms of MACE (p=0.02) aa well as death or MI (p=0.016). Predominantly non-homogeneous neointima in patients treated with DCB was associated with a higher incidence of MACE. Conclusions Our results indicate that there is a significant interaction between treatment modality of ISR (DES vs. DCB) and neointimal pattern as determined by intravascular OCT. These results land initial support to an OCT-guided treatment of ISR and should be confirmed by larger trials. Funding Acknowledgement Type of funding source: None

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.Although drug-eluting stents are safe and effective for treatment of the ULMCA, increased rates of repeat revascularization have been observed.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.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/mMortality 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.

Background Outcome data after extended long-term follow-up of patients with coronary artery disease treated with drug-eluting stents (DES) in randomized clinical trials is scant. Objective Performance differences between devices may be expected to emerge over time depending on whether stenting is done with polymer-free or durable polymer DES. We assessed the 10-year outcomes of patients enrolled in the ISAR-TEST 5 trial. Methods 3002 patients were randomized to treatment with either polymer-free sirolimus- and probucol-eluting stents (PF-SES) (n=2002) or durable polymer zotarolimus-eluting stents (DP-ZES) (n=1000). The primary endpoint was the composite of cardiac death, target vessel-related myocardial infarction or target lesion revascularisation (a device-oriented composite endpoint, DOCE). Additional endpoints of interest were the patient-oriented composite endpoint (POCE), including all-cause death, any myocardial infarction or any revascularisation, individual components of the composite endpoints, and definite or probable stent thrombosis. Results The median age of the patients at randomization was 67.8 years. At 10-years, 63.9% of patients were alive. The rates of DOCE and POCE were high in both groups with no difference in the incidence between PF-SES and DP-ZES, (DOCE: 43.8% versus 43.0%, respectively, hazard ratio = 1.01, 95% CI, 0.89–1.14; P=0.90), (POCE: 66.2% versus 67.7%, respectively, hazard ratio = 0.94, 95%CI, 0.86–1.04; P=0.22). The rates of the individual components of the composite endpoints were comparable in both groups. The incidence of definite/probable stent thrombosis over 10 years was low and comparable in both groups (1.6% vs. 1.9%; hazard ratio = 0.85 [95% CI, 0.46–1.54], P=0.58). Conclusion At 10 years there were no measurable differences in outcomes between patients treated with polymer-free versus durable polymer DES. The incidence of stent thrombosis was low and comparable in both groups. High overall adverse clinical event rates were observed during extended follow-up.

Aims To investigate the clinical outcomes associated with an antithrombotic therapy with or without clopidogrel after transcatheter aortic valve replacement (TAVR). Methods and results This is a study-level meta-analysis including all randomized trials investigating antithrombotic regimens after TAVR. The protocol was registered with PROSPERO (CRD42020191036). We searched electronic scientific databases for eligible studies. The primary outcome was all-cause death. Main secondary outcome was major bleeding. Other outcomes were life-threatening (or disabling) bleeding, myocardial infarction (MI) and stroke. Six eligible trials randomly allocated 3056 TAVR patients to aspirin or oral anticoagulation (OAC) with clopidogrel (n = 1525) versus aspirin and/or OAC without clopidogrel (n = 1531). In the overall estimates, an antithrombotic therapy with clopidogrel versus without displayed a comparable risk of all-cause death [Risk Ratio—RR = 0.83, 95% Confidence intervals—CI (0.57–1.20); P = 0.25] and major bleeding [RR = 1.33, 95% CI (0.61–2.92); P = 0.39]. However, the combination of aspirin or OAC with clopidogrel doubled the risk of major bleeding as compared to aspirin or OAC without clopidogrel [RR = 2.08, 95% CI (1.27–3.42); P = 0.015, P for interaction = 0.021]. Treatment strategies did not differ with respect to the risk of life-threatening bleeding, MI and stroke. Conclusions In patients receiving TAVR, a therapeutic strategy of aspirin or OAC with clopidogrel significantly increases the risk of major bleeding without impact on mortality and ischemic outcomes compared to aspirin or OAC without clopidogrel. The performance of different antithrombotic regimens in terms of long-term clinical outcomes and bioprosthesis valve function requires further investigation. Graphic abstract Forest plots from pairwise and network meta-analyses associated with an antithrombotic therapy with or without clopidogrel Risk ratio for all outcomes of interest calculated with the pairwise meta-analysis (left side) and for main outcomes calculated with the network meta-analysis (right side) in patients allocated to an antithrombotic therapy with clopidogrel or without. The diamonds indicate the point estimate and the left and the right ends of the lines the [95% CI]. CI: Confidence intervals; OAC; oral anticoagulation.

Objectives The present study aims to analyze the angiographic anti-restenotic performance of durable polymer everolimus-eluting stents (EES) for the treatment of in-stent restenosis (ISR) in daily practice. Background Randomized data is available supporting the use of drug-coated balloons and drug-eluting stents for the treatment of ISR; however, additional real-world data including angiographic follow-up is needed. Methods Patients who underwent EES-implantation for the treatment of drug-eluting stent ISR and attended for a 6-8 months angiographic surveillance were analyzed. Off-line assessment of the angiograms was conducted at a central quantitative coronary angiographic core laboratory. Results A total of 426 patients with ISR were treated with EES and had undergone angiographic follow-up. The mean age was 66.8 ± 9.9 years and 27.5% suffered from diabetes. A total of 459 lesions were treated. The diameter stenosis decreased from 64.3 ± 19.1% (preprocedural) to 12.0 ± 6.4% (postprocedural). At 6-8 months angiographic follow-up, the in-segment diameter stenosis was 38.3 ± 21.7% and the in-stent late luminal loss was 0.54 ± 0.74 mm in the treated area analysis. The rate of recurrent binary restenosis was 25.7%. Conclusions In the setting of ISR, the angiographic anti-restenotic efficacy of stenting with EES is comparable to that observed in randomized clinical trials and less favorable than its performance in patients undergoing stenting for de novo disease.

In patients with acute myocardial infarction (MI) receiving percutaneous coronary intervention (PCI), the role of systemic therapeutic hypothermia remains controversial. We sought to investigate the role of systemic therapeutic hypothermia versus standard of care in patients with acute MI treated with PCI. This is a study-level meta-analysis of randomized trials. The primary outcome was all-cause death. The main secondary outcome was infarct size. Other secondary outcomes were recurrent MI, ischemia-driven target vessel revascularization (TVR), major adverse cardiovascular events, and bleeding. A total of 1012 patients with acute MI receiving a PCI in nine trials (503 randomly assigned to hypothermia and 509 to control) were available for the quantitative synthesis. The weighted median follow-up was 30 days. As compared to controls, patients assigned to hypothermia had similar risk of all-cause death (risk ratio, [95% confidence intervals], 1.25 [0.80; 1.95], p = 0.32), with a trend toward higher risk of ischemia-driven TVR (3.55 [0.80; 15.87], p = 0.09) mostly due to acute or subacute stent thrombosis. Although in the overall cohort, infarct size was comparable between groups (standardized mean difference [95% Confidence intervals], 0.06 [− 0.92; 1.04], p = 0.92), patients effectively achieving the protocol-defined target temperature in the hypothermia group had smaller infarct size as compared to controls (p for interaction = 0.016). Treatment strategies did not differ with respect to the other outcomes. As compared to standard of care, systemic therapeutic hypothermia in acute MI patients treated with PCI provided similar mortality with a signal toward more frequent repeat revascularization. Among patients assigned to hypothermia, those effectively achieving the protocol-defined target temperature displayed smaller infarct size. PROSPERO, CRD42019138754.

Aims The ultrathin-strut biodegradable polymer sirolimus-eluting stent (SES) is a new-generation drug-eluting stent (DES) developed to improve the percutaneous treatment of patients with coronary artery disease. Here, we sought to investigate whether the performance of the ultrathin-strut biodegradable polymer SES is superior to that of the benchmark thin-strut fluoropolymer-based everolimus-eluting stent (EES). Methods and results We undertook a study-level meta-analysis of trials in which patients receiving percutaneous coronary intervention (PCI) were randomly assigned to either SES or EES. Primary efficacy and safety outcomes were target lesion revascularisation (TLR) and definite/probable stent thrombosis (ST), respectively. Secondary outcomes were myocardial infarction (MI), death, target lesion failure (TLF) and target vessel failure (TVF). A total of 4,853 patients received a PCI with either SES (n=2,816) or EES (n=2,037) in six trials. After a weighted median follow-up of 12 months, patients treated with SES had a risk of TLR (odds ratio [95% confidence interval]: 1.24 [0.83-1.85], p=0.30), definite/probable ST (0.84 [0.53-1.33], p=0.45) and MI related to the target vessel (0.77 [0.55-1.07], p=0.12) comparable to that of patients treated with EES. We found no significant difference with regard to other secondary outcomes. Conclusions At one-year follow-up, the ultrathin-strut biodegradable polymer sirolimus-eluting stent displays a performance comparable to that of the fluoropolymer-based everolimus-eluting stent.

Background Drug-eluting stents with biodegradable polymer coatings have shown promising outcomes in randomised studies. Methods We compared neointimal healing patterns including strut coverage and assessed neointimal maturity using a novel algorithm in coronary lesions treated with sirolimus-eluting stents with biodegradable polymer coating (BP-SES) or everolimus eluting stents with permanent polymer coating (PP-EES) using optical coherence tomography after 6months. Results A total of 39 patients were randomised to BP-SES ( n =19) or PP-EES ( n =20) for the treatment of coronary lesions. Of those, 29 patients (14 BP-SES and 15 PP-EES) underwent optical coherence tomography (OCT) and angiography at 6-month follow-up. Tissue coverage and apposition were assessed in a total of 6162 struts (BP-SES, n =2889; PP-EES, n =3273). Neointimal maturity was assessed in 3672 neointimal regions above struts using grey scale intensity analysis. OCT analysis showed neointimal coverage of 2433 (BP-SES) vs. 2702 (PP-EES) struts (84.2% vs. 82.6%, p =0.70), whereas the remainder was uncovered after 6months. Mean neointimal thickness did not differ significantly between groups (54.3±7.8μm vs. 80±14.6μm, p =0.12). The rate of malapposed struts was comparable between groups (1.3% vs. 2.2%, p =0.27). Grey scale signal intensity analysis showed mature tissue coverage of struts in 46.2% in BP-SES vs. 31.8% in PP-EES ( p =0.31) of neointimal regions. Conclusion The present study showed comparable early vascular healing response characterised by neointimal coverage with mainly immature neointima in both BP-SES and PP-EES.

Background In the ISAR-CABG (Is Drug-Eluting-Stenting Associated with Improved Results in Coronary Artery Bypass Grafts?) trial, clinical outcomes at 1 year in patients undergoing treatment of saphenous vein graft lesions were superior with drug-eluting stents (DES) versus bare-metal stents. Objectives The authors compared outcomes between treatment groups at 5 years. Methods Patients were randomized (1:1:1:3) to receive DES (either permanent-polymer paclitaxel-eluting stents, permanent-polymer sirolimus-eluting stents, or biodegradable-polymer sirolimus-eluting stents) or bare-metal stents. The primary endpoint was the combined incidence of death, myocardial infarction (MI), or target lesion revascularization (TLR). Secondary endpoints were the composite of death or MI and TLR. Results A total of 610 patients were allocated to treatment with DES (n = 303) or bare-metal stents (n = 307). At 5 years, the primary endpoint occurred in 159 (55.5%) versus 157 (53.6%) patients in the DES and bare-metal stent groups, respectively (hazard ratio [HR]: 0.98; 95% confidence interval [CI]: 0.79 to 1.23; p = 0.89). There was interaction between treatment effect and time (p interaction = 0.005), with a lower event rate in the DES group at 1 year (HR: 0.64; 95% CI: 0.44 to 0.94; p = 0.02) but a numerically higher rate between 1 and 5 years (HR: 1.24; 95% CI: 0.94 to 1.63; p = 0.13). Death or MI occurred in 93 (32.8%) versus 108 (36.6%) patients, respectively (HR: 0.85; 95% CI: 0.64 to 1.12; p = 0.24), without significant interaction between treatment effect and time (p interaction = 0.57). TLR occurred in 84 (33.1%) versus 69 (25.5%) patients in the DES and bare-metal stent groups, respectively (HR: 1.20; 95% CI: 0.87 to 1.64; p = 0.27). There was interaction between treatment effect and time (p interaction Conclusions In patients undergoing treatment of saphenous vein graft lesions, the advantage of DES over bare-metal stents demonstrated at 1 year was lost at 5 years due to higher attrition of efficacy in the DES group. (Efficacy Study of Drug-Eluting and Bare Metal Stents in Bypass Graft Lesions [ISAR-CABG]; NCT00611910)

Background Angioplasty with paclitaxel-coated balloons (PCB) is recommended for treatment of patients with coronary in-stent restenosis (ISR) according to European clinical practice guidelines. Most clinical trials have investigated iopromide-based PCB and there is a paucity of data comparing efficacy against butyryl-tri-hexyl citrate (BTHC)-based PCB. Our aim was to compare the performance of two widely-used PCB in the treatment of coronary ISR. Methods We analysed patients treated with BTHC- or iopromide-PCB for treatment of drug-eluting stent ISR in the setting of 2 consecutive trials with identical inclusion and exclusion criteria. The primary endpoint was diameter stenosis at 6–8 month angiographic surveillance. The secondary endpoint of interest was the composite of death, myocardial infarction (MI) or target-lesion revascularisation (TLR) at 1 year. Multivariate analysis was performed to adjust for differences in baseline characteristics between groups. Results In total, 264 patients were treated with BTHC-PCB (n = 127) or iopromide-PCB (n = 137). Baseline patient characteristics were similar for both groups. Post-procedure stenosis was slightly larger with BTHC-PCB (22.3 [SD 8.2]% vs. 18.4 [SD 9.9]%, P = 0.001). At 6–8 month angiography, diameter stenosis was 40.4 [SD 21.9]% vs. 37.4 [SD 21.4]% in the BTHC-PCB and iopromide-PCB groups, respectively (P = 0.16, Padjusted = 0.32). At 1 year, death, MI or TLR occurred in 29 (23.2%) vs. 32 (23.4%) patients in the BTHC-PCB and iopromide-PCB groups, respectively (HR 1.03 [95% CI 0.62–1.70], P = 0.91, Padjusted = 0.96). Conclusions In patients undergoing intervention for ISR, angioplasty with BTHC-PCB showed similar angiographic and clinical results at 1 year compared with iopromide-PCB.

Objectives The aim of this study was to compare neointimal modification with scoring balloon pre-dilation before drug-coated balloon (DCB) versus DCB standard therapy in patients presenting with drug-eluting stent (DES) restenosis. Background DCB angioplasty for the treatment of coronary drug-eluting stent restenosis has demonstrated encouraging results. The efficacy of DCB treatment relies on rapid initial drug transfer and tissue retention of the antiproliferative drug. Neointimal modification with scoring balloon pre-dilation may enhance the efficacy of DCB therapy. Methods In this randomized, open-label, active-controlled trial, 252 patients with clinically significant DES restenosis were enrolled at 4 centers in Germany. Patients undergoing DCB angioplasty were randomly assigned to treatment with scoring balloon pre-dilation or standard therapy. The primary endpoint of the study was in-segment percentage diameter stenosis on 6- to 8-month follow-up angiography. The secondary endpoints included binary angiographic restenosis and late lumen loss on follow-up angiography, the combined incidence of death or myocardial infarction, target lesion revascularization, and target lesion thrombosis at 1 year. Results Follow-up angiographic data at 6 to 8 months were available for 203 patients (80.6%). Scoring balloon pre-dilation compared with standard therapy showed significantly lower rates with respect to the primary endpoint (35.0 ± 16.8% vs. 40.4 ± 21.4%; p = 0.047) and binary angiographic restenosis (18.5% vs. 32.0%; p = 0.026). Late lumen loss was numerically lower after scoring balloon pre-dilation compared with standard therapy (0.31 ± 59 mm vs. 0.41 ± 0.74 mm; p = 0.27). There was no difference between the groups in the incidence of death or myocardial infarction (4.0% vs. 3.4%; p = 0.73). Scoring balloon versus standard therapy showed comparable rates of target lesion revascularization (16.2% vs. 21.8%; p = 0.26). No target lesion thrombosis occurred out to 1 year. Conclusions In patients presenting with drug-eluting stent restenosis, neointimal modification with scoring balloon improves the antirestenotic efficacy of DCB therapy. (Intracoronary Stenting and Angiographic Results: Optimizing Treatment of Drug Eluting Stent In-Stent Restenosis 4 [ISAR-DESIRE 4]; NCT01632371)

Objectives The aim of this study was to report clinical outcomes in patients treated in routine practice 2 years after everolimus-eluting bioresorbable stent (BRS) implantation. Background Long-term results in patients undergoing BRS implantation in routine clinical practice are sparse, and existing evidence from randomized trials considers mostly selected patients. Methods The ISAR-ABSORB registry enrolled consecutive patients undergoing BRS implantation in routine clinical practice at 2 high-volume centers in Germany. Angiographic follow-up was scheduled after 6 to 8 months and clinical follow-up to 24 months. The primary endpoint was the composite of death, myocardial infarction, or target lesion revascularization, and secondary endpoints included individual components of the primary endpoint and definite stent thrombosis. Event rates were calculated using the Kaplan-Meier method. Results A total of 419 patients were included. The mean age was 66.6 ± 10.9 years, 31.5% had diabetes, and 39.0% presented with acute coronary syndrome. Forty-nine percent of lesions were considered complex (American College of Cardiology/American Heart Association type B2 or C), and 13.1% were bifurcation lesions. The mean reference vessel diameter was 2.89 ± 0.46 mm. At 2 years, the primary endpoint had occurred in 21.6% of patients: death in 6.3%, myocardial infarction in 3.9%, target lesion revascularization in 16.0%, and definite stent thrombosis in 3.8%. Conclusions Long-term follow-up of patients treated with BRS in routine practice showed higher event rates than expected. Future studies are required to determine the impact of changes in implantation technique and to define the optimal duration of dual antiplatelet therapy in these patients.

Drug-eluting Stents (DES) der neusten Generation versprechen gut etablierte Losungen fur die Behandlung von KHK-Patienten mit einer stetig wachsenden Auswahl unterschiedlichster DES. Bezuglich bioabsorbierbarer Koronarscaffolds wachsen Zweifel, ob deren aktuelle Ausreifung tatsachlich dazu beitragt, Sicherheit und Effektivitat im Vergleich zu DES der neuen Generation zu verbessern.

Background Outcome data after extended long-term follow-up of patients with coronary artery disease treated with drug-eluting stents (DES) in randomized clinical trials are scant. Objectives Performance differences among devices may be expected to emerge over time depending on whether stenting is done with polymer-free or durable polymer DES. This study assessed the 10-year outcomes of patients enrolled in the ISAR-TEST-5 (Test Efficacy of Sirolimus- and Probucol-Eluting Versus Zotarolimus-Eluting Stents) trial. Methods A total of 3,002 patients were randomized to treatment with either polymer-free sirolimus- and probucol-eluting stents (n = 2,002) or durable polymer zotarolimus-eluting stents (n = 1,000). The primary endpoint was the composite of cardiac death, target vessel–related myocardial infarction, or target lesion revascularization (a device-oriented composite endpoint [DOCE]). Additional endpoints of interest were the patient-oriented composite endpoint (POCE), including all-cause death, any myocardial infarction, or any revascularization; individual components of the composite endpoints; and definite or probable stent thrombosis. Results The median age of the patients at randomization was 67.8 years. At 10 years, 63.9% of patients were alive. The rates of DOCE and POCE were high in both groups with no difference in the incidence between polymer-free sirolimus- and probucol-eluting stents and durable polymer zotarolimus-eluting stents (DOCE: 43.8% vs. 43.0%, respectively; hazard ratio: 1.01; 95% confidence interval [CI]: 0.89 to 1.14; p = 0.90; POCE: 66.2% vs. 67.7%, respectively; hazard ratio: 0.94; 95% CI: 0.86 to 1.04; p = 0.22). The rates of the individual components of the composite endpoints were comparable in both groups. The incidence of definite/probable stent thrombosis over 10 years was low and comparable in both groups (1.6% vs. 1.9%; hazard ratio: 0.85; 95% CI: 0.46 to 1.54; p = 0.58). Conclusions At 10 years, there were no measurable differences in outcomes between patients treated with polymer-free versus durable polymer DES. The incidence of stent thrombosis was low and comparable in both groups. High overall adverse clinical event rates were observed during extended follow-up. (Test Efficacy of Sirolimus- and Probucol-Eluting Versus Zotarolimus-Eluting Stents [ISAR-TEST-5]; NCT00598533 )