Very long-term efficacy and safety of paclitaxel-eluting balloon after a bare-metal stent for the treatment of ST-elevation myocardial infarction: 8-year results of a randomized clinical trial (PEBSI study).

Background: Drug-eluting stents (DES) are considered the therapy of choice in ST-segment elevation myocardial infarction (STEMI); however, a low persistent rate of revascularizations and stent thrombosis exist over the time. We have previously shown that a paclitaxel (PTX)-drug-coated balloon (DCB) after a bare-metal stent (BMS) implantation (DCB-combined strategy) yields superior angiographic and clinical results compared to BMS in the short term. However, the long-term safety and efficacy of this approach remain uncertain. Methods: An 8-year clinical follow-up was conducted on patients enrolled in the randomized PEBSI-1 trial (NCT01839890). The original trial included patients who suffered a STEMI, patients were randomly assigned to receive a DCB-combined strategy or BMS only and the primary endpoint was in-stent late luminal loss (LLL) at 9-month follow-up. After the completion of this study, death, myocardial re-infarction, ischemia-driven repeated revascularizations included target lesion revascularization (TLR) and target vessel revascularization (TVR), and stent thrombosis, were assessed by yearly contact by a clinical visit, telephone or by electronic records. These outcomes were adhered to ARC-2 criteria. Results: The rate of incomplete follow-up was very low, with only 3 out of 111 patients (2.7%) in the DCB-combined strategy group and 1 out of 112 patients (0.9%) in the BMS group. At 8 years there were a lower rate of TVR [3.7% vs. 14.3%; hazard ratio (HR): 0.243; 95% confidence interval (CI): 0.081-0.727; P=0.006], and a trend towards lower TLR (2.8% vs. 8.9%; HR: 0.300; 95% CI: 0.083-1.090; P=0.052) in the DCB-combined strategy group. No statistical difference between the DCB-combined strategy and BMS groups were found for all causes of death, deaths from cardiovascular disease, reinfarctions or stent thrombosis. Notably in the DCB-combined strategy group, no episode of stent thrombosis occurred after the first year. Similarly, there were no cardiovascular deaths, TVR and TLR in the DCB-combined strategy group after 5 years. In contrast, during the period from year 5 to 8, the BMS group experienced an additional cardiovascular death, as well as one case of TVR, one case of TLR, and one case of stent thrombosis. Conclusions: In STEMI patients, the DCB-combined strategy maintains its safety and clinical efficacy over time. Our rates of TVR, TLR, and very late stent thrombosis (VLST) at very long-term are the lowest ever found in a STEMI trial. Further studies are warranted to assess the potential superiority of this novel strategy as compared with new-generation DES to prevent very late events in these patients. Trial Registration: ClinicalTrials.gov; identifier: NCT01839890.

Early coronary healing in ST segment elevation myocardial infarction: sirolimus-eluting stents vs. drug-coated balloons after bare-metal stents. The PEBSI-2 optical coherence tomography randomized study.

OBJECTIVES: Drug-coated balloons (DCBs) have theoretical advantages over drug-eluting stents (DESs) to facilitate stent healing. We studied whether, in patients undergoing primary coronary interventions (pPCIs), a strategy of DCB after bare-metal stent improves early healing as determined by optical coherence tomography (OCT) compared with new-generation DES. METHODS: pPCI patients were randomized (1:1) to treatment with new-generation sirolimus-eluting stents (DES group) or DCB-strategy. Vessel healing was assessed by OCT at 90 days. RESULTS: Fifty-three patients were randomized (26 DES vs. 27 DCB). At 90 days, both strategies showed a low rate of uncovered struts (3.2 vs. 3.2%, P = 0.64) and a very high and similar rate of covered and apposed struts (96.6 vs. 96.1%, respectively; P = 0.58). However, DCB group had a significantly lower rate of major coronary evaginations (68 vs. 37%, P = 0.026), and more frequently developed a thin homogeneous neointimal layer (20 vs. 70.4%, P = 0.001) suggesting distinct superior healing at 3 months compared to DES. CONCLUSIONS: In pPCI both, sirolimus-DES and DCB-strategy, provide excellent strut coverage at 3 months. However, DCB ensures more advanced and optimal stent healing compared to sirolimus-DES. Further research is needed to determine whether, in patients undergoing pPCI, DCB offers superior long-term clinical and angiographic outcomes than new-generation DES (NCT03610347).

Intracoronary tenecteplase versus abciximab as adjunctive treatment during primary percutaneous coronary intervention in patients with anterior myocardial infarction.

AIMS: We sought to compare the effects of intracoronary administration of a fibrinolytic drug (tenecteplase) to those of a glycoprotein IIb/IIIa inhibitor (abciximab) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). METHODS AND RESULTS: In this pilot trial, 76 patients (59 male) with anterior STEMI were randomised to intracoronary infusion of reduced-dose tenecteplase or abciximab during PPCI. Angiography was repeated at 48 hours to assess corrected TIMI frame count (cTFC) and TIMI myocardial perfusion grade (TMPG). The primary endpoint was infarct size as assessed by cardiac MRI. The abciximab group showed lower cTFC (median 14.1 [IQR 9.4-17.1]) than the tenecteplase group (18.2 [10.0-28.2]) (p=0.02), and the proportion of patients with TMPG grade 2/3 was higher in the abciximab group (90.3% vs. 67.7%; p=0.03). Major cardiac and cerebrovascular event rates did not differ; however, notably, 2/38 patients in the tenecteplase group experienced subacute stent thrombosis. At four months, there were no significant differences in infarct size between the tenecteplase and abciximab groups (17.0 g [9.6-27.5] vs. 21.1 g [11.3-35.0], p=0.33). CONCLUSIONS: Intracoronary administration of tenecteplase did not reduce infarct size compared to abciximab in STEMI patients undergoing PPCI. Tenecteplase exhibited poorer myocardial reperfusion and might be associated with increased subacute stent thrombosis.

A randomised trial of paclitaxel-eluting balloon after bare metal stent implantation vs. bare metal stent in ST-elevation myocardial infarction (the PEBSI study).

AIMS: Our aim was to assess the safety and efficacy of paclitaxel-eluting balloon (PTX-B) treatment after bare metal stent (BMS) implantation in patients undergoing primary angioplasty. METHODS AND RESULTS: After BMS implantation, patients were randomised (1:1) to treatment with a PTX-B or no PTX-B treatment (BMS group). The primary endpoint was in-stent late luminal loss (LLL) at nine-month follow-up. OCT was carried out on the first 20% of consecutive patients included in the study. Two hundred and twenty-three patients were randomised (BMS: 112, PTX-B: 111). At nine months, median LLL was 0.80 mm (interquartile range [IQR] 0.36-1.26) in the BMS group vs. 0.31 mm (IQR 0.00-0.58) in the PTX-B group, p<0.0001. Binary restenosis was significantly lower in the PTX-B group: 29.8% vs. 2.2%, p<0.0001, 95% confidence interval (CI): 3.2-54.2. Nine-month OCT showed good strut coverage in both groups but greater in the BMS group (100±0.0% vs. 99.52±1.11%, p=0.03) with very low rates of malapposed struts per lesion. One-year MACE was significantly lower in the PTX-B group (12.5% vs. 3.6%, p=0.016). CONCLUSIONS: PTX-B after successful BMS implantation resulted in less LLL and better clinical outcomes as compared with a BMS-only strategy. This was associated with good stent strut coverage and very low rates of malapposed struts.

Estudio aleatorizado para comparar el stentbioactivo de titanio con el stent de everolimus en pacientes diabéticos (TITANIC XV), resultados a 1 año / A Randomized Study to Compare Bioactive Titanium Stents and Everolimus-eluting Stents in Diabetic Patients (TITANIC XV): 1-year Results

Introducción y objetivos Hasta un 25% de los pacientes sometidos a intervencionismo coronario percutáneo presentan alguna limitación para la utilización de los stents farmacoactivos. Nuestro objetivo es evaluar si el stent bioactivo de titanio y óxido nítrico podía ser una buena alternativa al stent de everolimus para pacientes diabéticos.MétodosSe aleatorizó a 173 pacientes diabéticos con lesiones de riesgo de reestenosis intermedio (criterios de exclusión: diámetro < 2,5 mm o longitud > 28 mm en vasos < 3 mm, oclusión crónica): 83 pacientes en el grupo con titanio y 90 en el grupo con everolimus.ResultadosLas variables basales estaban bien equilibradas, el 28,3% eran insulinodependientes. Al año, las incidencias de eventos adversos cardiacos mayores (muerte, infarto de miocardio no fatal, ictus o nueva revascularización del vaso tratado) eran significativamente más frecuente en el grupo con titanio que en el grupo con everolimus (total, el 14,5 frente al 4,4%; p = 0,02; subgrupo no insulinodependiente, el 9,7 frente al 3,2%; p = 0,14; insulinodependiente, el 28,6 frente al 7,1%; p = 0,04) y de muerte, infarto de miocardio no fatal, ictus o cualquier revascularización, del 16,9% en el grupo con titanio y el 7,8% en el grupo con everolimus (p = 0,06). La revascularización de la lesión diana se produjo en el 8,4 frente al 3,3% (p = 0,15), y la del vaso tratado, el 13,3 frente al 3,3% (p = 0,01). El seguimiento angiográfico a 9 meses mostró una pérdida luminal tardía significativamente menor en el grupo con everolimus (en el segmento, 0,52 ± 0,58 frente a -0,05 ± 0,32 mm; en el stent, 0,76 ± 0,54 frente a 0,13 ± 0,31 mm; p < 0,0001). ConclusionesEl stent de everolimus fue superior al titanio en pacientes diabéticos incluso con lesiones de riesgo de eventos clínicos y angiográficos intermedio (AU)

Introduction and objectives Up to 25% of patients who undergo a percutaneous coronary intervention show some limitation in the use of drug-eluting stents. The aim of this study was to evaluate if titanium-nitride-oxide-coated stents could be a good alternative to everolimus-eluting stents in diabetic patients.MethodsA total of 173 diabetic patients with lesions at moderate risk of restenosis (exclusion criteria: diameter < 2.5 mm or length > 28 mm in vessels < 3 mm, chronic occlusion) were randomized to a titanium group (83 patients) or an everolimus group (90 patients).ResultsBaseline characteristics were well balanced; 28.3% of patients were insulin dependent. At 1 year, the incidence of major adverse cardiac events (death, nonfatal myocardial infarction, stroke, or repeat target vessel revascularization) was significantly higher in the titanium group than in the everolimus group (total, 14.5% vs 4.4%; P = .02; noninsulin-dependent subgroup, 9.7% vs 3.2%; P = .14; insulin-dependent subgroup, 28.6% vs 7.1%; P = .04). The incidence of death, nonfatal myocardial infarction, stroke, or any revascularization was 16.9% in the titanium group and 7.8% in the everolimus group (P = .06). Target lesion and vessel revascularizations occurred in 8.4% compared with 3.3% (P = .15) and in 13.3% compared with 3.3% (P = .01) in the titanium and everolimus groups, respectively. Angiographic follow-up at 9 months showed significantly less late lumen loss in the everolimus group (in-segment, 0.52 [standard deviation, 0.58) mm vs -0.05 [0.32] mm; in-stent, 0.76 [0.54] mm vs 0.13 [0.31] mm; P < .0001).ConclusionsThe everolimus-eluting stent is superior to the titanium stent for clinical and angiographic end points in diabetic patients with lesions at moderate risk of restenosis (AU)

A randomized study to compare bioactive titanium stents and everolimus-eluting stents in diabetic patients (TITANIC XV): 1-year results.

INTRODUCTION AND OBJECTIVES: Up to 25% of patients who undergo a percutaneous coronary intervention show some limitation in the use of drug-eluting stents. The aim of this study was to evaluate if titanium-nitride-oxide-coated stents could be a good alternative to everolimus-eluting stents in diabetic patients. METHODS: A total of 173 diabetic patients with lesions at moderate risk of restenosis (exclusion criteria: diameter < 2.5 mm or length > 28 mm in vessels < 3mm, chronic occlusion) were randomized to a titanium group (83 patients) or an everolimus group (90 patients). RESULTS: Baseline characteristics were well balanced; 28.3% of patients were insulin dependent. At 1 year, the incidence of major adverse cardiac events (death, nonfatal myocardial infarction, stroke, or repeat target vessel revascularization) was significantly higher in the titanium group than in the everolimus group (total, 14.5% vs 4.4%; P = .02; noninsulin-dependent subgroup, 9.7% vs 3.2%; P = .14; insulin-dependent subgroup, 28.6% vs 7.1%; P = .04). The incidence of death, nonfatal myocardial infarction, stroke, or any revascularization was 16.9% in the titanium group and 7.8% in the everolimus group (P = .06). Target lesion and vessel revascularizations occurred in 8.4% compared with 3.3% (P = .15) and in 13.3% compared with 3.3% (P = .01) in the titanium and everolimus groups, respectively. Angiographic follow-up at 9 months showed significantly less late lumen loss in the everolimus group (in-segment, 0.52 [standard deviation, 0.58) mm vs -0.05 [0.32] mm; in-stent, 0.76 [0.54] mm vs 0.13 [0.31] mm; P < .0001). CONCLUSIONS: The everolimus-eluting stent is superior to the titanium stent for clinical and angiographic end points in diabetic patients with lesions at moderate risk of restenosis.

A prospective randomised study of the paclitaxel-coated balloon catheter in bifurcated coronary lesions (BABILON trial): 24-month clinical and angiographic results.

AIMS: Paclitaxel drug-eluting balloons (pDEB) could be an attractive option to minimise side branch (SB) restenosis in bifurcated coronary lesions. We compared angiographic and clinical outcomes with pDEB plus bare metal stent (BMS) versus drug-eluting stents (DES) in de novo bifurcated lesions. METHODS AND RESULTS: This multicentre randomised trial included 108 patients. Sequential main branch (MB)/SB dilatation with pDEB, with provisional T-stenting with BMS in the MB was performed in the pDEB group, and with everolimus DES in the DES group. The primary endpoint was late lumen loss (LLL) at nine months. The secondary endpoint was the incidence of major adverse cardiac events (MACE: death, myocardial infarction, or target lesion revascularisation). In-segment MB LLL was 0.31±0.48 mm in the pDEB group, and 0.16±0.38 mm in the DES group (p=0.15); mean difference was 0.15 mm (upper limit one-sided 95% CI: 0.27 mm; p=0.001; non-inferiority test). LLL in SB was -0.04±0.76 mm in the pDEB group and -0.03±0.51 mm in the DES group (p=0.983). MACE and TLR were higher in the pDEB group (17.3% vs. 7.1%; p=0.105, and 15.4% vs. 3.6%; p=0.045), due to higher MB restenosis (13.5% vs. 1.8%; p=0.027). CONCLUSIONS: pDEB bifurcation pretreatment with BMS implantation in MB showed greater LLL (ns) and increased incidence of MACE compared to everolimus DES. Both strategies showed similar results in the SB.

[Previous restenosis as a prognostic indicator in new conventional stent implantation at a different location]. / El comportamiento reestenótico previo como predictor pronóstico ante nueva implantación de stent convencional en distinta localización.

INTRODUCTION AND OBJECTIVES: The aim was to determine whether data on restenosis of a previous stent are useful for predicting outcome in patients who need to undergo a second conventional stent implantation at a different location because of coronary disease progression. METHODS: The study included 80 patients who, during 2000-2004, underwent a second conventional (i.e., not drug-eluting) stent implantation for de novo lesions at a different location to that of the previous stent. Major adverse cardiac events (MACE) were defined as death, non-fatal myocardial infarction, or the need for target lesion revascularization (TLR). RESULTS: One year after the second procedure, the cumulative incidence of MACE was significantly higher in patients who experienced significant restenosis of the previous stent than in those who did not (40.6% vs 12.5%, P=.004). Univariate predictors of MACE were: evidence of previous stent restenosis, previous myocardial infarction, and a small vessel (< or =2.75 mm). However, the only independent predictor (Cox regression) of a MACE was previous stent restenosis (hazard ratio 3.85, 95% confidence interval, 1.46-10.18; P=.007). At one year, the TLR rate was also higher in patients with previous stent restenosis (31.3% vs 8.3%; P=.008), in those with small vessels, and in diabetics. Previous stent restenosis and a small vessel were independent predictors of TLR. CONCLUSIONS: Restenosis of a previous stent is a strong predictor of major adverse events in patients undergoing a second conventional stent implantation at a different location because of coronary disease progression.

El comportamiento reestenótico previo como predictor pronóstico ante nueva implantación de stent convencional en distinta localización / Previous restenosis as a prognostic indicator in new conventional stent implantation at a different location

Introducción y objetivos. Averiguar si, en pacientes que requieren un segundo procedimiento de implante de stent convencional en una nueva localización por progresión de enfermedad coronaria, la información aportada por la respuesta reestenótica frente al stent previo es útil para predecir la evolución. Métodos. Se incluye a los 80 pacientes que recibieron un segundo procedimiento de implante de stent convencional (no farmacoactivo) sobre lesiones de novo de distinta localización de la del stent previo en el período 2000-2004. Se definió como evento mayor la ocurrencia de muerte, infarto no mortal o necesidad de revascularización de la lesión diana de novo (RLD). Resultados. Al año del segundo procedimiento, los pacientes que habían evidenciado reestenosis significativa del stent del procedimiento previo tuvieron una incidencia de eventos mayores superior a los pacientes sin reestenosis previa (el 40,6 frente al 12,5%; p = 0,004). Los predictores univariables de eventos mayores fueron la evidencia de reestenosis previa, el infarto previo, y el vaso pequeño (<= 2,75 mm), aunque el único predictor independiente de eventos (regresión de Cox) fue la reestenosis previa (hazard ratio = 3,85; intervalo de confianza del 95%, 1,46-10,18; p = 0,007). La RLD al año fue también mayor en los pacientes con reestenosis previa (el 31,3 frente al 8,3%; p = 0,008), en vasos pequeños y en diabéticos, siendo predictores independientes los dos primeros. Conclusiones. El comportamiento reestenótico frente a un stent previo es un potente predictor de eventos mayores en pacientes que reciben un segundo procedimiento de implante de stent convencional en distinta localización por progresión de su enfermedad coronaria (AU)

Introduction and objectives. The aim was to determine whether data on restenosis of a previous stent are useful for predicting outcome in patients who need to undergo a second conventional stent implantation at a different location because of coronary disease progression. Methods. The study included 80 patients who, during 2000-2004, underwent a second conventional (i.e., not drug-eluting) stent implantation for de novo lesions at a different location to that of the previous stent. Major adverse cardiac events (MACE) were defined as death, non-fatal myocardial infarction, or the need for target lesion revascularization (TLR). Results. One year after the second procedure, the cumulative incidence of MACE was significantly higher in patients who experienced significant restenosis of the previous stent than in those who did not (40.6% vs 12.5%, P=.004). Univariate predictors of MACE were: evidence of previous stent restenosis, previous myocardial infarction, and a small vessel (<=2.75 mm). However, the only independent predictor (Cox regression) of a MACE was previous stent restenosis (hazard ratio 3.85, 95% confidence interval, 1.46-10.18; P=.007). At one year, the TLR rate was also higher in patients with previous stent restenosis (31.3% vs 8.3%; P=.008), in those with small vessels, and in diabetics. Previous stent restenosis and a small vessel were independent predictors of TLR. Conclusions. Restenosis of a previous stent is a strong predictor of major adverse events in patients undergoing a second conventional stent implantation at a different location because of coronary disease progression (AU)