Drug-eluting or bare-metal stents for percutaneous coronary intervention: a systematic review and individual patient data meta-analysis of randomised clinical trials.

BACKGROUND: New-generation drug-eluting stents (DES) have mostly been investigated in head-to-head non-inferiority trials against early-generation DES and have typically shown similar efficacy and superior safety. How the safety profile of new-generation DES compares with that of bare-metal stents (BMS) is less clear. METHODS: We did an individual patient data meta-analysis of randomised clinical trials to compare outcomes after implantation of new-generation DES or BMS among patients undergoing percutaneous coronary intervention. The primary outcome was the composite of cardiac death or myocardial infarction. Data were pooled in a one-stage random-effects meta-analysis and examined at maximum follow-up and a 1-year landmark. Risk estimates are reported as hazard ratios (HRs) with 95% CIs. This study is registered in PROSPERO, number CRD42017060520. FINDINGS: We obtained individual data for 26 616 patients in 20 randomised trials. Mean follow-up was 3·2 (SD 1·8) years. The risk of the primary outcome was reduced in DES recipients compared with BMS recipients (HR 0·84, 95% CI 0·78-0·90, p<0·001) owing to a reduced risk of myocardial infarction (0·79, 0·71-0·88, p<0·001) and a possible slight but non-significant cardiac mortality benefit (0·89, 0·78-1·01, p=0·075). All-cause death was unaffected (HR with DES 0·96, 95% CI 0·88-1·05, p=0·358), but risk was lowered for definite stent thrombosis (0·63, 0·50-0·80, p<0·001) and target-vessel revascularisation (0·55, 0·50-0·60, p<0·001). We saw a time-dependent treatment effect, with DES being associated with lower risk of the primary outcome than BMS up to 1 year after placement. While the effect was maintained in the longer term, there was no further divergence from BMS after 1 year. INTERPRETATION: The performance of new-generation DES in the first year after implantation means that BMS should no longer be considered the gold standard for safety. Further development of DES technology should target improvements in clinical outcomes beyond 1 year. FUNDING: Bern University Hospital.

Rationale and design of the LEADERS FREE trial: A randomized double-blind comparison of the BioFreedom drug-coated stent vs the Gazelle bare metal stent in patients at high bleeding risk using a short (1 month) course of dual antiplatelet therapy.

BACKGROUND AND RATIONALE: Major bleeding is a powerful predictor of morbidity and mortality after percutaneous coronary intervention (PCI). To avoid prolonged dual antiplatelet therapy (DAPT), current guidelines recommend using a bare metal stent when PCI is indicated to treat patients at high risk of bleeding. The Biolimus A9-coated BioFreedom is a new stainless steel drug-coated stent devoid of polymer and has been shown to be associated with a low median late-loss of 0.17 mm at 12 months of follow-up. In an animal model, 98% of the drug has diffused into the vessel wall at 1 month. It is therefore reasonable to consider that such a device may have a potential safety advantage, and a lesser dependence on prolonged DAPT than a polymer-coated drug-eluting stent. TRIAL DESIGN: A total of 2456 patients considered at high risk of bleeding will be randomized in a double-blind fashion to the BioFreedom drug-coated stent or to a control arm (Gazelle bare metal stent). Both groups will be treated with DAPT during 1 month only, followed by long-term aspirin alone. At 1-year follow-up, the primary safety endpoint (a composite of cardiac death, myocardial infarction and stent thrombosis) will be assessed by a non-inferiority analysis, and the primary efficacy endpoint (clinically driven target lesion revascularization) by a superiority analysis. CONCLUSIONS: This trial should help better characterize a neglected subset of PCI patients and quantify both their thrombotic and bleeding risks. It has the potential to decrease the need for target lesion revascularization in patients unable to tolerate a prolonged course of DAPT and will assess the shortest DAPT course ever used with an active stent.

Drug-Eluting or Bare-Metal Stents for Left Anterior Descending or Left Main Coronary Artery Revascularization.

Background New-generation drug-eluting stents (DES) reduce target-vessel revascularization compared with bare-metal stents (BMS), and recent data suggest that DES have the potential to decrease the risk of myocardial infarction and cardiovascular mortality. We evaluated the treatment effect of DES versus BMS according to the target artery (left anterior descending [LAD] and/or left main [LM] versus other territories [no-LAD/LM]). Methods and Results The Coronary Stent Trialist (CST) Collaboration gathered individual patient data of randomized trials of DES versus BMS for the treatment of coronary artery disease. The primary outcome was the composite of cardiac death or myocardial infarction. Hazard ratios (HRs) with 95% CIs were derived from a 1-stage individual patient data meta-analysis. We included 26 024 patients across 19 trials: 13 650 (52.4%) in the LAD/LM and 12 373 (47.6%) in the no-LAD/LM group. At 6-year follow-up, there was strong evidence that the treatment effect of DES versus BMS depended on the target vessel (P-interaction=0.024). Compared with BMS, DES reduced the risk of cardiac death or myocardial infarction to a greater extent in the LAD/LM (HR, 0.76; 95% CI, 0.68-0.85) than in the no-LAD/LM territories (HR, 0.93; 95% CI, 0.83-1.05). This benefit was driven by a lower risk of cardiac death (HR, 0.83; 95% CI, 0.70-0.98) and myocardial infarction (HR, 0.74; 95% CI, 0.65-0.85) in patients with LAD/LM disease randomized to DES. An interaction (P=0.004) was also found for all-cause mortality with patients with LAD/LM disease deriving benefit from DES (HR, 0.86; 95% CI, 0.76-0.97). Conclusions As compared with BMS, new-generation DES were associated with sustained reduction in the composite of cardiac death or myocardial infarction if used for the treatment of LAD or left main coronary stenoses. Registration URL: https://www.crd.york.ac.uk/PROSPERO; Unique identifier: CRD42017060520.

Impact of vascular access on outcome after PCI in patients at high bleeding risk: a pre-specified sub-analysis of the LEADERS FREE trial.

INTRODUCTION AND OBJECTIVES: The prognostic impact of bleeding in high bleeding risk (HBR) patients depending on the location of bleeding and prognosis in nonaccess site bleeding is unknown. We aimed to assess the impact of vascular access site on bleeding complications after percutaneous coronary interventions for HBR patients at 30-day and 2-year follow-up. METHODS: The LEADERS FREE trial included 2432 HBR PCI patients. A Biolimus A9 drug-coated stent was superior to a bare-metal stent for safety and efficacy. This is a predefined sub-analysis of the LEADERS FREE trial. RESULTS: Transradial access (TRA) was used in 1454 patients (59.8%) and transfemoral access (TFA) in 978 (40.2%), according to operator preference. The safety and benefits of drug-coated stents over bare-metal stents were independent of vascular access. At 30 days and 2 years, major bleeding had occurred in 2.4% and 7.5% of TRA patients and 4.6% and 10.9% of TFA patients (P=.003), respectively. Most of these events in both groups (2.1% and 7.0% for TRA; 3.2% and 9.4% for TFA, respectively) were nonaccess site-related. TRA was associated with a significant reduction in adjusted rates of major bleeding both at 30 days (HR, 1.98; 95%CI, 1.25-3.11; P=.003) and at 2 years of follow-up (HR, 1.51; 95%CI, 1.14-2.01; P=.003). This difference was driven by both access and nonaccess bleeding. CONCLUSIONS: Operators preferred TRA for most HBR patients, which was associated with a significant reduction in major bleeding events. However, most of these events in this population are unrelated to vascular access.

Impacto del acceso vascular en el pronóstico tras la angioplastia coronaria en pacientes con alto riesgo hemorrágico: subanálisis predefinido del estudio LEADERS FREE / Impact of vascular access on outcome after PCI in patients at high bleeding risk: a pre-specified sub-analysis of the LEADERS FREE trial

INTRODUCCIÓN Y OBJETIVOS: El objetivo es evaluar el impacto del acceso vascular en las complicaciones hemorrágicas tras una intervención coronaria percutánea en pacientes con alto riesgo de sangrado (ARS) a los 30 días y a los 2 años. MÉTODOS: El presente estudio es un subanálisis predefinido del estudio LEADERS FREE, que incluyó a 2.432 pacientes con ARS y en el que el stent farmacoactivo Biolimus A9 resultó superior al stent convencional en seguridad y eficacia. RESULTADOS: El acceso radial (AR) se utilizó en 1.454 pacientes (59,8%) y el femoral (AF), en 978 (40,2%), ambos a elección del operador. La seguridad y los beneficios del stent farmacoactivo sobre el convencional fueron independientes del acceso vascular. A los 30 días y a los 2 años, habían sufrido un sangrado mayor el 2,4 y el 7,5% de los pacientes con AR y el 4,6 y el 10,9% de los pacientes con AF (p = 0,003), la mayoría en ambos grupos (el 2,1 y el 7,0% del de AR; el 3,2 y el 9,4% del de AF) no relacionados con el sitio de acceso vascular. El AR se asoció con una reducción significativa en las tasas ajustadas de sangrado mayor tanto a 30 días (HR=1,98; IC95%, 1,25-3,11; p = 0,003) como a 2 años de seguimiento (HR=1,51; IC95%, 1,14-2,01; p = 0,003). CONCLUSIONES: Los operadores prefirieron el AR en la mayoría de los pacientes con ARS, lo cual se asoció con una reducción significativa del sangrado mayor. Asimismo, un número significativo de sangrados en el seguimiento de esta población son no relacionados con el acceso vascular

INTRODUCTION AND OBJECTIVES: The prognostic impact of bleeding in high bleeding risk (HBR) patients depending on the location of bleeding and prognosis in nonaccess site bleeding is unknown. We aimed to assess the impact of vascular access site on bleeding complications after percutaneous coronary interventions for HBR patients at 30-day and 2-year follow-up. METHODS: The LEADERS FREE trial included 2432 HBR PCI patients. A Biolimus A9 drug-coated stent was superior to a bare-metal stent for safety and efficacy. This is a predefined sub-analysis of the LEADERS FREE trial. RESULTS: Transradial access (TRA) was used in 1454 patients (59.8%) and transfemoral access (TFA) in 978 (40.2%), according to operator preference. The safety and benefits of drug-coated stents over bare-metal stents were independent of vascular access. At 30 days and 2 years, major bleeding had occurred in 2.4% and 7.5% of TRA patients and 4.6% and 10.9% of TFA patients (P=.003), respectively. Most of these events in both groups (2.1% and 7.0% for TRA; 3.2% and 9.4% for TFA, respectively) were nonaccess site-related. TRA was associated with a significant reduction in adjusted rates of major bleeding both at 30 days (HR, 1.98; 95%CI, 1.25-3.11; P=.003) and at 2 years of follow-up (HR, 1.51; 95%CI, 1.14-2.01; P=.003). This difference was driven by both access and nonaccess bleeding. CONCLUSIONS: Operators preferred TRA for most HBR patients, which was associated with a significant reduction in major bleeding events. However, most of these events in this population are unrelated to vascular access

Six-month results of a randomized study to evaluate safety and efficacy of a Biolimus A9 eluting stent with a biodegradable polymer coating.

OBJECTIVES: The STEALTH (STent Eluting A9 BioLimus Trial in Humans) trial was the first-in-man study to assess the safety and efficacy of the bioabsorbable-polymer-coated Biolimus A9-eluting BioMATRIX-Stent, as compared to a bare metal stent control (S-Stent). METHODS: One hundred twenty patients were enrolled in a prospective, 2:1 randomised, double-blind, multi-center clinical study. Patients with single de novo coronary lesions received either a Biolimus-eluting stent (n=80 patients with 82 lesions) or bare metal control stent (n=40 patients with 40 lesions). The primary study endpoint was in-lesion late lumen loss at 6 month follow-up. RESULTS: The six month in-lesion late loss was significantly reduced in the Biolimus-eluting stent group (0.14 +/- 0.45mm) as compared to the control (0.40 +/- 0.41mm) (p=0.004). The in-stent late loss was 0.26 +/- 0.43mm in the Biolimus-eluting stent group vs. 0.74 +/- 0.45mm in the control (p<0.001). The secondary study endpoint of event-free survival at 6-months was similar in both groups (96.3% Biolimus group vs. 97.5% control; p=0.72). There was no significant difference in target lesion revascularizations due to the low binary restenosis rates in both groups (3.9% in Biolimus group vs. 7.7% in control; p=ns). CONCLUSIONS: In this first-in-man feasibility trial, the bioabsorbable-polymer-coated Biolimus A9-eluting stent demonstrated superior efficacy in reducing 6-month in-stent and in-lesion late loss and percent diameter stenosis, with clinical safety similar to bare metal control stents.