Dabigatran Dual Therapy vs Warfarin Triple Therapy Post-Percutaneous Coronary Intervention in Patients with Atrial Fibrillation With/Without a Proton Pump Inhibitor: A Pre-Specified Analysis of the RE-DUAL PCI Trial
有/无质子泵抑制剂的房颤患者经皮冠状动脉介入治疗后达比加群与华法林三联疗法的对比: 再次双重 PCI 试验的预先指定分析
- 作者列表："Nicolau, José C.","Bhatt, Deepak L.","Hohnloser, Stefan H.","Kimura, Takeshi","Lip, Gregory Y. H.","Miede, Corinna","Nordaby, Matias","Oldgren, Jonas","Steg, Philippe Gabriel","ten Berg, Jurriën M.","Godoy, Lucas C.","Cannon, Christopher P.","The RE-DUAL PCI Steering Committee and Investigators
Background and Objective In patients with atrial fibrillation following percutaneous coronary intervention, if a proton pump inhibitor is used, could that allow the use of warfarin triple therapy, or is there additional reduction in bleeding while using it with dual therapy? Methods The RE-DUAL PCI trial randomized 2725 patients with atrial fibrillation post-percutaneous coronary intervention to dabigatran dual therapy (110 or 150 mg twice daily, with clopidogrel or ticagrelor) or warfarin triple therapy (with clopidogrel or ticagrelor, and aspirin for 1–3 months). This prespecified subgroup analysis evaluated risks of a first major bleeding event or clinically relevant non-major bleeding event, all gastrointestinal bleeding, and a composite efficacy endpoint of all-cause mortality/thromboembolic event or unplanned revascularization according to baseline use of a proton pump inhibitor. Results Of 2678 analyzed patients, 1641 (61.3%) were receiving a proton pump inhibitor at baseline. Dabigatran 110 and 150 mg dual therapy reduced the risk of major bleeding events or clinically relevant non-major bleeding events vs warfarin triple therapy regardless of proton pump inhibitor use, with comparable risk of the composite efficacy endpoint (all interaction p values > 0.05). For gastrointestinal bleeding, no interaction was observed between study treatment and proton pump inhibitor use (interaction p values 0.84 and 0.62 for dabigatran 110 and 150 mg dual therapy, respectively, vs warfarin triple therapy). Conclusions Dabigatran 110 and 150 mg dual therapy reduced the risk of major bleeding events or clinically relevant non-major bleeding events vs warfarin triple therapy, regardless of proton pump inhibitor use at baseline, in patients with atrial fibrillation who underwent percutaneous coronary intervention. Risk of the composite efficacy endpoint appeared to be similar for dabigatran dual therapy vs warfarin triple therapy in patients receiving/not receiving a proton pump inhibitor. ClinicalTrials.gov unique identifier NCT02164864. Video abstract
背景与目的经皮冠状动脉介入治疗后房颤患者，如果使用质子泵抑制剂，是否可以使用华法林三联疗法,或者在使用双重治疗时是否有额外的出血减少？方法再次 PCI 试验将 2725 例经皮冠状动脉介入术后房颤患者随机分为达比加群双联治疗 (110 或 150 mg，每日 2 次，联合氯吡格雷或替格瑞洛) 或华法林三联疗法 (与氯吡格雷或替格瑞洛，和阿司匹林 1-3 个月)。这个预先设定的亚组分析评估了首次大出血事件或临床相关非大出血事件的风险，所有消化道出血,以及根据质子泵抑制剂基线使用的全因死亡率/血栓栓塞事件或计划外血运重建的复合疗效终点。结果在 2678 例分析患者中，1641 例 (61.3%) 在基线时接受质子泵抑制剂治疗。达比加群 110 和 150 mg 双重治疗降低了主要出血事件或临床相关非主要出血事件的风险 vs 无论使用质子泵抑制剂，华法林三联治疗,具有相当的复合疗效终点风险 (所有相互作用 p值> 0.05)。对于消化道出血，未观察到研究治疗与质子泵抑制剂使用之间的相互作用 (达比加群 0.84 和 0.62 mg 双重治疗与华法林三联治疗的相互作用 p值分别为 110 和 150)。结论与华法林三联疗法相比，达比加群 110 和 150 mg 双重疗法降低了主要出血事件或临床相关非主要出血事件的风险，而不管基线时质子泵抑制剂的使用情况如何,在接受经皮冠状动脉介入治疗的房颤患者中。在接受/未接受质子泵抑制剂的患者中，达比加群双重治疗与华法林三联治疗的复合疗效终点风险似乎相似。ClinicalTrials.gov 唯一标识符 nct02164864。视频摘要
METHODS:Aims : We sought to investigate the thrombogenicity of different DES and BMS in an in vitro system of stent perfusion. Material and Methods: The experimental model consisted of a peristaltic pump connected to 4 parallel silicone tubes in which different stents were deployed. Blood was drawn from healthy volunteers and the amount of stent surfaced -induced thrombus deposition was determined using 125 I -fibrinogen. Results: Compared to Resolute, Biomatrix and Vision, Xience was associated with the lowest amount of stent surface -induced thrombus formation, with a significant difference compared to Vision (125 I -fibrinogen median value deposition [IQ range]: 50 ng [25 -98] versus 560 ng [320 - 1,520], respectively, p<0.05), but not to other DES. In the second set of experiments Fluoropolymer -coated BMS not eluting drug was associated with a significant 3 -fold reduction in 125 I -fibrinogen deposition (245 ng [80 -300]) compared to Vision (625 ng [320 -760], p<0.05), but a 7 -fold increase compared to Xience (35 ng [20 -60], p<0.05). Finally Xience was associated with a significantly greater absorption of albumin compared to BMS. Conclusions: In an in vitro system of stent perfusion, Xience was associated with the lowest amount of stent surface -induced thrombus formation compared with Resolute, Biomatrix and Vision, with a noted synergistic effect between the fluoropolymer and the drug.
METHODS::Fibronectin-splice variant containing extra domain A (Fn-EDA) is associated with smooth muscle cells (SMCs) following vascular injury. The role of SMC-derived Fn-EDA in SMC phenotypic switching or its implication in neointimal hyperplasia remains unclear. Herein, using human coronary artery sections with a bare metal stent, we demonstrate the expression of Fn-EDA in the vicinity of SMC-rich neointima and peri-strut areas. In mice, Fn-EDA colocalizes with SMCs in the neointima of injured carotid arteries and promotes neointima formation in the comorbid condition of hyperlipidemia by potentiating SMC proliferation and migration. No sex-based differences were observed. Mechanistic studies suggested that Fn-EDA mediates integrin- and TLR4-dependent proliferation and migration through activation of FAK/Src and Akt1/mTOR signaling, respectively. Specific deletion of Fn-EDA in SMCs, but not in endothelial cells, reduced intimal hyperplasia and suppressed the SMC synthetic phenotype concomitant with decreased Akt1/mTOR signaling. Targeting Fn-EDA in human aortic SMCs suppressed the synthetic phenotype and downregulated Akt1/mTOR signaling. These results reveal that SMC-derived Fn-EDA potentiates phenotypic switching in human and mouse aortic SMCs and neointimal hyperplasia in the mouse. We suggest that targeting Fn-EDA could be explored as a potential therapeutic strategy to reduce neointimal hyperplasia.
METHODS:OBJECTIVE:The goal of this study was to determine the impact of late-acquired stent malapposition (LASM) on long-term clinical outcomes in patients treated with coronary stent implantation. Approach and Results: We investigated major adverse cardiac event during 10 years after 6-month intravascular ultrasound examination using our previous studies database. A total of 732 patients treated with bare-metal stent (54 LASM versus 678 non-LASM) and 529 patients treated with first-generation drug-eluting stent (82 LASM versus 447 non-LASM), who did not have clinical event or censoring at the time of follow-up intravascular ultrasound, were included for the present analysis. major adverse cardiac event was defined as the composite of cardiac death, target vessel-related myocardial infarction, target lesion revascularization and stent thrombosis. Multivariable adjustment and inverse probability weight were performed to consider baseline differences. After multivariable adjustment, LASM was related to a greater risk of major adverse cardiac event (hazard ratio, 1.666 [95% CI, 1.041-2.665]; P=0.0333) and very-late stent thrombosis (hazard ratio, 3.529 [95% CI, 1.153-10.798]; P=0.0271) than non-LASM in patients treated with first-generation drug-eluting stent, but not in those treated with bare-metal stent. Results were consistent after inverse probability weight. Among patients with LASM of first-generation drug-eluting stent, no late stent thrombosis occurred in patients who continued to receive dual antiplatelet therapy. CONCLUSIONS:The relationship between LASM and major adverse cardiac event might depend on the type of implanted stents during the long-term follow-up, highlighting the clinical significance of polymers and drugs in drug-eluting stent system.