Sporter Robert J, Kim Joon-Hyuk, Frishman William H
Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York, USA.
Cardiol Rev. 2008 Nov-Dec;16(6):280-7. doi: 10.1097/CRD.0b013e318188591c.
Chronic heart failure (CHF) remains a leading cause of mortality and morbidity, despite the use of optimal standard-of-care medical therapies. Although the role of the immune system in the pathogenesis and progression of CHF has been well-appreciated, attempts to modify specific systemic immune mediators have been unsuccessful. Building on the modest successes of more broad-spectrum immune therapies, Celacade therapy was developed, a device that induces apoptosis in an ex vivo blood sample. Upon reinjection into the body, the treated blood sample has been shown to have an anti-inflammatory effect. Celacade has been successful in several animal models of disease where inflammation plays an important pathogenic role. Two phase III clinical trials of Celacade have been undertaken. A trial on the use of Celacade in peripheral arterial disease with intermittent claudication was terminated early due to a lack of clinical effect, and a larger trial of Celacade treatment in CHF (ACCLAIM) was completed in 2006. ACCLAIM did not reach the primary end point for the overall study population; however, the study results demonstrated a reduced risk of death or first cardiovascular hospitalization by 39% in patients with New York Heart Association class II CHF and a 26% reduction in patients with class II, III, and IV disease who had no prior history of myocardial infarction. Celacade has been approved for treatment of CHF in these groups of patients in the European Union, and an FDA-mandated confirmatory study of Celacade for possible approval in the United States is in progress.
尽管采用了最佳的标准医疗疗法，但慢性心力衰竭（CHF）仍然是导致死亡和发病的主要原因。虽然免疫系统在CHF的发病机制和进展中的作用已得到充分认识，但试图改变特定的全身免疫介质的尝试均未成功。基于更广泛的免疫疗法取得的一定成功，开发了Celacade疗法，这是一种能诱导离体血样发生凋亡的装置。经处理的血样重新注入体内后，已显示出具有抗炎作用。Celacade在炎症起重要致病作用的几种疾病动物模型中已取得成功。已开展了两项Celacade的III期临床试验。一项关于Celacade用于治疗伴有间歇性跛行的外周动脉疾病的试验，由于缺乏临床效果而提前终止，一项更大规模的Celacade治疗CHF的试验（ACCLAIM）于2006年完成。ACCLAIM未达到总体研究人群的主要终点；然而，研究结果表明，纽约心脏协会II级CHF患者死亡或首次心血管住院的风险降低了39%，在无心肌梗死病史的II级、III级和IV级疾病患者中降低了26%。在欧盟，Celacade已被批准用于治疗这些患者群体的CHF，并且一项由美国食品药品监督管理局要求进行的关于Celacade在美国可能获批的验证性研究正在进行中。
