From the Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada (C.A.M., L.B., B.M., P.R.-M., J.P., S.J.C., S.Y.); Cardiology Division, Internal Medicine Department, Medical School of Riberao Preto (J.A.M.-N.), Instituto Dante Pazzanese de Cardiologia, São Paulo (A.A., A.M.), Hospital do Coração Anis Rassi, Goiãnia (A. Rassi Jr., A. Rassi), and Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Molecular e Doenças Endêmicas, Rio de Janeiro (C.B.) - all in Brazil; Instituto Nacional de Parasitología Dr. Mario Fatala Chaben-Administración Nacional de Laboratorios e Institutos de Salud, Buenos Aires (S.S.-E., E. Velazquez); Fundación Clínica Abood Shaio (F.R.) and CIMPAT-Facultad de Ciencias, Universidad de los Andes (F.G.), Bogota, and Fundación Cardiovascular de Colombia, Bucaramanga (R.Q.) - all in Colombia; Hospital Eduardo Eguia, Programa Chagas, Tupiza, Bolivia (E. Villena); Hospital Nacional Rosales, San Salvador, El Salvador (R.B.); and Independent Advisor, Neglected Tropical Diseases, Geneva (J.L.).
N Engl J Med. 2015 Oct;373(14):1295-306. doi: 10.1056/NEJMoa1507574. Epub 2015 Sep 1.
The role of trypanocidal therapy in patients with established Chagas' cardiomyopathy is unproven.
We conducted a prospective, multicenter, randomized study involving 2854 patients with Chagas' cardiomyopathy who received benznidazole or placebo for up to 80 days and were followed for a mean of 5.4 years. The primary outcome in the time-to-event analysis was the first event of any of the components of the composite outcome of death, resuscitated cardiac arrest, sustained ventricular tachycardia, insertion of a pacemaker or implantable cardioverter-defibrillator, cardiac transplantation, new heart failure, stroke, or other thromboembolic event.
The primary outcome occurred in 394 patients (27.5%) in the benznidazole group and in 414 (29.1%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.81 to 1.07; P=0.31). At baseline, a polymerase-chain-reaction (PCR) assay was performed on blood samples obtained from 1896 patients; 60.5% had positive results for Trypanosoma cruzi on PCR. The rates of conversion to negative PCR results (PCR conversion) were 66.2% in the benznidazole group and 33.5% in the placebo group at the end of treatment, 55.4% and 35.3%, respectively, at 2 years, and 46.7% and 33.1%, respectively, at 5 years or more (P<0.001 for all comparisons). The effect of treatment on PCR conversion varied according to geographic region: in Brazil, the odds ratio for PCR conversion was 3.03 (95% CI, 2.12 to 4.34) at 2 years and 1.87 (95% CI, 1.33 to 2.63) at 5 or more years; in Colombia and El Salvador, the odds ratio was 1.33 (95% CI, 0.90 to 1.98) at 2 years and 0.96 (95% CI, 0.63 to 1.45) at 5 or more years; and in Argentina and Bolivia, the odds ratio was 2.63 (95% CI, 1.89 to 3.66) at 2 years and 2.79 (95% CI, 1.99 to 3.92) at 5 or more years (P<0.001 for interaction). However, the rates of PCR conversion did not correspond to effects on clinical outcome (P=0.16 for interaction).
Trypanocidal therapy with benznidazole in patients with established Chagas' cardiomyopathy significantly reduced serum parasite detection but did not significantly reduce cardiac clinical deterioration through 5 years of follow-up. (Funded by the Population Health Research Institute and others; ClinicalTrials.gov number, NCT00123916; Current Controlled Trials number, ISRCTN13967269.).
在已确诊的恰加斯心肌病患者中，杀锥虫治疗的作用尚未得到证实。
我们进行了一项前瞻性、多中心、随机研究，共纳入 2854 例恰加斯心肌病患者，他们接受苯硝唑或安慰剂治疗，最长 80 天，并随访平均 5.4 年。在时间事件分析中，主要结局是死亡、复苏性心脏骤停、持续性室性心动过速、植入起搏器或植入式心脏除颤器、心脏移植、新发心力衰竭、卒中和其他血栓栓塞事件的复合结局的首次事件。
苯硝唑组 394 例（27.5%）和安慰剂组 414 例（29.1%）发生主要结局（风险比，0.93；95%置信区间[CI]，0.81 至 1.07；P=0.31）。在基线时，对 1896 例患者的血液样本进行了聚合酶链反应（PCR）检测；60.5%的患者 PCR 检测出克氏锥虫阳性。治疗结束时，苯硝唑组的 PCR 转阴率为 66.2%，安慰剂组为 33.5%，治疗 2 年后，分别为 55.4%和 35.3%，治疗 5 年或以上时，分别为 46.7%和 33.1%（所有比较 P<0.001）。治疗对 PCR 转阴的影响因地理区域而异：在巴西，PCR 转阴的比值比为 2 年时为 3.03（95%CI，2.12 至 4.34），5 年或以上时为 1.87（95%CI，1.33 至 2.63）；在哥伦比亚和萨尔瓦多，比值比为 2 年时为 1.33（95%CI，0.90 至 1.98），5 年或以上时为 0.96（95%CI，0.63 至 1.45）；在阿根廷和玻利维亚，比值比为 2 年时为 2.63（95%CI，1.89 至 3.66），5 年或以上时为 2.79（95%CI，1.99 至 3.92）（交互作用 P<0.001）。然而，PCR 转阴率与临床结局无显著相关性（交互作用 P=0.16）。
在已确诊的恰加斯心肌病患者中，采用苯硝唑进行杀锥虫治疗可显著降低血清寄生虫检出率，但在 5 年随访期间，并未显著降低心脏临床恶化。（由人口健康研究所和其他机构资助；临床试验.gov 编号，NCT00123916；当前对照试验编号，ISRCTN13967269。）
