美国杜克大学Daniel B. Mark团队研究了依地酸二钠（EDTA）螯合剂是否能改善心梗患者预后。相关论文于2024年8月14日发表在《美国医学会杂志》上。

2013年，评估螯合疗法的试验（TACT）报告称，基于依地酸二钠（EDTA）的螯合作用显著降低了1708名既往心肌梗死（MI）患者中18%的心血管疾病（CVD）事件。为了在糖尿病和既往心肌梗死患者中重现TACT的发现，研究组在美国和加拿大的88个地点进行的一项2×2析因、双盲、安慰剂对照、多中心试验，招募50岁或以上、患有糖尿病且在招募前至少6周经历过心肌梗死的参与者，比较了基于EDTA的螯合剂与安慰剂输注对CVD事件的影响，并比较了高剂量口服多种维生素和矿物质与口服安慰剂的影响。还比较了螯合剂与安慰剂输注的效果。

符合条件的参与者被随机分配到每周40次输注基于EDTA的螯合溶液或匹配的安慰剂组，以及每天两次口服高剂量多种维生素和矿物质补充剂或匹配安慰剂组，持续60个月。研究组探讨了螯合作用的效果。主要终点是全因死亡率、心肌梗死、卒中、冠状动脉血运重建或不稳定型心绞痛住院的综合指标。中位随访时间为48个月。对至少接受过一次指定输注的患者进行了初步比较。

在959名参与者中（中位年龄为67岁[IQR，60-72岁]；27%为女性；78%为白人，10%为黑人，20%为西班牙裔），483人至少接受了一次螯合剂输注，476人至少接受过一次安慰剂输注。螯合组172名（35.6%）和安慰剂组170名（35.7%）受试者发生了主要终点事件（调整后的风险比[HR]，0.93；95%CI，0.76-1.16；P=0.53）。

螯合剂组和安慰剂组的5年主要事件累积发生率分别为45.8%和46.5%。螯合组89名（18.4%）和安慰剂组94名参与者（19.7%）发生心血管死亡、心肌梗死或卒中事件（调整后的HR，0.89；95%CI，0.66-1.19）。螯合组84名（17.4%）和安慰剂组84名参与者（17.6%）全因死亡（调整后的HR为0.96；95%CI为0.71-1.30）。螯合将血铅水平中位数从基线时的9.03μg/L降低到输注40次时的3.46μg/L（P<0.001）。安慰剂组的相应水平分别为9.3μg/L和8.7μg/L。

研究结果表明，尽管EDTA螯合剂有效地降低了血铅水平，但在减少患有糖尿病和心肌梗死病史的冠状动脉疾病稳定患者的心血管事件方面效果不显著。

附：英文原文

Title: Edetate Disodium–Based Chelation for Patients With a Previous Myocardial Infarction and Diabetes: TACT2 Randomized Clinical Trial

Author: Gervasio A. Lamas, Kevin J. Anstrom, Ana Navas-Acien, Robin Boineau, Hayley Nemeth, Zhen Huang, Jun Wen, Yves Rosenberg, Mario Stylianou, Teresa L. Z. Jones, Bonnie R. Joubert, Qilu Yu, Regina M. Santella, Ana C. Mon, Francisco Ujueta, Esteban Escolar, David M. Nathan, Vivian A. Fonseca, Y. Wady Aude, Jonathan K. Ehrman, Thomas Elliott, Rakesh Prashad, Eldrin F. Lewis, Renato D. Lopes, Michael E. Farkouh, Anne-Marie Elliott, Jonathan D. Newman, Daniel B. Mark, TACT Investigators, Philip Bear, Donna Prouty, Jodi Baxter, Jonathan Ehrman, Heather Golden, Vikrant Katoch, Raffi Krikorian, Andre Paixao, Fujiko Anazawa, Leybi Ramirez-Kelly, Abby Nolen, Venus Barney, Gerald Natzke, Rodica Pop-Busui, Cindy Plunkett, Laura Meyer, James Roberts, Scott Rollins, Tamra Hollis, Nampalli Vijay, Melinda Washam, David Zidar, Terence Semenec, Lauren Huntington, Amanda Klumpp, Matthew Scott Doughty, Jeffrey Baker, Joseph Allen, Rebecca Cortez, Bhaskar Purushottam, Kirstin Stauffacher, Kelly Airey, Elena Christofides, Jordyn Conway, David Hoffman, Patty Schuler, Ronald Solbrig, Loni Chacon, Phillip Levy, Linda Gojcevic, Roy Collins, John Miles McClure II, Ellen Mook, Christopher DeFilippi, Wendy Sheaffer, Antoinette Bonaccorso, Daniel Donovan

Issue&Volume: 2024-08-14

Abstract:

Importance  In 2013, the Trial to Assess Chelation Therapy (TACT) reported that edetate disodium (EDTA)–based chelation significantly reduced cardiovascular disease (CVD) events by 18% in 1708 patients with a prior myocardial infarction (MI).

Objective  To replicate the finding of TACT in individuals with diabetes and previous MI.

Design, Setting, and Participants  A 2×2 factorial, double-masked, placebo-controlled, multicenter trial at 88 sites in the US and Canada, involving participants who were 50 years or older, had diabetes, and had experienced an MI at least 6 weeks before recruitment compared the effect of EDTA-based chelation vs placebo infusions on CVD events and compared the effect of high doses of oral multivitamins and minerals with oral placebo. This article reports on the chelation vs placebo infusion comparisons.

Interventions  Eligible participants were randomly assigned to 40 weekly infusions of an EDTA-based chelation solution or matching placebo and to twice daily oral, high-dose multivitamin and mineral supplements or matching placebo for 60 months. This article addresses the chelation study.

Main Outcomes and Measures  The primary end point was the composite of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for unstable angina. Median follow-up was 48 months. Primary comparisons were made from patients who received at least 1 assigned infusion.

Results  Of the 959 participants (median age, 67 years [IQR, 60-72 years]; 27% females; 78% White, 10% Black, and 20% Hispanic), 483 received at least 1 chelation infusion and 476 at least 1 placebo infusion. A primary end point event occurred in 172 participants (35.6%) in the chelation group and in 170 (35.7%) in the placebo group (adjusted hazard ratio [HR], 0.93; 95% CI, 0.76-1.16; P=.53). The 5-year primary event cumulative incidence rates were 45.8% for the chelation group and 46.5% for the placebo group. CV death, MI, or stroke events occurred in 89 participants (18.4%) in the chelation group and in 94 (19.7%) in the placebo group (adjusted HR, 0.89; 95% CI, 0.66-1.19). Death from any cause occurred in 84 participants (17.4%) in the chelation group and in 84 (17.6%) in the placebo group (adjusted HR, 0.96; 95% CI, 0.71-1.30). Chelation reduced median blood lead levels from 9.03 μg/L at baseline to 3.46 μg/L at infusion 40 (P<.001). Corresponding levels in the placebo group were 9.3 μg/L and 8.7 μg/L, respectively.

Conclusions and Relevance  Despite effectively reducing blood lead levels, EDTA chelation was not effective in reducing cardiovascular events in stable patients with coronary artery disease who have diabetes and a history of MI.

DOI: 10.1001/jama.2024.11463

Source: https://jamanetwork.com/journals/jama/fullarticle/2822472