Abstract 10466: Post-myocardial Infarction Treatment With Edetate Disodium was Safe in the Trial to Assess Chelation Therapy

Introduction: Treatment with edetate disodium has been in use for nearly 60 years for cardiovascular disease despite safety concerns, including deaths from hypocalcemia. No careful prospective evaluation of safety had been reported prior to the NIH-sponsored Trial to Assess Chelation Therapy (TACT).

Methods: In TACT, 1,708 post-MI patients age ≥ 50 and creatinine ≤ 2.0 mg/dL were randomized doule blind to edetate-based chelation (n=839) or placebo (n=869). TACT implemented extensive site education prior to site activation. During the infusion period, there was close monitoring of vitals and labs, particularly creatinine and calcium, special lab-based (creatinine, calcium, and platelets) algorithms to delay infusions or reduce infusion rate when abnormal criteria were met, and early intervention to respond to safety concerns. Electronic and in-person monitoring took place to ensure adherence to TACT infusion protocols.

Results: There were 100 (12%) serious adverse events (SAEs) in the edetate group and 127 (15%) in the placebo group (p=0.1009). Two deaths were possibly or definitely attributed, by the blinded safety monitor, to study therapy, 1 in the chelation group and 1 in the placebo group. Heart failure was reported in 57 edetate patients (7%) and 71 placebo patients (8%) (p=.28). Physical exams were identical over the course of the study, except for more tachycardia (heart rate >100) in the placebo arm (0.1% vs 1.3% p=0.006). There was more infusion site discomfort (1.5% vs. 0.6%, p=0.049) with chelation and more abdominal cramping with placebo (1.7% v. 3.3%, p= 0.029) Reductions in calcium (<8.5mg/dL) occurred in 52 chelation patients (6.2%) and 30 placebo patients (3.5%) during the infusion phase (p=.008). Calcium at last blood draw was not different between groups (mean calcium 9.3 vs 9.3, p=0.15). There was no adverse effect on renal function from edetate disodium (mean creatinine 1.04 (edetate) vs 1.07 (placebo), p=0.03)

Conclusions: The experience with 55,222 infusions of edetate disodium or placebo in TACT shows that this therapy is extremely safe when used according to the TACT safe infusion protocol. This finding will be pivotal in informing the design of the TACT2 confirmatory study.