- 2025-05-01
- JAMA internal medicine 185(5)
- Francisco Ujueta
- Gervasio A Lamas
- Kevin J Anstrom
- Ana Navas-Acien
- Robin Boineau
- Yves Rosenberg
- Mario Stylianou
- Teresa L Z Jones
- Bonnie R Joubert
- Qilu Yu
- Jun Wen
- Hayley Nemeth
- Zhen Huang
- Vivian Fonseca
- David M Nathan
- Gabriel Uwaifo
- Ivan A Arenas
- Lan Luo
- Jeffrey Baker
- Diana Visentin
- Andre Paixao
- John F Schmedtje
- Daniel B Mark
Study Design
- Type
- Randomized Controlled Trial (RCT)
- Sample size
- n = 1,708
- Population
- 1000 adults with diabetes and prior myocardial infarction, aged ≥50 years
- Methods
- randomized, multicenter double-masked 2×2 factorial clinical trial; six caplets daily of a 28-component multivitamin/multimineral or placebo; 40 weekly infusions of EDTA chelation or placebo
- Blinding
- Double-blind
- Duration
- 48 months
- Funding
- Unclear
- Large Human Trial
- Rigorous Journal
Importance
In 2013, the Trial to Assess Chelation Therapy (TACT) reported that in 1708 patients with stable coronary disease and prior myocardial infarction (MI), oral multivitamins and multiminerals (OMVMs), in a factorial design with edetate disodium (EDTA) chelation therapy, did not reduce cardiovascular events relative to placebo OMVMs, but active EDTA combined with active OMVMs was superior to placebo OMVM/placebo EDTA.Objective
To compare OMVM vs placebo in terms of efficacy for reducing major adverse cardiovascular events in patients with diabetes and prior MI.Design, setting, and participants
The TACT2 randomized, multicenter double-masked 2 × 2 factorial clinical trial took place across 88 sites in the US and Canada. Participants were 50 years or older, had diabetes, and had an MI 6 weeks ago or more. TACT2 participants were enrolled between September 2016 and December 2020. Data were collected between October 2016 and June 2023.Interventions
Six caplets daily of a 28 component OMVM or matching OMVM placebo, and 40 weekly infusions of an EDTA-based chelation solution or matching placebo, in a 1:1:1:1 allocation ratio.Main outcomes and measures
The primary end point was the composite of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for unstable angina.Results
A total of 1000 participants were randomized (500 in the active OMVM group and 500 in the placebo group). The median (IQR) age was 67 (60-72) years, and 730 (73%) were male. Median (IQR) follow-up was 48 (34-58) months. The primary end point occurred in 175 participants (35%) in the active OMVM group and 175 (35%) in the placebo group (hazard ratio [HR], 0.99 [95% CI, 0.80-1.22]; P = .92). The 5-year event rate for the primary end point in the EDTA chelation + active OMVM group was 34.0%; in the EDTA chelation + placebo OMVM group, 35.7%; in the placebo infusion + active OMVM group, 36.0%; and in the placebo infusion + placebo OMVM group, 34.3%. The comparison of the active infusion + active OMVM with the placebo infusion + placebo OMVM was not significant (HR, 0.91 [95% CI, 0.67-1.23]; P = .54). Although nonsignificant, there was a numerically higher event rate of MI, stroke, mortality from cardiovascular causes in the active OMVM compared to placebo OMVM group.Conclusions and relevance
The results of this randomized clinical trial demonstrated that, for participants with chronic coronary disease, diabetes, and a previous MI, high-dose OMVM alone or in conjunction with EDTA-based chelation did not reduce cardiovascular events.Trial registration
ClinicalTrials.gov Identifier: NCT02733185.