1. For the TACT Investigators
Clinical Benefit of EDTA Chelation Therapy in Patients with Diabetes in the Trial to Assess Chelation Therapy (TACT)
Esteban Escolar, Gervasio A. Lamas, Daniel Mark, Pamela Ouyang, Allan Magaziner, Robin Boineau, Ralph Miranda, Christine Goertz, Yves Rosenberg, Richard Nahin, Richard Nahas, Eldrin Lewis, Lauren Lindblad, Kerry L Lee
For the TACT Investigators
No disclosures to report
The National Center for Complementary and Alternative Medicine (U01AT001156) and the National Heart, Lung and Blood Institute (U01HL092607) provided sole support for this study.

2. Background
Disodium ethylene diamine tetra acetic acid (EDTA) binds metal cations and permits renal excretion
Since 1956, EDTA chelation has been used to treat atherosclerotic disease without evidence of benefit.
In 2001, NCCAM and NHLBI released an RFA for a definitive trial of EDTA chelation

3. Background
TACT showed a statistically significant reduction of a combined cardiovascular endpoint (HR 0.82 [95% CI, ]; p = 0.035) with an EDTA-based infusion regimen in patients with prior MI
There was an interaction between chelation infusion and self- reported diabetes
The present analyses provide greater detail on the effect of chelation therapy in patients with diabetes
Lamas GA, Goertz C, Boineau R , et. al. JAMA. 2013;309(12):

4. Design Overview Chelation + high-dose vitamins
Placebo chelation + high-dose vitamins
Chelation + placebo
vitamins
Placebo chelation + placebo vitamins
40 infusions at least 3 hours each; 30 weekly infusions followed by 10 maintenance infusions 2-8 weeks apart.
Lamas GA, Goertz C, Boineau R, et. al. Am Heart J Jan;163(1):7-12. 

5. Infusion components Chelation Infusion Placebo Infusion
disodium EDTA, 3 grams (adjusted by GFR)
ascorbic acid, 7 grams
magnesium chloride, 2 grams
potassium chloride, 2 mEq
sodium bicarbonate, 840 mg
pantothenic acid, thiamine, pyridoxine
procaine, 100 mg
unfractionated heparin, 2500 U
sterile water to 500 mL
Placebo Infusion
Normal Saline
1.2% dextrose, 500 mL
Lamas GA, Goertz C, Boineau R, et. al. Am Heart J Jan;163(1):7-12. 

6. Inclusion Criteria Age 50 or older MI > 6 months prior
Creatinine < 2.0 mg/dL
No coronary or carotid revascularization within 6 months
No active heart failure or heart failure hospitalization within 6 months
Able to tolerate 500cc infusions weekly
No cigarette smoking within 3 months
Signed informed consent

7. End points Primary endpoint: Time to first occurrence of either
death from any cause,
reinfarction,
stroke,
coronary revascularization, or
hospitalization for angina
Secondary endpoint:
cardiovascular death,
reinfarction, or
stroke

8. DM definition Self-reported diabetes Treated for diabetes
Fasting blood glucose ≥126 mg/dL prior to enrollment
These criteria expanded the population with diabetes from 538 to 633 patients, or 37% of the study subjects
Fix a bit original and revised.
Change before analysis was completed

9. Statistical Analysis
Log-rank test – Comparisons between arms for clinical events.
Intention to treat analysis
Treatment comparisons:
Cumulative event rates - Kaplan-Meier method
RR expressed as HR with 95% CI (Cox model) and nominal p values are reported
Bonferroni adjusted confidence intervals and p-values, adjusted for 9 different subgroup factors

10. Baseline characteristics of patients with or without Diabetes
No Diabetes
(N=1075)
P-value
Age
65(59,71)
65(58,72)
0.784
Female (%) 19 17
0.280
BMI
31(28,36)
28(25,32)
<0.001
CHF (%) 23 15
PVD (%) 22 12
HTN (%) 78 63
Hypercholesterolemia (%) 85 80
0.013
CABG (%) 49 43
0.008
PCI (%) 56 61
0.040
Statin (%) 76 72
0.063
ACE or ARB (%) 73 58
ASA/clopidogrel/warfarin 92 91
0.202
Fasting Glucose (mg/dL)
131(109,162)
97 (90,105)
For all continuous variables [median (25th, 75th)].

11. Baseline characteristics of patients with Diabetes by infusion arm
Chelation
(N=322)
Placebo
(N=311)
Age
65 (60,71)
66 (58,71)
Female (%) 17 21
BMI
31(28,36)
32(28,36)
Anterior MI (%) 40 36
HTN (%) 78
Hypercholesterolemia (%) 86 84
PCI or CABG (%) 85
Statin (%) 77 75
ACE or ARB (%) 73
ASA/clopidogrel/warfarin (%) 93 92
LDL (mg/dL)
81(63,105)
85(63,115)
Fasting Glucose(mg/dL)
129 (107,160)
134(109,165)
For all continuous variables [median (25th, 75th)] p >0.05 for all comparisons

12. Primary Endpoint by infusion arm Diabetes
Placebo Infusions
Placebo
EDTA Chelation vs. Placebo
HR (95% CI): 0.59 (0.44, 0.79); P =
Bonferroni Adjusted: (0.39, 0.88); P = 0.002
EDTA Chelation
EDTA Chelation
RR = 41%
NNT = 6.5 over 5 years CI (4.4, 12.7)
Number at Risk:

13. Primary Endpoint by infusion arm
Diabetes
No Diabetes
Placebo
Placebo Infusions
EDTA Chelation vs. Placebo
HR (95% CI): 1.02 (0.81, 1.28); P =
HR (95% CI): 0.59 (0.44, 0.79); P =
Adjusted: (0.39, 0.88); P = 0.002
EDTA Chelation
EDTA Chelation
Number at Risk:

14. Secondary Endpoint by infusion arm Diabetes
EDTA Chelation vs. Placebo
HR (95% CI): 0.60 (0.39, 0.91); P =
Bonferroni Adjusted: (0.32, 1.09); P = 0.153
Placebo
EDTA Chelation
Number at Risk:

15. Death by infusion arm - Diabetes
EDTA Chelation vs. Placebo
HR (95% CI): 0.57 (0.36, 0.88); P =
Bonferroni Adjusted: (0.30, 1.06); P = 0.099
Placebo
EDTA Chelation
Number at Risk:

16. Limitations
Although this subgroup analysis was prespecified, subgroup findings, regardless of how robust they appear, must be considered hypothesis-generating
A moderate number of patients withdrew consent, limiting somewhat the events that could be accrued and attributed during follow-up

17. Conclusions
Post-MI diabetic patients age 50 or older on evidence-based medications demonstrated a marked reduction in cardiovascular events with EDTA-based chelation therapy
These findings support the initiation of clinical trials in patients with diabetes and vascular disease to replicate these findings, and define the mechanisms of benefit
They do not, as yet, constitute sufficient evidence to indicate routine use of chelation therapy for post-MI diabetic patients

18. This article is now available online in
Circulation: Cardiovascular Quality & Outcomes