Original Article

The Effect of an EDTA-based Chelation Regimen on Patients

With Diabetes Mellitus and Prior Myocardial Infarction in
the Trial to Assess Chelation Therapy (TACT)
Esteban Escolar, MD; Gervasio A. Lamas, MD; Daniel B. Mark, MD, MPH;
Robin Boineau, MD, MA; Christine Goertz, DC, PHD; Yves Rosenberg, MD;
Richard L. Nahin, PhD, MPH; Pamela Ouyang, MBBS; Theodore Rozema, MD;
Allan Magaziner, DO; Richard Nahas, MD; Eldrin F. Lewis, MD, MPH; Lauren Lindblad, MS;
Kerry L. Lee, PhD

Background—The Trial to Assess Chelation Therapy (TACT) showed clinical benefit of an EDTA-based infusion regimen
in patients aged ≥50 years with prior myocardial infarction. Diabetes mellitus before enrollment was a prespecified
subgroup.
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Methods and Results—Patients received 40 infusions of EDTA chelation or placebo. A total of 633 (37%) patients had
diabetes mellitus (322 EDTA and 311 placebo). EDTA reduced the primary end point (death, reinfarction, stroke, coronary
revascularization, or hospitalization for angina; 25% versus 38%; hazard ratio, 0.59; 95% confidence interval [CI], 0.44–
0.79; P<0.001) for over 5 years. The result remained significant after Bonferroni adjustment for multiple subgroups
(99.4% CI, 0.39–0.88; adjusted P=0.002). All-cause mortality was reduced by EDTA chelation (10% versus 16%; hazard
ratio, 0.57; 95% CI, 0.36–0.88; P=0.011), as was the secondary end point (cardiovascular death, reinfarction, or stroke;
11% versus 17%; hazard ratio, 0.60; 95% CI, 0.39–0.91; P=0.017). However, after adjusting for multiple subgroups,
those results were no longer significant. The number needed to treat to reduce 1 primary end point over 5 years was
6.5 (95% CI, 4.4–12.7). There was no reduction in events in non–diabetes mellitus (n=1075; P=0.877), resulting in a
treatment by diabetes mellitus interaction (P=0.004).
Conclusions—Post–myocardial infarction patients with diabetes mellitus aged ≥50 demonstrated a marked reduction in
cardiovascular events with EDTA chelation. These findings support efforts to replicate these findings and define the
mechanisms of benefit. However, they do not constitute sufficient evidence to indicate the routine use of chelation therapy
for all post–myocardial infarction patients with diabetes mellitus.
Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00044213.  
(Circ Cardiovasc Qual Outcomes. 2014;7:00-00.)
Key Words: diabetes mellitus ◼ myocardial infarction ◼ secondary prevention

F or >50 years, ethylene diamine tetraacetic acid (EDTA)-

based chelation therapy has been used by practitioners to
treat complications of atherosclerosis, without a robust evi-
dence base, and with increasing controversy.1–3 The Trial to
Assess Chelation Therapy (TACT), developed in response
to a Request for Proposals4 by the National Center for
Complementary and Alternative Medicine and the National
Heart, Lung, and Blood Institute, was designed as a pivotal
trial of disodium EDTA chelation therapy for patients who
had a myocardial infarction (MI). EDTA chelation therapy
was found to offer a modest, but significant, reduction in the
primary composite cardiovascular end point.5 As part of the
prospective analysis plan,6 the presence of diabetes mellitus
before enrollment was prespecified for subgroup analysis.
Our initial report of TACT included the observation that
there was an interaction between EDTA treatment and a
self-reported history of diabetes mellitus.5 EDTA is a potent
metal chelator.7 Therefore, our preliminary observations were

Received October 8, 2013; accepted October 29, 2013.

From the Columbia University Division of Cardiology at Mount Sinai Medical Center, Miami Beach, FL (E.E., G.A.L.); National Heart, Lung, and
Blood Institute, Bethesda, MD (R.B., Y.R.); Palmer Center for Chiropractic Research, Davenport, IA (C.G.); The National Center for Complementary
and Alternative Medicine, Bethesda, MD (R.L.N.); Johns Hopkins University, Baltimore, MD (P.O.); Biogenesis Medical Center, Landrum, SC (T.R.);
Magaziner Center for Wellness, Cherry Hill, NJ (A.M.); Seekers Centre for Integrative Medicine, Ottawa, ON (R.N.); Brigham and Women’s Hospital and
Harvard Medical School, Boston, MA (E.F.L.); and Duke Clinical Research Institute, Durham, NC (D.B.M., K.L.L., L.L.).
The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Heart, Lung, and
Blood Institute, the National Center for Complementary and Alternative Medicine, or the National Institutes of Health.
The online-only Data Supplement is available at http://circoutcomes.ahajournals.org/lookup/suppl/doi:10.1161/CIRCOUTCOMES.113.000663/-/DC1.
Correspondence to Gervasio A. Lamas, MD, Columbia University, Division of Cardiology, Mount Sinai Medical Center, 4300 Alton Rd, Suite 2070A,
Miami Beach, FL 33140. E-mail gervasio.lamas@msmc.com
© 2013 American Heart Association, Inc.
Circ Cardiovasc Qual Outcomes is available at http://circoutcomes.ahajournals.org DOI: 10.1161/CIRCOUTCOMES.113.000663

1
 2   Circ Cardiovasc Qual Outcomes   January 2014
What is Known
• EDTA-based chelation infusions have been used
for decades to treat atherosclerosis without proof of
efficacy.
• The recently-published Trial to Assess Chelation
Therapy (TACT) demonstrated a modest improve-
ment in outcomes for patients with post-MI. The
prespecified subgroup of patients with self-reported
diabetes mellitus showed a particular benefit.
What the Study Adds
• Patients with diabetes mellitus, when compared with
patients without diabetes mellitus, demonstrated a
major reduction in the primary end point, and con-
sistent reductions in the individual components of
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the primary end point.
• This analysis suggests that novel mechanism to treat
atherosclerosis in patients with diabetes mellitus
may be at play.
consistent with research supporting an important role for
metal-catalyzed oxidation reactions in the development of
advanced glycation end-products,8 mediators of complications
of diabetes mellitus. The present report provides greater detail
on the effect of EDTA-based chelation therapy on patients
with diabetes mellitus who have had a prior MI.
Methods
The detailed methodology of TACT has been published.5 TACT was
a double-blind 2X2 factorial trial in which patients (1708) were
randomized to receive 40 infusions of disodium EDTA chelation or
placebo and additionally to an oral high-dose vitamin and mineral
regimen or oral placebo. This report describes the results of EDTA
chelation versus placebo in a prespecified subgroup of patients with
diabetes mellitus.
Study Population
Patients were aged ≥50 years and had a history of MI ≥6 weeks be-
fore enrollment. Major exclusion criteria were women of childbear-
ing potential, a creatinine level >176.8 μmol/L (2.0 mg/dL), platelet
count <100 000 per μL, abnormal liver function studies, blood pres-
sure >160/100 mm Hg, past intolerance to the chelation or vitamin
components, chelation therapy within 5 years, or revascularization
within 6 months. The study enrolled 1708 patients in 134 sites across
the United States and Canada (Figure 1). The median duration of fol-
low-up was 55 months. The institutional review board at each clini-
cal site approved the study, and patients provided written informed
consent. A Data and Safety Monitoring Board monitored the study.
Diabetes Mellitus Definition
Our prior report demonstrating a significant interaction (P=0.02) of
EDTA therapy with the diagnosis of diabetes mellitus was based on
patients’ self-reported diagnosis of diabetes mellitus, present in 538
(31.5%) cases. The present analyses broadened the definition of dia-
betes mellitus to be more consistent with current guidelines.9 Thus,
patients included in the present diabetes mellitus subgroup had self-
reported diabetes mellitus, were taking oral or insulin treatment for
diabetes mellitus, or had a fasting blood glucose of ≥6.99 mmol/L
(126 mg/dL) at the time of enrollment in the study. This led to 633
(37.1%) patients with a diagnosis of diabetes mellitus eligible for
analysis. The expansion of the diabetes mellitus definition was ap-
proved by the TACT Operations Group before performing the result-
ing analyses. However, results are also provided for the previously
defined group of 538 patients (Tables I–III in the online-only Data
Supplement).
Treatment
The 10-component 500-mL intravenous solution in TACT consisted
of 3 g of disodium EDTA, adjusted downward based on estimated
glomerular filtration rate; 7 g of ascorbic acid; 2 g of magnesium
chloride; B-vitamins; and other components (Table IV in the online-
only Data Supplement). The placebo solution consisted of 500 mL
of normal saline and 1.2% dextrose (2.5 g total). The solution was
infused for ≥3 hours through a peripheral intravenous line weekly for
30 weeks and then biweekly to bimonthly to complete 40 infusions.
All patients in the trial received a low-dose vitamin and mineral
regimen daily while receiving infusions to prevent depletion by the
chelation regimen.6 Evidence-based post-MI therapy was encouraged
and monitored by the Coordinating Centers.
Follow-Up
Patients were seen at the baseline visit and at each infusion visit.
Once patients completed the infusion phase, they were followed via
quarterly telephone calls, annual clinic visits, and a final visit at the
5-year follow-up or at the end of the study whichever came first.
Laboratory evaluations included fasting blood glucose levels at base-
line and throughout the infusion phase of the trial and fasting lipids at
baseline and before infusion 30.
End Points
The primary end point was a composite of death from any cause,
reinfarction, stroke, coronary revascularization, or hospitalization for
angina. The principal secondary end point consisted of a composite
of cardiovascular death, reinfarction, or stroke. All end point events
were reviewed and adjudicated by a clinical events committee blind-
ed to the randomized treatment assignment.
Statistical Analysis
Secure Web-based permuted block randomization was stratified
by clinical site (diabetes mellitus was not a stratification factor).
Baseline characteristics of patients were descriptively summarized
using the median and interquartile range for continuous variables and
frequencies and percentages for categorical variables. The charac-
teristics of patients with diabetes mellitus were compared with the
patients without diabetes mellitus using the Wilcoxon rank-sum test
for continuous variables and the conventional χ2 test for categorical
variables. The Wilcoxon test was also used for comparing treatment
groups with respect to the change in fasting blood glucose from base-
line to the last infusion measurement. The log-rank test was used for
comparing diabetes mellitus versus non–diabetes mellitus and the
chelation versus placebo treatment arms with respect to the primary
and secondary clinical outcomes. Although patients could experience
>1 component of the composite primary and secondary end points,
each patient was counted only once in treatment comparison of these
end points using the time until the occurrence of their first event. All
treatment comparisons were performed using 2-sided significance
tests and included all patients in the treatment group to which they
were randomized (intention to treat). Cumulative event rates were
calculated according to the Kaplan–Meier method.10 Relative risks
were expressed as hazard ratios (HRs) with associated confidence in-
tervals (CIs) and were calculated using the Cox proportional hazards
model.11 The Cox model was also used for assessing a treatment by
diabetes mellitus interaction. Although nominal P values for treat-
ment comparisons are reported, conservative Bonferroni-adjusted12
CIs and P values, adjusted for 9 different subgroup factors, are also
reported. Consistent with the overall study report5, statistical sig-
nificance for comparisons of the primary end point was defined as
 Escolar et al   Chelation for Diabetes Mellitus With CAD   3
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P<0.036. For other comparisons, significance was defined as P<0.05.
Number needed to treat with associated CI was calculated using the
inverse of the absolute risk reduction in 5-year Kaplan–Meier event
rates. Final statistical analyses were performed using SAS software,
versions 8.2 and 9.2 (SAS Institute Inc).
Sensitivity Analyses
To assess the robustness of study findings in the face of patients that
withdrew consent or were lost to follow-up, post hoc sensitivity anal-
yses were performed with imputation of missing outcome data, as
previously published.6 The event rates among patients that withdrew
or were lost to follow-up in each treatment group were varied across
a broad spectrum and included scenarios that were markedly unfavor-
able to chelation. These imputed event rates were combined with the
observed event rates to assess the treatment effect and the robustness
of the findings in the treatment group comparisons.
Results
A total of 1708 patients were enrolled in TACT, of which
633 (37.1%) had diabetes mellitus according to the expanded
definition.
Baseline Characteristics of Patients With and
Without Diabetes Mellitus
Compared with patients without diabetes mellitus, fasting
blood sugar and body mass index were higher in patients with
Figure 1. Consort Diagram.
*Screened patients not
randomized because of
inclusion/exclusion criteria,
unwillingness to participate,
or other reasons. **Among
patients who withdrew from the
study or were lost to follow-up,
18 met the primary end point
before withdrawal or becoming
lost. Among the patients who
had not experienced an event
before withdrawal or becoming
lost, 6 were found through
search of death registries to
have died. All of these events
were included in the primary
end point analysis. IV indicates
intravenous.
diabetes mellitus (Table 1). Patients with diabetes mellitus also
had a higher prevalence of congestive heart failure, stroke,
hypertension, and hypercholesterolemia than patients without
diabetes mellitus. There was a particularly high prevalence
of peripheral artery disease in patients with diabetes mellitus
compared with patients without diabetes mellitus. The propor-
tion of patients who had undergone a coronary revasculariza-
tion procedure (either coronary artery bypass or percutaneous
coronary intervention) was >80% and similar in the 2 groups.
Patients with diabetes mellitus were treated more aggressively
with blockade of the renin–angiotensin system (73% versus
58%; P<0.001) and β-blockers (75% versus 70%; P=0.012)
than patients without diabetes mellitus. Patients with diabetes
mellitus had a lower fasting low-density lipoprotein-choles-
terol than patients without diabetes mellitus but lower high-
density lipoprotein at study enrollment (Table 1).
Outcome Events by Diabetes Mellitus Status
When compared with patients without diabetes mellitus,
patients with diabetes mellitus were more likely to experi-
ence the primary end point (197 [31%] versus 286 [27%]; log-
rank, P=0.009), the secondary end point (87 [14%] versus 122
[11%]; P=0.057), and death from any cause (82 [13%] versus
98 [9%]; log-rank, P=0.003).
 4   Circ Cardiovasc Qual Outcomes   January 2014

Table 1.  Baseline Characteristics of Patients With or Without Diabetes Mellitus

Diabetes Mellitus (n=633) Non–Diabetes Mellitus (n=1075) P Value
Demographics
 Age, y 65.4 (59.7, 71.3) 65.2 (58.7, 72.5) 0.784
 Women 119 (19%) 180 (17%) 0.280
 Minority (Hispanic or non-white) 68 (11%) 88 (8%) 0.077
 BMI, kg/m 2
31.8 (28.0, 36.0) 28.8 (25.9, 32.3) <0.001
History
 Time from qualifying MI to 4.5 (1.5, 9.2) 4.6 (1.8, 9.2) 0.467
randomization, y*
 Anterior MI 239 (38%) 435 (40%) 0.269
 Congestive heart failure 145 (23%) 162 (15%) <0.001
 Valvular heart disease 68 (11%) 107 (10%) 0.570
 Stroke 51 (8%) 60 (6%) 0.045
 Peripheral vascular disease 136 (22%) 132 (12%) <0.001
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 Hypertension 494 (78%) 675 (63%) <0.001

 Hypercholesterolemia 528 (85%) 842 (80%) 0.013
 Atrial fibrillation 85 (14%) 110 (11%) 0.041
 Former cigarette smoker 354 (56%) 601 (56%) 0.994
Coronary revascularization
 CABG 313 (49%) 461 (43%) 0.008
 PCI 353 (56%) 654 (61%) 0.040
 Either CABG or PCI 515 (81%) 899 (84%) 0.230
Presenting characteristics
 Blood pressure
  
Systolic 130 (120, 140) 130 (118, 140) 0.094
  
Diastolic 74 (68, 80) 77 (70, 81) 0.001
Concomitant medications
 Aspirin 531 (84%) 896 (83%) 0.772
β-Blocker
  477 (75%) 749 (70%) 0.012
 Statin 479 (76%) 769 (72%) 0.063
 ACEI or ARB 460 (73%) 624 (58%) <0.001
 Clopidogrel 161 (27%) 264 (25%) 0.642
 Warfarin 65 (11%) 83 (8%) 0.070
 Aspirin, warfarin, or clopidogrel 582 (92%) 970 (91%) 0.202
 Diabetes mellitus medication
  
Insulin 160 (26%) 0 (0%) <0.001
  
Oral hypoglycemic 380 (61%) 0 (0%) <0.001
 Multivitamin 242 (40%) 473 (45%) 0.026
 Other vitamins/minerals 292 (47%) 560 (53%) 0.020
 Herbal products 190 (31%) 370 (36%) 0.088
Laboratory examinations
 Fasting glucose, mmol/L 7.3 (6, 9) 5.4 (5, 5.8) <0.001
 Creatinine, μmol/L 97.2 (79.6, 114.9) 97.2 (79.6, 106.1) 0.030
 Total cholesterol, mmol/L 4.2 (3.6, 5) 4.3 (3.7, 5.1) 0.047
 HDL, mmol/L 1.1 (0.9, 1.2) 1.1 (0.9, 1.3) <0.001
 LDL, mmol/L 2.1 (1.6, 2.9) 2.3 (1.8, 3) <0.001
 Triglycerides, mmol/L 1.7 (1.2, 2.6) 1.5 (1, 2.1) <0.001
ACEI indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BMI, body mass index; CABG,
coronary artery bypass graft; HDL, high-density lipoprotein; LDL, low-density lipoprotein; MI, myocardial infarction; and PCI,
percutaneous coronary intervention.
*Median, 25th and 75th percentiles are reported for all continuous variables. To convert to mg/dL, divide by: fasting glucose
(0.0555), creatinine (76.26), total cholesterol, HDL and LDL (0.0259), triglycerides (0.0113).
 Escolar et al   Chelation for Diabetes Mellitus With CAD   5
Baseline Characteristics of Patients With Diabetes
Mellitus by Infusion Arm
Among patients with diabetes mellitus, 322 were randomized
to receive the EDTA chelation-based infusion regimen and
311 received placebo infusions. Baseline characteristics were
similar between the treatment groups (Table 2).
Fasting Glucose and Diabetes Mellitus Medications
During Follow-Up
There was no EDTA-treatment–based difference in fast-
ing blood glucose from baseline to last infusion requiring a
blood draw (chelation glucose change from baseline to last
follow-up, 1.0 mg/dL [−29, 24]; placebo, 1.5 mg/dL [−23,
25]; P=0.64). Among patients with diabetes mellitus who
completed 30 infusions and had paired medication data on
insulin status at the prerandomization visit and at the 30th
infusion (n=429), 101 (23.5%) received insulin for diabetes
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mellitus management at baseline when compared with 100
(23.3%) patients at the 30th infusion. Among the 438 patients
with paired data on oral hypoglycemic status, 282 (64.3%)
took oral hypoglycemics at baseline when compared with 272
(62.1%) patients at the 30th infusion. These numbers, which
reflect minimal changes in medications for diabetes mellitus,
were consistent in the 2 treatment arms.
Outcome Events in Patients With Diabetes Mellitus
by Infusion Group
The incidence of the primary end point for an extended fol-
low-up of ≈5 years was significantly lower in the EDTA che-
lation group when compared with placebo (HR, 0.59; 95%
CI, 0.44–0.79; P<0.001), with a 15% absolute decrease in the
5-year Kaplan–Meier primary event rate (Figure 2A; Table 3)
and a relative reduction of 41%. The result remained sig-
nificant after Bonferroni adjustment for multiple subgroups
(99.4% CI, 0.39–0.88; adjusted P=0.002). The number needed
to treat to prevent a single event over 5 years was 6.5 (95% CI,
4.4–12.7). Rates of the secondary end point in patients with
diabetes mellitus were also lower for patients randomized to
EDTA chelation (HR, 0.60; 95% CI, 0.39–0.91; P=0.017),
with a 5.1% absolute decrease in the 5-year Kaplan–Meier
event rate and a relative reduction of 40% (Figure 3A). How-
ever, this result was not significant after adjusting for multiple
subgroups (99.4% CI, 0.32–1.09; adjusted P=0.153). In con-
trast to the treatment effect observed in patients with diabetes
mellitus, patients without diabetes mellitus (n=1075) did not
have a treatment effect with regards to the primary end point
(HR, 1.02; 95% CI, 0.81–1.28; P=0.877) or the secondary
end point (HR, 1.06; 95% CI, 0.74–1.50; Figures 2B and 3B;
Table 4). There was a significant interaction between diagno-
sis of diabetes mellitus and EDTA treatment (P for interaction
for the primary end point, 0.0037).
Patients with diabetes mellitus randomized to EDTA che-
lation had a significant reduction in recurrent MI (HR, 0.48;
95% CI, 0.26–0.88; P=0.015; Figure 4A), in all-cause mortal-
ity (HR, 0.57; 95% CI, 0.36–0.88; P=0.011; Figure 4B), and
in coronary revascularizations (HR, 0.68; 95% CI, 0.47–0.99;
P=0.042). However, after applying the Bonferroni adjust-
ment to these results, they no longer met the criterion for
significance. We also analyzed whether patients with diabe-
tes mellitus randomized in chelation sites were more likely
to demonstrate a therapeutic benefit of EDTA chelation than
patients randomized in conventional sites. The results show
the opposite to be the case (Figure I in the online-only Data
Supplement).
Treatment Adherence
Among the subgroup with diabetes mellitus, the median num-
ber of infusions received was 40 (25, 40); 73% completed 30
infusions; 61% completed 40 infusions; and 34% discontin-
ued study infusions (n=120 [39%] in the placebo group and
n=95 [30%] in the chelation group).
Safety
There were 95 serious adverse events (non–end point events)
in the population with diabetes mellitus (56 placebo and 39
active). Adverse events attributable to the study medication
led 5.7% to withdraw from the trial (20 placebo and 16 active).
Sensitivity Analyses
As a sensitivity analysis, we assessed the baseline characteris-
tics of the subgroup of patients who withdrew consent (Table
V in the online-only Data Supplement). We then assessed how
the primary treatment comparison in the subgroup of patients
with diabetes mellitus would be affected under a variety of
assumptions on the occurrence of primary end point events
among the patients who withdrew consent or were lost to
follow-up and did not have an end point event before exit-
ing the study (106 consent withdrawals and 9 lost to follow-
up; Table VI in the online-only Data Supplement). To assess
robustness of the results, these analyses focused on scenarios
in which events among withdrawn or lost patients in the active
arm were assumed to occur at a higher rate than withdrawn or
lost patients in the placebo arm. For all realistic scenarios, the
comparison of the 2 arms remained highly significant even if
the relative increase of events among patients in the active arm
who withdrew or were lost was as much as 100% higher than
among withdrawn or lost patients in the placebo arm. The HR
for all scenarios was in the range of 0.60 to 0.80, the P val-
ues were very robust, and significance of the treatment effect
was maintained, even for imputation scenarios that were very
unfavorable to the EDTA chelation arm. Finally, we reported
the small number of missing values for baseline character-
istics in the overall population (Table VII in the online-only
Data Supplement) and in the population with diabetes mellitus
(Table VIII in the online-only Data Supplement).
Discussion
The present study of EDTA-based chelation therapy in patients
with diabetes and a prior MI demonstrates a 41% (P<0.001)
relative reduction in the risk of a combined cardiovascular end
point; a reduction in risk of the composite of cardiovascular
mortality, nonfatal stroke, or nonfatal MI of 40% (P=0.017);
a 52% reduction in recurrent MI (P=0.015); and a reduction
in death from any cause of 43% (P=0.011). These findings,
if replicable, would have an effect on the health of patients
with diabetes mellitus. However, we emphasize that these
 6   Circ Cardiovasc Qual Outcomes   January 2014

Table 2.  Baseline Characteristics of Patients With Diabetes by Infusion Arm

EDTA Chelation (N=322) Placebo (N=311) P Value
Demographics
 Age, y 65.1 (60.3, 71.1) 66.2 (58.8, 71.5) 0.843
 Women 55 (17%) 64 (21%) 0.260
 Minority (Hispanic or non-white) 31 (10%) 37 (12%) 0.357
 BMI, kg/m 2
31.1 (27.9, 35.9) 32.1 (28.4, 36.4) 0.208
History
 Time from qualifying MI to 4.2 (1.6, 8.8) 5.1 (1.4, 9.5) 0.457
randomization, y*
 Anterior MI 128 (40%) 111 (36%) 0.292
 Congestive heart failure 76 (24%) 69 (22%) 0.672
 Valvular heart disease 34 11%) 34 (11%) 0.821
 Stroke 26 (8%) 25 (8%) 0.987
 Peripheral vascular disease 69 (22%) 67 (22%) 0.954
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 Hypertension 251 (78%) 243 (78%) 0.955

 Hypercholesterolemia 273 (86%) 255 (84%) 0.436
 Atrial fibrillation 36 (12%) 49 (16%) 0.086
 Former cigarette smoker 181 (56%) 173 (56%) 0.882
Coronary revascularization
 CABG 163 (51%) 150 (48%) 0.548
 PCI 187 (58%) 166 (53%) 0.234
 Either CABG or PCI 271 (84%) 244 (78%) 0.065
Presenting characteristics
 Blood pressure
  
Systolic 130 (120, 140) 130 (120, 140) 0.681
  
Diastolic 74 (68, 80) 74 (68, 80) 0.937
Concomitant medications
 Aspirin 278 (86%) 253 (81%) 0.088
β-blocker
  248 (77%) 229 (74%) 0.323
 Statin 247 (77%) 232 (75%) 0.536
 ACEI or ARB 234 (73%) 226 (73%) 1.000
 Clopidogrel 86 (28%) 75 (25%) 0.550
 Warfarin 34 (11%) 31 (11%) 0.845
 Aspirin, warfarin, or clopidogrel 296 (93%) 286 (92%) 0.909
 Diabetes mellitus medication
  
Insulin 73 (23%) 87 (29%) 0.114
  
Oral hypoglycemic 191 (60%) 189 (63%) 0.585
 Multivitamin 115 (37%) 127 (43%) 0.112
 Other vitamins/minerals 142 (45%) 150 (51%) 0.147
 Herbal products 94 (30%) 96 (33%) 0.419
Laboratory examinations
 Fasting glucose, mmol/L 7.1 (5.9, 8.9) 7.4 (6, 9.1) 0.167
 Creatinine, μmol/L 88.4 (79.6, 114.9) 97.2 (79.6, 114.9) 0.019
 Total cholesterol, mmol/L 4.1 (3.5, 4.9) 4.3 (3.6, 5.2) 0.037
 HDL, mmol/L 1.1 (0.9, 1.2) 1.1 (0.9, 1.2) 0.553
 LDL, mmol/L 2.1 (1.6, 2.7) 2.2 (1.6, 3) 0.111
 Triglycerides, mmol/L 1.7 (1.2, 2.5) 1.8 (1.2, 2.7) 0.299
ACEI indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BMI, body mass index; CABG,
coronary artery bypass graft; HDL, high-density lipoprotein; LDL, low-density lipoprotein; MI, myocardial infarction; and PCI,
percutaneous coronary intervention.
*Median, 25th and 75th percentiles are reported for all continuous variables.
 Escolar et al   Chelation for Diabetes Mellitus With CAD   7
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Figure 2. Primary end point in patients with diabetes mellitus (A) and non–diabetes mellitus (B). CI indicates confidence interval; and
TACT, Trial to Assess Chelation Therapy.

results are based on a subgroup of the overall trial, albeit pre-
specified, and, therefore, must be interpreted with caution.
Although there was a significant interaction of treatment with
diabetes mellitus status, we have provided conservatively
adjusted CIs and P values to account for the multiplicity of
prespecified subgroups. However, even with adjustment, the
effect of EDTA chelation therapy in reducing the primary
composite end point is highly significant. Although the Bon-
ferroni-adjusted results for the components of the primary
end point and for the secondary end point do not meet the
nominal criterion for significance, the magnitude of the treat-
ment effect for each major component, including mortality,
and for the key secondary end point is remarkably consistent
with the primary result.
The US Centers for Disease Control and Prevention
report that there are >24 million Americans with diabe-
tes mellitus diagnosed and an estimated 6 million more
undiagnosed.13 Minorities are disproportionately affected
adding to their burden of disease.14 In a meta-analysis of
almost a million patients, diabetes mellitus was associated
with a 2-fold increased risk of vascular death.15 Diabetes
mellitus increases the risk of mortality and cardiovascular
events in patients with established cardiovascular disease.16
This excess risk was demonstrated within our study as
well, with a 27% relative increase in risk of the primary
end point when compared with the patients without dia-
betes mellitus and a 56% relative increase in the risk of
death. Moreover, patients with diabetes mellitus were more
likely to be obese and were more likely to have a history of
congestive heart failure, stroke, peripheral artery disease,
hypertension, and hypercholesterolemia than those patients
without diabetes mellitus. These differences in risk factors,
of course, may explain some of the differences in clinical
outcomes overall.
Analyses of prespecified subgroups in TACT suggested that
patients with diabetes mellitus accrued particular benefit from

Table 3.  Clinical End Points by Infusion Arms for Patients With Diabetes Mellitus
Adjusted*
EDTA Chelation
End Point (n=322) Placebo (n=311) Hazard Ratio (95% CI) P Value CI P Value
Primary end point 80 (25%) 117 (38%) 0.59 (0.44–0.79) <0.001 0.39–0.88 0.002
Death 32 (10%) 50 (16%) 0.57 (0.36–0.88) 0.011 0.30–1.06 0.099
MI 16 (5%) 30 (10%) 0.48 (0.26–0.88) 0.015 0.20–1.13 0.135
Stroke 4 (1%) 3 (1%) 1.19 (0.27–5.30) 0.829 0.14–9.88 …
Coronary 48 (15%) 62 (20%) 0.68 (0.48–0.99) 0.042 0.40–1.16 0.378
revascularization
Hospitalization for 5 (2%) 6 (2%) 0.72 (0.22–2.36) 0.588 0.13–3.87 …
angina
Secondary end point 35 (11%) 52 (17%) 0.60 (0.39–0.91) 0.017 0.32–1.09 0.153
Cardiovascular death 19 (6%) 27 (9%) 0.63 (0.35–1.13) 0.118 0.27–1.44 …
CI indicates confidence interval; and MI, myocardial infarction.
*Bonferroni adjustment for 9 subgroup factors. CIs are adjusted to a level of 99.4%, and P value is 9× the nominal P value.
 8   Circ Cardiovasc Qual Outcomes   January 2014
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Figure 3. Secondary end point in patients with diabetes mellitus (A) and without diabetes mellitus (B). CI indicates confidence interval;
CV, cardiovascular; MI, myocardial infarction; and TACT, Trial to Assess Chelation Therapy.

EDTA-based infusions.6 The present work expands on those
preliminary observations.
In this study, the EDTA-based chelation regimen markedly
improved the clinical outcomes of patients with diabetes mel-
litus, with a number needed to treat to prevent 1 primary end
point event of 6.5 >5 years (95% CI, 4.4–12.7). Thus, the mul-
ticomponent EDTA-based chelation regimen demonstrated
a robust reduction in events in this subgroup analysis. This
has particular relevance when considering that patients were
taking standard, evidence-based medications for patients with
post-MI, and patients with diabetes mellitus had a median
low-density lipoprotein of 83 mg/dL. We found no improve-
ment in glycemia in the diabetes mellitus subgroup. Other
mechanisms must underlie these findings.
The benefits of the multicomponent EDTA-based infu-
sions may be mediated through the chelation of metals,
thereby reducing direct end-organ toxicity, as well as toxic-
ity mediated through enhanced metal-catalyzed oxidation.
Epidemiological studies support the concept that metals,
including lead and cadmium, are linked to cardiovascular
risk17–20 and EDTA chelates both.21 Clinical trials of patients
with advanced chronic kidney disease and chelatable lead,
treated with EDTA infusions, have shown preservation of
renal function.22,23 Yet these observations do not explain why
there is a significant interaction of chelation treatment with
diabetes mellitus status.
However, there are hypotheses on specific effects of met-
als on patients with diabetes mellitus that have been proposed
for >20 years. Complications of diabetes mellitus are at least
partially mediated through the accumulation of advanced gly-
cation end products and activation of the receptor of advanced
glycation end products,24 with downstream inflammatory cas-
cades.25,26 Glycation end-products are created by the nonenzy-
matic interaction of glucose with proteins, lipids, and nucleic
acids.27 Most advanced glycation end-products require metal-
catalyzed oxygen chemistry for their formation. Metals bind
to glycation end-products and promote the formation of reac-
tive oxygen species in an autocatalytic reaction. The resultant
oxidized end-products accumulate in tissues and promote
inflammation and oxidative stress, hallmarks of atherosclero-
sis. Thus, chelation of metal ions may have particular impor-
tance in patients with diabetes mellitus.28,29 Interestingly, some
medications commonly used in diabetes mellitus may also
have chelating properties.30–32

Table 4.  Clinical End Points by Infusion Arms for Patients Without Diabetes Mellitus
End Point EDTA Chelation (n=517) Placebo (n=558) Hazard Ratio (95% CI) P Value
Primary end point 142 (27%) 144 (26%) 1.02 (0.81–1.28) 0.877
Death 55 (11%) 43 (8%) 1.35 (0.90–2.01) 0.137
MI 36 (7%) 37 (7%) 1.03 (0.65–1.64) 0.872
Stroke 6 (1%) 10 (2%) 0.65 (0.24–1.80) 0.406
Coronary revascularization 82 (16%) 95 (17%) 0.90 (0.67–1.21) 0.474
Hospitalization for angina 8 (2%) 12 (2%) 0.71 (0.29–1.74) 0.440
Secondary end point 61 (12%) 61 (11%) 1.06 (0.74–1.50) 0.760
Cardiovascular death 31 (6%) 24 (4%) 1.37 (0.81–2.34) 0.239
CI indicates confidence interval; and MI, myocardial infarction.
 Escolar et al   Chelation for Diabetes Mellitus With CAD   9
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Figure 4. Myocardial infarction (A) and mortality (B) in patients with diabetes mellitus by infusion group.
The benefits reported here for EDTA chelation potentially
support a mechanism linking metal ions to oxidative stress
and vascular complications, particularly in patients with dia-
betes mellitus and certainly merit further study. Of particular,
albeit inferential importance is the continued separation of
event curves late in the trial, long after infusions have stopped,
suggesting that removal of toxic xenobiotic metals may have
long-term benefit in these patients.
There remain important limitations of these analyses. First
and foremost, although this subgroup analysis was prespeci-
fied, subgroup findings, regardless of how robust they appear,
must be considered hypothesis generating, rather than con-
clusive or definitive and must be replicated. Likewise, P
values, although nominally significant, must also be inter-
preted cautiously, particularly as there were multiple sub-
groups analyzed. Adjusted P values, using the conservative
Bonferroni correction, have been displayed for comparison.
An unexpectedly high number of patients withdrew con-
sent, including a slightly higher percentage among patients
with diabetes mellitus compared with patients without
diabetes mellitus, somewhat limiting the events that could
be accrued and attributed during follow-up. Given that more
placebo patients than chelation patients withdrew consent,
however, the bias is conservative. That is, the effect of active
treatment is likely underestimated by the analyses pre-
sented. We performed sensitivity analyses of patients that
withdrew consent, making adverse assumptions as to their
outcomes in the active therapy arm, and found that the find-
ings reported here remain robust. Finally, although there are
plausible hypotheses on the effects of this therapy, we do
not have measurements of the levels of metals, glycation
end-products, or oxidative stress to corroborate or refute our
hypotheses. Therefore, future studies should be planned and
include bioassay assessment of potential pathways to clarify
the mechanisms of benefit.
Conclusions
Patients with post-MI diabetes mellitus aged ≥50 years on
evidence-based medications demonstrated a marked reduction
in cardiovascular events, including total mortality in the unad-
justed analyses, with EDTA-based chelation therapy. These
findings support the initiation of clinical trials in patients with
diabetes mellitus and vascular disease to replicate these find-
ings and define the mechanisms of benefit. However, they do
not constitute sufficient evidence to indicate the routine use
of chelation therapy for all patients with post-MI diabetes
mellitus.
Acknowledgments
The authors gratefully acknowledge the scientific contributions and
support of Mario Stylianou PhD, at the National Heart, Lung, and
Blood Institute; the organizational skills of Ana Mon Project Leader at
the Clinical Coordinating Center, Alyssa Cotler at the National Center
for Complementary and Alternative Medicine, Susan Dambrauskas
(formerly at the National Heart, Lung, and Blood Institute), and
Vivian Thompson at the Duke Clinical Research Institute for their
competent professional assistance.
Sources of Funding
The National Heart, Lung, and Blood Institute and the National
Center for Complementary and Alternative Medicine provided fund-
ing and oversight, grant U01AT001156 and U01HL092607.
Disclosures
Dr Lamas reports that from 2000 to 2003 he served as a consultant
to OmniComm, the electronic data capture company used in the trial.
No funds were received, and all ties were severed as of September 10,
2003. The other authors report no conflicts.
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 The Effect of an EDTA-based Chelation Regimen on Patients With Diabetes Mellitus and
Prior Myocardial Infarction in the Trial to Assess Chelation Therapy (TACT)
Esteban Escolar, Gervasio A. Lamas, Daniel B. Mark, Robin Boineau, Christine Goertz, Yves
Rosenberg, Richard L. Nahin, Pamela Ouyang, Theodore Rozema, Allan Magaziner, Richard
Nahas, Eldrin F. Lewis, Lauren Lindblad and Kerry L. Lee
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Circ Cardiovasc Qual Outcomes. published online November 19, 2013;

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SUPPLEMENTAL MATERIAL

1
 Table of Contents
Supplemental Methods

Analysis of original cohort of 538 self-identified diabetic patients 3

Sensitivity Analyses with Imputation of Outcomes in Patients

Who Withdrew Consent or Were Lost to Follow-up 4

Supplemental Tables

Baseline Characteristics of Patients with or without Diabetes 6

Outcomes by infusion group for the original cohort of self-identified patients

with diabetes 10

Outcomes by infusion group for the original cohort of patients without diabetes 11

Components of the TACT chelation solution 12

Baseline Characteristics of Diabetic Patients Who Withdrew Consent

by Treatment Group 13

Sensitivity analyses with imputation of outcomes 17

Missing values for baseline characteristics of diabetics vs. non-diabetics 18

Missing values for baseline characteristics of diabetics by infusion arm 22

Supplemental Figures

Analysis of CAM versus non-CAM sites 26

TACT investigators, leadership, and trial committees 27

2
Analysis of original cohort of 538 self-identified diabetic patients.
These analyses are based on the diabetes cohort as identified in the 2013 JAMA publication, and

are provided for completeness. They include baseline characteristics, and EDTA effect on

patients with and without diabetes. While statistical significance for some comparisons is

occasionally lost due to smaller numbers, the point estimates track very nicely with the more

accurate cohort defined in the body of the paper. Moreover, statistical significance is preserved

for the primary and secondary endpoints. See eTables 1-2.

3
Sensitivity Analyses with Imputation of Outcomes in Patients Who Withdrew
Consent or Were Lost to Follow-up
As a sensitivity analysis, we have assessed how the primary treatment comparison in the
subgroup of patients with diabetes would be affected under a variety of assumptions regarding
the occurrence of primary endpoint events among the patients who withdrew consent or were lost
to follow-up. In these analyses, we have imputed events only among the consent withdrawal or
lost patients who did not have a documented occurrence of one of the primary events. This
number includes 124-18=106 consent withdrawal patients and 9 patients who were lost to
follow-up. We performed treatment comparisons where a certain percentage of the withdrawn or
lost patients in each arm was assumed to have a primary event. To simplify the calculations, the
event was assumed to occur at the censoring time. The different percentages of the patients who,
in the sensitivity analyses were assumed to have an event, are shown in eTable 6, along with the
results of the treatment comparison under each assumption. Since only a certain percentage of
the patients were assumed to have an event, 500 replications were performed for each scenario
using these percentages to randomly select the patients with events, and the results of these
replications were then averaged to obtain the estimate of treatment effect.

To explain the analyses for the 20 different scenarios listed in eTable 6, the placebo event rate
listed in the table pertains only to the patients randomly allocated to the placebo infusion arm
who were among the 106 consent withdrawal patients and the 9 patients lost to follow-up
referenced above. Similarly the event rate in the EDTA column pertains only to the patients
allocated to the active infusion arm who withdrew consent or were lost to follow-up. The
imputed events among the patients who withdrew consent or were lost to follow-up were then
combined with the event data from all of the other patients (those who did not withdraw consent
and were not lost to follow-up) to compute a hazard ratio, confidence interval, and p-value. If
we postulate, for example, that among the patients who withdrew from the study or were lost to
follow-up, 20% of the placebo patients and 40% of the EDTA patients had events, the patients
for whom an event was imputed were randomly chosen from among the candidates. As
explained above, 500 replications were performed for each scenario (each time randomly
selecting the patients with events), and the results of those replications averaged to obtain the
hazard ratio, confidence interval, and p-value.

The percentage of events among the placebo patients who withdrew consent or were lost to
follow-up was varied in these sensitivity analyses from 10% to 40%. As reported in Table 2 of
the manuscript, the percentage of diabetic patients in the placebo arm who, during the course of
the trial, experienced a primary event was 38%. However, it is unlikely that the proportion of
events among the withdrawn or lost patients would be that high, as these patients had survived
and were event-free during the portion of the trial in which they were followed.

For the chelation arm of the trial, we considered percentages of events among the withdrawn or
lost patients that ranged from the same percent as in the placebo arm to the extreme case of

4
100% higher than the percentage in the placebo arm. The major objective of these sensitivity
analyses was to assess the robustness of the results in the diabetic subgroup in the event that
among the group of patients who withdrew consent or were lost to follow-up, there were more
patients in the active arm with events compared to the placebo arm.

Scenario 1, for example, is based on the assumption that 10% of the withdrawn or lost patients in
the placebo arm experienced an event, and that the percentage in the active arm was also 10%.
Scenarios 2-6 reflect increasingly higher percentages of events in the active arm compared to the
placebo arm (up to 100% higher) while maintaining the level at 10% in the placebo arm.
Scenarios 7-12 have a similar pattern except the percentage of events in the placebo arm is 20%.
In scenarios 13-18, the pattern is again similar except that the percentage of events in the placebo
arm is 30%. Scenarios 19 and 20 represent cases where the percentage of events in the placebo
arm is 40%. Thus, we have covered a broad spectrum of possibilities with these scenarios where
the withdrawn or lost patients in the active arm were assumed to have a higher rate of events
compared to the placebo patients.

To explain the other quantities in eTable 6, the “Relative Increase” is simply the relative change
in the percentage of events among the withdrawn or lost patients in the active arm compared to
the percentage of events among the withdrawn or lost patients in the placebo arm. The hazard
ratio and confidence interval in each case is based on the comparison of EDTA vs. placebo
(derived from the Cox model), and the p-value is based on the log-rank test. The expected
number of events is simply the number of events projected in each arm for each different
scenario.

Based on the other data observed in the trial and because the baseline risk factors of the patients
who withdrew consent very similar in the two arms of the trial, the most plausible scenarios
would be those where the percentages of events among the withdrawn or lost patients in the two
arms actually favor the active arm. However, to assess robustness of the results, we have
focused on scenarios in which the events in the active arm were assumed to occur at the same or
a higher rate than in the placebo arm. As shown in eTable 6, the comparison of the two arms for
all realistic scenarios remains highly significant if the relative increase of events in the active
arm is as much as 100% higher than in the placebo arm. The hazard ratio for all scenarios was in
the range of 0.60 to 0.80, the p-values are very robust, and except for scenario 20, significance of
the treatment effect is maintained, even for imputation scenarios that are very unfavorable to the
EDTA arm.

5
eTable 1. Baseline Characteristics of Patients With or Without Diabetes

Diabetes No Diabetes
(N=538) (N=1170) P-value

Demographics

Age (years) 65.7 (59.7, 71.5) 65.1 (58.7, 72.0) 0.333

Female 106 (20%) 193 (16%) 0.105

Caucasian 503 (93%) 1102 (94%) 0.576

Minority (Hispanic or non-Caucasian) 57 (11%) 99 (8%) 0.155

BMI 32.0 (28.4, 36.4) 28.9 (26.1, 32.3) <0.001

History
Time from qualifying MI to randomization 4.4 (1.5, 9.2) 4.6 (1.7, 9.3) 0.474
(years)*
Anterior MI 200 (37%) 474 (41%) 0.190

Congestive heart failure 127 (24%) 180 (15%) < 0.001

Valvular heart disease 50 (10%) 125 (11%) 0.394

Stroke 48 (9%) 63 (5%) 0.006

Peripheral vascular disease 124 (23%) 144 (12%) < 0.001

Hypertension 427 (79%) 742 (63%) < 0.001

Hypercholesterolemia 456 (86%) 914 (80%) 0.003

Atrial fibrillation 73 (14%) 122 (11%) 0.053

Former cigarette smoker 303 (56%) 652 (56%) 0.819

(continued on next page)

6
 eTable 1. Baseline Characteristics of Patients With or Without Diabetes (continued)
Diabetes No Diabetes
(N=538) (N=1170) P-value

Coronary revascularization

CABG 265 (49%) 509 (44%) 0.027

PCI 301 (56%) 706 (60%) 0.086

Either CABG or PCI 438 (81%) 976 (83%) 0.308

Presenting Characteristics

Blood Pressure

Systolic 130.0 (120.0, 140.0) 130.0 (118.0, 140.0) 0.152

Diastolic 74.0 (68.0, 80.0) 76.5 (70.0, 81.0) <0.001

NYHA Functional Class 0.005

No heart failure 407 (76%) 942 (81%)

Class I 65 (12%) 145 (12%)

Class II 53 (10%) 69 (6%)

Class III 13 (2%) 14 (1%)

Class IV 0 (0%) 0 (0%)

(continued on next page)

7
 eTable 1. Baseline Characteristics of Patients With or Without Diabetes (continued)
Diabetes No Diabetes
(N=538) (N=1170) P-value

Concomitant Medications
Aspirin 451 (84%) 976 (83%) 0.832

Beta-blocker 401 (75%) 825 (71%) 0.086

Statin 411 (76%) 837 (72%) 0.036

ACE or ARB 399 (74%) 685 (59%) < 0.001

Clopidogrel 134 (26%) 291 (26%) 0.949

Warfarin 57 (11%) 91 (8%) 0.051

Aspirin or warfarin 481 (90%) 1021 (88%) 0.211

495 (93%) 1057 (91%) 0.205

Aspirin, warfarin or clopidogrel

Aspirin or clopidogrel 470 (88%) 1017 (87%) 0.716

Diabetes medication

Insulin 156 (30%) 4 (0%) < 0.001

Oral hypoglycemic 370 (70%) 10 (1%) < 0.001

Multivitamin 206 (40%) 509 (45%) 0.052

Other vitamins/minerals 240 (46%) 612 (54%) 0.003

Herbal products 150 (29%) 410 (36%) 0.005

(continued on next page)

8
 eTable 1. Baseline Characteristics of Patients With or Without Diabetes (continued)
Diabetes No Diabetes
(N=538) (N=1170) P-value

Laboratory Examinations

Glucose (mg/dL) 130.0 (105.0, 165.0) 98.0 (91.0, 107.0) <0.001

Creatinine (mg/dL) 1.1 (0.9, 1.3) 1.1 (0.9, 1.2) 0.044

Total cholesterol (mg/dL) 161.0 (137.0, 193.0) 166.0 (143.0, 195.0) 0.027

HDL (mg/dL) 41.0 (35.0, 48.0) 43.0 (37.0, 52.0) <0.001

LDL (mg/dL) 81.0 (62.0, 109.0) 91.0 (71.0, 116.0) <0.001

(continued on next page)

* Median, 25th and 75th percentiles are reported for all continuous variables.

9
eTable 2.
This table shows outcomes by infusion group for the original cohort of self-identified patients with
diabetes.

EDTA Chelation Placebo Hazard Ratio

Endpoint (N= 265) (N= 273) (95% CI) P Value
Primary Endpoint 67 (25%) 102 (37%) 0.61 (0.45, 0.83) 0.002
Death 28 (11%) 40 (15%) 0.67 (0.41, 1.09) 0.107
MI 16 (6%) 29 (11%) 0.53 (0.29, 0.98) 0.042
Stroke 3 (1%) 3 (1%) 0.99 (0.20, 4.89) 0.979
Coronary revascularization 41 (15%) 54 (20%) 0.72 (0.48, 1.09) 0.114
Hospitalization for angina 4 (2%) 6 (2%) 0.60 (0.17, 2.14) 0.435
Secondary Endpoint 30 (11%) 46 (17%) 0.62 (0.39, 0.99) 0.043
Cardiovascular Death 15 (6%) 21 (8%) 0.69 (0.36, 1.34) 0.275

10
eTable 3.
This table shows outcomes by infusion group for the original cohort of patients without diabetes.

EDTA Chelation Placebo Hazard Ratio

Endpoint (N= 574) (N= 596) (95% CI) P Value
Primary Endpoint 155 (27%) 159 (27%) 0.96 (0.77, 1.20) 0.725
Death 59 (10%) 53 (9%) 1.12 (0.77, 1.63) 0.529
MI 36 (6%) 38 (6%) 0.96 (0.61, 1.51) 0.875
Stroke 7 (1%) 10 (2%) 0.73 (0.28, 1.91) 0.516
Coronary revascularization 89 (16%) 103 (17%) 0.85 (0.64, 1.14) 0.279
Hospitalization for angina 9 (2%) 12 (2%) 0.76 (0.32, 1.81) 0.528
Secondary Endpoint 66 (11%) 67 (11%) 0.99 (0.71, 1.40) 0.977
Cardiovascular Death 35 (6%) 30 (5%) 1.19 (0.73, 1.93) 0.486

11
eTable 4. Components of the TACT Chelation Infusion

Component Amount

Disodium EDTA 3 g*

Ascorbic acid 7g

Magnesium chloride 2g

Potassium chloride 2 mEq

Sodium bicarbonate 840 mg

Pantothenic acid 250 mg

Thiamine, 100 mg

Pyridoxine 100 mg

Procaine 100 mg

Unfractionated heparin 2500 U

Sterile water 500 ml

* adjusted downward based on eGFR

12
eTable 5. Baseline Characteristics of Diabetic Patients Who Withdrew
Consent by Treatment Group
EDTA Chelation Placebo
(N=54) (N=70) P-value

Demographics

Age (years) 65.2 (59.4, 70.9) 64.1 (58.1, 70.4) 0.424

Female 14 (26%) 26 (37%) 0.185

Minority (Hispanic or non-Caucasian) 4 (7%) 9 (13%) 0.326

BMI 33.9 (29.8, 39.9) 33.3 (29.6, 38.8) 0.620

History

Time from qualifying MI to 3.7 (1.9, 9.6) 4.4 (1.4, 10.3) 0.772
randomization (years)*

Anterior MI 28 (52%) 31 (44%) 0.403

Congestive heart failure 20 (37%) 14 (20%) 0.035

Valvular heart disease 4 (8%) 6 (9%) 1.000

Stroke 6 (11%) 8 (11%) 0.956

Diabetes 46 (85%) 64 (91%) 0.276

Peripheral vascular disease 12 (23%) 14 (20%) 0.722

Hypertension 48 (89%) 55 (79%) 0.129

Hypercholesterolemia 41 (82%) 55 (80%) 0.755

Atrial fibrillation 8 (17%) 9 (14%) 0.654

Former cigarette smoker 26 (48%) 37 (53%) 0.603

(continued on next page)

13
eTable 5. Baseline Characteristics of Diabetic Patients Who Withdrew
Consent by Treatment Group (continued)
EDTA Chelation Placebo
(N=54) (N=70) P-value

Coronary revascularization

CABG 31 (57%) 35 (50%) 0.412

PCI 34 (63%) 38 (54%) 0.332

Either CABG or PCI 47 (87%) 56 (80%) 0.300

Presenting Characteristics

Blood Pressure

Systolic 131.0 (120.0, 144.0) 130.0 (120.0, 138.0) 0.095

Diastolic 78.0 (70.0, 80.0) 70.0 (66.0, 80.0) 0.243

NYHA Functional Class 0.132

No heart failure 34 (63%) 57 (81%)

Class I 9 (17%) 6 (9%)

Class II 8 (15%) 5 (7%)

Class III 3 (6%) 2 (3%)

Class IV 0 (0%) 0 (0%)

(continued on next page)

14
eTable 5. Baseline Characteristics of Diabetic Patients Who Withdrew
Consent by Treatment Group (continued)
EDTA Chelation Placebo
(N=54) (N=70) P-value

Concomitant Medications

Aspirin 47 (87%) 61 (87%) 0.986

Beta-blocker 45 (83%) 46 (66%) 0.028

Statin 37 (69%) 52 (74%) 0.479

ACE or ARB 42 (78%) 51 (73%) 0.530

Clopidogrel 12 (24%) 16 (25%) 0.864

Warfarin 10 (20%) 4 (6%) 0.026

Aspirin or warfarin 51 (96%) 64 (91%) 0.464

Aspirin, warfarin or clopidogrel 52 (98%) 66 (94%) 0.389

Diabetes medication
Insulin 19 (39%) 24 (36%) 0.745

Oral hypoglycemic 26 (52%) 45 (66%) 0.120

Multivitamin 18 (36%) 36 (55%) 0.047

Other vitamins/minerals 14 (28%) 34 (52%) 0.009

Herbal products 17 (35%) 20 (32%) 0.728

(continued on next page)

15
eTable 5. Baseline Characteristics of Diabetic Patients Who Withdrew
Consent by Treatment Group (continued)
EDTA Chelation Placebo
(N=54) (N=70) P-value

Laboratory Examinations

Glucose (mg/dL) 140.0 (115.0, 169.0) 138.5 (112.0, 169.0) 0.910

Creatinine (mg/dL) 1.0 (0.9, 1.3) 1.0 (0.9, 1.2) 0.838

Total cholesterol (mg/dL) 164.0 (140.0, 195.0) 173.0 (147.0, 207.0) 0.394

HDL (mg/dL) 40.0 (34.0, 47.0) 42.0 (35.5, 49.5) 0.403

LDL (mg/dL) 86.5 (64.5, 117.5) 92.0 (63.0, 120.0) 0.574

Triglycerides (mg/dL) 175.0 (127.0, 238.0) 163.0 (122.0, 215.0) 0.909

* Median, 25th and 75th percentiles are reported for all continuous variables.

16
 eTable 6. Sensitivity Analyses with Imputation of Outcomes for Patients
Who Withdrew from the Study or were Lost to Follow-up
Percent Percent
events events EDTA Placebo
Placebo EDTA Relative Hazard Lower Upper events events
Scenario Arm* arm* Increase Ratio** CI CI P-value (expected) (expected)

1 10 10 0 0.60 0.46 0.80 0.0003 86 123

2 10 11 10% 0.61 0.46 0.81 0.0004 87 123

3 10 12 20% 0.62 0.47 0.81 0.0005 88 123

4 10 12.5 25% 0.62 0.47 0.81 0.0005 88 123

5 10 15 50% 0.63 0.48 0.82 0.0007 89 123

6 10 20 100% 0.65 0.49 0.85 0.0014 91 123

7 20 20 0 0.62 0.48 0.81 0.0005 91 127

8 20 22 10% 0.64 0.49 0.83 0.0008 93 127

9 20 24 20% 0.64 0.49 0.84 0.0010 94 127

10 20 25 25% 0.64 0.49 0.84 0.0010 94 127

11 20 30 50% 0.66 0.51 0.86 0.0020 97 127

12 20 40 100% 0.70 0.54 0.91 0.0069 103 127

13 30 30 0 0.63 0.49 0.82 0.0006 97 133

14 30 33 10% 0.65 0.50 0.84 0.0009 99 133

15 30 36 20% 0.66 0.51 0.85 0.0015 101 133

16 30 37.5 25% 0.66 0.51 0.86 0.0018 102 133

17 30 45 50% 0.69 0.53 0.89 0.0041 106 133

18 30 60 100% 0.75 0.58 0.96 0.0205 114 133

19 40 60 50% 0.72 0.56 0.92 0.0093 114 138

20 40 80 100% 0.79 0.62 1.01 0.0581 126 138

* Imputed event rates in patients who withdrew consent or were lost to follow-up and did not
have a primary outcome event prior to censoring

** Hazard ratio calculated by combining the imputed outcomes for patients who withdrew
consent or were lost to follow-up with the outcomes of patients who completed the study

17
 eTable 7. Missing values for Baseline Characteristics of Patients With or Without Diabetes (Hx
DM, Meds or High Glucose)
Diabetes No Diabetes
(N=633) (N=1075) All Patients

Demographics

Age (years) 0 (0%) 0 (0%) 0 (0%)

Gender 0 (0%) 0 (0%) 0 (0%)

Minority (Hispanic or non-Caucasian) 0 (0%) 0 (0%) 0 (0%)

American Indian or Alaska Native 0 (0%) 0 (0%) 0 (0%)

Asian 0 (0%) 0 (0%) 0 (0%)

Black 0 (0%) 0 (0%) 0 (0%)

Caucasian 0 (0%) 0 (0%) 0 (0%)

Hawaiian 0 (0%) 0 (0%) 0 (0%)

BMI 0 (0%) 0 (0%) 0 (0%)

History

Time from qualifying MI to randomization (years)* 0 (0%) 2 (0%) 2 (0%)

Anterior MI 0 (0%) 0 (0%) 0 (0%)

Congestive heart failure 0 (0%) 0 (0%) 0 (0%)

(continued on next page)

18
 eTable 7. Missing values for Baseline Characteristics of Patients With or Without Diabetes (Hx DM, Meds
or High Glucose)
Diabetes No Diabetes
(N=633) (N=1075) All Patients
Valvular heart disease 15 (2%) 18 (2%) 33 (2%)

Stroke 0 (0%) 0 (0%) 0 (0%)

Peripheral vascular disease 5 (1%) 6 (1%) 11 (1%)

Hypertension 0 (0%) 0 (0%) 0 (0%)

Hypercholesterolemia 10 (2%) 21 (2%) 31 (2%)

Atrial fibrillation 21 (3%) 31 (3%) 52 (3%)

Former cigarette smoker 0 (0%) 0 (0%) 0 (0%)

Coronary revascularization

CABG 0 (0%) 0 (0%) 0 (0%)

PCI 0 (0%) 0 (0%) 0 (0%)

Either CABG or PCI 0 (0%) 0 (0%) 0 (0%)

Presenting Characteristics
Blood Pressure

Systolic 0 (0%) 0 (0%) 0 (0%)

Diastolic 0 (0%) 0 (0%) 0 (0%)

(continued on next page)

19
 eTable 7. Missing values for Baseline Characteristics of Patients With or Without Diabetes (Hx DM, Meds
or High Glucose)
Diabetes No Diabetes
(N=633) (N=1075) All Patients

NYHA Functional Class 0 (0%) 0 (0%) 0 (0%)

Aspirin 0 (0%) 0 (0%) 0 (0%)

Beta-blocker 0 (0%) 0 (0%) 0 (0%)

Statin 0 (0%) 0 (0%) 0 (0%)

ACE or ARB 0 (0%) 0 (0%) 0 (0%)

Clopidogrel 26 (4%) 39 (4%) 65 (4%)

Warfarin 29 (5%) 49 (5%) 78 (5%)

Aspirin or warfarin 2 (0%) 5 (0%) 7 (0%)

Aspirin, warfarin or clopidogrel 3 (0%) 4 (0%) 7 (0%)

Aspirin or clopidogrel 3 (0%) 4 (0%) 7 (0%)

Diabetes medication

Insulin 23 (4%) 50 (5%) 73 (4%)

Oral hypoglycemic 15 (2%) 51 (5%) 66 (4%)

(continued on next page)

20
 eTable 7. Missing values for Baseline Characteristics of Patients With or Without Diabetes (Hx DM, Meds
or High Glucose)
Diabetes No Diabetes
(N=633) (N=1075) All Patients
Multivitamin 25 (4%) 34 (3%) 59 (3%)

Other vitamins/minerals 18 (3%) 26 (2%) 44 (3%)

Herbal products 28 (4%) 34 (3%) 62 (4%)

Laboratory Examinations

Glucose (mg/dL) 0 (0%) 1 (0%) 1 (0%)

Creatinine (mg/dL) 0 (0%) 1 (0%) 1 (0%)

Total cholesterol (mg/dL) 60 (9%) 99 (9%) 159 (9%)

HDL (mg/dL) 69 (11%) 118 (11%) 187 (11%)

LDL (mg/dL) 101 (16%) 139 (13%) 240 (14%)

Triglycerides (mg/dL) 60 (9%) 101 (9%) 161 (9%)

21
 eTable 8. Missing values for Baseline Characteristics of Diabetic Patients By Treatment Arm
EDTA Chelation Placebo
(N=322) (N=311) All Patients

Demographics

Age (years) 0 (0%) 0 (0%) 0 (0%)

Gender 0 (0%) 0 (0%) 0 (0%)

Minority (Hispanic or non-Caucasian) 0 (0%) 0 (0%) 0 (0%)

American Indian or Alaska Native 0 (0%) 0 (0%) 0 (0%)

Asian 0 (0%) 0 (0%) 0 (0%)

Black 0 (0%) 0 (0%) 0 (0%)

Caucasian 0 (0%) 0 (0%) 0 (0%)

Hawaiian 0 (0%) 0 (0%) 0 (0%)

BMI 0 (0%) 0 (0%) 0 (0%)

History

Time from qualifying MI to randomization (years)* 0 (0%) 0 (0%) 0 (0%)

Anterior MI 0 (0%) 0 (0%) 0 (0%)

(continued on next page)

22
eTable 8. Missing values for Baseline Characteristics of Diabetic Patients By Treatment Arm
EDTA Chelation Placebo
(N=322) (N=311) All Patients
Congestive heart failure 0 (0%) 0 (0%) 0 (0%)

Valvular heart disease 5 (2%) 10 (3%) 15 (2%)

Stroke 0 (0%) 0 (0%) 0 (0%)

Peripheral vascular disease 2 (1%) 3 (1%) 5 (1%)

Hypertension 0 (0%) 0 (0%) 0 (0%)

Hypercholesterolemia 4 (1%) 6 (2%) 10 (2%)

Atrial fibrillation 10 (3%) 11 (4%) 21 (3%)

Former cigarette smoker 0 (0%) 0 (0%) 0 (0%)

Coronary revascularization

CABG 0 (0%) 0 (0%) 0 (0%)

PCI 0 (0%) 0 (0%) 0 (0%)

Either CABG or PCI 0 (0%) 0 (0%) 0 (0%)

Presenting Characteristics
Blood Pressure
Systolic 0 (0%) 0 (0%) 0 (0%)
Diastolic 0 (0%) 0 (0%) 0 (0%)
(continued on next page)

23
eTable 8. Missing values for Baseline Characteristics of Diabetic Patients By Treatment Arm
EDTA Chelation Placebo
(N=322) (N=311) All Patients

NYHA Functional Class 0 (0%) 0 (0%) 0 (0%)

Aspirin 0 (0%) 0 (0%) 0 (0%)

Beta-blocker 0 (0%) 0 (0%) 0 (0%)

Statin 0 (0%) 0 (0%) 0 (0%)

ACE or ARB 0 (0%) 0 (0%) 0 (0%)

Clopidogrel 10 (3%) 16 (5%) 26 (4%)

Warfarin 13 (4%) 16 (5%) 29 (5%)

Aspirin or warfarin 1 (0%) 1 (0%) 2 (0%)

Aspirin, warfarin or clopidogrel 2 (1%) 1 (0%) 3 (0%)

Aspirin or clopidogrel 2 (1%) 1 (0%) 3 (0%)

Diabetes medication

Insulin 11 (3%) 12 (4%) 23 (4%)

Oral hypoglycemic 6 (2%) 9 (3%) 15 (2%)

(continued on next page)

24
 eTable 8. Missing values for Baseline Characteristics of Diabetic Patients By Treatment Arm
EDTA Chelation Placebo
(N=322) (N=311) All Patients

Multivitamin 9 (3%) 16 (5%) 25 (4%)

Other vitamins/minerals 4 (1%) 14 (5%) 18 (3%)

Herbal products 8 (2%) 20 (6%) 28 (4%)

Laboratory Examinations

Glucose (mg/dL) 0 (0%) 0 (0%) 0 (0%)

Creatinine (mg/dL) 0 (0%) 0 (0%) 0 (0%)

Total cholesterol (mg/dL) 29 (9%) 31 (10%) 60 (9%)

HDL (mg/dL) 34 (11%) 35 (11%) 69 (11%)

LDL (mg/dL) 49 (15%) 52 (17%) 101 (16%)

Triglycerides (mg/dL) 29 (9%) 31 (10%) 60 (9%)

25
 eFigure 1. Analysis of the primary endpoint in CAM vs non-CAM sites by treatment group.

TACT
Kaplan-Meier Estimates of the Primary Composite Endpoint
EDTA Chelation Therapy vs. Placebo TACT
Subset of Patients in CAM Sites with Diabetes: Hx, Med Use or Baseline Glucose>=126 Kaplan-Meier Estimates of the Primary Composite Endpoint
EDTA Chelation Therapy vs. Placebo
0.5 Hazard Ratio 95% CI P-value (log-rank) Subset of Patients in Non-CAM Sites with Diabetes: Hx, Med Use or Baseline Glucose>=126
EDTA:Placebo 0.76 0.53, 1.08 .1280
0.5 Hazard Ratio 95% CI P-value (log-rank)
EDTA:Placebo 0.38 0.24, 0.62 .0001
0.4
0.4
Placebo Placebo
EDTA Chelation EDTA Chelation
0.3
Event Rate

0.3

Event Rate
0.2
0.2

0.1
0.1

0.0
0.0
0 6 12 18 24 30 36 42 48 54 60
0 6 12 18 24 30 36 42 48 54 60

Months since randomization Months since randomization

Number at Risk Number at Risk
EDTA Chelation 197 170 153 141 128 117 108 103 90 71 41 EDTA Chelation 125 116 109 102 89 81 79 74 67 55 33
Placebo 198 170 153 141 126 115 104 88 75 61 43 Placebo 113 100 82 73 61 53 51 46 41 33 20

26
In addition to the authors the following Investigators and Coordinators
participated in the Trial to Assess Chelation Therapy.

United States
Biogenesis Medical Center- Theodore Rozema, Dolly Corbin; Tru Med- Rajiv Chandra, Terry
Murphy; Comprehensive Heart Care- James Roberts, Debra Braun; Brian Dieterle MD, PhD,
Internal Medicine-Brian Dieterle, Debra Louderback; Arkansas Center for Physical Medicine
and Rehabilitation, Northeast LA Anti-Aging and Wellness Center, Louisiana Anti-Aging &
Wellness Care- Linda Bunch, April Archey, Shauna Gallien, Kim Robinson; Celebration of
Health Association- Terry Chappell, Marcia Arnold; The Castle Clinic, PLLC- Robert C. Allen,
Laura Whitaker; Patrick A Golden-Patrick Golden, Kathy Sasser; Born Preventive Health Care
Clinic & Crossroads Healing Arts- Tammy Born, Judy Schneider; Full Circle Medical Center-
Charles Adams, Crystal Montgomery; Wellness and Longevity Center of Louisiana- Sangeeta
Shah, Debbie Vige; Heart and Vascular Center for Research, Inc.- Clayton Bredlau, Amy
Heineman; Integrative Medical Associates- Connie Ross, Michelle Simpson; University of
Missouri Health Care System- Greg Flaker, Sharon Clasby; Waters Preventive Medical Center-
Robert Waters, Sarah B. Chapman; Heart Care Center- Russell Silverman, Sherri Loucks;
Wellness Works- Carol Roberts, Berni McClendon; Mayo Clinic and Foundation Cardiovascular
Health Clinic- Gerald Gau, Dawn Shelstad; Aurora Denver Cardiology Associates- Nampalli
Vijay, Melinda Washam; Scripps Center for Integrative Medicine- Erminia Guarneri, Eva Stuart;
Family Health Medical Services- Robert Berke, Paige Davidson; The Cardiovascular Center for
Research- Anita Arnold, Dana Kappel; Complementary Medical Services- James Carter,
Kaylynn LeBlanc; Magaziner Center for Wellness- Allan Magaziner, Betty Ann Persico; The
Preventive Medicine Center- Kenneth Ganapini, Venus Barney; Upper Valley Family Care-
Richard Plumb, Lynn Shough; Family/ Complimentary Medicine- Karen Dantin, Laurie McDuff;
Baystate Medical Center-Mara Slawsky, Judith Fleurent; Florida Cardiovascular Institute- John
Sullebarger, Leona Stewart; Freedom Center for Advanced Medicine- William David Voss,
Lorna Gordon; Tequesta Family Practice- R.J. Oenbrink, Joe Militello; Virginia Beach General
Hospital- John Griffin, Pam Hollsten; Johns Hopkins University- Pamela Ouyang, Jeanne
Wingo; Bircher Chiropractic and Wellness Center- Donald Riemer, Laura Sembach; Jack E.
Young, MD, Estela Fransbergen; Chris Hatlestad, MD, PC, Center for Environmental Medicine-
Chris Hatlestad, Christine Ohlemann, Cambor Wade; The Blend Institute- Timothy Blend,
Helena Williams; University of Arkansas for Medical Sciences, Central Arkansas Veterans
Healthcare System- Joseph Bissett, Sandra McLaren, Sharon Locke;Care Foundation Inc-
Timothy Logeman, Karen Olson; COR Research- Clinton Corder, Clinton, Michael Stout;
Androscoggin Cardiology Associates- Robert Weiss, Sarah Dumais; Chelation Centers of Texas-
Dorothy Merritt, Elizabeth Collins; Deborah Heart and Lung Center- Alexander Poulathas,
Linda Dewey; Innovative Research of West Florida- Miguel Trevino, Kimberly Mai; The
Cardiovascular Group- Lawrence Miller, Deanna Overbeck; Advantage Health Center, LLC-
Donald Tice; Hope Medical Holistic Clinic- Zbigniew Grudzien, Maryna Kuzmin; Hudson

27
Valley Heart Center- Glenn Gerber, Patricia O'Brien; Integrative Medicine Center at Schneck
Medical Center- Steven Windley, Stephanie Pyle; Land Clinical Studies-James Garofalo,
Krystle Chavez; Mount Sinai Medical Center of Florida- Todd Heimowitz, Helen Garcia;
Advanced Family Medicine- James Johnson, Rosemary Stevenson; Life Family Practice Center
for Complementary and Alternative Medicine- Nelzon Kraucak, Mariann Haring; Parchment
Family Practice- Eric Born, Julie Ladkrood; Schachter Center for Complementary Medicine-
Michael Schachter, Sally Minniefield; The Ohio State University Medical Center- Raymond
Magorien, Luba Mazanec; Wholistic Health Center- Ralph Miranda, Barb Casella; Athens
Surgery Clinic- Joseph Holliday, Vivian Holliday; Henry Ford Health System- Jonathan
Ehrman, Matthew Saval; Preventive Medicine- Varsha Rathod, Heather Moran; The Heart
Group- Joseph O'Bryan, Mary Barr; Cardiac Solutions- Vishal Patel, Denise Wells; New York
University, School of Medicine-Harmony Reynolds, Chao Wang; Riverside Family Medical-
Lisa Merritt, Lisa Lockett; White-Wilson Medical Center, P.A.- Leslie Fleischer, Cheri Penas;
Caring Cardiology- Roy Heilbron, Celia Heilbron; Hillsboro Family Medicine- Paul Kotturan,
Nalini Reddy; Phoenix Wellness Group- Eleanor Hynote, Katie Lacey; Tyler Total Wellness
Center- Pieter deWet, Cindy deWet; University Hospitals of Cleveland- Austin Halle, Lian
Yang; Dr. Yulius Poplyansky- Yulius Poplyansky, Marjorie Patino; Main Line Health Heart
Center- Robert Bulgarelli, Susan Herring; Marino Center for Integrative Medicine- Guy Pugh,
Vivian Cole; Northwest Indiana Cardiovascular Physicians Inc.- Hector Marchand, Cheryl
Kwiatkowski; Alaska Cardiovascular Research Foundation- Paul Peterson, Lori Heaney; John F.
Kennedy Medical Center- Steven Borzak, Jamie Kosik; Grace Medical Association- Smart
Idemudia, Krista Fallin; Mark O'Neal Speight, MD- Mark O'Neal Speight, Janine Speight; New
York VA, Cardiovascular Clinical Research Center-Steven Sedlis, Estelita Anteola; Baptist
Cardiac and Vascular Institute- Barry Katzen, Ivette Cruz; Bronx-Lebanon Hospital Center-
Bhalodkar, Narendra, Noneta Montinola; Cardiology Consultants of South Florida- Ricky
Schneider, Rochelle Mckenzie; Grossman Wellness Center- Terry Grossman, Paula Quezada;
Longevity Medical , PA- Ivan Krohn, Lewis S. Korb; Pearsall Medical and Bariatrics- Gurney
Fields Pearsall, Marina M Pearsall; The Center for the Improvement of Human Functioning
International- Ron Hunninghake, Mavis Schultz; University of Kansas Medical Center- Jeanne
Drisko, Elizabeth Schrick; West Holt Medical Clinic- Robert Randall, Teresa Kohle; Boice
Willis Clinic- Shalendra Varma; Florida Medical Clinic, P.A- Hector Fontanet, Precious Hoyle;
Jenks Health Team- Gerald Wootan, Susan Shaw; Maine Integrative Wellness- Sean McCloy;
Marjon Fariba- Marjon Fariba, Sepideh Arvin Matthew; Mount Sinai Medical Center- Robert
Ciccia-Maclean, Pablo Guala; Stockton Family Practice- Stuart Freedenfeld, Falecia Wasicko;
The Institute of Integrative Medicine- Majid Ali, Mahboobullah Baig; Woodlands Healing
Research- Robert Schmidt, Rose Neuweiler; Berman Center for Outcomes and Clinical
Research- Richard Grimm, Mary Perron; Casdorph Clinic- Richard Casdorph, Heather
Browning; Coyote Healing Center Integrative Medicine and Psychiatry- Richard Dexter,
Christine Rupley; Staten Island Heart- James Lafferty, Lenora Tafuri-Acevedo; Hyperbaric
Medicine Inc.-Albert Zant, Michelle Potpan; Lake Cable Medical Center- Jack Slingluff, John

28
Mountford; The Center for Optimal Health- Ann McCombs, Arlene Sellereite;
ACT/Cardiovascular Research Institute- Ronald Karlsberg, Tracey S. Gerez; Gordon Medical
Associates- Eric Gordon, Win Bertrand; Heart Specialists- Rajinder Bhalla, Teresa Hicks; Matrix
Clinic- Lisa Lichota, Keith Rost; Mueller Institute For Functional Medicine & Research- Jeffrey
Mueller, Jeffrey, B. J. West; Pain and Healing Center- Angelique Hart; Rhinebeck Health
Center- Kenneth Bock, Debra Truin; St. Charles Health System- Bruce McLellan, Noura Sall;
Wellness Center- Jose Oblena, Bonita Harris; Wright Health & Wellness Center- Robert Wright,
Alma Steffen.

Canada
Seekers Centre for Integrative Medicine- Richard Nahas (Country Leader), Shadi Nahas;
Chelox- Shmuel Bergman, Mary Toro; Chelation & Natural Therapy, Chelation Center of Don
Valley Inc, Chelation Center of Barrie - Fred Hui, Eva Pacaba; Markham Integrative Medicine-
John Gannage, Tony Estacio; Jaconello Health Centre- Paul Jaconello, Hildegard Beath; The
Wellness Centre- Ben Boucher, Robyn Whitty; North Bay Complementary- Jean Aubry, Barbara
Brooks; Anti-Aging & Family Wellness Clinic- Arun Dosaj, Diane Dosaj; Montreal Heart
Institute- Jean-Claude Tardif, Randa Zamrini; Dr. Clare Minielly; Cline Medical Centre- John
Cline, Frank Pluta; Recherche Cardiologie Hôtel-Dieu du CHUM- François Reeves; Saskatoon
Chelation Centre- Edward Nykiforuk, Val Kalyn.

Data and Safety Monitoring Board: Howard Hodis (Chair), Steven Buckley, Barry R. Davis,
Theodore Ganiats, Gail Geller, Robert Nash, George Wyse.

Committees and Coordinating Centers.

Clinical Events Committee at the Brigham & Women’s Hospital: Marc A Pfeffer, Scott D.
Solomon, Eldrin F. Lewis, Peter V. Finn, Sateesh Kesari, Satish Kenshai, Amita Singh, Chau
Duong, Renée Mercier, Rebecca Messing.

Data Coordinating Center at the Duke Clinical Research Institute, Durham, NC: Kerry Lee
(Principal Investigator), Sandra Tourt-Uhlig, Joyce Good, Lauren Lindblad, Sharon Stroud,
Loren Lytle, Vivian Thompson, Linda Szczech, Gerard Esposito, Meredith Smith, Trevorlyn
Haddock, Constance Bardinelli, Madeline Earnest, Wanda Parker, Lindsey Lambe, Cresha
Cianciolo, Mary Nahm, Brian Fox, Anthony Wilson, Emlie Johnson, Brenda Vann, Mary
Molina, Rita Weber, Leslie Williams.

Economics and Quality of Life Coordinating Center at the Duke Clinical Research
Institute, Durham, NC: Daniel Mark (Principal Investigator), Nancy Clapp-Channing, Diane
Minshall- Liu, Jason Blevins, Kevin Anstrom, David Knight, Thomas Redick, Andrea Davis,
Miguel Pena.

29
Clinical Coordinating Center at Mount Sinai Medical Center, Miami Beach, FL: Gervasio
Lamas (Principal Investigator), Ana Mon, Esteban Escolar, Steven Hussein, Pablo Guala,
Kayvan Amini, Faisal Shamshad, Jacqueline Arciniega, Jamie Zimmerman, Danielle Hollar,
Beatriz Acevedo, Helen Garcia, Adam Williams, Matthew Shields, Renea Moss, Virginia
Martini, Parminder Singh, Jewmaull Reed, Maria Salas, Carlos Zamora, Tristan Edwards,
Stephanie Escalante, Laura Davila, Rachel Margolis.

30