Randomized Comparison of High-Dose Oral Vitamins versus Placebo in the Trial to Assess Chelation...
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Transcript of Randomized Comparison of High-Dose Oral Vitamins versus Placebo in the Trial to Assess Chelation...
Randomized Comparison of High-Dose Oral Vitamins versus Placebo in the Trial
to Assess Chelation Therapy (TACT)
Gervasio A. Lamas, MD, FACC
Professor of Clinical Medicine
Columbia University Division of
Cardiology
Mount Sinai Medical Center
Miami Beach, FLFor the TACT Investigators
Study Organization
• Funding agencies: NHLBI and NCCAM• Clinical Coordinating Center: Mount Sinai Medical
Center, Miami Beach FL• Data Coordinating Center and EQOL Coordinating
Center: Duke Clinical Research Institute• Clinical Events Committee: Brigham and Women’s
Hospital• Central Pharmacy: Universal Arts, Miami FL• Vitamins: Douglas Labs, Pittsburgh PA
Background
TACT tested whether EDTA chelation reduced a composite cardiovascular endpoint in post-MI patients.
Chelation practitioners use high doses of anti-oxidant vitamins and minerals in conjunction with intravenous chelation.
Uncontrolled use of oral vitamins and minerals therefore constituted a potential confounder.
Design Rationale
• To clarify the relative contributions of high- dose vitamins and IV chelation, TACT was designed as a 2 x 2 factorial trial, with patients randomized to 4 groups:
1. Active oral vitamins + active IV chelation 2. Placebo oral vitamins + active IV chelation3. Active oral vitamins + placebo IV chelation4. Placebo oral vitamins + placebo IV chelation
TACT: High-Dose Oral Treatment
Double-blind active or placebo high dose vitamins were shipped from a central pharmacy to sites.
3 caplets twice a day for the duration of the study.
Lamas GA, Goertz C, Boineau R, et. al. Design of the Trial to Assess Chelation Therapy (TACT). Am Heart J. 2012 Jan;163(1):7-12.
Calcium Iodine
MagnesiumZinc
SeleniumCopper
Manganese Chromium
MolybdenumPotassium
CholineBoron
InositolPABA
VanadiumCitrus Flavonoids
Vitamin AVitamin CVitamin D3
Vitamin EVitamin KThiaminNiacin
VitaminB6
FolateVitamin B12
BiotinPanthothenic Acid
Eligibility
Age 50 or older MI > 6 weeks 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 No cigarette smoking within 3 months Signed informed consent
Primary Endpoint
Primary composite endpoint: time to first occurrence of either death, MI, stroke, coronary revascularization, or hospitalization for angina
Statistical Plan
Designed to have 85% power to detect a 25% difference
Treatment comparisons as randomized (intent to treat)
Two-sided statistical testing Log-rank test using time to first event Prespecified analysis of factorial groups
Baseline Characteristics1708 patients randomized
High Dose Vitamins(N=853)
Placebo (N=855)
Age (years) 65 (59, 72) 65 (60, 72)BMI (kg/m2) 29 (26, 33) 30 (27, 34)Female (%) 17 18
Hispanic or non-Caucasian (%) 9 9
Diabetes (%) 33 30
Prior revascularization (%) 83 83
Statin (%) 74 72Beta Blocker (%) 71 73Aspirin (%) 85 82Aspirin, clopidogrel, or warfarin (%) 92 90
LDL (mg/dL) 88 89
TACT Primary Endpoint Resultsfor EDTA Chelation (presented at AHA 2012)
EDTA: Placebo
HR (95% CI)0.82 (0.69, 0.99)
P = 0.035
Death, MI, stroke, coronary revascularization, hospitalization for angina
TACT Vitamin Primary Endpoint Results
Vitamins: Placebo
HR (95% CI)0.89 (0.75, 1.07)
P = 0.212
Death, MI, stroke, coronary revascularization, hospitalization for angina
34%
37%
Median follow-up 55 months
Components of the Primary Endpoint
High Dose Vitamins(N= 853)
Placebo(N= 855)
Hazard Ratio (95% CI)
P Value
Primary Endpoint 230 (27%) 253 (30%) 0.89 (0.75, 1.07) 0.212
Death 87 (10%) 93 (11%) 0.93 (0.69, 1.24) 0.614
Myocardial Infarction 58 (7%) 61 (7%) 0.95 (0.66, 1.36) 0.786
Stroke 8 (1%) 15 (2%) 0.53 (0.22, 1.25) 0.139
Coronary revascularization
132 (15%) 155 (18%) 0.84 (0.66, 1.05) 0.131
Hospitalization for angina
12 (1%) 19 (2%) 0.72 (0.35, 1.47) 0.359
Subgroup Results for Vitamin Analyses
Participant Group NInteraction
P-value HR 95% CI
All participants 1708 0.89 0.75, 1.07
Infusions 0.94EDTA 839 0.89 0.68, 1.15Placebo 869 0.90 0.7, 1.15
Gender 0.17Male 1409 0.84 0.69, 1.03Female 299 1.17 0.75, 1.83
Anterior MI 0.79 Yes 674 0.93 0.69, 1.26No 1034 0.88 0.7, 1.09
Diabetes 0.72Yes 538 0.84 0.62, 1.14No 1170 0.90 0.72, 1.12
Statins at baseline 0.01
Yes 1248 1.03 0.84, 1.27No 460 0.62 0.44, 0.87
CAM site 0.39Yes 1089 0.84 0.67, 1.05No 619 0.99 0.74, 1.33
4.01.00.25High-Dose
Vitamins BetterPlacebo
Better
2.00.5
TACT Primary Endpoint: Factorial Groups
EDTA Chelation/High-dose Vitamins vs. Placebo/Placebo
HR (95% CI): 0.74 (0.57, 0.95)
P = 0.016 Δ=8.3%
Adherence
• 75.6% took study vitamins for at least 1 year. – The most common reason for discontinuation was patient
refusal (75%)– Median duration of treatment: 33.4 months.– No difference in discontinuation rate in active vs placebo
vitamins.
Limitations
•Compliance with high-dose vitamin regimen was challenging, leading to some non-adherence.
•High consent withdrawal rate (17%).
•The therapeutic mechanisms by which high-dose vitamins and chelation might provide benefits are unclear.
Summary
High dose oral vitamins reduced the composite outcome by 11%, which was not statistically significant.
When combined with EDTA chelation, the small vitamin benefit was additive, and the combined effect was statistically significant.
Caveats
• The results of this study do not support the use of high-dose vitamin and mineral therapy as an adjunct to optimal evidence-based medical therapy in patients with prior myocardial infarction.
• These findings should stimulate further research, but are not, by themselves, sufficient to recommend the routine use of chelation therapy and high-dose vitamins in post-MI patients.
Thank you