Project Concept Review
Council Date: June 6, 2014
Practitioners have used ethylene diamine tetraacetic acid (EDTA-based) chelation therapy to treat complications of atherosclerosis for decades, but without robust evidence of its efficacy. The Trial to Assess Chelation Therapy (TACT) study exhibited clinical benefit of an EDTA-based infusion regimen (40 infusions plus high-dose vitamins) in patients (>50 yoa) who had a prior myocardial infarction (MI). Patients were randomized to:
- Na2EDTA chelation + vitamins,
- Na2EDTA chelation + placebo vitamins,
- placebo chelation + vitamins, or
- placebo chelation + placebo vitamins.
Diabetes prior to enrollment was pre-specified for subgroup analysis. Diabetic patients were more likely to be obese and to have a history of congestive heart failure, stroke, peripheral vascular disease (PVD), hypercholesterolemia, and hypertension. A total of 633 (37%) patients with diabetes (post MI) taking evidence-based medications were analyzed, 322 randomized to EDTA chelation and 311 to placebo. During 5 years of follow-up, diabetics in combined EDTA (1 & 2) compared with placebo (3 & 4) groups demonstrated a marked reduction in cardiovascular (CV) events, including a decrease in the primary composite endpoint1 (hazard ratio [HR]=0.59, p<0.001), particularly among 153 patients with PVD (HR=0.42, p=0.002). Chelation also reduced the components of the primary endpoint. The non-CAM sites (HR=0.38) showed a larger treatment benefit and were at greater CV risk than CAM sites (HR=0.76). Clinical events did not decrease (p=0.877) among the remaining non-diabetic patients, resulting in a treatment by diabetes interaction (p=0.004).
Purpose of Proposed Initiative
Although diabetes-related CV complications have declined in the past two decades, a heavy disease burden persists due to the rise in prevalence of diabetes. Based on the above findings, NCCAM proposes to partner with NHLBI, NIDDK, and NIEHS to replicate this study among diabetics, using a sample enriched with PVD patients. Should these results be replicated, this may not only impact the health of diabetics, but could reduce overall health care costs. Minorities are disproportionately affected by diabetes, but only comprised 9-11% of the TACT sample. Further, women comprised only 18-20% of the TACT sample. Thus, this initiative aims to enrich the sample with both minorities and women, and to emphasize the non-CAM sites.
- To determine whether chelation therapy confers benefit in diabetic patients, this follow-up study will replicate the earlier study to examine among diabetics the effect of chelation therapy on:
- CV events (total mortality, recurrent MI, stroke, coronary revascularization, or hospitalization for angina);
- Safety outcomes (in circulation and urine, as well as clinical outcomes);
- Quality of life, pain, and cost effectiveness.
- To enhance participation by women, minorities, and non-CAM sites, as well as those with PVD.
- To capitalize on the opportunity to explore the potential mechanisms by which EDTA exerts its effect in this population, assessment of urinary metals in relation to disease-related biomarkers is of interest.
1 Primary endpoint: composite of total death, recurrent myocardial infarction, stroke, coronary revascularization, hospitalization for angina.