The National Institutes of Health is giving money to support the planning of a second trial to test the potential role of chelation therapy in treating patients with myocardial infarction.
The first Trial to Assess Chelation Therapy (TACT) was extremely controversial. It was funded by the NIH more than a dozen ago as part of an initiative to study alternative medicine. Chelation therapy with EDTA to remove heavy metals from the blood in order to treat coronary disease has been around– and provoked criticism– since the 1950s. Until TACT the mainstream medical community had completely dismissed chelation therapy.
TACT was a double-blind trial testing active or placebo infusions of chelation in 1,708 stable patients with a history of MI. In the chelation group there was a modest but statistically significant reduction in the primary endpoint of the trial — the composite of death, MI, stroke, coronary revascularization, or hospitalization for angina (26% vs 30%, HR 0.82, CI 0.69-0.99, p=0.035).
The rationale for TACT2 is based on the observation in the earlier study that nearly all the benefit occurred in the subgroup of 633 patients who had diabetes. For this group there was a highly significant 41% reduction in the primary endpoint (25% vs 38%, HR 0.59, CI 0.44–0.79, P<0.001), as well as a 43% reduction in overall mortality and a 52% reduction in recurrent MI.
To followup on these findings the National Center for Complementary and Integrative Health (NCCIH) has now awarded $800,000 to initiate planning for TACT2. “A subgroup analysis of the original trial results suggests major benefit in diabetics with cardiovascular disease. The disease burden in this group of patients is devastating, so a replication of these findings is of some urgency,” said Josephine P. Briggs, the Director of the National Center for Complementary and Integrative Health, in an NIH press release.
“The hallmark of science is the ability to replicate results”, said the study chairman, Gervasio Lamas, of the Mount Sinai Medical Center in Miami Beach, Florida. “Unless we can show a consistent effect across the two TACT Trials and establish a similar mechanism to deliver the treatment safely, it will be difficult for chelation to enter the mainstream of other cardiovascular therapies”.
Eugene Braunwald gave a strong endorsement to TACT2 in the press release: “The results of TACT were both surprising and intriguing. I am very pleased that TACT2 is building on these findings to determine if they can be replicated in diabetic patients who have experienced a myocardial infarction – a particularly high risk group of patients in need of effective therapy.”
Gervasio Lamas
While p = 3.5% is better than Fisher’s 5%, it does not meet my personal criterion of <= 1%. So yes, it is statistically significant, if one applies the measures originally developed in the context of agricultural Latin Square estimation.
When a composite endpoint has been used to estimate mean differences, without presentation of the individual endpoints, I raise at least one eyebrow & wonder if there has been some exaggeration of the effect.
I hope I never have to decide whether to accept or reject any proposed treatment!
Thank you for your your blog.
The main trial result was interesting but certainly not strong enough to change practice. The subgroup result was much more promising, but since it was a subgroup it needs further exploration and confirmation. Thus TACT2.
After 41 chelation IV I have yncreased my ejection fraction from 33% to 47% as measured by nucllear stress test at Mayo clinic Jacksonville Fl. Most of the time I am totally asymptomatic for heart failure and have avoided having a defibulator installed.