March 15, 2013

SAN FRANCISCO — The use of high-dose oral vitamin therapy failed to reduce the risk of cardiovascular events in the Trial to Assess Chelation Therapy (TACT), a 2x2 factorial-design, randomized, double-blind trial that previously showed chelation therapy modestly improved clinical outcomes in patients after an acute MI.

The use of multivitamin therapy, which included an alphabet of vitamins, including A, B, C, D, E, K, niacin, folate, calcium, magnesium, and zinc, among others, did not reduce the time to first occurrence of death, MI, stroke, coronary revascularization, or hospitalization for angina. When the use of vitamin therapy was combined with chelation and compared with patients who received placebo chelation and placebo vitamins, there was a statistically significant 26% relative reduction in the risk of the primary end point.

Still, despite the additive benefit of chelation and vitamin therapy, the researchers who presented the results at the American College of Cardiology 2013 Scientific Sessions are apprehensive that the results will be interpreted as a resounding win for this alternative-medicine strategy, stressing that more study is still needed to move such a strategy into mainstream cardiology practice.

Dr Gervasio Lamas

Speaking with the media, lead researcher Dr Gervasio A Lamas (Mount Sinai Medical Center, Miami Beach, FL) explained that TACT was designed as a 2x2 factorial study because patients treated with chelation also received high-dose vitamin therapy to offset the effects of treatment. Had they studied chelation vs no-chelation alone, it would have been impossible to determine whether the results were confounded by the use of vitamins. As a result, patients were randomized to four groups: active oral vitamin therapy and active chelation infusions; placebo vitamin therapy and active chelation; active vitamin therapy and placebo chelation; and placebo vitamin therapy and placebo chelation.

In the vitamin arm of TACT, treatment with high-dose vitamin therapy resulted in a statistically nonsignificant 11% relative reduction in the risk of death, MI, stroke, coronary revascularization, or hospitalization for angina when compared with patients who received placebo vitamins. In contrast, the use of active chelation and active vitamin therapy reduced the risk of the primary end point 26% compared with patients randomized to placebo chelation and placebo vitamin therapy.

"The message here really is a cautious message," Lamas told the media during a press conference. "We've moved something from alternative medicine into, perhaps, the reality of scientific inquiry and found some unexpected results that merit further research. We don't think the results of any single trial are enough to carry this novel hypothesis into daily use for patients who have had an acute myocardial infarction."

As reported previously by heartwire , TACT has been mired in controversy. Ethics questions had been raised about the quality of disclosure to patients about possible treatment effects and criticisms leveled at a perceived waste of public money, given that TACT is sponsored by National Center for Complementary and Alternative Medicine (NCCAM) and the National Heart, Lung, and Blood Institute (NHLBI). Enrollment had been slow, and it was stopped and restarted a number of times. When the main results were presented last fall at the American Heart Association annual meeting, experts received the positive results from the chelation arm of the trial with caution, saying the results were "surprising," "intriguing," and "unexpected." Like the vitamin arm of the trial, they said the data raised more questions than answers.