TACT Substudy Suggests Possible Strong Benefit for Chelation in Diabetics Reply

One year ago the results of the TACT trial were published in JAMA, sparking an enormous controversy over the propriety of publishing a trial suggesting that chelation therapy might be beneficial in people with cardiovascular disease. Chelation therapy has long been a staple of alternative medicine, but until the publication of TACT it had received no credit whatsoever in mainstream medicine. TACT was supported by the NIH as part of an initiaitve to test the scientific basis of alternative medical therapies.

The JAMA paper reported positive results for the prespecified subgroup of patients who had diabetes at the start of the trial. Now a new paper, presented at the American Heart Association Scientific Sessions and published online in Circulation: Cardiovascular Quality and Outcomes, focuses on this important subgroup, and provides even stronger evidence for a possible benefit for chelation in patients with diabetes. The authors speculate that ethylene diamine tetra-acetic acid (EDTA) chelation might have an effect on metal-catalyzed oxidation reactions in the development of advanced glycation end-products, which appear to play a central role in diabetic complications.

The primary endpoint of the main trial – the composite of death, MI, stroke, coronary revascularization, or hospitalization for angina – was significantly lowered from 30% in the placebo group to 26% in the chelation group (HR 0.82, 0.69-0.99, p=0.035).

Click here to read the full post on Forbes.

 

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Controversial NIH Chelation Trial Published In JAMA Reply

Final results of the troubled NIH-sponsored TACT trial testing chelation therapy for coronary disease have now been published in JAMA. Last November, when the preliminary results were presented at the American Heart Association meeting, the positive finding in favor of chelation therapy surprised many observers, though the investigators and senior AHA representatives expressed considerable caution  about the proper interpretation of the results. Full publication of the main results should now allow for a more thorough consideration of the trial.

The Trial to Assess Chelation Therapy (TACT) was initially funded by the NIH more than a decade ago to test chelation therapy with EDTA, an alternative medicine therapy received by more than 100,000 people every year but with no evidence base for support. The highly controversial trial was temporarily suspended in 2008 in response to ethical concerns but was then allowed to resume. The trial was also hampered by slow enrollment, eventually resulting in a downsizing of the trial population. To maintain the trial’s power to achieve a meaningful result the follow-up time was increased. (Because of this change, and because the data and safety monitoring board reviewed the data multiple times over the course of the study, the threshold for statistical significance was lowered to 0.036.)

TACT was a double-blind study testing active or placebo infusions of chelation in 1,708 stable patients with a history of MI.  The primary endpoint of the trial– the composite of death, MI, stroke, coronary revascularization, or hospitalization for angina– was significantly lowered in the chelation group:

  • 26% in the chelation group versus 30% in the placebo group (HR 0.82, 0.69-0.99, p=0.035)

Nissen

Steve Nissen

The editorial by the JAMA editors is itself evidence of the extraordinary sensitivity of the TACT trial. The JAMA editors, in a highly unusual situation, discuss their detailed review of TACT and explain their decision to publish the trial. Although they acknowledge multiple limitations of the trial, they defend its value: “reports of rigorous investigations should not be censored because of preexisting ideological positions,” they write.

In his editorial, Steve Nissen agrees with the JAMA editors decision to publish the trial but issues a fierce indictment of the trial and its conduct. The TACT paper, Nissen writes, “represents a situation in which many important limitations in the design and execution of a clinical trial compromise the reliability of the study and render the results difficult to interpret. Unfortunately, the efforts of these investigators fell short of the minimum level of quality necessary to adequately answer the question they sought to investigate.”

Daniel Mark

Daniel Mark

TACT investigator Daniel Mark provided CardioBrief with the following detailed response to Nissen’s criticism. (Nissen declined to respond to Mark.)

In his editorial, Dr. Nissen asserts that the “logical” explanation for the greater withdrawals in the placebo group is that patients were unblinded. He further implies that the CAM sites were more likely to be responsible for such unmasking.

His editorial is written from the perspective of someone who is absolutely sure that the trial results are wrong and his mission is to identify where the flaws originate.

Click here to read the full story on Forbes.

Small Study Suggests Yoga May Benefit AF Patients Reply

A small study published online in the Journal of the American College of Cardiology suggests that yoga may benefit people who have atrial fibrillation. The study, which the authors describe as “a small, proof-of-concept study,” is the first of its kind. The findings raise the possibility that yoga may reduce AF symptoms and arrhythmia burden. Other physiological and quality of life benefits were also observed. But, the authors caution, large randomized trials will be required to confirm the finding.

 

Click here to read the full post on Forbes.

 

A yoga class.

 

NIH Trial Gives Surprising Boost To Chelation Therapy 3

With a result that is likely to surprise and baffle much of the mainstream medical community, a large NIH-sponsored trial has turned up the first substantial evidence in support of chelation therapy for patients with coronary disease.  Known as TACT (Trial to Assess Chelation Therapy),  the highly controversial trial was presented today at the AHA by Gervasio Lamas. The trial was sponsored by two NIH institutes, the National Center for Complementary and Alternative Medicine and the National Heart Lung and Blood Institute.

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. Despite a lack of evidence and the skepticism of the medical community, passionate supporters have kept the therapy alive in alternative medicine circles.

TACT was funded by the NIH more than a decade ago as part of a much-publicized initiative to study the claims of alternative medicine. In 2008 enrollment in TACT was temporarily suspended in response to claims that the trial was unethical. The trial was additionally hampered by slow enrollment.

Now the results of TACT will likely provide ammunition to chelation defenders, but the trial investigators and other experts have expressed considerable caution about the proper interpretation of the results.

TACT was a double blind study testing active or placebo infusions of chelation in stable patients with a history of MI. Due to slow enrollment the trial was downsized, ultimately enrolling 1,708 patients instead of the planned 2,372 patients. To maintain the trial’s power to achieve a meaningful result the follow-up time was increased. Because of the this change, and because the data and safety monitoring board reviewed the data multiple times over the course of the study, the threshold for statistical significance was lowered to 0.036.

The primary endpoint of the trial– the composite of death, MI, stroke, coronary revascularization, or hospitalization for angina– was significantly lowered in the chelation group:

  • 26.5% in the chelation group versus 30% in the placebo group (HR 0.82, 0.69-0.99, p=0.035)

There were no significant differences in any of the individual components of the primary endpoint. Most of the difference between the groups was due to a lower rate of coronary revascularization in the chelation group:

  • 15.5% versus 18.1% (HR 0.81, CI 0.64-1.02, p=0.076)

Nearly all the benefit in the trial was found to occur among the one-third of patients in the trial who had diabetes:

  • 102 events versus 67 events (HR 0.61, CI 0.45-0.83, p=0.002)

The investigators were cautious in their interpretation, noting that the trial barely achieved statistical significance, most of the difference was found in the softer endpoint of revascularization, and the finding is less reliable since there was a high withdrawal rate (17%) of patients in the trial.

The authors said their findings were “unexpected and additional research will be needed to confirm or refute our results and explore possible mechanisms of therapy.” TACT, they concluded, “does not constitute evidence to recommend the clinical application of chelation therapy.”

At an AHA press conference, Paul Armstrong said that TACT was a response to an unusual situation. On the one hand, most physicians and scientists have dismissed chelation therapy as lacking any evidence or rationale. On the other hand, chelation therapy is strongly supported by the alternative medicine community and more than 100,000 people receive chelation therapy each year. Armstrong said the results of the trial were “hypothesis generating, not practice changing.”
Click here to read the AHA press release…