John Mandrola, MD

Disclosures

March 19, 2017

(updated March 25, 2017) Dr Seung-Jung Park from the Asan Medical Center in Seoul South Korea presented the DECISION-CTO trial at the American College of Cardiology (ACC) 2017 Scientific Sessions.[1] It is the first randomized clinical trial of stenting vs optimal medical therapy for coronary chronic total occlusion (CTO).

Noting the absence of high-level evidence for this procedure, a panelist at the late-breaking clinical-trial sessions said this:

"It's a stake in the ground to see a randomized trial for percutaneous chronic total occlusion therapy."

He did not say there was a white flag attached to that stake. But the DECISION-CTO trial was decidedly negative.

In light of the rise in exuberance over this risky and unproven procedure, I feel DECISION-CTO was the most important trial presented during the day's sessions.

Here are some day-of-the-presentation thoughts.

I believe the excitement over CTO interventions are normal and benevolent. Doctors want to help people. New tools lead to new possibilities for doing good. Interventionalists like to intervene.

But CTO procedures are special. Dr David Kandzari (Piedmont Heart, Atlanta, GA), who was the discussant for DECISION-CTO, confirmed that CTO PCI comes with higher complication rates and lower success rates relative to regular PCI. He said success depends a lot on an operator's skill and experience.

The evidence before today in support of CTO PCI came from observational trials, most of which compared outcomes in successful and failed CTO procedures without a control group. Although there are more than 35,000 patients enrolled in observational studies of CTO PCI, selection bias renders these deeply flawed data.

Other hoped-for merits of CTO procedures include improved quality of life from angina relief, possible improvement in LV function, and less ventricular arrhythmia. But again, these possible advantages combined with favorable anecdotal experience are hardly a solid foundation for the growth of the risky procedure.

That's why DECISION-CTO is so important. It provides evidence where there was essentially none.

Now to the details:

DECISION-CTO was a prospective, multicenter (19) open-label randomized trial comparing optimal medical therapy with or without stenting for CTO in patients with silent ischemia, stable angina, or ACS.

The researchers used a noninferiority design for the primary end point, which was a composite of death, MI, stroke, and repeat revascularization. The data and safety monitoring board recommended premature trial termination because of slow enrollment.

Over a 6-year period, 834 patients were randomized; 398 to optimal medical therapy and 417 to optimal medical therapy plus CTO PCI. The success rate of PCI was 90.6%. There was crossover going both ways. The baseline characteristics of the groups were similar, except angina was more frequent in the medical-therapy group.

After 3 years, 19.6% of the medical-therapy patients reached the primary end point vs 20.6% of the CTO-PCI group. This met the noninferiority margin, with P=0.008. None of the components of the composite end point were significantly different.

The second major finding from the trial were no improvements in quality-of-life scores or angina. Not even a hint of improvement.

The authors also did a per-protocol and as-treated analysis. They found event rates did not significantly differ between the groups.

Comments

Unlike many of the other late-breaking clinical trials, DECISION-CTO did not earn simultaneous publication in a major journal. One can speculate that this was due to its negative findings. The more likely reason, however, were its methodological flaws—of which there were many.

The trial was terminated early due to slow enrollment. That's a problem because it limits the power of the trial.

Dr Ajay Kirtane (Columbia University, NY) pointed me to a slide set from 2011 suggesting that DECISION-CTO was originally designed as a superiority trial with the goal of reducing death/MI by 40% relative to optimal medical therapy. Switching to a noninferiority design and changing the primary end point would be unconventional.

[In an email exchange with theheart.org | Medscape Cardiology, Pil Hyung Lee, replying on behalf of Dr Park, said that the trial was "always a noninferiority trial" and that the primary end point was "always a composite of death, MI, stroke, and any revascularization"; the clinicaltrials.gov record supports this.]

Missing data are also a problem. About 25% of patients in both groups did not have their quality-of-life or angina scores measured. Would these data points have made a difference?

I understand these weaknesses. But there was no signal of benefit.

It's not surprising that hard outcomes were not different, but the lack of angina improvement is quite stunning. This is what CTO proponents promote as the procedure's main benefit.

Also, as a longtime observer of how cardiologists interpret trials, I can't help wonder whether the vigor of criticism would have differed if the results were positive.

I have two conclusions from DECISION-CTO:

This data, flawed as it may be, raises the bar for doing this procedure. Patients should be carefully selected, maximally treated with medication, and thoroughly informed as to the unproven nature and risks of this procedure.

If cardiologists continue to do this procedure in the face of a negative trial, then another trial looking at both outcomes and angina relief is not welcomed but necessary.

JMM

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