TCT.15: Researcher explains trial that led to FDA notification of potential TAVR, SAVR issues

The lead author of a recent trial that led to an FDA notification of potential issues with bioprosthetic aortic valves reiterated that the findings related to neurologic events were preliminary and inconclusive.

Raj R. Makkar, MD, director of the cardiovascular interventional center at Cedars-Sinai Medical Center in Los Angeles, discussed the results of the study on Oct. 14 during a press conference at the Transcatheter Cardiovascular Therapeutics scientific symposium in San Francisco.

On Oct. 5, Makkar and colleagues published results of their trial in The New England Journal of Medicine. They found 40 percent of a small group of patients enrolled in a transcatheter aortic valve replacement (TAVR) clinical trial and 13 percent of patients from two clinical registries who underwent TAVR or surgical aortic valve replacement (SAVR) had reduced leaflet motion. They used a 4D, volume-rendered CT to assess reduced leaflet motion.

That same day, the FDA announced it was working with the American College of Cardiology, the Society of Thoracic Surgeons and device manufacturers to design clinical studies to evaluate the situation.

“Clinical decisions in how we treat patients are made [based on] properly conducted clinical trials with hard outcomes,” Makkar said. “In this particular case, what we would like to do is learn from this imaging finding and do further research. But we should not take a leap from this imaging finding and make the conclusion that everybody that is getting transcatheter aortic valves should be on blood thinning medications, which have a risk in themselves. But what is required is to study this in a proper context.”

The incidence of reduced leaflet motion was 0 percent in patients receiving warfarin and 55 percent in patients receiving dual antiplatelet therapy in the clinical trial. Meanwhile, the incidence was 0 percent and 29 percent in the pooled registries. All 11 patients receiving anticoagulation who were reevaluated with a follow-up CT had a restoration in their leaflet motion compared with only 1 of 10 patients who did not receive anticoagulation.

In the pooled registries, significantly more patients with reduced leaflet motion had stroke or TIA compared with patients with normal leaflet motion, although the incidence was not different in the clinical trial.

However, the researchers said there were only 6 total strokes or TIA: 2 patients with reduced leaflet motion in the clinical trial, 3 patients with reduced leaflet motion in the registries and 1 patients with normal leaflet motion leaflet motion in the registries. They added that TIA is difficult to adjudicate in older patients who have comorbidities.

The researchers also noted that the study did not show a temporal or causal relationship between the imaging findings and stroke.

“As we move towards lower-risk patients, is it reasonable there to actually do a good clinical trial with different blood thinning medications and regimens?,” Makkar said. “The answer is yes. That is what this research leads to rather than jumping to the conclusion that we need to treat patients with blood thinning medications.”

Jonathon A. Leipsic, MD, chairman of the department of radiology for Providence Health Care in Vancouver, said CT scans could still be useful.

“I think CT is providing us an opportunity to understand perhaps not mechanisms of stroke but perhaps early signals for mechanisms of valve degeneration down the road,” he said. “While there’s a great deal of sensationalism that can come from these findings, as was shown and spoken to by Raj, as we take a step back and look at this it’s a really exciting opportunity I think for the field to improve on what are already excellent clinical outcomes in the CoreValve trial and elsewhere. We can really build on that.”