October 10th, 2013
CardioMEMS Heart Failure Device Gets Mixed Reception From FDA Advisory Panel
Larry Husten, PHD
The FDA’s Circulatory System Devices Panel sent a mixed message to the FDA today about the CardioMEMS Champion HF Pressure Measurement System. The small implantable device provides daily pulmonary artery pressure measurements to guide physicians in their treatment of patients with congestive heart failure.
In December 2011 the same panel voted 9-1 that the device was safe, 7-3 that the device had not been shown to be effective, and 6-4 that the benefits did not outweigh the risks. Now, two years later, the vote wasn’t much different: the panel agreed unanimously (11-0) that the device was safe; 7-4 that it had not been shown to be effective, and 6-4-1 that the benefits outweighed the risks.
Panel member Rick Lange said that the panel today tried to look beyond the pivotal Champion clinical trial, which was the subject of considerable controversy at the earlier meeting. Instead, the panel today wrestled with the followup study, but found it difficult to draw conclusions based on unrandomized and unblinded followup data of a segment of the original trial population. The problem, according to Lange, is that although the patients seemed to have less heart failure, it was impossible for the panel members to tie the daily measurements of the pulmonary artery to a decrease in hospitalizations or other important clinical outcomes. “We couldn’t connect the dots,” said Lange.
Another major dilemma faced by the panel was the complete lack of evidence showing efficacy in women. “You can’t assume in today’s world that what’s effective in males is effective in females,” said Lange.
One Response to “CardioMEMS Heart Failure Device Gets Mixed Reception From FDA Advisory Panel”
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Drs. Loh, Barbash, and Waksman wrote an insightful review in JACC regarding the initial FDA decision earlier this year (http://content.onlinejacc.org/article.aspx?articleid=1565860). It was a fascinating read, and described in detail the issue of an imbalance in the number of sponsor-generated communications that favored the treatment arm:
“The Panel voted 7 to 3 against the statement that there is reasonable assurance that the CardioMEMS Champion HF Monitoring System is effective for use in patients with Class III HF who meet the criteria specified in the proposed indication. Most Panel members who voted negatively on this question reiterated the following points: the treatment effect seen in the trial was a combination of device and support mechanism; there was no way to tease out the treatment effect of each; and major elements in the support system will not be applicable in the general population… The Panel members who voted “for” considered the entirety of the treatment effect and voiced hope that this support system could be replicated by the Sponsor outside of the trial setting.”
On the last point, I was also intrigued by what “the support system” entailed, and whether it can improve our understanding of how to care for HF patients with and without implantable monitoring devices. However, the latest briefing to the FDA (http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/CirculatorySystemDevicesPanel/UCM370692.pdf) stated that, after reviewing the details, the medication changes reasonably attributed to sponsor generated nurse communications were likely to have a small effect:
“(Page 70) Concordant changes in medications other than diuretics and nitrates would be expected to have prevented less than one hospitalization for heart failure in the Treatment group during the first 6 months of Randomized Access.
Concordant changes in diuretics or nitrates appeared to have had only a minor impact on the rate of hospitalizations for heart failure, because the number of concordant changes in diuretics and nitrates was small when compared with the total number of changes in diuretics and nitrates made in response to knowledge of pulmonary artery pressures, especially if adjustments are made for background rate of changes in these medications.”
As Dr. Lange’s comments above suggest, this was not enough to reassure the panel. Although full clarity is still lacking, I hope to see more of these valuable discussions, especially in instances where the FDA decision, based on more comprehensive data, differ from the “topline” announced/published results. This would allow us to better understand the complexities and importance of rigorous trial conduct, as well as challenge us to more critically assess published literature.