Less Acute MI, More HF: European Task Force Shifts Support for ‘Overhyped’ Cell Therapy Research

The decade-old excitement surrounding the potential for autologous cell therapy to treat cardiovascular disease may have fizzled into futility for many clinicians. But according to a new European consensus document, it’s possible this technology will yet find a way into future practice .

“One of the problems the field has faced is that people got super excited 10 years ago because it was overhyped, and essentially . . . it led to the expectation that every time we presented [something] at clinical meetings, the field would move forward. And of course that wasn’t the case,” chair of the European Society of Cardiology stem cell task force and lead author Anthony Mathur, MD (St Bartholomew’s Hospital West Smithfield, London, England), told TCTMD.

The reason why I think people have run out of steam on this one is that they’ve shared the 10-year journey with us. Anthony Mathur

Mathur contrasted the story of cell therapy to that of drug or device development, which is usually kept private until promising phase III data are available to support its routine use. “What we've done is we’ve exposed the clinical and scientific community to a journey that in pharma we just wouldn't see as clinicians,” he said. “The reason why I think people have run out of steam on this one is that they’ve shared the 10-year journey with us.”

The document, which appeared online February 15, 2017, ahead of print in the European Heart Journal, was written as an update to a slightly more optimistic statement from the same task force published in 2006.

Of all of the recommendations that the original document made, very few have borne fruit. For example, the task force suggested the completion of a randomized trial for the use of autologous stem cells to treat acute MI patients presenting after more than 12 hours or who fail to respond to therapy. A trial such as this has not been undertaken and likely won’t happen, given that primary angioplasty practice in Europe and the United States has “revolutionized the treatment of acute MI” and drastically lowered mortality, Mathur said. Any new method of treating acute MI “will find it really tough to demonstrate an improvement unless it’s a complete game changer.”

Since “these patients may well develop heart failure, for which chronic cell therapy strategies are under development,” research efforts should refocus there for now, the task force writes.

However, they stand by one 2006 recommendation for a randomized trial of autologous cells in acute MI patients presenting within 12 hours and treated with immediate revascularization. The ongoing phase III BAMI trial, undertaken by members of this task force including Mathur, will study just that but results are not expected for several years. Once these results are available, it will be time to “either draw a line under it or ask for regulatory approval, but it's sort of pointless to keep rehashing the whole thing and going back asking the same question,” Mathur said.

Careful But Hopeful

Looking back, Mathur said that the trajectory of cell therapy in cardiology has taught him to be “self-critical and very careful about what we say,” and to understand that it is okay to “stop doing certain things” that were once thought to be appropriate. Also, because those involved in translational research “lack the tools that give us an evidence or an idea of the signal that we should expect in larger clinical trials, [a] lot of what we’ve come across is potentially unexpected. Unfortunately, it also means . . . we’ve probably disregarded areas of research based on the signals we haven't seen in smaller studies simply because, in a way, the tools we have aren’t sensitive enough to pick it up,” he said.

If there is any biological signal found in a phase II study, Mathur stressed the importance of trying to complete a phase III study in order to unlock these unexpected kernels.

Far from being defeated, he said he is hopeful that cell therapy will pan out in some way for cardiac patients. “Whether cell therapy worked or not, it's all about the amazing stories and how it changed people's lives seemingly for the better. So that’s something that’s difficult to drop,” Mathur said. “We have seen a signal for patients in heart failure in which there seems to be some sort of benefit. And some might say it’s purely psychological. Fine, but these people who were told there was nothing else that could be done got better.”