By BARRY MEIER
Published: December 9, 2013 The New York Times
A new report showing an increase in blood clots associated with a
popular heart device is dividing experts over whether a clinical trial of the implant is potentially too
risky for patients.
The debate, which involves a heart pump called
the HeartMate II, sheds light on how researchers calculate whether to expose
patients to a trial’s risks.
Medical researchers say such decisions are based
on objective evidence. But a look at their decisions about HeartMate II trial shows how subjective those
choices can be.
The trial, which has already faced delays, is set
to start soon, if it receives a final go-ahead. But at least two hospitals that
originally agreed to recruit patients for the trial have now withdrawn because of the
new findings, while others have decided to stay in.
Some
experts contend other factors might also be in play in those decisions,
including an investment of years by some researchers to set up the study. In
addition, more than $13 million has been earmarked for the trial by the
HeartMate II’s maker, Thoratec, and the federal National Heart
Lung and Blood Institute.
“You could argue it both ways,” said Dr. Carmelo
A. Milano, a cardiologist at Duke University, which has decided not to
participate, as has the Cleveland Clinic. “It certainly would be better if we
didn’t have this problem.
The HeartMate
II is a small pump that continuously pushes blood through the heart. Patients
who get the device now are those facing imminent death from heart failure. Even
the researchers who put together the new report said they would continue to use
the pump in those cases.
The trial,
called Revive-It, is intended to determine whether a HeartMate II can also
benefit patients who have not quite reached that stage of heart failure.
Such patients, who take drugs for their condition, typically struggle to
perform physical activities, like walking short distances.
Because heart failure is a progressive condition,
the new blood clot study has complicated the question of how to weigh the
device’s risks and benefits to less sick patients.
“I would not embark on a clinical study until this problem is understood
and mitigated,” said Dr. Robert G. Hauser of the Minneapolis Heart
Institute Foundation, who is not involved in the trial.
In the new study, three big hospitals, the
Cleveland Clinic, Duke and Washington University in St. Louis, jointly reported
that the rate of HeartMate II-related blood clots had increased by nearly fourfold in devices
implanted after early 2011.
Some patients died and others underwent emergency
operations to get new pumps or transplanted hearts, according to a report in
The New England Journal of Medicine.
Experts
have yet to find a reason for the increase. But they say it most likely
involves factors like changes in the device and changes in how doctors use
anti-clotting drugs with such patients.
Long before the new report, however, word of a
growing problem with the HeartMate II had been circulating among device
experts. And researchers involved with Revive-It had already begun scrambling
to understand its potential impact on the trial.
The issue began to take shape in March, when the
Cleveland Clinic reported to the Food and Drug Administration and Thoratec that
it was seeing a rise in pump-related clots. Physicians at other hospitals were
also seeing an increase and were discussing the problem with colleagues at
medical meetings or privately.
“There is
an incestuous nature to our field,” said Dr. Scott Silvestry,
a cardiologist at Washington University
In May, the principal investigators leading the
trial — Dr. Keith Aaronson and Dr. Frank D. Pagani of the University of
Michigan and Dr. Robert Kormos of the University of Pittsburgh — decided to
delay the start of patient recruitment to examine the problem.
At that time, doctors at the Cleveland Clinic were keeping their
findings confidential because they hoped to publish them in a medical journal.
But
another source of data was available. In recent years, a federally funded
registry at the University of Alabama at Birmingham has been tracking the
safety of heart pumps like the HeartMate II. Known as Intermacs, the registry was showing that
pump-related blood clots associated with the HeartMate II had risen to about 5
percent since early 2011, compared with about 2 percent in previous years.
But the
registry also showed a variation in clot rates at differing hospitals, raising
the possibility that facilities such as the Cleveland Clinic were outliers.
The trial’s lead investigators, Dr. Aronson, Dr.
Pagani and Dr. Kormos, declined to be interviewed. But in a statement, they
said the added risk detected by Intermacs was “small” and did not alter the
trial’s balance of benefits and risks.
Based on the Intermacs data, officials at the
F.D.A. and the National Heart Lung and Blood Institute and a panel of experts appointed by
the institute to monitor the study’s safety came to the same conclusion.
“F.D.A. reviewed the Intermacs data and supported
the Revive-It team’s decision to move forward,” the three researchers said a
statement.
As a result, about 18 major hospitals nationwide
again prepared to enroll patients. But now, the recent New England Journal of Medicine study
published late last month has raised questions about which blood clot data is
more reliable.
In their study, the Cleveland Clinic, Duke and
Washington University reported a pump-related clot rate of 8.4 percent, compared with 2.2 percent in
earlier years. The increase was significantly higher than the 5 percent rate
reported by Intermacs.
Dr. Randall Starling of the Cleveland Clinic said
he thought that Intermacs’ data was understating the problem’s scope.
“We believe our data is more accurate,” Dr.
Starling said.
However, the import of new report was quickly
disputed by the three investigators heading Revive-It. In a statement, they
described the hospitals as outliers and said the Intermacs data was more
reliable.
Dr. Milano, the cardiologist at Duke, said he
thought that the reaction of researchers, who have spent years setting up the
Revive-It study, was understandable.
“They are more apt to look at the data that
suggests there is less of a problem,” Dr. Milano said. Still, at this point, he cannot see
asking less-sick patients to get a device. “Knowing what I know, I
probably won’t sign up,” he said. The three researchers leading the trial said
it was imperative, given the shortage of donor hearts to know whether the
device worked in earlier stage patients.
Whatever the case, the National Heart Lung and
Blood Institute said in a statement that the study’s safety panel would soon
review the new journal report and its implication, if any, for the trial.
In the meantime, specialists are going their
separate ways. For example, while Dr. Hauser, the device expert in Minneapolis,
says he thinks that the trial should be delayed, cardiologists at the hospital
where he works are going forward. And unlike Duke and the Cleveland Clinic, Dr.
Silvestry said Washington University hospital was also staying in the trial
because it thought that the device’s potential benefits still outweighed its
risks.
“We feel our patients will be served by a
possibility of enrollment,” Dr. Silvestry said.
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