By Bill Berkrot
(Reuters) - Researchers have found a higher rate of dangerous blood clots in patients who received Thoratec Corp's HeartMate II heart pump than had been seen in clinical trials or prior experience, according to a study published on Wednesday.
They also found that when blood clots do develop, they are occurring closer to the time of HeartMate implantation than had been previously observed. The findings were reported in the New England Journal of Medicine.
The HeartMate II is a so-called LVAD, or left ventricular assist device, that is used to keep alive heart patients who are either ineligible for or awaiting a heart transplant. The devices have been shown to significantly improve the quality of life by assisting the heart's pumping function, primarily in those with advanced heart failure.
HeartMate is by far Thoratec's most important product line. It reported third quarter HeartMate sales of $112.8 million out of total revenue of $126.4 million.
Researchers examined the outcomes of 895 HeartMate II implants in 837 patients from 2004 through mid-2013 to try to determine if there had been an increase in incidence of pump thrombosis, or blood clots in or around the heart pump.
Since March 2011, they found clot formation had occurred in 8.4 percent of HeartMate II implants compared with a rate of 2.2 percent prior to that date.
They also noted that thrombosis was forming on average 2.7 months after implant since March 2011 compared with a median of 18.6 months prior to that date.
"There are no changes that have been made to the device that the manufacturer has identified as potentially responsible," Dr. Randall Starling, the study's lead author, said in a telephone interview.
"From our data set, at this point in time we do not have an explanation," said Starling, head of heart failure and cardiac transplant management at the Cleveland Clinic.
Starling said researchers planned to collect comprehensive data and work with Thoratec "and be in a position hopefully by the middle of next year to have more detailed information."
Dr. Alex Reyentovich, medical director of the LVAD program at NYU Langone Medical Center in New York, said the problem of pump thrombosis had been observed at many centers.
"What's unique to this study is their reported incidence seems to be quite a bit higher than what has been reported in the mandatory registry for LVAD. It is worrisome," said Reyentovich, who was not involved in the study.
"Unfortunately, for these patients there really are not other options. This is a therapy of last resort," he added.
Implant patients are typically treated with the blood thinners warfarin and aspirin to prevent clots.
Starling said variations in anticoagulation therapy did not appear to account for the increased clot risk, but Reyentovich said anticoagulation must be carefully determined and monitored for each patient to minimize clot and serious bleeding risks.
HIGHER DEATH RATE
Overall, the incidence of pump thrombosis was low. There were 72 pump thromboses found in 66 of the patients, researchers said. Pump thrombosis was defined as a blood clot found in or on the Thoratec device during pump replacement, heart transplant or autopsy, researchers said.
The death rate among patients who did not get an urgent heart transplant or replacement pump was 48 percent at 90 days after the thrombosis was diagnosed. Those who developed clots in the pump and underwent a heart transplant or had their pump replaced had a mortality rate of about 10 percent, roughly equivalent to those who did not have a clot.
Researchers also found levels of the enzyme lactate dehydrogenase (LDH) in the blood had more than doubled in the six weeks leading up to diagnosis of pump thrombosis. That should be used as an important biomarker in helping to identify patients at risk of developing dangerous clots, they said.
Data from the study was compiled by researchers at three centers with extensive LVAD implantation experience - the Cleveland Clinic, Duke University Medical Center in Durham, North Carolina, and Washington University Barnes-Jewish Hospital in St. Louis.
"The takeaway to me is that physicians and patients need to realize that this is a known adverse event that can occur with the pump that appears to occur more frequently than was originally recognized," Starling said.
"When you see early signs of pump thrombosis, hopefully you can abort it or stabilize it," Starling said. "If there are signs and symptoms of recurrent heart failure from suspected pump thrombosis, you intervene quickly if your index of suspicion is high."
Researchers in the Journal article called for further investigation of the increased clotting risk and said "preventive and therapeutic strategies are urgently needed to resolve this important safety issue."
"We recognize that LVADs provide life-sustaining treatment for many patients with advanced heart failure. However, recommendations for LVAD therapy should account for this updated risk-benefit profile," the article concluded.
The study was undertaken after Cleveland Clinic physicians observed an apparent increase in pump thrombosis in patients who received the HeartMate II. The findings were reported to Thoratec and the U.S. Food and Drug Administration.
"We take every potential complication seriously and work closely with clinicians to optimize all aspects of the patient experience with HeartMate II," Thoratec Chief Executive Gary Burbach said in an emailed statement.
Thoratec said survival of HeartMate II patients has improved since the device's initial clinical trial with six-month survival rates at 86 percent.
(Editing by Leslie Adler and Bob Burgdorfer)