(Repeating item that initially moved on Saturday)
* Blood-clotting rate more than 9 pct per patient year
* Higher than doctors or Wall Street expected
* Rate could slow enrollment in clinical trial
By Toni Clarke and Debra Sherman
BOSTON/CHICAGO, April 16 Patients implanted with a mechanical heart-assistance device made by HeartWare International Inc (HTWR.O) have an unexpectedly high 9.2 percent chance of developing a potentially life-threatening blood clot per year, newly-released data shows.
The data, presented late Friday at the International Society of Heart and Lung Transplantation in San Diego, surprised many physicians who in interviews prior to the release had predicted the company would report rates of 3-6 percent at most.
HeartWare's device, known as the HVAD, is approved in Europe and awaiting approval in the United States to keep patients alive while they wait for a heart transplant. The company is currently enrolling patients in a trial to test the device as a long-term treatment for patients who are not eligible, or who may not be able to get, a heart transplant.
The question now is whether concerns about pump-associated thrombosis - the formation of blood clots - will slow enrollment in the new clinical trial or hurt market share.
Data showed that the 250 patients in the trial contributed a total of 174 patient years. There were 16 cases of pump-related blood clots, of which 11 required the device to be replaced.
The HVAD competes with a device made by Thoratec Corp THOR.O called the HeartMate II. While there are no direct comparisons between the rate of thrombosis between the two devices, physicians and analysts believe the rate with the HeartMate II to be around 3 percent.
Many investors have been betting HeartWare's device will eventually eclipse the HeartMate II since it is smaller and takes less time to implant. But HeartWare's shares have fallen 18 percent from their year high of $99.10 on Jan. 13, amid concerns about the potential for blood clots.
Early this year, a patient at Aurora St. Luke's Medical Center in Milwaukee, Wisconsin, was treated with a blood-thinning medication known as tissue-type plasminogen activator (tPA) after developing a clot that caused the HVAD device to malfunction.
The episode led Dr. Andrew Boyle, the hospital's medical director for heart failure, cardiac transplantation and mechanical circulatory support, to place a moratorium on the use of the device. The hospital has not implanted any HVADs since. Boyle did not respond to requests for comment.
Excessively Some investment analysts and physicians dismissed Dr. Boyle's action as excessively cautious. But behind the scenes the topic has been hotly debated.
"In the (medical) community I do believe there is some concern about it," said Dr. Aly El Banayosy, Medical Director of Mechanical Circulatory Support at Penn State Hershey Medical Center, though he stressed that he has not had any cases of thrombosis himself.
In its analysis of the data, HeartWare said it found a subset of patients -- those who took 325 milligrams of aspirin a day, rather than the previously recommended "baby" aspirin of about 81 milligrams a day -- had fewer blood clots. As a result, the company recently changed the protocol for its clinical trials to raise the aspirin dose to 325 milligrams.
"It's a trend called out by retrospective analysis but it's a powerful trend," said Douglas Godshall, HeartWare's chief executive officer. "I feel quite certain that this is the highest rate of thrombus that we will see because we've learned from this experience."
Thrombus is the term for the blood clot itself and thrombosis for its formation.
HeartWare is also tweaking its technology to add a more textured surface to the pump, which the company believes will help reduce the blood clot rate.
Still, the effect of these changes still has to be proven in trials. In the meantime, physicians involved in HeartWare's clinical trials are eager to defend the pump.
Dr. Joseph Rogers, Medical Director of Cardiac Transplant and Mechanical Circulatory Support Program at Duke University Medical Center, said prior to Friday's meeting that he would consider any thrombosis rate below 5 percent reasonable.
On Saturday, Rogers said that although the newly reported rate was high, he is not willing to condemn the technology.
"A lot of this may be related to our drug management strategy and the inappropriate use of low-dose aspirin with this particular pump," he said.
Patients who receive a ventricular-assist device typically receive blood-thinning, or anti-coagulation, medications to prevent blood clots. Physicians monitor the effectiveness of blood-thinners by using a benchmark known as the International Normalized Ratio, or INR. The higher the INR, the thinner the blood. The average INR in the latest data was 2.1.
Higher levels of anti-coagulation medicine and aspirin, which also thins the blood, can increase the risk of bleeding. The challenge for doctors is to give patients enough blood-thinning medication to prevent clotting but not enough to increase bleeding. HeartWare said on Friday that it has not so far seen a higher rate of bleeding with patients taking the higher dose of aspirin.
El-Banayosy said he suspects a certain percentage of thrombosis cases were due to physician error or inexperience.
"Many of these cases may be related to the positioning of the pump, not the pump's design," he said.
(Reporting by Toni Clarke, Editing by Martin Howell)