|Thoratec's HeartMate II left ventricular assist device--Courtesy of Thoratec|
The FDA issued a public warning about the risks of left ventricular assist devices used to pump the blood of patients with end-stage heart failure, including strokes, the formation of blood clots inside the pump and bleeding complications.
The agency told caregivers to consider the risks when determining therapy for patients, read the labeling and return all explanted devices and components to the manufacturer, either HeartWare's ($HTWR) HVAD or Thoratec's ($THOR) HeartMate II. However, the FDA stressed that it believes the benefits of the device outweigh the risks, and did not announce any concrete action against either manufacturer.
Both devices are used as a bridge to transplantation for patients awaiting a heart transplant. The HeartMate II is also approved as a long-term destination therapy for patients who are not candidates for a transplant; the HVAD is in clinical trials for that expanded indication.
The warning contained risks specific to each device. It pointed to studies showing HeartMate II pump thrombosis (or blood clot) rates of 8.4% three month post implant or 6% after 6 months. Those rates are higher than the device's two clinical trials. One trial produced a thrombosis rate of 1.6% after one year and the other 3.8% after two years. "Pump thrombosis is a serious complication that can require repeat surgery to replace the pump or can lead to death," the FDA said.
Thoratec is conducting a clinical trial to assess the incidence of HeartMate II pump thrombosis and identify risk factors associated with the event.
Meanwhile, the FDA restated the results of a recent HVAD clinical trial to earn destination therapy status, which produced a surprisingly high 28.7% stroke rate over a two year period, compared to 12.1% among those on the HeartMate II. Once again, the trial results were not consistent with those experienced outside of a controlled, experimental context.
Registry data from Europe, where the device is already used on a long-term basis, found the device's stroke rate to be 14%. HeartWare said the strokes experience by HVAD patients during the trial were less severe than those experienced by patients on the HeartMate II, which helped the HVAD meet its primary endpoint of noninferiority to the rival device, as measured by the stroke-free survival rate after two years.
All this will make for a very interesting advisory panel deliberation and FDA decision. Leerink equity analysts believe the agency will grant the expanded indication, but the safety communication shows the FDA is concerned about the stroke rate.
HeartWare said the trial's high stroke rate is the result of a lack of emphasis on blood pressure management, and is conducting a supplemental trial that requires optimal blood pressure management, with results due in October 2016.
The FDA also said a risk posed by both devices is bleeding complications, and said one factor may be the use of anticoagulants in an attempt to lower the aforementioned risks, pump thrombosis and embolic stroke. Increased bleeding is a side effect of blood thinners such as warfarin.
Left unmentioned in the notice were a plethora of usability issues with the devices, though that isn't too surprising given the inherent challenges of wearing critical components of a blood pump around the waist (such as batteries), walking around with a wire underneath your shirt that connects to the implanted pump, or being tethered to a power outlet that connects to an electrical socket (when the batteries are not in use).
HeartWare has been hit with 6 of the FDA's most severe Class 1 recalls since April 2014.
In May, it sent customers a letter on proper usage of the device. Among other things, it instructed patients to avoid accidental snagging or pulling of the driveline, which could cause disconnection or damage to the component. The driveline is the cable attached to the implanted pump that passes through the skin to connect to the controller.
And in March 2014, Thoratec was hit with four separate Class 1 recalls of its own after four patients on its HeartMate II pump died after struggling to switch to backup system controllers when their external battery pack ran low on power.
Both companies are developing next-generation LVADs with an emphasis on ease of implantation.
Thoratec recently agreed to be bought over by St. Jude Medical ($STJ) for $3.4 billion, though it is trying to field better offers during the deal's 30-day "go-shop" period. The company said it shipped 3,618 LVADs last year, out of an estimated market of about 6,500 implantations per year.
- read the FDA notice