Thoratec (NSDQ:THOR) shares are under pressure after a New England Journal of Medicine study showing a sharp increase in the rate of thrombosis, or blood clots, in patients implanted with its HeartMate II left ventricular assist device.
The Nov. 27 study examined data from 3 centers (Cleveland Clinic, Washington University Barnes-Jewish Hospital and Duke University Medical Center) that implanted 895 HeartMate II LVADs in 837 patients from January 2004 through May 2013.
The researchers found a total of 72 confirmed cases of pump thrombosis in 66 patients and another 36 cases of suspected pump thrombosis, according to the NEJM study.
"The occurrence of confirmed pump thrombosis increased steeply after approximately March 2011, from 2.2% (95% confidence interval [CI], 1.5 to 3.4) at 3 months after implantation to 8.4% (95% CI, 5.0 to 13.9) by January 2013," the researchers wrote. "A similar pattern was observed at all 3 institutions and for multiple surgeons."
The study also revealed a sharp decrease in the amount of time from implantation with the HeartMate II device until blood clots developed, from 18.6 months to just 2.7 months. And elevated levels of a compound called lactate dehydrogenase was found to precede confirmed cases of blood clots, meaning LDH levels could serve as a marker for the risk of thrombosis with the pump.
The researchers theorized that a buildup of fibrin and denatured protein near the HeartMate II’s inflow bearing could be a factor in the formation of the clots, according to the study.
"The bearing–fibrin deposition theory could explain the hemolysis that develops as thrombus deposition begins, escalates into frank pump thrombosis, and culminates in hemodynamic compromise. We theorize that the changes occur in 3 stages: the initial stage is hemolysis with thrombus deposition but no hemodynamic compromise (thrombus formation); this may progress to hemolysis and abnormal pump function (incomplete thrombosis); and ultimately, complete thrombosis and pump stoppage may occur," they wrote. "Any perturbation that might reduce flow and heat dissipation from the bearing, or inadequate anticoagulation, might represent precipitating conditions. Known clinical factors that might transiently impair flow include the development of aortic regurgitation, arrhythmias, kinking of the inflow graft because of bending, and hypovolemia. As of this writing, the exact cause of the increased rate of pump thrombosis remained unknown."
"[T]here are a number of factors that could contribute to thrombosis, including underlying patient condition, ongoing patient and device management practices, pump implantation technique, and device-related factors. We have performed extensive analysis on HeartMate II and have not identified any change that would cause the increase observed in the [Interagency Registry for Mechanically Assisted Circulatory Support ] registry," Thoratec told heartwire in an emailed statement, pointing out that the registry analysis also showed higher survival rates after 6 months (86%) than were found during a clinical trial of the HeartMate II device (75%).
The news sent THOR shares down 6.5% to a $39.37 close in abbreviated trading Nov. 29 and down another 1.0% today, to $39.98 apiece.
Rival LVAD maker HeartWare International (NSDQ:HTWR) gained on the news, with HTWR shares rising 3.1% to $96.40 apiece Nov. 29. HTWR shares were trading at $96.28 each as of about 10:15 a.m. today, down 0.1%. HeartWare is not stranger to the blood clot issue; 2 years ago its share price suffered after clinical trial results of its HVAD pump showed thrombosis rates that were much higher than expected.
Leerink Swann analyst Danielle Antalffy cautioned that the study’s small sample size and the lack of a clear cause for the spike in blood clot rates make the NEJM study’s results inconclusive.
"While the findings from the pooled analysis at these 3 high-volume LVAD centers is concerning, we’re inclined to believe the relatively small sample set – 895 patients over the January 2004-May 2013 timeframe vs. well over 10,000 U.S. LVAD implants performed over the same period – is still inconclusive. This study is likely to generate some buzz amongst the clinical community – particularly given that the increasing rate did not seem to plateau at last reading – but we also believe it’s unlikely to change current practice as: 1) centers generally adjust practice according to their own experience vs. that of others; and 2) an increasing thrombus rate with HeartMate II is not "new news" as INTERMACS has already noted an increase of thrombus rates to ~5% in implants from May 2011-September 2012 vs. ~2% in implants from April 2008-May 2011," Antalffy wrote in a note to investors last week. "Ultimately, we believe with continued improvements in patient selection and patient management, adverse event rates settle into a range more in line with that seen in clinical trials."
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