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NEW ORLEANS -- A trial comparing the Impella heart pump and an intra-aortic balloon pump for hemodynamic support during high-risk percutaneous coronary intervention failed to meet its primary endpoint -- but researchers say the device still holds some promise.

The PROTECT II trial was stopped early because an interim analysis found the primary endpoint, 30-day rates of a composite of 10 major adverse events, did not differ between the two groups -- a finding that held up in the most updated analysis of 447 patients (P=0.312), according to principal investigator William O'Neill, MD, of the University of Miami in Florida.

The findings were confounded by the more frequent and aggressive use of rotational atherectomy in the patients in the Impella group, likely because of the superior hemodynamic support provided by the device during PCI, O'Neill explained at the American College of Cardiology meeting here.

In a prespecified analysis of the patients who did not undergo rotational atherectomy, Impella significantly reduced major adverse events (RR 0.75, 95% CI 0.60 to 0.95, P=0.015).

In an interview with 番茄社区, Mark Turco, MD, an interventionalist at Washington Adventist Hospital, said it was important to consider the differential use of rotational atherectomy because the procedure results in the release of cardiac enzymes -- which could have triggered the MI component of the primary endpoint.

Although O'Neill predicted that there would be more interest in learning how to use the Impella heart pump with the release of the PROTECT II results, Turco, who was not involved in the study, said he thought the clinical impact would be more subtle.

"Do I think that this particular trial data that you see in a short 10-minute presentation is going to change clinical practice tremendously?" he asked. "No, but I think as the story is continuing to be built ... that one will see that there is very good data to support the use of the Impella versus the intra-aortic balloon pump."

An intra-aortic balloon pump is used to provide hemodynamic support in about 28,000 high-risk patients undergoing PCI each year in the U.S., O'Neill said.

He said that preliminary studies have shown that Impella, which received FDA clearance in 2008 and pumps up to 2.5 liters of blood per minute from the left ventricle into the ascending aorta, provides better hemodynamic support, which was confirmed in the current trial through assessments of cardiac power output.

To compare the two devices, O'Neill and his colleagues enrolled patients at 67 sites in the U.S., four in Canada, and one in the Netherlands.

The study patients were undergoing nonemergent PCI and required hemodynamic support. All had complex anatomy -- either unprotected left-main disease or triple-vessel disease -- accompanied by a low ejection fraction.

According to O'Neill, the patient population was at higher risk than participants in any other PCI trial. The PROTECT II patients were about a decade older (mean age 68), had a high rate of congestive heart failure (more than 83%) and diabetes (about 50%), and were mostly inoperable (63%).

The trial's Data Safety Monitoring Board recommended stopping the trial because of futility in December 2010 after a planned interim analysis of the first 324 patients. The current analysis included 447 patients because enrollment continued before the interim results were known.

The primary endpoint was a composite of 10 major adverse events -- death, MI (defined as more than three times the upper limit of normal CK-MB or troponin), stroke/transient ischemic attack, repeat vascularization, need for any cardiovascular operation for limb ischemia, acute renal dysfunction, increase in aortic insufficiency, severe hypotension, CPR or arrhythmia requiring treatment, and failure to adequately reopen the vessel -- at 30 days post procedure.

In the intention-to-treat population, there was no significant benefit for Impella versus the intra-aortic balloon pump on the primary endpoint at either 30 or 90 days. A prespecified per-protocol analysis of patients who met all inclusion and exclusion criteria was more favorable for Impella at 90 days.

The PROTECT II findings were substantially confounded in that interventionalists used rotational atherectomy in the Impella group more frequently (14.9% versus 9.5%, P=0.088) and more aggressively, according to O'Neill.

That equated to a doubling of the rate of major adverse events in patients in the Impella group who underwent atherectomy compared with patients in the intra-aortic balloon group who also underwent the procedure (70% versus 35%).

Turco said that he was pleased with the results, which -- when considering the effect of rotational atherectomy -- are supportive of the Impella over the intra-aortic balloon pump in these high-risk patients.

Although a cost analysis has not been completed, Turco said that he expects Impella to be cost-effective, despite being a more expensive device.

He pointed to the fact that the intra-aortic balloon pumps were left in the patients for a longer time than Impella was (average 8.2 versus 1.9 hours, P<0.001)

That will work out to a shorter stay in the intensive care unit with Impella, which will lead to a cost savings for the public, Turco said.

O'Neill also touted the likely cost-effectiveness of Impella, estimating that the device would save about $14,000 over the 90 days post-procedure because of a reduction in hospitalizations.

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