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WASHINGTON -- A rare randomized trial and a new meta-analysis both failed to find any evidence that Impella mechanical circulatory support devices are any better than intra-aortic balloon pumps (IABPs) for patients with cardiogenic shock.
For many years, the intra-aortic balloon pump has been the standard device to increase circulation in cardiogenic shock, but its use has been sharply curtailed in recent years after studies found no benefit with the devices. The newer Impella devices, which have been shown to deliver more powerful hemodynamic support, are now often used in place of IABPs, though there has been no firm evidence demonstrating clinical benefit. Now the new study and meta-analysis may raise additional questions about the device.
In the IMPRESS trial, Dutch investigators led by José Henriques, MD, PhD, randomized 48 patients with cardiogenic shock to the Impella CP or the IABP. At 30 days, there was no significant difference in mortality (50% for IABP versus 46% for Impella). At 6 months, the mortality rate was 50% in both groups.
Results of the trial are being presented at the Transcatheter Cardiovascular Therapeutics meeting in Washington, D.C., and to be published in the Journal of the American College of Cardiology.
The meta-analysis, also led by Henriques, combined the IMPRESS results with data from the two prior randomized controlled trials comparing Impella to IABP in patients with cardiogenic shock. In total, 95 patients were randomized, and no differences in mortality or other important endpoints between the groups was found at 30 days or 6 months.
"Although the Impella has repeatedly shown to provide more hemodynamic support than the IABP, this did not translate in improved clinical outcome in these very sick patients at a high mortality risk," the authors wrote.
The authors noted that, because of their "all-comer" shock population, it is possible that there may be a subgroup or subgroups of patients who might still benefit from the device. One possibility is earlier use of the Impella device prior to revascularization, since most patients in the three studies were started on support afterwards.
In an accompanying editorial, Uwe Zeymer, MD, and Holger Thiele, MD, wrote that IMPRESS was "markedly underpowered," so the lack of difference in mortality is not surprising. "However, the lack of benefit in any of the other parameters including serum lactate is a concern with respect to the efficacy of the device." They expressed hope, however, suggesting that mechanical circulatory support is still promising and worthy of additional research.
Richard Lange, MD, MBA, of Texas Tech University Health Sciences Center at El Paso, served on the FDA cardiac devices advisory panel and has followed the Impella story closely. He said he also still holds out hope that Impella "might be useful in certain patient subsets or when delivered earlier." But, he said, he remains "amused that studies -- whether well or poorly conducted -- that confirm our preconceived ideas are enthusiastically embraced. Conversely, those that don't confirm them are explained away (i.e., flawed, too small, not timed correctly, not enrolling proper patients, etc)."
Sanjay Kaul, MD, of Cedars-Sinai Medical Center, wondered if one potential danger of the Impella is that the device "makes the interventionalist feel better and bolder; not the patient." He noted that, in the PROTECT II trial, interventionalists may have been emboldened to use atherectomy more often because of the greater hemodynamic support.
Sanket Dhruva, MD, of Yale, said he was concerned "about the unfortunately slippery slope that we have descended with FDA Premarket Approvals. The data used to justify Impella's approval were shaky and uncertain, including the premature stopping of the PROTECT II study for futility and safety concerns in three pre-specified patient cohorts. The FDA approved the Impella 2.5 on 'probable' benefits outweighing risks. Unfortunately, as we have seen, and as these new papers show, this device is not benefiting patients in RCTs."
Dhruva pointed out that it is now widely accepted that IABPs don't improve mortality. "Unfortunately, Impella use has been rising rapidly as IABP use has decreased," despite the absence of evidence showing Impella is superior to IABP. "I worry that we are just trading one device with unclear benefit but certain risk (IABP) for another device with just as unclear benefit and even greater patient risk (Impella)." Dhruva did hold out hope that some patient subgroups may benefit from Impella.
Seth Bilazarian, MD, is the chief medical officer of Abiomed, which manufactures Impella. He pointed out that Abiomed has faced numerous challenges trying to enroll patients in randomized trials of Impella. "Unfortunately we always end up with underpowered studies with complex results like crossover treatment and heterogeneous patients."
Bilazarian said that "the IMPRESS paper provides an important contribution to our understanding of the critical importance of case selection in clinical management and interpretation of published literature." He pointed out that "nearly half of the population died of complications related to anoxic encephalopathy, highlighting the hazard of including these patients in comparative trials to assess optimal strategies. These patients do not recover, regardless of the quality of care."
IMPRESS, then, "provides an important validation that there is a subset of patients with cardiogenic shock in whom poor outcomes is inevitable. These features -- cerebral anoxia, out of hospital cardiac arrest and mechanical ventilation -- may help define patients in whom therapeutic intervention should be used cautiously or withheld because of futility. This difficult question and the need for clarity in patient decision making is the real controversy surrounding this data."
Bilazarian said that the keys to successful use of mechanical circulatory support are "appropriate patient selection, early implantation/hemodynamic support, and excellent implantation technique (use of modern strategies for access such as ultrasound guidance and micropuncture technique)."
Bilazarian said that Abiomed will announce during TCT a new quality assurance program "designed to improve outcomes in Protected PCI and AMI cardiogenic shock."