Impella Flops for Acute Coronary Syndrome Patients Not in Shock

NEW ORLEANS — Microaxial flow pump circulatory support with the Impella device during percutaneous coronary intervention (PCI) didn’t help outcomes for complex patients not in cardiogenic shock, two randomized trials at the American College of Cardiology (ACC) annual meeting showed.

In an elective and largely stable but high-risk population in the CHIP-BCIS3 trial, Bayesian win ratio favored PCI without planned circulatory support (0.85, 95% CI 0.63-1.15), with 43.0% of wins in pairwise hierarchical comparisons in that group compared with 36.6% in patients randomized to pump support, reported Divaka Perera, MD, of King’s College London.

At the top of the hierarchy, wins on all-cause mortality came out 7 percentage points higher in the protected PCI group (HR 1.54, 95% CI 0.99-2.41, P=0.054), driven by a significantly higher risk of death from cardiovascular (CV) causes (HR 1.91, 95% CI 1.11-3.30, P=0.018).

In the STEMI Door to Unload (DTU) trial, delayed reperfusion with Impella for 30 minutes before PCI for ST-segment elevation myocardial infarction without shock had no impact on infarct size in the intent-to-treat analysis (30.8% vs 31.9% among controls, P=0.50) or per protocol analysis (31.8% vs 33.7%, P=0.28), reported Gregg W. Stone, MD, of Icahn School of Medicine at Mount Sinai in New York City.

Nor was there an impact on clinical outcomes in secondary endpoints, with a win ratio of 1.04 (95% CI 0.84-1.28, P=0.73) compared with immediate coronary angiography plus PCI without the temporary circulatory support device, although all-cause and CV mortality at 30 days tended to favor the intervention in this trial (both P=0.08).

The CHIP findings were simultaneously published in the New England Journal of Medicine (NEJM); STEMI DTU was published in the Journal of the American College of Cardiology.

CHIP Implications

“Over the last decade, we have increasingly adopted mechanical circulatory support for high-risk PCI, particularly the microaxial flow pumps, largely driven by physiological rationale and observational experience,” said ACC study discussant Roxana Mehran, MD, of the Mount Sinai School of Medicine in New York City. With prior inconclusive randomized evidence, “the current guidelines rightly — American and European — remain cautious with the class 2b recommendations, reflecting a field where clinical enthusiasm has clearly outpaced high quality evidence.”

Benny Levenson, MD, PhD, of Freie Universität Berlin, and ACC press conference discussant for CHIP, said its results didn’t really come as a surprise, given the lack of benefit from extracorporeal life support in the treatment of infarct-related cardiogenic shock in the ECLS-SHOCK randomized trial.

With these “landmark” data from CHIP on elective unloading, “routine use of this strategy cannot be recommended. But perhaps the most important insight is not simply that unloading doesn’t work, but that timing and patient selection are critical,” Mehran concluded.

Panelist Ajay Kirtane, MD, of Columbia University Irving Medical Center/New York-Presbyterian Hospital in New York City, agreed: “There are cases where you simply could not do the case without a hemodynamic support device, but the decision to put that device in [requires] a careful consideration of risks, as [the CHIP trial has] shown, and potential benefits which at present remains somewhat unproven. So I do think we have to go away from ‘protected PCI’ and bill it as PCI with hemodynamic support.”

“The use of a more nuanced evaluation of direct hemodynamic measures — such as elevated left-sided filling pressures and reduced cardiac output — may offer better selection criteria but requires further evaluation,” stated Brahmajee Nallamothu, MD, MPH, and Brett Wanamaker, MD, both of the University of Michigan in Ann Arbor, an accompanying NEJM editorial.

Mehran cautioned against over-broad interpretation, noting the clear benefit of microaxial flow pump support in the DanGer SHOCK trial in active infarct-related shock.

STEMI DTU Implications

Attempts to mitigate reperfusion injury have failed again and again, but this new failure in STEMI DTU “doesn’t shut the door,” said ACC press conference study discussant Wayne Batchelor, MD, MHS, MBA, of Inova Heart and Vascular Institute in Fairfax, Virginia.

“There are some other questions that need to be asked in terms of what happens if we are able to miniaturize these devices, eliminate or reduce vascular complications and bleeding, would that signal of efficacy — if it was deployed at the right time and the delay was the right amount of time — would it come through to fruition?” he said.

“This does tell us, though, that right now it is business as usual for the cath lab,” Batchelor said. “We have no justification for deploying Impellas in non-cardiogenic shock ST elevation MIs until further research is done.”

The key secondary safety endpoint of major device-related bleeding and vascular complications came in at 30.8%, which was above a pre-specified performance goal of 26.5% that had been established in concert with FDA.

Stone noted that a lot of the bleeding was oozing and hematomas, with what he called a very weak association with long-term mortality in the Impella group, suggesting that complications were much more impactful in the control group.

In comparison, Perera noted that in CHIP, bleeding and vascular complications were numerically but not statistically more common in the microaxial flow pump group, “but the rates were actually quite low and lower than in registries, and I don’t think that accounts for the cardiovascular mortality difference.” Exactly what accounts for the higher mortality requires more analysis and in-depth exploration, he said.

The CHIP protocol included several measures to ensure low risk, with pre-procedure CT planning carried out in more than two-thirds of patients in both arms, ultrasound guided micropuncture used in all patients, and percutaneous access closure with a dedicated device in the vast majority of these patients.

Trial Details

CHIP included 300 patients at 29 centers in the U.K. who had complex coronary disease and a left ventricular ejection fraction of 35% or less (median 27%). Participants were randomized to elective unloading with a microaxial flow pump in planned complex PCI or to standard care (mechanical circulatory support only for emergency bailout) during the procedure. Perera noted that median BCIS-Jeopardy Score was 12 on the 12-point scale, with a lot of calcification, left main, and chronic total occlusion.

STEMI DTU included 527 patients, ages 18 to 85, with no prior MI who presented at 55 hospitals in the U.S., Canada, and Europe with acute anterior STEMI within 1-6 hours of symptom onset. Participants were randomized to open-label treatment with Impella insertion followed by a 30-minute period of delay before PCI versus immediate PCI alone. The Impella device was left in place for 4-24 hours, at the physician’s discretion, with a median 10.4 additional hours. The strategy resulted in a median about 47 minutes greater total ischemic time than in the usual care group.

Longer-than-expected Impella dwell times with anticoagulation (mean 14 hours) and suboptimal closure techniques may have contributed to bleeding complications, Stone said. A limitation was that STEMI DTU was not powered for clinical outcomes. Also, higher than expected systolic blood pressure of around 143 mm Hg might have impacted efficacy, he added, which future studies might address by combining Impella with blood pressure lowering and other adjunctive therapy to optimize loading conditions before PCI.

Mehran noted the PROTECT IV trial of Impella-supported PCI in high-risk, complex coronary artery disease patients with reduced left ventricular function is expected to report results within the next year.

“While [CHIP] provides clarity for contemporary stabilization of high-risk PCI, moving us away from routine use, PROTECT IV will help us determine whether a different trial design, larger population, or longer follow-up may [show] a subgroup that might benefit from this,” she said.