Experts say the results specific to STEMI patients with cardiogenic shock are surprising, but many challenges lie ahead.
ATLANTA, GA—For patients with acute MI complicated by cardiogenic shock (AMICS), routine use of mechanical circulatory support (MCS) using the Impella CP (Abiomed) microaxial flow pump compares to standard care. The mortality rate at 180 days seems to decrease. According to long-awaited data from the randomized DanGer Shock trial.
According to Jacob Eifer Moller, MD, PhD, DMSc (Copenhagen University Hospital Rigshospitalet, Denmark), who presented the study results today at the 2024 Scientific Sessions of the American College of Cardiology (ACC), researchers stated that the incidence of safety events was higher when using impeller devices. . And because the trial only enrolled STEMI patients, “the results cannot be extrapolated to other causes of cardiogenic shock, including OHCA, non-STEMI, and non-ischemic cardiogenic shock,” he said. said in his latest presentation.
The DanGer Shock trial was simultaneously published online. New England Medical Journal In conjunction with the ACC meeting.
The field of impellers has long had its supporters and detractors. It remains to be seen whether today's data is enough to sway skeptics about the balance of risks and benefits.
In an editorial accompanying the NEJM paper, Sunil V. Rao, MD, NYU Langone Health, New York, NY, says the study results are a milestone for the field. “These surprising results represent the first treatment strategy to show benefit for AMICS patients since the SHOCK trial published in 1999 established percutaneous coronary intervention as the cornerstone of treatment.” he writes.
Developed over a decade, Danger Shock began registration in Denmark in 2013, expanded to Germany in 2019 and the UK in 2021. This comes amid a controversial debate over what exactly observational data is. Some of it is cloudy because it comes in the absence of large randomized controlled trials. During that time, Impella usage skyrocketed.
“This long-term enrollment is a result of researchers continuing to test microaxial flow pumps despite a significant increase in clinical adoption despite a lack of solid evidence to justify their use. It reflects patience and persistence,” Rao said. “It also highlights the difficulties in conducting randomized trials in AMICS patients due to issues related to informed consent, lack of proportionality, and appropriate patient selection, which are contributing to the difficulty of conducting trials. It may impede progress.”
Remarkably, over the past decade, AMICS-related mortality rates in the wider world remained unchanged, he added.
“It's great for the field to finally have positive randomized trial data to back it up.” [earlier] ” agreed Ajay Kirtan, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), who commented on the new findings in TCTMD. He expects Impella outcomes to continue to improve, with fewer complications and adverse events, as technology, patient selection, and the device itself evolve.
Manesh Patel, MD, Duke University School of Medicine in Durham, North Carolina, also said the DanGer Shock advances the field. However, it is important to note that the researchers “identified patients who were at high risk and had an opportunity to benefit.” [enough to] overcome some of the risks associated with any of these [MCS] Patel pointed to the device, particularly vascular complications.
Kirtan said doctors can be confident that the treatment is effective when they apply the findings to individual patients, but the study does not suggest Impella should be used routinely in all AMICS patients. He emphasized that it did not mean anything. “It's great to hear this news, but I think it's a mistake to take this news and say, 'Anyone in shock needs hemodynamic support.'”
While there is certainly much left to learn about using Impella, the DanGer Shock is “a good lesson in how powerful randomized data can be,” he added.
[It’s] It's a good lesson in how powerful randomized data can be.Ajay Kirtan
Nihar Desai, MD, MPH (Yale University School of Medicine in New Haven, Conn.), lead author of a 2020 JAMA paper that used propensity matching to overcome the downsides of observational data, also said the analysis was controversial. , extolled the danger. The investigators are shocked by his tenacity. But like Kirtane and Patel, he also cautioned about generalizability. Desai said the trial was relatively small, enrolling selected STEMI patients, a subset of the overall cardiogenic shock population, at experienced centers in just a few countries. Furthermore, we did not directly compare the Impella with the intra-aortic balloon pump.
“That said, it's very exciting to have data that suggests this device plays a role in these patients,” he commented.
Decrease in 180-day mortality
For DanGer Shock, researchers screened 1,211 potential participants and ultimately randomized 360 AMICS patients from 14 institutions to receive standard treatment alone or Impella CP microaxial flow. I added a pump and started receiving standard treatment. All were in stage C, D, or E shock according to the Society for Cardiovascular Angiography and Interventions Cardiogenic Shock Working Group definition.
Cardiogenic shock is defined as hypotension (systolic blood pressure < 100 mm Hg or continued need for vasopressor support), end-organ hypoperfusion with arterial lactate level ≥ 2.5 mmol/L, and LVEF < 45%. established by two criteria.
After excluding 5 patients for whom informed consent could not be obtained, 355 patients were included in the final analysis. The average age was 67 years, and 79% were male. Median arterial lactate, systolic blood pressure, and LVEF were 4.5 mmol/L, 82 mmHg, and 25%, respectively.
Almost all (96.6%) underwent PCI of the culprit vessel, and 1.4% underwent emergency CABG surgery.
Of the 179 patients in the Impella group, 170 (95.0%) were successfully fitted with the device. Three of the remaining patients (1.7%) transitioned to standard treatment, and another six (3.3%) had unsuccessful Impella placement. For 28 patients (15.6%), treatment was escalated from her Impella CP to another her MCS type (i.e., Impella 5.0, Impella RP, or extracorporeal life support) .
Of the 176 patients in the standard treatment group, 3 (1.7%) used microaxial flow pumps. For 37 patients (21.0%), treatment was escalated to another support system. Although extracorporeal life support was the preferred option, the use of Impella 5.0 was permitted.
By 180 days of follow-up, 82 patients (45.8%) randomized to Impella CP had died from any cause, compared with 103 patients (58.5%) assigned to standard care. (HR 0.74, 95% CI 0.55 to 0.99, P = 0.04). Mean survival and hospital discharge were 82 days with Impella treatment and 73 days with standard treatment, with no significant difference.
However, the study's composite safety endpoint (severe bleeding, limb ischemia, hemolysis, device failure, or worsening of aortic regurgitation) was higher with Impella than with standard treatment alone (24% vs. 6.2% , relative risk) [RR] 4.74; 95% CI 2.36-9.55). Individual endpoints of moderate/severe bleeding (RR 2.06; 95% CI 1.15-3.66), limb ischemia (RR 5.15; 95% CI 1.11-23.84), and renal replacement (RR 1.98; 95% CI 1.27-) But there was an increase. 3.09), and sepsis with positive blood culture (RR 2.79; 95% CI 1.20-6.48).
The number needed to treat to avoid one death was eight, but the number needed to cause harm was six.
Subgroup analysis showed that Impella was associated with a significant reduction in mortality in men, but not in women. The survival benefit was shown to be greater in patients with mean arterial pressure ≤63 mm Hg (compared with higher) and in patients with multivessel disease (compared with single vessel).
“Safety”
Desai said the important thing to consider when digesting the DanGer Shock is that while mortality rates have decreased, “at the same time we've seen a pretty significant increase in safety risks.” Stated. Now, he continued, “The big question is, how does this device work in a non-select facility with non-select medical personnel, with a more diverse group of cardiogenic shock patients? That's what I mean.'' And I think that's still a big open question. ”
Desai said the U.S. Food and Drug Administration's recent announcement of a Class I recall for the labeling of various Impella models (49 deaths have been reported) means that if not used with care, “these devices can “This is a reminder that it can lead to potentially fatal complications.”
Bringing the treatment to these “very difficult and critical patients who need it” and the appropriate expertise “so that we can deploy the device in the safest way that will actually be most effective.” He said there needed to be a balance between holding the He pointed out and emphasized that this applies not only to the catheterization lab, but also to what happens before and after. In settings such as cardiovascular intensive care units, “these teams need to be educated and equally meticulous and diligent about monitoring device location, performance, safety, and potential complications.” “Because the complications can be very serious,” Desai said.
The big question is how will this device work in unselected facilities with unselected health care workers for a more diverse group of cardiogenic shock patients?Nihal Desai
According to the researchers, DanGer Shock “differs from other modern randomized trials of mechanical circulatory support in that it was conducted in a more homogeneous patient population.” The requirement that participants have elevated arterial lactate levels even in the absence of cardiac arrest meant that the population had “severe left lactate, as reflected in the substantial mortality observed after 30 days of follow-up.” “higher incidence of ventricular failure and adverse events.” ” they wrote, adding that this late mortality rate reflects previous data from the National Cardiogenic Shock Initiative and other registries.
However, Professor Rao also noted that the new results depart from the previously published negative findings regarding MCS in the IABP-SHOCK II and ECLS-SHOCK trials. This may be related to the population studied, the timing of the primary endpoint, the degree of hemodynamic support, or all of the above, he suggests.
For Rao, there are still unknowns that must be resolved to optimize use of Impella, such as timing of pump installation, details of shock protocols, and clarity about how best to combine different types of MCS. There are a few things. Some of these questions have already been answered in observational studies and are now being addressed in trials like RECOVER IV, he added. “Until these data are available, the DanGer Shock trial will continue to evaluate the treatment of his AMICS patients whose peripheral vessels can be adapted to microaxial flow pumps in terms of safe vascular access and closure, and standardized weaning and removal protocols.” evidence of progress in
Once you know something works, the next step is how to actually implement it to get the results you want. [step].Manesh Patel
A more detailed analysis of Danger Shock would also be interesting, Kirtan said. He suggested that a partial explanation for the difference in complications could be that the controls simply did not survive long enough for some events to occur. “But if you examine a patient alive who has a 14 Fr device inserted into a small ilium, all else being equal, you're more likely to have problems than if you didn't insert that device. We know that it increases sex.”
Kirtan said prompt diagnosis and treatment of cardiogenic shock, including right heart catheterization, can contribute to better outcomes.
Dr. Patel emphasized training based on best practices and a team-based approach to cardiogenic shock. “I think these are achievable results,” he said. As for what should happen after DanGer Shock, Patel says: [step]”