Delays in STEMI Cardiogenic Shock Care Come at a Cost: DanGer Shock

The survival benefit associated with the use of Impella CP (Abiomed) for patients with STEMI-related cardiogenic shock in the DanGer Shock trial progressively shrank as the time between symptom onset and randomization grew longer, a new analysis shows.

Making a splash at the 2024 American College of Cardiology meeting as the first-ever large RCT in this population, DanGer Shock’s main results showed a 26% relative reduction in all-cause mortality at 180 days, decreasing 59% to 46%, with the mechanical circulatory support device versus standard care alone. Since then, further analyses have delved into nuances related to the 10-year outcomes, eligible population, bleeding, and hemodynamics and renal function.

For this latest look, “we wanted to see if the Impella device was as good if the patients came late as when they came early,” lead investigator Lisette Okkels Jensen, MD, DMSci, PhD (Odense University Hospital, Denmark), told TCTMD.

Numerous initiatives in the STEMI setting have been somewhat successful at decreasing delays to primary PCI, with the knowledge that faster treatment is tied to better survival.

Specifically for STEMI patients with cardiogenic shock, treatment delays have received less attention thus far. Mortality among these complex cases has hovered around 40-50%. Here, too, there has been observational evidence that faster care imparts better hemodynamics and survival, though less is understood about how much the delays matter and which groups get less-than-speedy care.

Jensen cautioned that the secondary analysis was not randomized or powered for time-based comparisons, but she said it’s not “surprising that the longer the time goes, the more profound the cardiogenic shock is [and] the more difficult it is for not only the medical therapy on top of the PCI, but also for the Impella, to work.”

More surprising was that women, older individuals, and transferred patients were overrepresented among the more-delayed groups, Jensen said. “It will be important to diagnose [these] patients as early as possible and get them transferred to a hospital where they have the capacity to do the Impella treatment,” not just primary PCI.

Some of the relationship between timing and outcomes may be due to the fact that not all patients were in severe cardiogenic shock at the time of primary PCI but developed it afterward, she suggested. Notably, though, there was no significant interaction between SCAI SHOCK stage and mortality with regards to delays.

Jensen highlighted two key messages from their study. For one, there’s a need to “fast-track” patients getting to a hospital with sufficient resources. After arrival, while survival is better with Impella for STEMI patients in cardiogenic shock, the benefit seems to diminish with longer waiting times.

A Case Against Watchful Waiting

The current analysis included 345 out of the trial’s 355 participants, stratifying them into quartiles based on the time between first symptoms and randomization to either the percutaneous left ventricular assist device or standard care alone. Whether randomization occurred before or during PCI, or after patients left the catheterization laboratory, was based on when cardiogenic shock first occurred; the shortest delays were seen in patients who received Impella before PCI.

Generally, the longest delays were in patients who transferred from an outside hospital, while a greater proportion of patients with shorter times were resuscitated before randomization. There were no imbalances between quartiles in lactate at randomization, LVEF, SCAI SHOCK stage, infarct location (anterior or nonanterior STEMI), culprit lesion, TIMI flow, presence of multivessel disease, or complete revascularization during index PCI. Moreover, across DanGer Shock’s 10-year enrollment period, there were no significant changes in timing.

Mortality rates at 180 days grew increasingly higher alongside longer delays (log-rank P = 0.002):

• Quartile 1 (0-140 minutes): 36%
• Quartile 2 (141-248 minutes): 53%
• Quartile 3 (249-650 minutes): 59%
• Quartile 4 (> 651 minutes): 62%

Patients with longer delays had different characteristics, however. They tended to be older, with a median age ranging from 66 years in the lowest quartile to 71 years in the highest (P = 0.005). They also were more likely to be women versus men, with the proportion of female patients rising from 15% to 34% across the quartiles (P = 0.006).

Yet even when adjusting for age and gender, mortality was higher with longer delays (OR 1.28 per doubling in time; 95% CI 1.10-1.51) and lower with Impella use (OR 0.53; 95% CI 0.33-0.86).

When combining the three lowest quartiles of delay, Impella use was associated with a significant reduction in 180-day mortality (OR 0.51; 95% CI 0.31-0.84). For those in the highest quartile, there was no survival benefit (OR 0.92; 95% CI 0.38-2.22). That said, the interaction did not reach statistical significance, with a P value of 0.26.

The findings suggest “that in cases of acute myocardial infarction complicated by cardiogenic shock, watchful waiting is detrimental to the patient,” the researchers note, pointing to a “time window of opportunity to place a microaxial flow pump and initiate other supportive treatments.” As such, they argue for an emphasis on early recognition of cardiogenic shock as well as efforts to steer patients toward specialized facilities with the ability to offer more advanced care.