More data on Impella complications emerge
Six months later, DanGer-Shock post hocs add detail on AKI and bleeding
The DanGer-Shock randomized trial allowed interventional cardiologists to breathe a bit easier, knowing that the Impella device resulted in improved survival 6 months after ST-elevation myocardial infarction with cardiogenic shock:
The trial also underscored the high risks associated with the Impella device:
Many more patients with Impellas required renal replacement therapy (41.9% vs 26.7%).
Severe bleeding, limb ischemia, and sepsis with bacteremia were also increased in the Impella group, with the composite outcome of adverse events occurring four times more often in Impella patients (24% vs 6%).
There were other major caveats and question marks attached to the trial results:
Patients were highly selected (360 enrolled out of 1211 screened) and enrollment took more than 10 years.
Conducted in Europe where intra-aortic balloon pumps are out of favor, the trial’s control arm did not receive IABP; 21% received ECMO.
Centers were highly experienced with Impellas and managing their potential complications. At less-experienced centers, whether Impella’s benefits would outweigh its high complication risks remained unknown.
There was no mortality benefit seen in the Impella group in the first 15 days. Only after that did the Kaplan-Meier survival curves start to diverge. Since the vast majority of mortality from cardiogenic shock occurs in the first 30 days, why would the survival benefit of an Impella be so delayed?
The control arm had 59% mortality at 6 months—higher than other trials enrolling cardiogenic shock patients at a similar severity of illness.
Secondary Analyses from DanGer-Shock
Three new secondary analyses of DanGer-Shock (performed by the trial’s investigators) provide additional details on the Impella’s potential for restoring perfusion, and also its high complication rates.
Impella worked (Udesen et al JAMA Cardiology 2024): Impella reduced the need for vasopressors and inotropes during the first 12 hours, and also improved lactate clearance.
Impella caused AKI (Zweck et al Circulation 2024): Impella caused high rates of acute kidney injury (AKI) with need for renal replacement. The secondary analysis verified that the higher AKI / RRT rates observed in the trial were due to the Impella, not due to Impella patients surviving longer than control patients (and thus needing more renal replacement).
AKI and RRT were both linked to higher mortality in patients in both arms.
The AKI appeared to be reversible, however: none of the surviving patients continued to require dialysis after 6 months of follow-up.
AKI was often predicted by “suction events,” when the Impella wobbles and becomes stuck to the myocardium by suction, stopping flow. Higher pump speed was also associated with AKI.
Impella caused nonfatal major bleeding (Sørensen, unpublished meeting data): Patients receiving Impellas were at increased risk for bleeding, but even for the patients experiencing serious hemorrhage (loss of hemoglobin >3 g/dL), bleeding was not associated with increased mortality.
Impellas were also associated with high rates of limb ischemia and sepsis in DanGer-Shock, but no new information on that complication was published in this trove of data.
Conclusions
Cardiologists and cardiac surgeons weren’t waiting for DanGer-Shock to decide whether to use Impellas: with the dismal alternatives of intra-aortic balloon pumps (mostly discredited) or ECMO (not widely available), the Impella had already been widely deployed to satisfy a desperate need for mechanical support in cardiogenic shock after STEMI. Abiomed reported revenues of over $800 million from Impellas in 2021 alone (before the company’s acquisition by J&J in 2022), despite the absence of a proven survival benefit.
After DanGer-Shock established Impellas can be potentially lifesaving, and now with secondary analyses establishing its hemodynamic and physiologic benefits, attention will shift toward understanding and reducing its high complication rates.
These analyses, published six months after the trial results, tell a reassuring story: Impellas save lives, cause AKI that resolves and bleeding that’s nonfatal.
But while the number needed to save a life was 8, the number needed to harm in DanGer-Shock was 6. Patients in the Impella arm had 2.8 times the risk of sepsis with bacteremia (implying their risk of culture-negative sepsis was far higher) and 5 times the rates of limb ischemia. Will we get to see those secondary analyses, as well?
Patients were first enrolled in DanGer-Shock more than 10 years ago, exclusively in Europe. As in any landmark trial, investigators held large reputational stakes in a positive result. New U.S.-based prospective observational studies—conducted by researchers distanced from the DanGer-Shock team geographically and professionally—would provide vital updated context to help inform the ongoing use of Impellas for cardiogenic shock worldwide.