Two brief reports in JACC on the DOBERMANN-T and DOBERMANN-D trials found that among patients with acute myocardial infarction (AMI) at increased risk of cardiogenic shock (CS), early interleukin‑6 (IL‑6) receptor inhibition with tocilizumab safely reduced systemic inflammation but showed inconclusive effects on NT‑proBNP. In contrast, early dobutamine infusion did not lower NT‑proBNP levels but did reduce systolic blood pressure (SBP) without raising safety concerns.

The single-center, double-blinded, 2x2 factorial DOBERMANN trial randomized 100 AMI patients at risk for CS 1:1 to a single intravenous dose of 280 mg tocilizumab (1-hour infusion) or placebo (DOBERMANN-T), or 24-hour low-dose dobutamine infusion or placebo (DOBERMANN-D) after acute PCI. About a quarter of the patients were women and the median age was 68 years.

For DOBERMANN-T, the primary endpoint was peak NT-proBNP up to 48 hours, and secondary endpoints were myocardial injury estimated by peak plasma troponin T (TnT) up to 48 hours, left ventricular (LV) infarct size according to CMR imaging at ≤48 hours and at three months, and temporal changes in NT-proBNP and C-reactive protein. Anterior STEMI was present in 73% of patients.

Results showed that the primary endpoint did not differ significantly between groups (geometric mean ratio 0.82; p=0.18), which corresponded to an 18% lower adjusted mean. Furthermore, Joakim Bo Kunkel, MD, et al., note that a significantly lower NT-proBNP level was detected at 12 hours, with 22% lower values in the tocilizumab group (ratio 0.78; p=0.04); a relative difference between the two groups persisted at 24 to 48 hours but did not reach statistical significance. LV infarct size and TnT levels remained similar between groups.

For DOBERMANN-D, the primary endpoint was peak NT-proBNP plasma concentration up to 48 hours, and secondary endpoints were LV infarct size at discharge and three months according to CMR, and temporal changes in NT-proBNP, heart rate and SBP.

According to Sarah Duus Holle, MD, et al., “peak NT-proBNP plasma concentration up to 48 hours were similar between the dobutamine and placebo groups,” (mean 3,618 ng/L vs. 3,709 ng/L; ratio 0.98; p=0.9), “corresponding to a nonsignificant 2% reduction in the dobutamine group.” No difference in LV infarct size was found between groups, but an 11% to 17% nonsignificant reduction in NT-proBNP at ≤48 hours was observed in the dobutamine group. SBP in the dobutamine group was lower throughout the 48 hours reaching statistical significance at 15 hours, 36 hours and 48 hours, and heart rate was higher in the dobutamine group during the first 24 hours but similar between groups after.

“…the DOBERMANN trials program takes an important step toward preventing rather than treating CS,” write Shashank S. Sinha, MD, FACC, et al., in an accompanying editorial. “The biological imperative is to intervene before that ‘bite’ - within a narrow biologic window when maladaptive pathways remain modifiable and collapse is not yet clinically entrenched.”