Impact of baseline beta-blocker use on inotrope response and clinical outcomes in cardiogenic shock: a subgroup analysis of the DOREMI trial

Abstract

Background: Cardiogenic shock (CS) is associated with significant morbidity and mortality. The impact of beta-blocker (BB) use on patients who develop CS remains unknown. We sought to evaluate the clinical outcomes and hemodynamic response profiles in patients treated with BB in the 24 h prior to the development of CS.

Methods: Patients with CS enrolled in the DObutamine compaREd to MIlrinone trial were analyzed. The primary outcome was a composite of all-cause mortality, resuscitated cardiac arrest, need for cardiac transplant or mechanical circulatory support, non-fatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary composite and hemodynamic response profiles derived from pulmonary artery catheters.

Results: Among 192 participants, 93 patients (48%) had received BB therapy. The primary outcome occurred in 47 patients (51%) in the BB group and in 52 (53%) in the no BB group (RR 0.96; 95% CI 0.73-1.27; P = 0.78) throughout the in-hospital period. There were fewer early deaths in the BB group (RR 0.41; 95% CI 0.18-0.95; P = 0.03). There were no differences in other individual components of the primary outcome or in hemodynamic response between the two groups throughout the remainder of the hospitalization.

Conclusions: BB therapy in the 24 h preceding the development of CS did not negatively influence clinical outcomes or hemodynamic parameters. On the contrary, BB use was associated with fewer deaths in the early resuscitation period, suggesting a paradoxically protective effect in patients with CS. Trial registration ClinicalTrials.gov Identifier: NCT03207165.

Keywords: Beta-blocker; Cardiogenic shock; Dobutamine; Inotropes; Milrinone.

Conflict of interest statement

None to declare.

© 2021. The Author(s).

Figures

Fig. 1

Study flow diagram. All participants in the DObutamine compaREd to MIlrinone study were included in the subgroup analysis. There were 49 (51%) patients on beta-blockers in the milrinone group and 44 (46%) patients on beta-blockers in the dobutamine group for a total of 93 (48%) patients on beta-blockers

Fig. 2

Time-to-event curves for the primary endpoint, death, and resuscitated cardiac arrest in the early resuscitation period. a Primary composite outcome, b all-cause mortality, and c death or resuscitated cardiac arrest within the first 48-h of initiation of inotropic therapy. Survival curves were constructed using Kaplan–Meier estimates. Adjusted relative risk using Chi-square testing was used for the primary outcome including age, sex, beta-blocker use, type of inotrope, and history of atrial fibrillation as covariates. Unadjusted relative risks using Chi-square testing was used for all-cause mortality and death or resuscitated cardiac arrest

Fig. 3

Key clinical and biochemical parameters. a Heart rate, b mean arterial pressure, c vasoactive-inotropic score, d serum lactate, e serum creatinine, and f hourly urine output within the first 48-h of initiation of inotropic therapy. A repeated measure mixed model was used to evaluate differences in continuous variables between groups. All panels demonstrate the mean and 95% confidence intervals between the beta-blocker (blue) and no beta-blocker (red) groups at a specific time interval. BPM beats per minute

Fig. 4

Key hemodynamic parameters. a Cardiac index, b systemic vascular resistance, c pulmonary capillary wedge pressure, and d mixed venous oxygen saturation within the first 48-h of initiation of inotropic therapy. A repeated measure mixed model was used to evaluate differences in continuous variables between groups. All panels demonstrate the mean and 95% confidence intervals between the beta-blocker (blue) and no beta-blocker (red) groups at a specific time interval

Fig. 5

Impact of beta-blocker therapy on dobutamine treated patients. In all patients treated with beta-blockers, there was no difference in a primary composite outcome, b heart rate or c mean arterial pressure when stratified by milrinone (green) and dobutamine (orange). d vasoactive inotropic score was different between beta-blocker patients treated with mirlinone versus dobutamine. In all patients treated with dobutamine, there was no difference in e primary composite outcome, f heart rate, g mean arterial pressure, or h vasoactive inotropic score when stratified by beta-blocker (blue) and no beta-blocker (red). Survival curves were constructed using Kaplan–Meier estimates. Unadjusted relative risks using Chi-square testing was used for the primary composite outcome. A repeated measure mixed model was used to evaluate differences in continuous variables between groups. b–d and e–g demonstrate the mean and 95% confidence intervals between groups. BPM beats per minute