Norepinephrine was associated with significantly higher all-cause mortality compared to phenylephrine in patients with aortic stenosis and cardiogenic shock (HR 1.622; 95% CI 1.204-2.185; p=0.0013).
Cohort (n=1,083)
Yes
Does phenylephrine reduce all-cause mortality compared to norepinephrine in adult patients with aortic stenosis complicated by cardiogenic shock?
In patients with aortic stenosis complicated by cardiogenic shock, phenylephrine was associated with significantly lower all-cause mortality compared to norepinephrine, potentially due to its pure alpha-1 agonist profile.
Effect estimate: HR 1.622 (95% CI 1.204-2.185)
Absolute Event Rate: 50.746% vs 37.811%
p-value: p=0.0013
Abstract Background Aortic stenosis (AS) complicated by cardiogenic shock (CS) represents a uniquely challenging clinical scenario due to the fixed obstruction to left ventricular outflow. In such patients, compensatory mechanisms to maintain cardiac output are severely limited, making vasopressor selection critical. While norepinephrine and phenylephrine are commonly used agents in shock, their differential impact on outcomes in AS remains unclear. This study investigates survival outcomes associated with norepinephrine versus phenylephrine in patients with AS and CS, addressing a key gap in evidence-based resuscitation strategies. Methods We performed a retrospective cohort analysis using the TriNetX Research Network, encompassing data from 112 healthcare organizations. Adult patients (≥18 years) diagnosed with AS (ICD-10 codes I35.0, I35.2, I06.0, I06.2) and CS (ICD-10: R57.0) who received either norepinephrine (n = 865) or phenylephrine (n = 218) within 24 hours of diagnosis were included. To minimize confounding, 1:1 propensity score matching was conducted based on demographics, comorbidities, procedures, medications, vital signs, laboratory values, genomics, and ejection fraction 40%, resulting in 201 matched patients per group. The primary outcome was all-cause mortality, assessed through risk analysis and Kaplan-Meier survival curves. Results After propensity-matching, analysis revealed a significantly higher mortality rate in the norepinephrine group compared to phenylephrine (50.746% vs. 37.811%; risk difference 12.935% (95% CI: 3.307-22.564%, p = 0.009). The risk ratio was 1.342 (95% CI: 1.073-1.678), and the odds ratio was 1.695 (95% CI: 1.139-2.521). Mean follow-up duration was 479 days for norepinephrine and 699 days for phenylephrine. Kaplan-Meier analysis demonstrated a significantly lower survival probability in the norepinephrine group (31.81% vs. 33.87%; log-rank p = 0.0013), with a hazard ratio of 1.622 (95% CI: 1.204-2.185). Conclusion In patients with AS complicated by CS, phenylephrine was associated with a significantly lower mortality risk compared to norepinephrine, potentially due to its distinct pharmacodynamic profile. As a pure alpha-1 agonist, phenylephrine increases systemic vascular resistance and diastolic pressure, thereby enhancing coronary perfusion without increasing myocardial oxygen demand. Reflex bradycardia associated with phenylephrine may also be beneficial in AS, where excessive tachycardia reduces diastolic filling time and exacerbates ischemia. While observational in nature, this study highlights an important clinical consideration and underscores the need for prospective trials to validate these results and elucidate the underlying mechanisms. Optimizing vasopressor selection could be pivotal in improving outcomes in AS with CS. This abstract is funded by: None
Maheshwari et al. (Fri,) conducted a cohort in Aortic stenosis complicated by cardiogenic shock (n=1,083). Norepinephrine vs. Phenylephrine was evaluated on All-cause mortality (HR 1.622, 95% CI 1.204-2.185, p=0.0013). Norepinephrine was associated with significantly higher all-cause mortality compared to phenylephrine in patients with aortic stenosis and cardiogenic shock (HR 1.622; 95% CI 1.204-2.185; p=0.0013).