Hemodynamics, fluids & transfusion
ACE inhibitors and angiotensin receptor blockers differentially alter the response to angiotensin II treatment in vasodilatory shock
Authors' conclusion
In vasodilatory shock patients, the cardiovascular and biological RAS response to angiotensin-II differed based upon prior exposure to ACEi and ARB medications. ACEi-exposure was associated with increased angiotensin II responsiveness, whereas ARB-exposure was associated with decreased responsiveness.
Study context
- Population
- Patients with vasodilatory shock in the ATHOS-3 trial
- Participants
- 321 patients
- Comparison
- Angiotensin-converting enzyme inhibitor (ACEi)/ARB-unexposed vs ACEi-exposed vs ARB-exposed
- ACEi/ARB-unexposedn = 270reference
- ACEi-exposedn = 29
- ARB-exposedn = 22
- Primary endpoint
- MAP after 1 h of treatment
- Follow-up
- 1 h
Methodological detailspost-hoc subgroup analysis, placebo-controlled
- Post-hoc subgroup analysis
- Placebo-controlled
Primary result
As reported in the abstract
Hour-1 MAP, angiotensin II vs placebo effect by subgroup
Difference, mmHg (95% CI)P value
Angiotensin II vs PlaceboACEi/ARB-unexposed
9.1(7.6–10.1)
P < 0.0001- ACEi-exposed vs ACEi/ARB-unexposed · similarly higher MAP
- difference in treatment-effect - 2.2 mmHg (95% CI - 7.0-2.6); P for interaction = 0.38
- ARB-exposed vs ACEi/ARB-unexposed · attenuated effect
- difference in treatment-effect - 6.0 mmHg (95% CI - 11.5 to - 0.6); P for interaction = 0.0299
Further findings
| Outcome | P value |
|---|---|
| Norepinephrine equivalent dose over 48 hAngiotensin II vs Placebo · lower in ACEi/ARB-unexposed | P = 0.0037 |
| Norepinephrine equivalent dose over 48 hACEi-exposed vs ACEi/ARB-unexposed · greater reduction | P for interaction = 0.0031 |
| Norepinephrine equivalent dose over 48 hARB-exposed vs ACEi/ARB-unexposed · attenuated effect | P for interaction < 0.0001 |
| Study-drug dose over 48 hAngiotensin II vs Placebo · lower in ACEi/ARB-unexposed | P < 0.0001 |
| Study-drug dose over 48 hACEi-exposed vs ACEi/ARB-unexposed · greater reduction | P for interaction < 0.0001 |
| Study-drug dose over 48 hARB-exposed vs ACEi/ARB-unexposed · attenuated effect | P for interaction = 0.0008 |
Baseline RAS biomarkers
- Baseline renin and angiotensin-I/angiotensin-II ratios highest in ACEi-exposed
Renin change · 3 h
- Angiotensin II reduced hour-3 renin in ACEi/ARB-unexposed and ACEi-exposed but not in ARB-exposed
Original publication
ACE inhibitors and angiotensin receptor blockers differentially alter the response to angiotensin II treatment in vasodilatory shock. Crit Care. Published 18 April 2024. doi:10.
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