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- Title
Renin and Survival in Patients Given Angiotensin II for Catecholamine-Resistant Vasodilatory Shock. A Clinical Trial.
- Authors
Bellomo, Rinaldo; Forni, Lui G.; Busse, Laurence W.; McCurdy, Michael T.; Ham, Kealy R.; Boldt, David W.; Hästbacka, Johanna; Khanna, Ashish K.; Albertson, Timothy E.; Tumlin, James; Storey, Kristine; Handisides, Damian; Tidmarsh, George F.; Chawla, Lakhmir S.; Ostermann, Marlies; ATHOS-3 Investigators
- Abstract
Rationale: Exogenous angiotensin II increases mean arterial pressure in patients with catecholamine-resistant vasodilatory shock (CRVS). We hypothesized that renin concentrations may identify patients most likely to benefit from such therapy.Objectives: To test the kinetic changes in renin concentrations and their prognostic value in patients with CRVS.Methods: We analyzed serum samples from patients enrolled in the ATHOS-3 (Angiotensin II for the Treatment of High-Output Shock) trial for renin, angiotensin I, and angiotensin II concentrations before the start of administration of angiotensin II or placebo and after 3 hours.Measurements and Main Results: Baseline serum renin concentration (normal range, 2.13-58.78 pg/ml) was above the upper limits of normal in 194 of 255 (76%) study patients with a median renin concentration of 172.7 pg/ml (interquartile range [IQR], 60.7 to 440.6 pg/ml), approximately threefold higher than the upper limit of normal. Renin concentrations correlated positively with angiotensin I/II ratios (r = 0.39; P < 0.001). At 3 hours after initiation of angiotensin II therapy, there was a 54.3% reduction (IQR, 37.9% to 66.5% reduction) in renin concentration compared with a 14.1% reduction (IQR, 37.6% reduction to 5.1% increase) with placebo (P < 0.0001). In patients with renin concentrations above the study population median, angiotensin II significantly reduced 28-day mortality to 28 of 55 (50.9%) patients compared with 51 of 73 patients (69.9%) treated with placebo (unstratified hazard ratio, 0.56; 95% confidence interval, 0.35 to 0.88; P = 0.012) (P = 0.048 for the interaction).Conclusions: The serum renin concentration is markedly elevated in CRVS and may identify patients for whom treatment with angiotensin II has a beneficial effect on clinical outcomes.Clinical trial registered with www.clinicaltrials.gov (NCT02338843).
- Subjects
CATECHOLAMINES; CLINICAL trials; ANGIOTENSIN II; MORTALITY; ALDOSTERONE; VASOCONSTRICTORS; RENIN; RESEARCH; PREDICTIVE tests; RESEARCH methodology; SHOCK (Pathology); EVALUATION research; MEDICAL cooperation; COMPARATIVE studies
- Publication
American Journal of Respiratory & Critical Care Medicine, 2020, Vol 202, Issue 9, p1253
- ISSN
1073-449X
- Publication type
journal article
- DOI
10.1164/rccm.201911-2172OC