Novel Vasopressors in the Treatment of Vasodilatory Shock: A Systematic Review of Angiotensin II, Selepressin, and Terlipressin

Abstract

Study Objective: Vasodilatory shock is the most common type of shock. Catecholamine vasopressors are the cornerstone of hemodynamic therapy but carry risks. Angiotensin II (AT2) was recently approved, and other novel agents (selepressin and terlipressin) are under investigation and used outside the United States (terlipressin). We performed a systematic review to summarize the efficacy and safety of these novel vasopressors and to offer guidance on their appropriate use. Design: Systematic review of controlled trials. Methods: Numerous databases were searched using terms related to angiotensin II, selepressin, terlipressin, vasopressor, and shock. Twenty-one citations, including 16 prospective comparative trials and 5 post hoc analyses reporting effects of AT2, selepressin, and terlipressin, were reviewed for data on outcomes related to hemodynamic measures, mortality, severity and duration of illness, concomitant vasopressor utilization, and adverse effects. Findings from eligible literature are described qualitatively using Cochrane methods. Results: Fourteen controlled trials were assessed after exclusion of 2 dated trials of a distinct AT2 formulation. Trials are limited for AT2 (n = 2) and selepressin (n = 1), while terlipressin was investigated in 11 small trials. Overall, the trials have an unclear risk of bias. Most report mean arterial pressure (MAP) as primary end point, and all indicate novel vasopressors increase MAP compared to placebo and to a similar degree as with catecholamine vasopressors. Mortality findings are preliminary, as they have been limited to specific subgroups in trials of terlipressin and post hoc analyses of one trial of AT2. Trials reported safety concerns for each agent including thromboembolism with AT2 and ischemia with terlipressin/selepressin. Conclusion: In this systematic review, controlled trials of novel vasopressors in treatment of vasodilatory shock were limited and of low quality. Angiotensin II, selepressin, and terlipressin appear to significantly increase MAP, but further study is required, particularly for selepressin, to determine their safety, efficacy, and role in treatment of vasodilatory shock.

Advances in therapeutic peptides targeting G protein-coupled receptors

“…For others, peptides lacked efficacy against established targets. Terlipressin has been used in the treatment of hypotension and septic shock ( phase IIB/III clinical trial of selepressin, which targets the same receptors, in sepsis 43 was terminated early for futility 44 .…”

Angiotensin II in Decompensated Cirrhosis Complicated by Septic Shock

“…[19][20][21] However, high doses of vasoconstrictors are associated with detrimental side effects, such as atrial fibrillation, cardiac ischemia, and mesenteric ischemia, and have been associated with increased mortality. [22][23][24][25] These vasopressors only target the sympathetic and arginine-vasopressin systems and do not have any activity on the RAAS. Vasopressor agents targeting the RAAS have been unavailable to clinicians for the past 20 years, but with the approval of Ang-2 by the Food and Drug Administration (FDA) in 2017, and now the European Medicines Agency in 2019, clinicians can now simultaneously target all 3 systems during septic shock.…”

Angiotensinogen Suppression: A New Tool to Treat Cardiovascular and Renal Disease

“…16,17 Sepsis is an acute and deadly health condition that triggers complex inflammatory responses. Ang II is used for vasodilatory septic shock, 74 whereas ARBs may benefit septic patients with high arterial pressure. 75 Recently, Rong et al 76 reported that inhibiting liver-derived AGT improves sepsis-induced myocardial dysfunction.…”