Giapreza, the brand name for synthetic angiotensin II, is used in the management of severe hypotension. It acts on the body's natural renin-angiotensin-aldosterone system (RAAS) to restore vascular tone. Its use is reserved for the most critically ill adults who do not respond to standard treatments.
The specific conditions Giapreza treats
Giapreza is approved by the U.S. Food and Drug Administration (FDA) to increase blood pressure in adults with septic or other distributive shock. This is a life-threatening condition where profound vasodilation leads to critically low blood pressure despite adequate fluid resuscitation. Giapreza is indicated for refractory hypotension, meaning low blood pressure that persists despite other vasopressor therapies.
How does Giapreza restore blood pressure?
Giapreza mimics the body's natural vasoconstrictor, angiotensin II.
- Vascular smooth muscle contraction: It binds to angiotensin II receptor type 1 on vascular smooth muscle cells, causing contraction and vasoconstriction. This raises systemic vascular resistance and increases blood pressure.
- Aldosterone release: Giapreza also stimulates the release of aldosterone, which promotes sodium and water retention by the kidneys, increasing blood volume and contributing to higher blood pressure.
- Rapid onset of action: Patients often achieve their target mean arterial pressure (MAP) within a median of 5 minutes.
Giapreza versus conventional vasopressors
Giapreza provides an alternative mechanism compared to traditional vasopressors. The table below compares Giapreza to other common vasopressors.
| Feature | Giapreza (Angiotensin II) | Norepinephrine (Levophed) | Vasopressin | Epinephrine (Adrenalin) |
|---|---|---|---|---|
| Mechanism of Action | Mimics endogenous angiotensin II, stimulating RAAS and AT1 receptors to cause vasoconstriction. | Primarily targets alpha-adrenergic receptors, causing vasoconstriction, with some beta-1 effects. | Acts on V1 receptors to cause vasoconstriction and increase water retention via V2 receptors. | Targets alpha- and beta-adrenergic receptors, leading to vasoconstriction and increased heart rate. |
| Indication | Refractory septic or distributive shock. | First-line agent for septic shock. | Adjunctive therapy for septic shock. | Adjunctive therapy for septic shock. |
| Onset | Rapid (median 5 minutes to target MAP). | Rapid. | Slower compared to catecholamines. | Rapid. |
| Common Side Effects | Thromboembolic events (including DVT), thrombocytopenia, tachycardia, fungal infection, delirium. | Tachycardia, arrhythmia, peripheral ischemia, hyperglycemia. | Arrhythmia, peripheral ischemia, water retention. | Tachycardia, arrhythmia, anxiety, hypertension. |
Important safety considerations and adverse effects
Giapreza is associated with an increased risk of blood clots. In the ATHOS-3 trial, there was a higher incidence of arterial and venous thrombotic events in patients receiving Giapreza. Concurrent venous thromboembolism (VTE) prophylaxis is strongly recommended.
Other common adverse reactions included:
- Thrombocytopenia
- Tachycardia
- Fungal infection
- Delirium
Patients require careful monitoring for side effects and continuous dose titration.
The clinical role of Giapreza
Giapreza is important for patients unresponsive to initial vasopressor therapy. Before its approval, options for refractory shock were limited. It provides an alternative mechanism to restore vascular tone.
Due to potential side effects and cost, Giapreza is not a first-line agent. It is used in intensive care units under expert supervision. It is typically added to standard vasopressor regimens. Its mechanism can sometimes reduce the required doses of other vasopressors. Further information on the ATHOS-3 study is available on PubMed Central: https://pmc.ncbi.nlm.nih.gov/articles/PMC6205124/.
Conclusion
Giapreza treats refractory hypotension in critically ill adults with septic or other distributive shock. It is a potent vasoconstrictor mimicking angiotensin II, used when conventional vasopressors fail. While life-saving, vigilance for adverse effects, especially blood clots, is necessary. It is typically an add-on therapy in intensive care for severe shock.
