Why GIAPREZA
Urgent and effective intervention is needed
Medical Need
Distributive shock can turn
into a fight for survival1
The longer hypotension persists, the higher the mortality risk1
Nearly 2/3 of ICU patients with distributive shock have low MAP (<65 mmHg) for ≥2 hours despite vasopressor support1
If low MAP persists for 0‑2 hours, mortality risk ranges from 22% to 31%1
If low MAP persists for 6‑8 hours, mortality risk ranges from 39% to 74%1
ICU=intensive care unit; MAP=mean arterial pressure.
Treating septic shock
comes at a great cost2
In the U.S., sepsis is the most expensive hospital-treated condition and may cost $41.5 billion a year3
- The cost of care for septic shock ranges from $31,704 to $68,671 per patient2
- The first day in the ICU may cost ~$25,000, with each subsequent day costing ~$14,0004
- Reducing mechanical ventilation or avoiding renal replacement therapy may save ~$15,000-$36,000 in total hospital charges4
Traditional vasopressors can be toxic at high doses and ineffective in some patients5,6
Catecholamines and vasopressin can cause cardiac toxicity and mortality at higher doses5,7
Mortality may reach 40%
at >0.2 mcg/kg/min of norepinephrine, and may
reach 90% at >1 mcg/kg/min8
Vasopressin may reduce
the need for high-dose catecholamines but less than 50% of patients respond to it6,9
The right catecholamine‑sparing agent may make the difference.
it’s time for RAAS
HARNESS THE POWER OF AN UNDERUTILIZED SYSTEM
The renin-angiotensin-aldosterone system (RAAS) is crucial for producing angiotensin II (ANG II), a naturally occurring peptide hormone that triggers vasoconstriction and increases blood pressure.10
Despite the crucial role of the RAAS pathway, standard-of-care vasopressors only target the vasopressin and adrenal systems.11-14
GIAPREZA is the first and only synthetic human ANG II treatment—the only RAAS regulator available to raise MAP in adults with septic or other distributive shock.14
QUICKLY REGULATE RAAS TO IMPROVE PATIENT SURVIVAl15
In patients with shock, the RAAS pathway may be disrupted by an ACE deficiency, leading to abnormally high ANG I/II ratios. This disruption can result in increased catecholamine use and can trap patients in a potentially fatal cycle.10,15
Slide image to view more
BREAK THE
DISRUPTIVE LOOP
GIAPREZA is a catecholamine-sparing agent that regulates RAAS to stabilize MAP in a median of 5 minutes.10,19
Patient Profiles
Identifying appropriate patients
When MAP drops, should you reach for GIAPREZA sooner?
Presents with bacterial pneumonia
Medical history: diabetes and hypertension
Admitted for: fever, cough, and dyspnea
Labs/Vitals:
Temperature: 102.7°F
White blood cell count: 18,000/mm3
Heart rate: 110 bpm
Blood pressure: 80/52 mmHg
Serum creatinine: 2.5 mg/dL
Blood urea nitrogen: 55 mg/dL
- 0 hrStarting MAP is 60 mmHg
Norepinephrine is initiated at 0.05 mcg/kg/min.
Michelle is also started on piperacillin‑tazobactam, vancomycin, and 3 L of IV fluid.
- 1 hrMAP drops to 58 mmHg
Vasopressin is initiated at 0.03 units/min.
- 2 hrsMAP drops to 54 mmHg
Norepinephrine is titrated up to 0.3 mcg/kg/min.
Vasopressin is titrated up to 0.06 units/min.
- 3 hrsMAP drops to 52 mmHg
In the ICU, if MAP drops <55 mmHg, mortality rate can be 31% and may rise to 74.6% if it persists for ≥6 h.1
Mortality may reach 40% at doses >0.2 mcg/kg/min of norepinephrine.8
Download a copy of Michelle's profile for future reference here
Connect with a GIAPREZA sales
representative for information and support.
References:
- Vincent JL, Nielsen ND, Shapiro NI, et al. Mean arterial pressure and mortality in patients with distributive shock: a retrospective analysis of the MIMIC-III database. Ann. Intensive Care. 2018;8(1):107. doi: 10.1186/s13613-018-0448-9
- Paoli CJ, Reynolds MA, Sinha M, et al. Epidemiology and Costs of Sepsis in the United States-An Analysis Based on Timing of Diagnosis and Severity Level. Crit Care Med. 2018;46(12):1889-1897. doi: 10.1097/CCM.0000000000003342
- McDermott KW, Roemer M. Most Frequent Principal Diagnoses for Inpatient Stays in U.S. Hospitals, 2018. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs; 2021. https://www.ncbi.nlm.nih.gov/books/NBK573113/. Accessed January 22, 2024.
- Self WH, Liu D, Strayer N, et al. Charge Reductions Associated With Shorter Time to Recovery in Septic Shock. Chest. 2019;155(2):315-321. doi: 10.1016/j.chest.2018.10.034
- Schmittinger CA, Torgersen C, Luckner G, et al. Adverse cardiac events during catecholamine vasopressor therapy: a prospective observational study. Intensive Care Med. 2012;38(6):950-8. doi: 10.1007/s00134-012-2531-2
- Sacha GL, Lam SW, Duggal A, et al. Predictors of response to fixed-dose vasopressin in adult patients with septic shock. Ann. Intensive Care. 2018;8(1):35. doi: 10.1186/s13613-018-0379-5
- Dünser MW, Mayr AJ, Tür A, et al. Ischemic skin lesions as a complication of continuous vasopressin infusion in catecholamine-resistant vasodilatory shock: incidence and risk factors. Crit Care Med. 2003;31(5):1394-8. doi: 10.1097/01.CCM.0000059722.94182.79
- Martin C, Medam S, Antonini F, et al. Norepinephrine: not too much, too long. Shock. 2015;44(4):305-9. doi: 10.1097/SHK.0000000000000426
- Reardon DP, DeGrado JR, Anger KE, et al. Early vasopressin reduces incidence of new onset arrhythmias. J Crit Care. 2014;29(4):482-5. doi: 10.1016/j.jcrc.2014.03.005
- Bellomo R, Forni LG, Busse LW, et al. Renin and Survival in Patients Given Angiotensin II for Catecholamine-Resistant Vasodilatory Shock. A Clinical Trial. Am J Respir Crit Care Med. 2020;202(9):1253-1261. doi: 10.1164/rccm.201911-2172OC
- Khanna A, English SW, Wang XS, et al. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med. 2017;377(5):419-430. doi: 10.1056/NEJMoa1704154
- Paravati S, Rosani A, Warrington SJ | Physiology, Catecholamines | StatPearls. Published 2022. https://www.ncbi.nlm.nih.gov/books/NBK507716/. Accessed January 22, 2024.
- Demiselle J, Fage N, Radermacher P, et al. Vasopressin and its analogues in shock states: a review. Ann. Intensive Care. 2020;10(1):9. doi: 10.1186/s13613-020-0628-2
- National Center for Biotechnology Information. PubChem Compound Summary for CID 172198, angiotensin II. https://pubchem.ncbi.nlm.nih.gov/compound/Angiotensin-II-human. Accessed January 22, 2024.
- Supplementary appendix to: Khanna A, English SW, Wang XS, et al. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med. 2017;377(5):419-430. doi: 10.1056/NEJMoa1704154
- Andrews L, Benken J, Benedetti E, et al. Effects of angiotensin II in the management of perioperative hypotension in kidney transplant recipients. Clin Transplant. 2022;36(9):e14754. doi: 10.1111/ctr.14754
- Fountain JH, Kaur J, Lappin SL. Physiology, Renin Angiotensin System. StatPearls Publishing; 2023. https://www.ncbi.nlm.nih.gov/books/NBK470410/. Accessed January 22, 2024.
- Wang Y, Seto SW, Golledge J. Angiotensin II, sympathetic nerve activity and chronic heart failure. Heart Fail Rev. 2014;19(2):187-98. doi: 10.1007/s10741-012-9368-1
- Buckley MS, Barletta JF, Smithburger PL, et al. Catecholamine Vasopressor Support Sparing Strategies in Vasodilatory Shock. Pharmacotherapy. 2019;39(3):382-398. doi: 10.1002/phar.2199
- Ristovic V, de Roock S, Mesana TG, et al. The Impact of Preoperative Risk on the Association between Hypotension and Mortality after Cardiac Surgery: An Observational Study. J Clin Med. 2020;9(7):2057. doi: 10.3390/jcm9072057
- Sun LY, Chung AM, Farkouh ME, et al. Defining an Intraoperative Hypotension Threshold in Association with Stroke in Cardiac Surgery. Anesthesiology. 2018;129(3):440-447. doi: 10.1097/ALN.0000000000002298
- Ngu JMC, Jabagi H, Chung AM, et al. Defining an Intraoperative Hypotension Threshold in Association with De Novo Renal Replacement Therapy after Cardiac Surgery. Anesthesiology. 2020;132(6):1447-1457. doi: 10.1097/ALN.0000000000003254
- Wieruszewski PM, Bellomo R, Busse LW, et al. Initiating angiotensin II at lower vasopressor doses in vasodilatory shock: an exploratory post‑hoc analysis of the ATHOS-3 clinical trial. Crit Care. 2023;27(1):175. doi: 10.1186/s13054-023-04446-1
Important Safety Information
Indication
GIAPREZA® (angiotensin II) increases blood pressure in adults with septic or other distributive shock.
Contraindications
None.
Warnings and Precautions
The safety of GIAPREZA was evaluated in 321 adults with septic or other distributive shock in a randomized, double-blind, placebo-controlled study, ATHOS-3. There was a higher incidence of arterial and venous thrombotic and thromboembolic events in patients who received GIAPREZA compared to placebo-treated patients in the ATHOS-3 study (13% vs. 5%). The major imbalance was in deep venous thromboses. Use concurrent venous thromboembolism (VTE) prophylaxis.
Adverse Reactions
The most common adverse reactions reported in greater than 10% of GIAPREZA-treated patients were thromboembolic events. Adverse reactions occurring in ≥4% of patients treated with GIAPREZA and ≥1.5% more often than placebo‑treated patients in the ATHOS-3 study were thromboembolic events (including deep vein thrombosis), thrombocytopenia, tachycardia, fungal infection, delirium, acidosis, hyperglycemia, and peripheral ischemia.
Drug Interactions
Angiotensin converting enzyme (ACE) inhibitors may increase response to GIAPREZA. Angiotensin II receptor blockers (ARBs) may reduce response to GIAPREZA.
You are encouraged to report negative side effects of prescription drugs to the FDA.
To report SUSPECTED ADVERSE REACTIONS, please contact:
Before administering, please see the Full Prescribing Information for GIAPREZA.