Hypotension is abnormally low blood pressure
. Blood pressure is the
force exerted by the blood to push against the arterial walls as the heart
pumps out the blood. When patients go into a state of shock, the blood pressure
drops down to a really low critical level such that the brain, kidneys and
other vital organs cannot receive enough blood flow to function properly.
‘The first synthetic human angiotensin II has been approved by the United States Food and Drug Administration for increasing blood pressure in patients with septic or other forms of distributive shock.’
"Shock, the inability to maintain blood
flow to vital tissues, can result in organ failure and death," said Norman
Stockbridge, M.D., Ph.D., director of the Division of Cardiovascular and Renal
Products in the FDA's Center for Drug Evaluation and Research. "There is a
need for treatment options for critically ill hypotensive patients who do not
adequately respond to available therapies."
Giapreza is a synthetic formulation of the naturally occurring human
peptide hormone angiotensin
II which is a part of
the renin-angiotensin-aldosterone system (RAAS) that causes vasoconstriction
and an increase in blood pressure.
Angiotensin II plays a variety of roles. It causes an
increase in blood pressure and an increase in effective circulating volume by
- Increasing sympathetic activity
- Increasing tubular reabsorption
of Na+ and Cl- in the kidneys and water retention, both on its own and through the release of
aldosterone by the adrenal cortex
- Binding to receptors that cause vasoconstriction
(constriction of blood vessels)
- Stimulating antidiuretic hormone or ADH
secretion that leads to increased water absorption in
the renal collecting ducts
Study - ATHOS-3 Trial
The clinical trial
involved 321 patients
with vasodilatory shock and a critically low blood pressure. Giapreza effectively and
significantly raised the blood pressure in these patients who did not respond to high
doses of a conventional
vasopressor (more than 0.2g/kg per minute of a catecholamine like norepinephrine
or a comparable dose of another vasopressor).
During the first 3 hours of
treatment, either dose of Giapreza or placebo were titrated to achieve a mean
arterial pressure (MAP) of ≥75 mm Hg while maintaining the doses of other
vasopressors. In the following 3 to 48 hours, Giapreza or placebo was titrated
to maintain a MAP between 65 and 70 mm Hg while reducing doses of other
The number of patients who achieved the acceptable blood pressure (measured
as MAP) after 3 hours was more among those treated with angiotensin II (70%) when compared to those treated
with placebo (23%).
A MAP of 75 mm Hg or higher
or an increase in MAP
of at least 10 mm Hg from baseline without an increase in background
vasopressor dose indicated an
acceptable blood pressure.
Also, patients receiving Giapreza required lower doses
of other vasopressors.
Giapreza can cause dangerous blood clots with serious consequences (clots in
arteries and veins, including deep venous thrombosis), it has been recommended that medications that
can treat blood clots be taken along with it.
occurs when there is an impaired distribution of blood flow to the smallest
blood vessels of
; this causes a reduced supply of oxygen levels in the blood that flows to the
body's tissues and organs. Septic shock the most common form of
distributive shock, is caused
by an infection
, most frequently by bacteria,
but viruses, fungi, and parasites. Shock results in fatally low blood pressures
and is a life-threatening condition. References:
- FDA approves drug to treat dangerously low blood pressure - (https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm590249.htm)
- FDA Approves Angiotensin-II for Septic Shock - (https://pulmccm.org/policy-ethics-education-review/fda-approves-angiotensin-ii-septic-shock/)
- Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med 2017; 377:419-430.
- La Jolla Pharmaceutical Company - GIAPREZA Update - (http://lajollapharmaceutical.com/wp-content/uploads/2017/12/La-Jolla-Pharmaceutical-Company-GIAPREZA-Update-December-2017.pdf)