A new chapter is opening in the treatment of arterial hypertension with the discovery of a new therapeutic pathway, the inhibition of aminopeptidases-A and a new site of action, the brain.
In arterial hypertension, there are still many expectations regarding treatment. It is a disease that would affect one French person in 3, but only one patient in 2 would be on target. This lack of treatment is linked either to the high blood pressure figures, or to the associated risk factors which make the objectives stricter and more difficult to achieve, or to certain populations of patients such as the obese, the populations of black-African origin who have different mechanisms of blood pressure regulation.
These 3 categories define “HTA difficult to treat” with currently available drugs. Due to the importance of the number of metabolic mechanisms concerned during hypertension, it is necessary to have drugs targeting pathways other than those currently targeted in therapy.
A new therapeutic route
Firibastat is a new and original molecule in hypertension, insofar as it acts with a completely original mechanism and site of action. It is, in fact, the first inhibitor of aminopeptidases-A and it acts only in the brain and not on the peripheral organs like most other anti-hypertensives.
By inhibiting aminopeptidases-A, fibastat will block the transformation of angiotensin II into angiotensin III in the brain. All this leads to a reduction in vasopressin release and sympathetic activity, as well as an improvement in the baroreflex response.
An original study
New-Hope is a study of phase II which was presented at the American congress of cardiology, the AHA, in Chicago. It was carried out on 218 hypertensive patients with a significantly high systolic blood pressure, since between 145 and 170 mm Hg and a diastolic lower than 105 mm Hg.
It concerns patients at risk, who are more difficult to treat, since a quarter of patients are over 65, 44% are women and 63% are obese, with a BMI of between 25 and 45 (average BMI = 33).
Three-quarters of them had already received treatment. Finally, it included nearly half of black or Hispanic patients, often difficult to treat and relatively little recruited in the usual studies.
Reduction in blood pressure regardless of group
At 8 weeks, automated systolic blood pressure fell by 9.7 mm Hg (p<0.0001) and diastolic by 4.3 mm Hg (p<0.0001) compared to the values measured at inclusion. This drop in pressure is obtained on the automated measurement of blood pressure, the predictive measurement of the tension load on the arteries and the most difficult criterion to achieve, but the most interesting criterion for patients.
The drop in blood pressure is consistent across all patient subgroups, including black and obese patients. Tolerance is good with side effects mainly of the headache type (4%) and skin reactions (3%). There is no significant change in blood potassium levels
The New-Hope study opens a new chapter in the treatment of arterial hypertension with the blocking of a new mechanism of hypertension, hitherto never targeted, and this study shows that blocking it makes it possible to significantly lower the blood pressure in difficult-to-treat patients.
Interview with Prof. Keith Ferdinand (New Orleans, USA)
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