A new chapter opens in the treatment of hypertension with the discovery of a new therapeutic pathway, the inhibition of aminopeptidases-A and a new site of action, the brain.
In high blood pressure, there are still many expectations regarding treatment. It is a disease that affects one in 3 French, but only one patient out of 2 would be objectives. This insufficiency of treatment is related either to the high blood pressure figures, or to the associated risk factors which make the objectives more strict and more difficult to reach, or to certain populations of patients such as the obese, the populations of black-African origin who have different voltage regulation mechanisms.
These 3 categories define "hard to treat HTAs" with currently available medications. Because of the importance of the number of metabolic mechanisms involved during hypertension, it is necessary to have drugs targeting other routes than those currently targeted in therapy.
A new therapeutic path
The firibastat is a new original molecule in hypertension, as it acts with a mechanism and a site of action quite original. It is indeed the first inhibitor of aminopeptidase-A and it acts only in the brain and not on peripheral organs like most other antihypertensives.
By inhibiting aminopeptidases-A, fibastat will block the transformation of angiotensin II to angiotensin III in the brain. All of 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 phase II study that was presented at the American Cardiovascular Congress, the AHA, in Chicago. It was performed on 218 hypertensive patients with a significantly high systolic blood pressure, ranging between 145 and 170 mmHg and diastolic less than 105 mmHg.
It concerns patients at risk, more difficult to treat, since a quarter of the patients are over 65, 44% are women and 63% are obese, with a BMI between 25 and 45 (mean BMI = 33).
Three-quarters of them had already received treatment. Finally, it included almost half of black or Hispanic patients, who are often difficult to treat and rarely recruited in standard studies.
Reduction of blood pressure regardless of the group
At 8 weeks, automated systolic blood pressure decreased by 9.7 mmHg (p <0.0001) and diastolic by 4.3 mmHg (p <0.0001) compared to baseline values. This drop in pressure is obtained on the automated measurement of blood pressure, the predictive measure of blood pressure on the arteries and the most difficult criterion to reach, but the most interesting criterion for patients.
The drop in blood pressure is consistent across all subgroups of patients, including black and obese patients. Tolerance is good with side effects mainly to headache type (4%) and cutaneous reactions (3%). There is no significant change in potassium levels in the blood
The New-Hope study opens a new chapter in the treatment of high blood pressure with the blocking of a new mechanism of hypertension, so far never targeted, and this study shows that blocking it can significantly reduce the incidence of hypertension. blood pressure in patients who are difficult to treat.
Interview with Prof. Keith Ferdinand (New Orleans, USA)