CHICAGO — Two novel medication confirmed promise for blood strain (BP) decreasing in individuals with treatment-resistant hypertension, in response to analysis introduced on the American Heart Association (AHA) annual assembly.
The first, twin endothelin receptor antagonist aprocitentan, acts by concentrating on the endothelin pathway implicated in hypertension. It lowered systolic BP after 4 weeks in the part III, placebo-controlled PRECISION trial of individuals with resistant hypertension that didn’t reply to traditional medicines, reported Markus Schlaich, MD, of University of Western Australia, Perth.
The second drug, baxdrostat, conferred BP reductions over placebo upon 12 weeks of therapy in the BrigHTN research. Baxdrostat lowers aldosterone manufacturing by blocking aldosterone synthase, and its part III program will start in 2023, in response to Mason Freeman, MD, of CinCor Pharma in Waltham, Massachusetts.
“These agents are exciting not because they lower pressure, but because their novel mechanisms may be better tolerated in many cases,” commented AHA session discussant Suzanne Oparil, MD, of University of Alabama at Birmingham.
Indeed, the principle treatment-emergent antagonistic occasions related to aprocitentan have been edema and fluid retention inside 30 days. These occasions have been manageable with addition or uptitration of diuretic remedy, indicating that enough diuretic remedy is essential, Schlaich mentioned.
As for baxdrostat, the largest security concern was any off-target results on cortisol, which didn’t floor in BrigHTN. Freeman acknowledged that longer-term follow-up will probably be wanted to evaluate the drug’s advantages and dangers, nevertheless.
Aprocitentan in PRECISION
PRECISION confirmed that 12.5 mg and 25 mg doses of aprocitentan considerably lowered imply trough sitting workplace systolic BP by 4 weeks, each beating placebo by roughly 5 mmHg.
Furthermore, aprocitentan customers withdrawn from remedy and positioned on placebo for 4 weeks noticed systolic BP rise again up considerably, in response to Schlaich.
“This study clearly shows that dual endothelin antagonism with aprocitentan may be a valuable new pharmacologic approach to resistant hypertension,” Oparil mentioned.
The part III trial included over 700 individuals with uncontrolled workplace BP regardless of being on three or extra antihypertensives. Eligibility standards included unattended sitting workplace systolic BP exceeding 140 mmHg, and members needed to endure durations of screening, standardized background remedy, and placebo use earlier than being randomized.
For the primary part of the research, members have been randomized to aprocitentan 12.5 mg (n=243) or 25 mg (n=243) or placebo (n=244) over 4 weeks, with customary remedy in the background for all three teams.
All individuals subsequently have been placed on 32 weeks of the upper dose of aprocitentan. At withdrawal of aprocitentan at week 36, they have been re-randomized to aprocitentan 25 mg or placebo in the third part of the research. Treatment ended at week 48, after which the 30-day security follow-up interval started.
The cohort averaged 52 years of age, and 60% have been males. BP on ambulatory monitoring was 138/83 mmHg at baseline.
PRECISION outcomes have been printed in The Lancet.
Baxdrostat in BrigHTN
Participants in BrigHTN who have been randomized to baxdrostat had vital reductions in imply seated systolic BP in 12 weeks, with the 2-mg dose decreasing it by 11 mmHg on common over placebo, Freeman reported at AHA.
This drug “seems to have a bright future in the area of resistant hypertension, particularly patients producing too much aldosterone,” Oparil commented.
The dose-ranging BrigHTN research included individuals who had seated blood pressures above 130/80 mmHg regardless of being on antihypertensives with a minimum of 70% adherence.
Investigators had 274 members randomized to placebo or three doses of baxdrostat after screening and run-in durations. Mean age was 62 years, and over half of the sufferers have been males. Baseline BP was 148/88 mmHg.
Baxdrostat’s aldosterone-lowering mechanism was corroborated by findings of lowered urinary aldosterone excretion and serum aldosterone. The drug elevated plasma renin exercise, Freeman added.
His group’s full report was printed in the New England Journal of Medicine.
Schlaich reported institutional grants and/or private charges from Medtronic, Abbot, ReCor Medical, Merck, Servier Laboratories; and serving as president of the High Blood Pressure Research Council of Australia and member of the International Society of Hypertension scientific committee.
Freeman is an worker of CinCor Pharma and receives stock-based compensation.
Oparil disclosed ties to Preventric Diagnostics, CinCor Pharma, Bayer, Idorsia Pharmaceuticals, and George Medicine Pty Limited.