‘Huge flurry of activity’ occurring in treatments for resistant hypertension
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LOUISVILLE, Ky. — Various potential treatments for patients with resistant hypertension should come on the market within the next few years, a speaker said during the American Society for Preventive Cardiology Congress on CVD Prevention.
“Things are going the wrong way” in terms of BP control in the U.S., Cardiology Today Editorial Board Member George L. Bakris, MD, FAHA, FASN, professor of medicine and director of the American Heart Association Comprehensive Hypertension Center at the University of Chicago Medicine, said during a presentation. “The trends are ... going in the wrong direction, and we are not paying attention to very simple things. We are not even paying attention to how to measure [BP] correctly, let alone improving control rates.”
However, he said, “There is about to be a huge flurry of activity over the next 5 to 7 years, specifically for resistant hypertension.”
Drug therapies
The AHA scientific statement on resistant hypertension calls for adding a mineralocorticoid receptor antagonist (MRA) such as spironolactone to patients whose BP is uncontrolled despite use of renin-angiotensin system blockers, calcium channel blockers and diuretics, but that is not simple to implement in practice because many patients with resistant hypertension have a low estimated glomerular filtration rate, and MRAs can cause hyperkalemia in that population, Bakris said.
“So, there are a number of agents being developed, and it’s important to keep in mind what could be coming soon,” he said.
Nonsteroidal MRAs “are very different in chemistry” from traditional MRAs such as spironolactone “and they don’t have anywhere near the side effects that the other agents do,” he said.
For example, ocedurenone (KBP Biosciences) “is a very effective agent with a very good pharmacological profile and a 56-hour half-life,” Bakris said.
In the BLOCK-CKD trial of patients with uncontrolled BP despite taking two to four agents and poor kidney function, ocedurenone lowered systolic BP by a placebo-subtracted 6.5 mm Hg and 10.9 mm Hg depending on dose compared with placebo at 84 days. Although some patients developed hyperkalemia, “there was really no difference between the low dose, the high dose and placebo,” he said. “Hyperkalemia was not a major reason for withdrawal from the trial.”
A phase 3 trial is underway, and the drug could be approved in the next 1 to 2 years, Bakris said.
Also coming soon is aprocitentan (Idorsia), a joint endothelin A/endothelin B receptor antagonist, which is being evaluated for treatment of resistant hypertension in the PRECISION trial, he said.
Firibastat (Quantum Genomics), a brain aminopeptidase A inhibitor that affects vasopressin, lowered BP over 8 weeks in a phase 2 trial, and appears to have a greater effect in Black patients, Bakris said.
IONIS-AGT-LRX (Ionis) is an antisense inhibitor of angiotensinogen in development that is administered by one injection every 6 months. “We’ve moved into the liver,” Bakris said, noting a small phase 2 study showed the agent was safe, was well tolerated, lowered angiotensinogen and in an exploratory outcome lowered BP. “We are cutting off the precursor of angiotensin II. This [development] is going to take longer, but it’s very interesting.”
Zilebesiran (Alnylam) is an RNA interference agent also targeting angiotensinogen, Bakris said. A phase 1 study showed it lowered systolic BP by 7 mm Hg to 9 mm Hg compared with placebo in patients already on triple therapy, he said.
Device therapies
There are also device therapies coming, most notably renal denervation, he said. “The reality is that renal denervation’s time has probably come,” Bakris said. “It is going to be evaluated by the FDA later this year or early next year. The [recent] data ... are consistent and compelling from a safety and efficacy standpoint.”
There is also baroreceptor activation, he said. “The notion is you are implanting something in the carotid [artery] and stretching the baroreceptors, and that causes precipitous falls in pressure,” he said. “I am still seeing patients that were in the trials, and they still have great blood pressure control, and they didn’t without it.
“There are at least four different classes of BP-lowering agents that are being developed, and I am confident that over the next 2 to 4 years, there is going to be a lot more in the armamentarium to use in these patients to get the pressure controlled with fewer side effects than what we have right now,” Bakris concluded.
References:
- Alnylam. investors.alnylam.com/press-release?id=26231. Published Nov. 13, 2021. Accessed Aug. 9, 2022.
- Bakris G, et al. Hypertension. 2020;doi:10.1161/HYPERTENSIONAHA.120.15199.
- Carey RM, et al. Hypertension. 2018;doi:10.1161/HYP.0000000000000084.
- Clinicaltrials.gov. clinicaltrials.gov/ct2/show/NCT03541174. Posted May 30, 2018. Accessed Aug. 9, 2022.
- Ferdinand KC, et al. Circulation. 2019;doi:10.1161/CIRCULATIONAHA.119.040070.
- Morgan ES, et al. JACC Basic Transl Sci. 2021;doi:10.1016/j.jacbts.2021.04.004.
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Bakris GL. Hypertension update. Presented at: American Society for Preventive Cardiology Congress on CVD Prevention; July 29-31, 2022; Louisville, Kentucky.
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