One Shot Solution for Hypertension?

In 2021, hypertension was a primary or contributing cause of 691,095 deaths in the United States. Nearly half of all American adults have hypertension (defined as a systolic blood pressure greater than 130 mmHg, a mean diastolic blood pressure greater than 80 mmHg, or taking medication for blood pressure control). Managing hypertension can involve taking multiple oral medications every day, which is inconvenient and can contribute to medication non-adherence.

The one-time dosing of Zilebesiran offers a potential solution to the challenges that come with obtaining and taking daily medications. Its single-shot approach targets daily pill fatigue, easing patients’ frustrations. Such innovations provide promise for improving patient compliance and enhancing overall blood pressure outcomes.

Key Study findings

A recent presentation at the American Heart Association’s Scientific Sessions 2023 revealed that a single injection of Zilebesiran safely and effectively lowered systolic blood pressure in adults with mild-to-moderate hypertension for up to six months. The study emphasized Zilebesiran’s ability to reduce systolic blood pressure by over 10 mm Hg on average, providing a novel approach to hypertension management.

Mechanism of Action

Zilebesiran, an investigational RNA interference agent, targets angiotensinogen (AGT), a protein predominantly produced in the liver that plays a crucial role in increasing blood pressure. The medication showed a remarkable 90% reduction in serum levels of AGT.

Clinical Significance

Lead study author George L. Bakris highlighted the importance of finding new treatments for sustained blood pressure control over longer periods. Uncontrolled hypertension remains a significant contributor to heart disease, which is the leading cause of death in the United States. Zilebesiran’s potential to improve medication adherence due to infrequent dosing could have a profound impact on reducing cardiovascular risk.

Study details

The KARDIA-1 trial, a placebo-controlled, randomized, double-blind study, included 394 participants with mild-to-moderate high blood pressure. Various doses of Zilebesiran were administered, and results demonstrated consistent reductions in both daytime and nighttime systolic blood pressure when compared to placebo. Adverse events were minimal, with mild reactions at the injection site being the most common.

Future prospects and Limitations

While the findings are promising, the study also has limitations. The population studied only includes patients with mild-to-moderate hypertension, thus neglecting patients with more severe forms of hypertension. Additionally, the study has a restricted time frame of only six months. Future research aims to assess Zilebesiran’s long-term safety and its impact on cardiovascular outcomes.

Conclusion

Zilebesiran’s breakthrough in lowering blood pressure with a single dose presents a paradigm shift in cardiovascular health management. The potential for infrequent dosing to enhance medication adherence and reduce cardiovascular risk marks a significant stride in the ongoing efforts to combat heart disease. As research progresses, the hope is that Zilebesiran can emerge as a transformative solution for individuals dealing with hypertension globally, offering a brighter future for cardiovascular health.

Written by Bhanu Ramachandran

Edited by Margaret Harris & Mallory Kane

References: 

1. Tsao, C., Aday, A., Almarzooq, C., et al. Heart Disease and Stroke Statistics - 2023 Update: A Report From the American Heart Association. AHA Journals. Jan 2023. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001123 

2. Single dose of Zilebesiran safely and effectively lowered blood pressure for six months. American Heart Association. Nov 2023. https://newsroom.heart.org/news/single-dose-of-zilebesiran-safely-and-effectively-lowered-blood-pressure-for-six-months 

3. Desai, A., Webb, D., Taubel J., et al. Zilebesiran, an RNA Interference Therapeutic Agent for Hypertension. The New England Journal of Medicine. N Engl J Med 2023; 389:228-238, DOI: 10.1056/NEJMoa2208391. https://www.nejm.org/doi/full/10.1056/NEJMoa2208391

4. Zilebesiran as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication (KARDIA-2) (KARDIA-2). ClinicalTrials.gov; U.S. National Library of Medicine. Dec 2023. https://classic.clinicaltrials.gov/ct2/show/record/NCT05103332?view=record