Systemic hypertension is defined as persistent elevation of systolic blood pressure greater than 130 mm Hg or diastolic pressure greater than 80 mm Hg [1]. It is associated with 12.8% of all deaths globally [2]. Almost 9.4 million deaths worldwide every year are due to complications of hypertension [3]. Developing countries make up four-fifths of the earth’s population. Communicable diseases have always been the prime cause of death. Still, now times have changed, and noncommunicable diseases like cardiac diseases have proven to be more dangerous and challenging to treat [4]. Because of the variety of affordable treatment options and widespread diagnosis in nearly all high-income countries, a substantial reduction in the number of people with hypertension is observed – and this has led to fewer deaths from heart diseases. For example, in the WHO region of the USA, the prevalence of hypertension was 18% in 2014, compared with 31% in the 1980s. In contrast, low-income countries have the highest rates of hypertension. An estimate shows that more than 30% of the adult population in many counties in the WHO African region have hypertension, and this proportion keeps on rising. The global average rate is much lower than this region [3].
Zilebesiran, a short double-stranded siRNA, covalently bonded to n-acetylgalactosamine, designed to target the liver at asialoglycoprotein receptor, is the latest potential treatment option for mild-to-moderate hypertension. It reduces the production of angiotensinogen, lowering blood pressure [5]. As siRNA is negatively charged and easily degraded, it is first conjugated to n-acetylgalactosamine [6, 7]. In this way, siRNA is delivered to the target organ and does not silence the extrahepatic AGT gene expression in the kidneys, heart, brain, etc [8].
KARDIA-1 (“A Randomized, Double-blind, Placebo-Controlled, Dose-Ranging Multicenter Study to Evaluate the Efficacy and Safety of ALN-AGT01 in Patients with Mild-to-Moderate Hypertension”) demonstrates the efficacy of zilebesiran, a subcutaneously administered siRNA, as a potential option for treatment of this silent killer disease. KARDIA-2 (“A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Zilebesiran Used as Add-on Therapy in Patients with Hypertension not Adequately Controlled by a Standard of Care Antihypertensive Medication”) is currently under process and seeks to compare the efficacy when combined with typical hypertensives [9, 10].
The National Diabetes Survey of Pakistan (NDSP) 2016–17 concluded a 46.2% prevalence of hypertension among the Pakistani population, which is well above the global average [4, 11]. Phase I trials suggest that zilebesiran subcutaneous injection is safe. Mild injection site reactions and headaches were the only common adverse effects. No hospitalization or medical intervention was needed when dealing with adverse effects [12]. Promising introductions like zilebesiran can prove to be life-altering treatment options in future clinical care, especially in patients who failed or have contractions for conventional therapy options. There is a need for further studies, such as the pending phase II clinical trials, to assess the ideal dose before prescribing it for public use.
Conflict of Interest Statement
The authors have no conflicts of interest to declare.
Funding Sources
This study was not supported by any sponsor or funder.
Author Contributions
M.S.B.F. contributed to conceptualization, validation, resources, writing – original draft, writing – review and editing, supervision and project administration.
