对轻度至中度高血压的RNA干扰:KARDIA-1随机临床试验
George L Bakris1, Manish Saxena2,3, Anil Gupta4
1University of Chicago Medicine, Chicago, Illinois.
JAMA
|February 16, 2024
概括
一种RNA干扰疗法Zilebesiran通过向血管激素显著降低了患有高血压的成年人的血压. 每三到六个月服用一次,证明了疗效和可控的安全性.
科学领域:
- 心血管医学
- 药理学
- 遗传学
背景情况:
- 氨酸 - 氨酸 - 氨酸系统调节血压 (BP),其中氨酸素是主要的前体.
- 齐勒贝西兰是一种正在研究中的RNA干扰疗法,旨在降低肝脏血管激素合成.
研究的目的:
- 在轻度至中度高血压的成年人中评估各种zilebesiran剂型的抗高血压疗效和安全性.
主要方法:
- 这是一项2期随机双盲剂量调整研究,涉及394名高血压成年人.
- 参与者接受皮下注射 (150,300或600毫克每6个月;或300毫克每3个月) 或安慰剂6个月.
- 主要终点是3个月后24小时平均门诊静脉血压 (SBP) 的变化.
主要成果:
- 在所有测试剂量和间隔的3个月内,与安慰剂相比,Zilebesiran显著降低了SBP (例如,每3个月或每6个月服用300 mg时降低-16. 7 mm Hg).
- 与安慰剂相比 (60. 9%) 的不良事件更频繁,但严重的不良事件与安慰剂相比 (3. 6%) 的不良事件更少.
- 不严重的与药物相关的不良反应包括注射部位反应和轻度高血症.
结论:
- 在患有轻度至中度高血压的成年人中,Zilebesiran 显示出显著的抗高血压功效.
- 这种疗法可用于不频繁 (每3个月或6个月一次) 的治疗,安全性概率较好.
相关概念视频
01:25Antihypertensive Drugs: Direct Renin Inhibitors
629
The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
629
01:15Antihypertensive Drugs: Thiazide-Class Diuretics
635
Thiazide diuretics are sulfonamide derivatives featuring a benzothiadiazine ring system in their molecular structure. Based on this structure, thiazide diuretics can be categorized into two groups: thiazide-type and thiazide-like diuretics. Thiazide-type diuretics, including hydrochlorothiazide and chlorothiazide, consist of a benzothiadiazine backbone with an attached sulfonamide group. Thiazide-like diuretics, such as chlorthalidone and indapamide, lack the thiazide ring but demonstrate...
635
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
638
Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
638
01:30Antihypertensive Drugs: Angiotensin II Receptor Blockers
731
In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
731
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
431
The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
431
01:28Antihypertensive Drugs: Potassium-Sparing Diuretics
554
Liddle syndrome is a genetically inherited form of hypertension characterized by the overactivity of epithelial sodium channels in the nephron, the functional unit of the kidney. This heightened activity leads to increased sodium reabsorption and excessive excretion of potassium. To counteract this, potassium-sparing diuretics such as amiloride are used. They function by blocking these sodium channels, thereby reducing the influx of sodium into the epithelial cells and minimizing the loss of...
554