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The New England Journal of Medicine Jul 2023Angiotensinogen is the sole precursor of angiotensin peptides and has a key role in the pathogenesis of hypertension. Zilebesiran, an investigational RNA interference... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Angiotensinogen is the sole precursor of angiotensin peptides and has a key role in the pathogenesis of hypertension. Zilebesiran, an investigational RNA interference therapeutic agent with a prolonged duration of action, inhibits hepatic angiotensinogen synthesis.
METHODS
In this phase 1 study, patients with hypertension were randomly assigned in a 2:1 ratio to receive either a single ascending subcutaneous dose of zilebesiran (10, 25, 50, 100, 200, 400, or 800 mg) or placebo and were followed for 24 weeks (Part A). Part B assessed the effect of the 800-mg dose of zilebesiran on blood pressure under low- or high-salt diet conditions, and Part E the effect of that dose when coadministered with irbesartan. End points included safety, pharmacokinetic and pharmacodynamic characteristics, and the change from baseline in systolic and diastolic blood pressure, as measured by 24-hour ambulatory blood-pressure monitoring.
RESULTS
Of 107 patients enrolled, 5 had mild, transient injection-site reactions. There were no reports of hypotension, hyperkalemia, or worsening of renal function resulting in medical intervention. In Part A, patients receiving zilebesiran had decreases in serum angiotensinogen levels that were correlated with the administered dose (r = -0.56 at week 8; 95% confidence interval, -0.69 to -0.39). Single doses of zilebesiran (≥200 mg) were associated with decreases in systolic blood pressure (>10 mm Hg) and diastolic blood pressure (>5 mm Hg) by week 8; these changes were consistent throughout the diurnal cycle and were sustained at 24 weeks. Results from Parts B and E were consistent with attenuation of the effect on blood pressure by a high-salt diet and with an augmented effect through coadministration with irbesartan, respectively.
CONCLUSIONS
Dose-dependent decreases in serum angiotensinogen levels and 24-hour ambulatory blood pressure were sustained for up to 24 weeks after a single subcutaneous dose of zilebesiran of 200 mg or more; mild injection-site reactions were observed. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov number, NCT03934307; EudraCT number, 2019-000129-39.).
Topics: Humans; Angiotensinogen; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Double-Blind Method; Hypertension; Irbesartan; RNA Interference; Tetrazoles; Diet; Injections, Subcutaneous
PubMed: 37467498
DOI: 10.1056/NEJMoa2208391 -
Drug Design, Development and Therapy 2019Minoxidil was first introduced as an antihypertensive medication and the discovery of its common adverse event, hypertrichosis, led to the development of a topical... (Review)
Review
Minoxidil was first introduced as an antihypertensive medication and the discovery of its common adverse event, hypertrichosis, led to the development of a topical formulation for promoting hair growth. To date, topical minoxidil is the mainstay treatment for androgenetic alopecia and is used as an off-label treatment for other hair loss conditions. Despite its widespread application, the exact mechanism of action of minoxidil is still not fully understood. In this article, we aim to review and update current information on the pharmacology, mechanism of action, clinical efficacy, and adverse events of topical minoxidil.
Topics: Animals; Antihypertensive Agents; Hair; Humans; Hypertrichosis; Minoxidil; Molecular Structure; Sulfotransferases
PubMed: 31496654
DOI: 10.2147/DDDT.S214907 -
Cardiovascular & Hematological Agents... 2020Stevia rebaudiana of the Asteraceae family is a perennial shrub. It is a sweetener herb also known as sweet weed, sweet leaf, sweet herbs and honey leaf, native to... (Review)
Review
Stevia rebaudiana of the Asteraceae family is a perennial shrub. It is a sweetener herb also known as sweet weed, sweet leaf, sweet herbs and honey leaf, native to Argentina, Brazil and Paraguay. The leaves of stevia are sweeter than sucrose with zero calories. Steviol, a diterpenoid glycoside derivative identified from this plant, is sweeter than sucrose and is safe when used as a sweetening agent. Diabetic and obese people with hyperglycemia who are in a condition to follow a strict diet can use stevioside as an alternative sweetener. In addition to its hypoglycemic property, the plant also exhibits antibacterial, anti-inflammatory, hypotensive, antiseptic, diuretic, anti-fertility and cardiotonic properties. It has also been documented to show good effects on treating skin diseases such as dermatitis, acne, eczema etc. The leaves of stevia with enriched phytoconstituents could be an alternative natural sweetener for children, adults and old age persons who have a craze to drink beverages and eat sweetened food products in their habitual life.
Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antihypertensive Agents; Biological Products; Glycosides; Humans; Hypoglycemic Agents; Stevia; Sweetening Agents
PubMed: 32031079
DOI: 10.2174/1871525718666200207105436 -
Lancet (London, England) Jul 2021Arterial hypertension is the most important contributor to the global burden of disease; however, disease control remains poor. Although the diagnosis of hypertension is... (Review)
Review
Arterial hypertension is the most important contributor to the global burden of disease; however, disease control remains poor. Although the diagnosis of hypertension is still based on office blood pressure, confirmation with out-of-office blood pressure measurements (ie, ambulatory or home monitoring) is strongly recommended. The definition of hypertension differs throughout various guidelines, but the indications for antihypertensive therapy are relatively similar. Lifestyle adaptation is absolutely key in non-pharmacological treatment. Pharmacologically, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, calcium channel blockers, and diuretics are the first-line agents, with advice for the use of single-pill combination therapy by most guidelines. As a fourth-line agent, spironolactone should be considered. The rapidly evolving field of device-based therapy, especially renal denervation, will further broaden therapeutic options. Despite being a largely controllable condition, the actual rates of awareness, treatment, and control of hypertension are disappointingly low. Further improvements throughout the process of patient screening, diagnosis, treatment, and follow-up need to be urgently addressed.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Diuretics; Humans; Hypertension; Life Style
PubMed: 34019821
DOI: 10.1016/S0140-6736(21)00221-X -
Critical Care Clinics Apr 2022Hypertensive crisis, especially in children, is a rare condition and is defined as a sudden and abrupt elevation in blood pressure that poses a threat of rapid onset of... (Review)
Review
Hypertensive crisis, especially in children, is a rare condition and is defined as a sudden and abrupt elevation in blood pressure that poses a threat of rapid onset of end-organ damage. Symptomatic hypertension requires urgent and thorough evaluation and management. In most patients with hypertensive crisis, a specific cause can be found with targeted investigation. History and physical examination will guide the assessment for cause and urgency of management. This article discusses common and rare causes of severe hypertension in infancy, childhood, and adulthood. Clinical features that indicate possible serious underlying disease associated with severe and symptomatic hypertension are outlined.
Topics: Adult; Antihypertensive Agents; Blood Pressure; Child; Emergencies; Humans; Hypertension; Risk Factors
PubMed: 35369952
DOI: 10.1016/j.ccc.2021.11.016 -
American Family Physician Mar 2020More than 70% of adults treated for primary hypertension will eventually require at least two antihypertensive agents, either initially as combination therapy or as... (Review)
Review
More than 70% of adults treated for primary hypertension will eventually require at least two antihypertensive agents, either initially as combination therapy or as add-on therapy if monotherapy and lifestyle modifications do not achieve adequate blood pressure control. Four main classes of medications are used in combination therapy for the treatment of hypertension: thiazide diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs). ACEIs and ARBs should not be used simultaneously. In black patients, at least one agent should be a thiazide diuretic or a calcium channel blocker. Patients with heart failure with reduced ejection fraction should be treated initially with a beta blocker and an ACEI or ARB (or an angiotensin receptor-neprilysin inhibitor), followed by add-on therapy with a mineralocorticoid receptor antagonist and a diuretic based on volume status. Treatment for patients with chronic kidney disease and proteinuria should include an ACEI or ARB plus a thiazide diuretic or a calcium channel blocker. Patients with diabetes mellitus should be treated similarly to those without diabetes unless proteinuria is present, in which case combination therapy should include an ACEI or ARB.
Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Drug Therapy, Combination; Humans; Hypertension
PubMed: 32163253
DOI: No ID Found -
Nephrology, Dialysis, Transplantation :... Nov 2023Hypertension is very common and remains often poorly controlled in patients with chronic kidney disease (CKD). Accurate blood pressure (BP) measurement is the essential... (Review)
Review
Hypertension is very common and remains often poorly controlled in patients with chronic kidney disease (CKD). Accurate blood pressure (BP) measurement is the essential first step in the diagnosis and management of hypertension. Dietary sodium restriction is often overlooked, but can improve BP control, especially among patients treated with an agent to block the renin-angiotensin system. In the presence of very high albuminuria, international guidelines consistently and strongly recommend the use of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker as the antihypertensive agent of first choice. Long-acting dihydropyridine calcium channel blockers and diuretics are reasonable second- and third-line therapeutic options. For patients with treatment-resistant hypertension, guidelines recommend the addition of spironolactone to the baseline antihypertensive regimen. However, the associated risk of hyperkalemia restricts the broad utilization of spironolactone in patients with moderate-to-advanced CKD. Evidence from the CLICK (Chlorthalidone in Chronic Kidney Disease) trial indicates that the thiazide-like diuretic chlorthalidone is effective and serves as an alternative therapeutic opportunity for patients with stage 4 CKD and uncontrolled hypertension, including those with treatment-resistant hypertension. Chlorthalidone can also mitigate the risk of hyperkalemia to enable the concomitant use of spironolactone, but this combination requires careful monitoring of BP and kidney function for the prevention of adverse events. Emerging agents, such as the non-steroidal mineralocorticoid receptor antagonist ocedurenone, dual endothelin receptor antagonist aprocitentan and the aldosterone synthase inhibitor baxdrostat offer novel targets and strategies to control BP better. Larger and longer term clinical trials are needed to demonstrate the safety and efficacy of these novel therapies in the future. In this article, we review the current standards of treatment and discuss novel developments in pathophysiology, diagnosis, outcome prediction and management of hypertension in patients with CKD.
Topics: Humans; Spironolactone; Hyperkalemia; Chlorthalidone; Hypertension; Antihypertensive Agents; Mineralocorticoid Receptor Antagonists; Renal Insufficiency, Chronic; Blood Pressure
PubMed: 37355779
DOI: 10.1093/ndt/gfad118 -
Cardiology Clinics May 2022Hypertension is possibly the most powerful, modifiable risk factor for the development of heart failure. Chronic hypertension drives cardiac remodeling within the left... (Review)
Review
Hypertension is possibly the most powerful, modifiable risk factor for the development of heart failure. Chronic hypertension drives cardiac remodeling within the left ventricle resulting in hypertensive heart disease, which ultimately manifests as heart failure. Early detection and appropriate management are necessary to prevent heart failure as well as other cardiovascular diseases. Achieving blood pressure goals in conjunction with using evidence-based treatments can improve clinical outcomes for patients with comorbid hypertension and heart failure.
Topics: Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Heart Failure; Humans; Hypertension
PubMed: 35465897
DOI: 10.1016/j.ccl.2021.12.011 -
Current Hypertension Reports Mar 2021Hypertension is remarkably prevalent, affecting an estimated 1.13 billion people worldwide. It often requires the use of multi-drug regimens and is commonly associated... (Review)
Review
PURPOSE OF REVIEW
Hypertension is remarkably prevalent, affecting an estimated 1.13 billion people worldwide. It often requires the use of multi-drug regimens and is commonly associated with a myriad of other comorbidities which increase medication use. The pervasive use of antihypertensive medications combined with the presence of polypharmacy in many hypertensive patients results in significant risk of drug interactions. This review will summarize the relevant literature to assist clinicians in mitigating drug interaction risks when prescribing antihypertensives.
RECENT FINDINGS
Pharmacokinetic interactions affect drug disposition in the body and can occur at the steps of absorption, distribution, metabolism, or elimination of involved medications. Data has established the calcium channel blockers, namely, diltiazem and verapamil, as potent inhibitors of CYP3A4, and the majority of significant drug interactions involving antihypertensives are attributable to these two agents. Although less common, pharmacokinetic drug interactions with other antihypertensive classes have also been identified. Pharmacodynamic drug interactions with antihypertensives lead to synergy or antagonism of blood pressure lowering effects and can increase or mitigate adverse effects depending on the agents involved. Knowledge is emerging about drug-induced phenoconversion, a phenomenon whereby a drug interaction results in a drug metabolizing phenotype that is different than that predicted by an individual's genotype. Antihypertensive use in patients with comorbidities and polypharmacy increases the likelihood of encountering important drug-drug interactions. Dedicated efforts to better understand the relationship between pharmacokinetic drug interactions and pharmacogenomic information is important to advance efforts related to personalized medicine.
Topics: Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Drug Interactions; Humans; Hypertension
PubMed: 33666764
DOI: 10.1007/s11906-021-01131-y -
The Medical Letter on Drugs and... May 2020
Topics: Antihypertensive Agents; Blood Pressure; Humans; Hypertension
PubMed: 32555118
DOI: No ID Found