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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 -
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 -
Pediatric Nephrology (Berlin, Germany) Dec 2016Diuretics have long been used for the treatment of hypertension. Thiazide diuretics are the most commonly prescribed diuretics for hypertension, but other classes of... (Review)
Review
Diuretics have long been used for the treatment of hypertension. Thiazide diuretics are the most commonly prescribed diuretics for hypertension, but other classes of diuretics may be useful in alternative circumstances. Although diuretics are no longer considered the preferred agent for treatment of hypertension in adults and children, they remain acceptable first-line options. Diuretics effectively decrease blood pressure in hypertensive patients, and in adults with hypertension reduce the risk of adverse cardiovascular outcomes. Because of varied pharmacokinetic and pharmacodynamic differences, chlorthalidone may be the preferred thiazide diuretic in the treatment of primary hypertension. Other types of diuretics (e.g., loop, potassium sparing) may be useful for the treatment of hypertension related to chronic kidney disease (CKD) and other varied conditions. Common side effects of thiazides are mostly dose-related and involve electrolyte and metabolic abnormalities.
Topics: Adolescent; Antihypertensive Agents; Child; Child, Preschool; Diuretics; Guidelines as Topic; Humans; Hypertension; Infant; Infant, Newborn; Thiazides
PubMed: 26983630
DOI: 10.1007/s00467-016-3334-4 -
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 -
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 -
Annals of Internal Medicine Mar 2018In November 2017, the American College of Cardiology (ACC) and the American Heart Association (AHA) released a clinical practice guideline for the prevention, detection,...
Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Synopsis of the 2017 American College of Cardiology/American Heart Association Hypertension Guideline.
DESCRIPTION
In November 2017, the American College of Cardiology (ACC) and the American Heart Association (AHA) released a clinical practice guideline for the prevention, detection, evaluation, and treatment of high blood pressure (BP) in adults. This article summarizes the major recommendations.
METHODS
In 2014, the ACC and the AHA appointed a multidisciplinary committee to update previous reports of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The committee reviewed literature and commissioned systematic reviews and meta-analyses on out-of-office BP monitoring, the optimal target for BP lowering, the comparative benefits and harms of different classes of antihypertensive agents, and the comparative benefits and harms of initiating therapy with a single antihypertensive agent or a combination of 2 agents.
RECOMMENDATIONS
This article summarizes key recommendations in the following areas: BP classification, BP measurement, screening for secondary hypertension, nonpharmacologic therapy, BP thresholds and cardiac risk estimation to guide drug treatment, treatment goals (general and for patients with diabetes mellitus, chronic kidney disease, and advanced age), choice of initial drug therapy, resistant hypertension, and strategies to improve hypertension control.
Topics: Adult; Antihypertensive Agents; Blood Pressure Determination; Comorbidity; Humans; Hypertension; Mass Screening; Secondary Prevention
PubMed: 29357392
DOI: 10.7326/M17-3203 -
The Medical Letter on Drugs and... May 2020
Topics: Antihypertensive Agents; Blood Pressure; Humans; Hypertension
PubMed: 32555118
DOI: No ID Found -
Advances in Experimental Medicine and... 2020Hypertension is still the number one global killer. No matter what causes are, lowering blood pressure can significantly reduce cardiovascular complications,... (Review)
Review
Hypertension is still the number one global killer. No matter what causes are, lowering blood pressure can significantly reduce cardiovascular complications, cardiovascular death, and total death. Unfortunately, some hypertensive individuals simply do not know having hypertension. Some knew it but either not being treated or treated but blood pressure does not achieve goal. The reasons for inadequate control of blood pressure are many. One important reason is that we are not very familiar with antihypertensive agents and less attention has been paid to comorbidities, complications as well as the hypertension-modified target organ damage in patients with hypertension. The right antihypertensive drug was not given to the right hypertensive patients at right time. This reviewer studied comprehensively the literature, hopefully that the review will help improve antihypertensive drug selection and antihypertensive therapy.
Topics: Antihypertensive Agents; Blood Pressure; Humans; Hypertension
PubMed: 32246447
DOI: 10.1007/978-981-15-2517-9_6 -
Advances in Chronic Kidney Disease Sep 2021Cancer is one of the leading causes of death worldwide. With the introduction of newer chemotherapeutic agents, targeted therapies, and immunotherapy, the prognosis and... (Review)
Review
Cancer is one of the leading causes of death worldwide. With the introduction of newer chemotherapeutic agents, targeted therapies, and immunotherapy, the prognosis and survival of patients with cancer has remarkably improved. As a result, patients are living longer and experiencing long-term cardiovascular complications. Hypertension is an important risk factor for cardiovascular diseases. Patients with malignancy have multiple etiologies of hypertension development, worsening, or association. This is because of the complex interplay between cancer type, chemotherapeutic agent, patient age, antihypertensive agent, and preexisting comorbidities in the etiology and pathogenesis of hypertension. Management of hypertension in patients with cancer requires accurate blood pressure measurement and considering factors such as adjuvant therapy and cancer-related pain. There are no set guidelines for management of hypertension in this unique cohort, and the therapy should be individualized based on the treatment guidelines for the general population. Onco-hypertension is an emerging subspeciality and entails a multidisciplinary approach between oncology, primary care physicians, nephrology, and cardiology.
Topics: Antihypertensive Agents; Antineoplastic Agents; Cardiology; Humans; Hypertension; Medical Oncology; Neoplasms
PubMed: 35190114
DOI: 10.1053/j.ackd.2021.09.011