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Stroke and Vascular Neurology Oct 2022Current guidelines recommend blood pressure (BP) lowering in patients after acute intracerebral haemorrhage (ICH) without guidance on initial choice of antihypertensive... (Clinical Trial)
Clinical Trial
INTRODUCTION
Current guidelines recommend blood pressure (BP) lowering in patients after acute intracerebral haemorrhage (ICH) without guidance on initial choice of antihypertensive class. This study sought to determine if initial antihypertensive class differentially effects acute BP lowering in a large multiethnic ICH cohort.
METHODS
Subjects enrolled in the Ethnic/Racial Variations in ICH study between August 2010 and August 2017 with elevated admission BP and who received labetalol, nicardipine or hydralazine monotherapy as initial antihypertensive were analysed. Primary outcomes were systolic and diastolic BP changes from baseline to first BP measurement after initial antihypertensive treatment. Secondary outcomes included haematoma expansion (HE), hospital length of stay (LOS) and modified Rankin Score (mRS) up to 12 months after ICH. Exploratory outcomes assessed effects of race/ethnicity. Linear and logistic regression analyses, adjusted for relevant covariates, were performed to determine associations of antihypertensive class with outcomes.
RESULTS
In total, 1156 cases were used in analyses. Antihypertensive class was associated with diastolic BP change (p=0.003), but not systolic BP change (p=0.419). Initial dosing with nicardipine lowered acute diastolic BP than labetalol (least square mean difference (labetalol-nicardipine)=5.47 (2.37, 8.57), p<0.001). Initial antihypertensive class was also found to be associated with LOS (p=0.028), but not with HE (p=0.406), mortality (p=0.118), discharge disposition (p=0.083) or mRS score at discharge, 3, 6 and 12 months follow-up (p=0.262, 0.276, 0.152 and 0.36, respectively). Race/ethnicity variably affected multivariable models.
CONCLUSION
In this large acute ICH cohort, initial antihypertensive class was associated with acute diastolic, but not systolic, BP-lowering suggesting differential effects of antihypertensive agents.
TRIAL REGISTRATION NUMBER
NCT01202864.
Topics: Humans; Antihypertensive Agents; Blood Pressure; Cerebral Hemorrhage; Hydralazine; Hypertension; Labetalol; Nicardipine
PubMed: 35443984
DOI: 10.1136/svn-2021-001101 -
American Journal of Obstetrics and... Feb 2022Chronic hypertension complicates 1% to 2% of pregnancies, and it is increasingly common. Women with chronic hypertension are an easily recognized group who are in touch... (Review)
Review
Chronic hypertension complicates 1% to 2% of pregnancies, and it is increasingly common. Women with chronic hypertension are an easily recognized group who are in touch with a wide variety of healthcare providers before, during, and after pregnancy, mandating that chronic hypertension in pregnancy be within the scope of many practitioners. We reviewed recent data on management to inform current care and future research. This study is a narrative review of published literature. Compared with normotensive women, women with chronic hypertension are at an increased risk of maternal and perinatal complications. Women with chronic hypertension who wish to be involved in their care can do by measuring blood pressure at home. Accurate devices for home blood pressure monitoring are now readily available. The diagnostic criteria for superimposed preeclampsia remain problematic because most guidelines continue to include deteriorating blood pressure control in the definition. It has not been established how angiogenic markers may aid in confirmation of the diagnosis of superimposed preeclampsia when suspected, over and above information provided by routinely available clinical data and laboratory results. Although chronic hypertension is a strong risk factor for preeclampsia, and aspirin decreases preeclampsia risk, the effectiveness specifically among women with chronic hypertension has been questioned. It is unclear whether calcium has an independent effect in preeclampsia prevention in such women. Treating hypertension with antihypertensive therapy halves the risk of progression to severe hypertension, thrombocytopenia, and elevated liver enzymes, but a reduction in preeclampsia or serious maternal complications has not been observed; however, the lack of evidence for the latter is possibly owing to few events. In addition, treating chronic hypertension neither reduces nor increases fetal or newborn death or morbidity, regardless of the gestational age at which the antihypertensive treatment is started. Antihypertensive agents are not teratogenic, but there may be an increase in malformations associated with chronic hypertension itself. At present, blood pressure treatment targets used in clinics are the same as those used at home, although blood pressure values tend to be inconsistently lower at home among women with hypertension. Although starting all women on the same antihypertensive medication is usually effective in reducing blood pressure, it remains unclear whether there is an optimal agent for such an approach or how best to use combinations of antihypertensive medications. An alternative approach is to individualize care, using maternal characteristics and blood pressure features beyond blood pressure level (eg, variability) that are of prognostic value. Outcomes may be improved by timed birth between 38 0/7 and 39 6/7 weeks' gestation based on observational literature; of note, confirmatory trial evidence is pending. Postnatal care is facilitated by the acceptability of most antihypertensives (including angiotensin-converting enzymes inhibitors) for use in breastfeeding. The evidence base to guide the care of pregnant women with chronic hypertension is growing and aligning with international guidelines. Addressing outstanding research questions would inform personalized care of chronic hypertension in pregnancy.
Topics: Antihypertensive Agents; Aspirin; Blood Pressure Monitoring, Ambulatory; Calcium; Chronic Disease; Contraindications, Drug; Decision Making, Shared; Delivery, Obstetric; Female; Humans; Hypertension; Platelet Aggregation Inhibitors; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Prenatal Care
PubMed: 32687817
DOI: 10.1016/j.ajog.2020.07.026 -
Phytomedicine : International Journal... Nov 2023Hypertension is a serious global public health issue. Blood pressure (BP) is still not effectively controlled in about 20 - 30% of hypertensive patients. Therefore, it...
BACKGROUND
Hypertension is a serious global public health issue. Blood pressure (BP) is still not effectively controlled in about 20 - 30% of hypertensive patients. Therefore, it is imperative to develop new treatments for hypertension. Veratrum alkaloids were once used for the clinical treatment of hypertension, the mechanism of which is still unclear. It was gradually phased out due to adverse reactions.
PURPOSE
This study aimed to investigate the short-term and long-term hypotensive profiles of different components of Veratrum alkaloids in spontaneously hypertensive rats (SHRs) to unveil their mechanisms of action.
RESULTS
Total Veratrum alkaloid (V), component A (A), and veratramine (M) quickly decreased BP within 30 min of treatment, reduced renal and cardiovascular damage, and improved relevant biochemical indicators (nitric oxide [NO], endothelin-1 [ET-1], angiotensin II [Ang II)], noradrenaline [NE], etc) in SHRs to delay stroke occurrence. Thereinto, A exhibited excellent protective effects in cardiovascular disease. The metabolomic profiles of SHRs treated with V, A, and M were significantly different from those of SHRs treated with vehicle. Thirteen metabolites were identified as potential pharmacodynamic biomarkers. Through Kyoto Encyclopedia of Genes and Genomes analysis, V, A, and M-induced hypotension was mainly related to alterations in nicotinate and nicotinamide metabolism, GABAergic synapses, linoleic acid metabolism, ketone body synthesis and degradation, arginine and proline metabolism, and urea cycle, of which nicotinate and nicotinamide metabolism was the key metabolic pathway to relieve hypertension.
CONCLUSION
This work shows that A is an effective and promising antihypertensive agent for hypertension treatment to reduce BP and hypertensive target organ damage, which is mainly mediated through modulating nicotinate and nicotinamide metabolism, RAS, and NO-ET homeostasis.
Topics: Humans; Animals; Rats; Antihypertensive Agents; Niacin; Veratrum Alkaloids; Hypertension; Data Analysis; Niacinamide
PubMed: 37647672
DOI: 10.1016/j.phymed.2023.155033 -
International Journal of Molecular... May 2023Arterial hypertension (AH) is a global challenge that greatly impacts cardiovascular morbidity and mortality worldwide. AH is a major risk factor for the development and... (Review)
Review
Arterial hypertension (AH) is a global challenge that greatly impacts cardiovascular morbidity and mortality worldwide. AH is a major risk factor for the development and progression of kidney disease. Several antihypertensive treatment options are already available to counteract the progression of kidney disease. Despite the implementation of the clinical use of renin-angiotensin aldosterone system (RAAS) inhibitors, gliflozins, endothelin receptor antagonists, and their combination, the kidney damage associated with AH is far from being resolved. Fortunately, recent studies on the molecular mechanisms of AH-induced kidney damage have identified novel potential therapeutic targets. Several pathophysiologic pathways have been shown to play a key role in AH-induced kidney damage, including inappropriate tissue activation of the RAAS and immunity system, leading to oxidative stress and inflammation. Moreover, the intracellular effects of increased uric acid and cell phenotype transition showed their link with changes in kidney structure in the early phase of AH. Emerging therapies targeting novel disease mechanisms could provide powerful approaches for hypertensive nephropathy management in the future. In this review, we would like to focus on the interactions of pathways linking the molecular consequences of AH to kidney damage, suggesting how old and new therapies could aim to protect the kidney.
Topics: Humans; Hypertension; Kidney; Renin-Angiotensin System; Antihypertensive Agents; Hypertension, Renal
PubMed: 37298378
DOI: 10.3390/ijms24119422 -
Journal of Hypertension Sep 2010The role of alpha-1 adrenoceptor antagonists (alpha-blockers) in the management of hypertension continues to evolve. Recent data support their use as add-on therapy in... (Review)
Review
The role of alpha-1 adrenoceptor antagonists (alpha-blockers) in the management of hypertension continues to evolve. Recent data support their use as add-on therapy in uncontrolled hypertension when used in combination with all other major classes of antihypertensive drug and there is increasing evidence suggesting that they have modest but significant beneficial effects on lipid and glucose metabolism. The availability of extended-release formulations has contributed to an excellent tolerability profile. New data from an observational analysis of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) suggest that doxazosin gastrointestinal therapeutic system (GITS) used as a third-line antihypertensive agent lowered blood pressure and caused modest reductions in plasma lipids. Furthermore, use of doxazosin in ASCOT was not associated with an increased risk of heart failure, in contrast to the earlier finding of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Overall, currently available data support the use of alpha-blockers as safe, well tolerated and effective add-on antihypertensive drugs, which have additional favourable metabolic effects.
Topics: Adrenergic alpha-1 Receptor Antagonists; Antihypertensive Agents; Blood Pressure; Clinical Trials as Topic; Doxazosin; Drug Therapy, Combination; Heart Failure; Humans; Hypertension; Lipids; Myocardial Infarction; Practice Guidelines as Topic
PubMed: 20543713
DOI: 10.1097/HJH.0b013e32833b912c -
The Cochrane Database of Systematic... Oct 2009Hypertension is associated with an increased risk of stroke, myocardial infarction and congestive heart failure. Methyldopa is a centrally acting antihypertensive agent,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hypertension is associated with an increased risk of stroke, myocardial infarction and congestive heart failure. Methyldopa is a centrally acting antihypertensive agent, which was commonly used in the 1970's and 80's for blood pressure control. Its use at present has largely been replaced by antihypertensive drug classes with less side effects, but it is still used in developing countries due to its low cost. A review of its relative effectiveness compared to placebo on surrogate and clinical outcomes is justified.
OBJECTIVES
To quantify the effect of methyldopa compared to placebo in randomized controlled trials (RCTs) on all cause mortality, cardiovascular mortality, serious adverse events, myocardial infarctions, strokes, withdrawals due to adverse effects and blood pressure in patients with primary hypertension.
SEARCH STRATEGY
We searched the following databases: Cochrane Central Register of Controlled Trials (1960-June 2009), MEDLINE (2005-June 2009), and EMBASE (2007-June 2009). Bibliographic citations from retrieved studies were also reviewed. No language restrictions were applied.
SELECTION CRITERIA
We selected RCTs studying patients with primary hypertension. We excluded studies of patients with secondary hypertension or gestational hypertension.
DATA COLLECTION AND ANALYSIS
Two reviewers independently extracted data and assessed trial quality using the risk of bias tool. Data synthesis and analysis was performed using RevMan 5. Data for blood pressure were combined using the generic inverse variance method.
MAIN RESULTS
Twelve trials (N=595) met the inclusion criteria for this review. None of these studies evaluated the effects of methyldopa compared to placebo on mortality and morbidity outcomes. Data for withdrawals due to adverse effects were not reported in a way that permitted meaningful meta-analysis. Data from six of the twelve trials (N=231) were combined to evaluate the blood pressure lowering effects of methyldopa compared to placebo. This meta-analysis shows that methyldopa at doses ranging from 500-2250 mg daily lowers systolic and diastolic blood pressure by a mean of 13 (95%CI 6-20) / 8 (95% CI 4-13) mmHg. Overall, the risk of bias was considered moderate.
AUTHORS' CONCLUSIONS
Methyldopa lowers blood pressure to varying degrees compared to placebo for patients with primary hypertension. Its effect on clinical outcomes, however, remains uncertain.
Topics: Antihypertensive Agents; Blood Pressure; Humans; Hypertension; Methyldopa; Randomized Controlled Trials as Topic
PubMed: 19821316
DOI: 10.1002/14651858.CD003893.pub3 -
American Heart Journal Dec 2022Despite broad treatment recommendations, there are limited published reports comparing the efficacy of different antihypertensive agents in patients with isolated...
Despite broad treatment recommendations, there are limited published reports comparing the efficacy of different antihypertensive agents in patients with isolated systolic hypertension or isolated diastolic hypertension. This study was a secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. We compared the use of chlorthalidone, amlodipine, or lisinopril on the primary outcome of combined coronary heart disease, stroke, or all-cause mortality in patients with isolated systolic hypertension or isolated diastolic hypertension.
Topics: Humans; Antihypertensive Agents; Isolated Systolic Hypertension; Hypertension; Chlorthalidone; Amlodipine; Lisinopril; Treatment Outcome
PubMed: 35932912
DOI: 10.1016/j.ahj.2022.07.006 -
Current Hypertension Reports Jul 2014While there are strong trial data to guide the selection of initial hypertension treatment choice and limited data to support second agent choice, beyond the first two... (Review)
Review
While there are strong trial data to guide the selection of initial hypertension treatment choice and limited data to support second agent choice, beyond the first two agents, subsequent steps are empiric. As medications are added, the resulting polypharmacy may be complex, inefficient and poorly tolerated, resulting in low treatment adherence rates. The selection of antihypertensive drug therapy based on hemodynamic mechanisms is not new but became practical with the availability of noninvasive hemodynamic parameters using impedance cardiography. Individualized therapy based on hormonal or hemodynamic measurements can effectively control hypertension as shown in several small clinical trials. Hemodynamic measurements are obtained quickly, painlessly and can be used in a serial fashion to guide treatment adjustments. Current limitations relate to availability of the measurement device and personnel trained in its use, reimbursement for the measurements, expertise in interpretation of the measurements and systems to adjust medication and repeat measurements in a serial fashion until targets are attained. The potential utility of this approach increases with greater complexity of the medication regimen. Further studies are indicated and may advance options for individualized treatment of hypertensive patients.
Topics: Antihypertensive Agents; Blood Pressure; Drug Therapy, Combination; Hemodynamics; Humans; Hypertension; Precision Medicine
PubMed: 24806735
DOI: 10.1007/s11906-014-0451-y -
Anti-cancer Drugs Jul 2024Repurposing existing drugs for cancer therapy has become an important strategy because of its advantages, such as cost reduction, effect and safety. The present study...
Repurposing existing drugs for cancer therapy has become an important strategy because of its advantages, such as cost reduction, effect and safety. The present study was designed to investigate the antimelanoma effect and possible mechanisms of action of nebivolol, which is an approved and widely prescribed antihypertensive agent. In this study, we explored the effect of nebivolol on cell proliferation and cell activity in melanoma in vitro and the potential antimelanoma mechanism of nebivolol through a series of experiments, including the analysis of the effects with regard to cell apoptosis and metastasis. Furthermore, we evaluated the antimelanoma effect on xenograft tumor models and inspected the antimelanoma mechanism of nebivolol in vivo using immunohistochemical and immunofluorescence staining assays. As results in this work, in vitro , nebivolol possessed a strong activity for suppression proliferation and cell cycle arrest on melanoma. Moreover, nebivolol significantly induced cell apoptosis in melanoma through a mitochondrial-mediated endogenous apoptosis pathway. Additionally, nebivolol inhibited melanoma cell metastasis. More importantly, nebivolol exhibited significantly effective melanoma xenograft models in vivo , which related to the mechanism of apoptosis induction, proliferation inhibition, metastasis blocking and angiogenesis arrest. Overall, the data of the present study recommend that nebivolol holds great potential in application as a novel agent for the treatment of melanoma.
Topics: Nebivolol; Animals; Humans; Melanoma; Apoptosis; Cell Proliferation; Mice; Antihypertensive Agents; Xenograft Model Antitumor Assays; Cell Line, Tumor; Mice, Nude; Cell Cycle Checkpoints; Antineoplastic Agents; Skin Neoplasms; Cell Movement
PubMed: 38602174
DOI: 10.1097/CAD.0000000000001597 -
Hypertension (Dallas, Tex. : 1979) Jan 2024
Review
Topics: Humans; Hypertension; Cardiovascular Diseases; Antihypertensive Agents; Blood Pressure
PubMed: 37795644
DOI: 10.1161/HYPERTENSIONAHA.123.21725