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Baker W.L.,University of Connecticut | White W.B.,Calhoun Cardiology Center
US Cardiology | Year: 2012

Objective: To evaluate the efficacy, safety, and clinical role of azilsartan medoxomil, an angiotensin-II receptor blocker (ARB) that recently gained US Food and Drug Administration approval for lowering of blood pressure (BP) in patients with hypertension. Methods: A systematic review of the literature was performed through October 2011 using the keywords and medical subject headings azilsartan, azilsartan medoxomil, TAK-491, TAK-536, and Edarbi. Citations eligible for inclusion were in vitro or in vivo evaluations of azilsartan medoxomil with no restrictions on patient population or indication used. Data related to the patient populations and outcomes of interest were extracted from each citation. Results: Three trials are available in full publication form, with others available only as abstracts. Azilsartan medoxomil 40 mg and 80 mg daily significantly improves both systolic and diastolic BP from baseline compared with placebo, and the 80 mg dose has greater efficacy than other ARBs, including olmesartan 40 mg daily and valsartan 320 mg daily. Improvements in both 24-hour BP using ambulatory monitoring and clinic BPs, as well as a higher proportion of patients reaching goal, have been seen with azilsartan medoxomil. Additional information shows added BP lowering when azilsartan medoxomil is combined with chlorthalidone. Adverse events are similar with azilsartan medoxomil compared to other ARBs and include headache, dizziness, urinary tract infections, and fatigue. Conclusions: Azilsartan medoxomil is a safe and effective ARB with a unique pharmacologic profile compared with other agents, including slowed angiotensin-II type 1 (AT1) receptor dissociation rates and improved receptor specificity. Studies have shown azilsartan medoxomil 80 mg once daily to reduce BP to a greater extent than valsartan and olmesartan, with similar safety and tolerability. © Touch Briefings 2012. Source


Baker W.L.,University of Connecticut | Nigro S.C.,MCPHS University | White W.B.,University of Connecticut | White W.B.,Calhoun Cardiology Center
Expert Review of Cardiovascular Therapy | Year: 2014

Azilsartan medoxomil (AZL) is the most recently approved angiotensin receptor blocker (ARB) for treating patients with hypertension. A fixed-dose combination product with AZL and the thiazide-like diuretic chlorthalidone (CLD) is now available to treat individuals who require additional blood pressure lowering. For this review, a literature search was conducted using MEDLINE and the keywords and MeSH terms azilsartan, azilsartan medoxomil, chlorthalidone, thiazide, blood pressure and hypertension. References for retrieved articles were also scanned for relevant citations. No language restrictions were used. AZL is structurally related to candesartan and has been shown to provide more potent angiotensin receptor antagonism versus other ARBs. CLD is a thiazide-like diuretic with a longer half-life and greater blood pressure lowering efficacy than hydrochlorothiazide. The combination of AZL plus CLD has superior efficacy to other ARBs alone or in combination with hydrochlorothiazide based on extensive evaluation in clinical trials. This superior efficacy is not offset by a large imbalance in clinically important adverse events. © Informa UK, Ltd. Source


Sobieraj D.M.,University of Connecticut | White W.B.,University of Connecticut | White W.B.,Calhoun Cardiology Center | Baker W.L.,University of Connecticut
Journal of the American Society of Hypertension | Year: 2013

Tobacco dependence is a potent risk factor for cardiovascular (CV) diseases and, despite known harms of smoking and benefits associated with smoking cessation, approximately 20% of the adult population with CV diseases or hypertension continue to smoke. Extensive research has demonstrated that nicotine replacement, varenicline, and bupropion sustained-release are superior to placebo for short- and intermediate-term smoking cessation. Because of their mechanisms of action, some smoking cessation therapies have been thought to have the potential to increase CV risk, particularly if the pharmacotherapies are taken while individuals are still smoking. Hence, we have analytically reviewed the literature describing the CV effects of therapies for smoking cessation, particularly as they apply to patients with CV disease. © 2013 American Society of Hypertension. All rights reserved. Source


Parthasarathy H.K.,Papworth Hospital | Menard J.,French Institute of Health and Medical Research | White W.B.,Calhoun Cardiology Center | Young W.F.,Mayo Medical School | And 6 more authors.
Journal of Hypertension | Year: 2011

Background: Eplerenone is claimed to be a more selective blocker of the mineralocorticoid receptor than spironolactone being associated with fewer antiandrogenic side-effects. We compared the efficacy, safety and tolerability of eplerenone versus spironolactone in patients with hypertension associated with primary aldosteronism. Methods: The study was multicentre, randomized, double-blind, active-controlled, and parallel group design. Following a single-blind, placebo run-in period, patients were randomized 1: 1 to a 16-week double-blind, treatment period of spironolactone (75-225 mg once daily) or eplerenone (100-300 mg once daily) using a titration-to-effect design. To be randomized, patients had to meet biochemical criteria for primary aldosteronism and have a seated DBP at least 90 mmHg and less than 120 mmHg and SBP less than 200 mmHg. The primary efficacy endpoint was the antihypertensive effect of eplerenone versus spironolactone to establish noninferiority of eplerenone in the mean change from baseline in seated DBP. Results: Changes from baseline in DBP were less on eplerenone (-5.6 ± 1.3 SE mmHg) than spironolactone (-12.5 ± 1.3 SE mmHg) [difference, -6.9 mmHg (-10.6, -3.3); P < 0.001]. Although there were no significant differences between eplerenone and spironolactone in the overall incidence of adverse events, more patients randomized to spironolactone developed male gynaecomastia (21.2 versus 4.5%; P = 0.033) and female mastodynia (21.1 versus 0.0%; P = 0.026). Conclusion: The antihypertensive effect of spironolactone was significantly greater than that of eplerenone in hypertension associated with primary aldosteronism. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source


Campbell P.,Calhoun Cardiology Center | Campbell P.,University of Connecticut | Baker W.L.,Calhoun Cardiology Center | Baker W.L.,University of Connecticut | And 4 more authors.
Journal of the American Society of Hypertension | Year: 2011

Due to observations of increased off-label use of intravenous hydralazine in area hospitals, we studied its use in a university teaching hospital. Patients were prospectively identified between April and October 2010 with a pharmacy order for intravenous hydralazine. Demographic and clinical information, including pretreatment blood pressure (BP), change in BP and heart rate within 2 hours after administration of hydralazine, and adverse events were obtained. Ninety-four patients (mean age, 69 ± 18 years, 48% women, 89% with known hypertension) received 201 intravenous hydralazine doses (mean dose of 11.4 ± 4.3 mg). Only 4 (2%) patients had evidence of an urgent hypertensive condition. Following hydralazine, BP was reduced by 24/9 ± 29/15 mmHg and heart rate increased by 4 ± 13 beats per minute. Changes from baseline in BP were related to baseline BP. Seventeen patients experienced an adverse event, the most common being hypotension (n = 11). Intravenous hydralazine is commonly prescribed for non-urgent cases of hypertension in the hospitalized patient. While changes in systolic BP are related to baseline BP values, they are highly variable, and associated with hypotension. Thus, this agent may not be useful for treating hypertension in many hospitalized patients and may cause harm if used inappropriately. © 2011 American Society of Hypertension. All rights reserved. Source

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