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Integrated control of hypertension by olmesartan medoxomil and hydrochlorothiazide and rationale for combination
Punzi HA
Integrated Blood Pressure Control , 2011, DOI: http://dx.doi.org/10.2147/IBPC.S12214
Abstract: tegrated control of hypertension by olmesartan medoxomil and hydrochlorothiazide and rationale for combination Review (2930) Total Article Views Authors: Punzi HA Published Date December 2011 Volume 2011:4 Pages 73 - 83 DOI: http://dx.doi.org/10.2147/IBPC.S12214 Henry A Punzi Trinity Hypertension and Metabolic Research Institute, Punzi Medical Center, Carrollton, TX, USA; Department of Family and Community Medicine, UT Southwestern Medical Center, Dallas, TX, USA Abstract: Hypertension affects nearly one-third of all individuals in the US, yet one-half of all treated patients achieve blood pressure (BP) controlled to recommended goals. The percentage of patients with uncontrolled BP is likely to be much higher when considering the number of patients who are not even aware of their hypertensive state. Elevated BP is associated with increased risks of cardiovascular events and end-organ damage. Antihypertensive monotherapy is not always sufficient to achieve BP goals, and thus more aggressive treatment regimens need to be considered. Antihypertensive combination therapy, which may improve tolerability, offers the benefit of targeting different mechanisms of action. Numerous outcomes studies support the use of a renin–angiotensin system inhibitor as a first-line choice in antihypertensive therapy. This review discusses the benefits of combination therapy with the angiotensin type II receptor blocker olmesartan medoxomil (OM) paired with the thiazide diuretic hydrochlorothiazide (HCTZ). The pharmacokinetic properties of OM will be reviewed in addition to efficacy studies that support OM + HCTZ combination therapy over other possible antihypertensive combinations. Finally, a rationale for choosing HCTZ over another diuretic, chlorthalidone, will also be discussed based on pharmacokinetic differences, clinical concerns, and trends in use.
Integrated control of hypertension by olmesartan medoxomil and hydrochlorothiazide and rationale for combination  [cached]
Punzi HA
Integrated Blood Pressure Control , 2011,
Abstract: Henry A PunziTrinity Hypertension and Metabolic Research Institute, Punzi Medical Center, Carrollton, TX, USA; Department of Family and Community Medicine, UT Southwestern Medical Center, Dallas, TX, USAAbstract: Hypertension affects nearly one-third of all individuals in the US, yet one-half of all treated patients achieve blood pressure (BP) controlled to recommended goals. The percentage of patients with uncontrolled BP is likely to be much higher when considering the number of patients who are not even aware of their hypertensive state. Elevated BP is associated with increased risks of cardiovascular events and end-organ damage. Antihypertensive monotherapy is not always sufficient to achieve BP goals, and thus more aggressive treatment regimens need to be considered. Antihypertensive combination therapy, which may improve tolerability, offers the benefit of targeting different mechanisms of action. Numerous outcomes studies support the use of a renin–angiotensin system inhibitor as a first-line choice in antihypertensive therapy. This review discusses the benefits of combination therapy with the angiotensin type II receptor blocker olmesartan medoxomil (OM) paired with the thiazide diuretic hydrochlorothiazide (HCTZ). The pharmacokinetic properties of OM will be reviewed in addition to efficacy studies that support OM + HCTZ combination therapy over other possible antihypertensive combinations. Finally, a rationale for choosing HCTZ over another diuretic, chlorthalidone, will also be discussed based on pharmacokinetic differences, clinical concerns, and trends in use.Keywords: antihypertensives, blood pressure, combination therapy, HCTZ
Adding thiazide to a rennin-angiotensin blocker regimen to improve left ventricular relaxation in diabetes and nondiabetes patients with hypertension
Takami T, Ito H, Ishii K, Shimada K, Iwakura K, Watanabe H, Fukuda S, Yoshikawa J
Drug Design, Development and Therapy , 2012, DOI: http://dx.doi.org/10.2147/DDDT.S35738
Abstract: dding thiazide to a rennin-angiotensin blocker regimen to improve left ventricular relaxation in diabetes and nondiabetes patients with hypertension Original Research (3048) Total Article Views Authors: Takami T, Ito H, Ishii K, Shimada K, Iwakura K, Watanabe H, Fukuda S, Yoshikawa J Published Date September 2012 Volume 2012:6 Pages 225 - 233 DOI: http://dx.doi.org/10.2147/DDDT.S35738 Received: 08 July 2012 Accepted: 24 August 2012 Published: 12 September 2012 Takeshi Takami,1 Hiroshi Ito,2 Katsuhisa Ishii,3 Kenei Shimada,4 Katsuomi Iwakura,5 Hiroyuki Watanabe,6 Shota Fukuda,7 Junichi Yoshikawa8 1Department of Internal Medicine, Clinic Jingumae, Kashihara, Japan; 2Department of Cardiovascular Medicine, Okayama University, Graduate School of Medicine, Okayama, Japan; 3Department of Cardiology, Kansai Electric Power Hospital, Osaka, Japan; 4Department of Internal Medicine and Cardiology, Osaka City University of Medicine, Osaka, Japan; 5Cardiovascular Center, Sakurabashi Watanabe Hospital, Osaka, Japan; 6Department of Cardiology, Sakakibara Heart Institute, Tokyo, Japan; 7Department of Medicine, Osaka Ekisaikai Hospital, Osaka, Japan; 8Nishinomiya Watanabe Cardiovascular Center, Nishinomiya, Japan Abstract: The urinary albumin to creatinine ratio (UACR) is an independent predictor of outcomes in patients with diastolic dysfunction. Thus, we investigated the relationship between diastolic dysfunction, UACR, and diabetes mellitus (DM) in the EDEN study. We investigated the effect of switching from an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) to a combination of losartan and hydrochlorothiazide on left ventricular (LV) relaxation in patients with hypertension and diastolic dysfunction. We enrolled 106 patients with and 265 patients without DM. All patients had diastolic dysfunction and had not achieved their treatment goals with an ACEi or ARB. The measurements of e′ velocity and E/e′ ratio was performed with echocardiography as markers of LV diastolic function. We switched the ACEi or ARB to losartan/hydrochlorothiazide and followed these patients for 24 weeks. UACR was decreased in patients with DM (123.4 ± 288.4 to 66.5 ± 169.2 mg/g creatinine; P = 0.0024), but not in patients without DM (51.2 ± 181.8 to 39.2 ± 247.9 mg/g creatinine; P = 0.1051). Among DM patients, there was a significant relationship between changes in UACR and changes in e′ velocity (r = –0.144; P = 0.0257) and between changes in estimated glomerular filtration rate and changes in the E/e′ ratio (r = –0.130; P = 0.0436). Among patients without DM, there was a significant relationship between changes in high-sensitivity C-reactive protein (hs-CRP) and changes in E/e′ (r = 0.205; P = 0.0010). Multivariate analysis demonstrated changes in hemoglobin A1c levels as one of the determinants of change of e′ and E/e′ in patients with DM, whereas hs-CRP was the determinant of change of e′ among patients without DM. These data suggest that improvem
Adding thiazide to a rennin-angiotensin blocker regimen to improve left ventricular relaxation in diabetes and nondiabetes patients with hypertension  [cached]
Takami T,Ito H,Ishii K,Shimada K
Drug Design, Development and Therapy , 2012,
Abstract: Takeshi Takami,1 Hiroshi Ito,2 Katsuhisa Ishii,3 Kenei Shimada,4 Katsuomi Iwakura,5 Hiroyuki Watanabe,6 Shota Fukuda,7 Junichi Yoshikawa81Department of Internal Medicine, Clinic Jingumae, Kashihara, Japan; 2Department of Cardiovascular Medicine, Okayama University, Graduate School of Medicine, Okayama, Japan; 3Department of Cardiology, Kansai Electric Power Hospital, Osaka, Japan; 4Department of Internal Medicine and Cardiology, Osaka City University of Medicine, Osaka, Japan; 5Cardiovascular Center, Sakurabashi Watanabe Hospital, Osaka, Japan; 6Department of Cardiology, Sakakibara Heart Institute, Tokyo, Japan; 7Department of Medicine, Osaka Ekisaikai Hospital, Osaka, Japan; 8Nishinomiya Watanabe Cardiovascular Center, Nishinomiya, JapanAbstract: The urinary albumin to creatinine ratio (UACR) is an independent predictor of outcomes in patients with diastolic dysfunction. Thus, we investigated the relationship between diastolic dysfunction, UACR, and diabetes mellitus (DM) in the EDEN study. We investigated the effect of switching from an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) to a combination of losartan and hydrochlorothiazide on left ventricular (LV) relaxation in patients with hypertension and diastolic dysfunction. We enrolled 106 patients with and 265 patients without DM. All patients had diastolic dysfunction and had not achieved their treatment goals with an ACEi or ARB. The measurements of e′ velocity and E/e′ ratio was performed with echocardiography as markers of LV diastolic function. We switched the ACEi or ARB to losartan/hydrochlorothiazide and followed these patients for 24 weeks. UACR was decreased in patients with DM (123.4 ± 288.4 to 66.5 ± 169.2 mg/g creatinine; P = 0.0024), but not in patients without DM (51.2 ± 181.8 to 39.2 ± 247.9 mg/g creatinine; P = 0.1051). Among DM patients, there was a significant relationship between changes in UACR and changes in e′ velocity (r = –0.144; P = 0.0257) and between changes in estimated glomerular filtration rate and changes in the E/e′ ratio (r = –0.130; P = 0.0436). Among patients without DM, there was a significant relationship between changes in high-sensitivity C-reactive protein (hs-CRP) and changes in E/e′ (r = 0.205; P = 0.0010). Multivariate analysis demonstrated changes in hemoglobin A1c levels as one of the determinants of change of e′ and E/e′ in patients with DM, whereas hs-CRP was the determinant of change of e′ among patients without DM. These data suggest that improvement in LV diastolic function is associated with an improvement of
Análisis crítico de un artículo:El estudio ALLHAT: Diuréticos tipo tiazidas serían el fármaco de elección para iniciar tratamiento en hipertensión arterial The antihypertensive and lipid lowering treatment to prevent heart attack: Major outcomes in high risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288: 2981-98  [cached]
Gabriel Rada G,Joaquín Montero L
Revista médica de Chile , 2004,
Abstract: Context: Antihypertensive therapy is well established to reduce hypertension related morbidity and mortality, but the optimal first step therapy is unknown. OBJECTIVE: To determine whether treatment with a calcium channel blocker or an angiotensin converting enzyme inhibitor lowers the incidence of coronary heart disease (CHD) or other cardiovascular disease (CVD) events vs treatment with a diuretic. DESIGN: The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double blind, active controlled clinical trial conducted from February 1994 through March 2002. Setting and participants: A total of 33357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor from 623 North American centers. INTERVENTIONS: Participants were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n = 15255); amlodipine, 2.5 to 10 mg/d (n = 9048); or lisinopril, 10 to 40 mg/d (n = 9054) for planned follow up of approximately 4 to 8 years. Main outcome measures: The primary outcome was combined fatal CHD or nonfatal myocardial infarction, analyzed by intent to treat. Secondary outcomes were all cause mortality, stroke, combined CHD (primary outcome, coronary revascularization, or angina with hospitalization), and combined CVD (combined CHD, stroke, treated angina without hospitalization, heart failure [HF], and peripheral arterial disease). Results: Mean follow up was 4.9 years. The primary outcome occurred in 2956 participants, with no difference between treatments. Compared with chlorthalidone (6 years rate, 11.5%), the relative risks (RRs) were 0.98 (95% CI, 0.90-1.07) for amlodipine (6 years rate, 11.3%) and 0.99 (95% CI, 0.91-1.08) for lisinopril (6 years rate, 11.4%). Likewise, all cause mortality did not differ between groups. Five years systolic blood pressures were significantly higher in the amlodipine (0.8 mm Hg, P =.03) and lisinopril (2 mm Hg, P <.001) groups compared with chlorthalidone, and 5 years diastolic blood pressure was significantly lower with amlodipine (0.8 mm Hg, P <.001). For amlodipine vs chlorthalidone, secondary outcomes were similar except for a higher 6 years rate of HF with amlodipine (10.2% vs 7.7%; RR, 1.38; 95% CI, 1.25-1.52). For lisinopril vs chlorthalidone, lisinopril had higher 6 years rates of combined CVD (33.3% vs 30.9%; RR, 1.10; 95% CI, 1.05-1.16); stroke (6.3% vs 5.6%; RR, 1.15; 95% CI, 1.02-1.30); and HF (8.7% vs 7.7%; RR, 1.19; 95% CI, 1.07-1.31). Conclusion: Thiazide type diuretics are superior in preventing 1 or more major forms of CVD and a
Evaluation of thiazide diuretic use as preferred therapy in uncomplicated essential hypertension patients
Greene,Ronald S.; Escobar Quinones,Marissa; Edwards,Krystal L.;
Pharmacy Practice (Internet) , 2007, DOI: 10.4321/S1886-36552007000300006
Abstract: thiazide diuretics are effective antihypertensive medications shown to reduce the risk of cardiovascular events and stroke. despite being the preferred choice for uncomplicated essential hypertension, thiazide diuretics continue to be underutilized. methods: uncomplicated essential hypertension patients taking a single antihypertensive medication were evaluated upon enrollment, diagnosis after enrollment or initiation of therapy in treatment na?ve patients. clinician prescribing habits were determined for both pre-existing and newly diagnosed hypertensive patients. for the cost savings analysis, hydrochlorothiazide (hctz) 25mg daily was selected as the preferred conversion medication. results: four hundred seventy-eight patients were included. ace inhibitors were the most prescribed at 35.4% (n=169), followed by dihydropyridine calcium channel blockers (dhp ccb) and thiazide diuretics, both at 20.3% (n=97). only 12.9% (n=33) of patients with hypertension that were taking an antihypertensive medication upon enrollment were either continued or started on thiazide diuretic therapy. newly diagnosed or treatment na?ve patients were prescribed a thiazide diuretic 28.8% (n=64) of the time. dhp ccb accounted for 58.8% of the total medication cost per month with thiazide diuretics responsible for 0.8% of the cost. if all patients had been prescribed hctz 25mg daily, 95.8% of the total medication cost per month could have been saved. conclusions: thiazide diuretics were underutilized as preferred therapy in patients with pre-existing or newly diagnosed uncomplicated essential hypertension. while cost of therapy should not be the sole reason for medication selection, thiazide diuretics are an attractive option and should be considered as a preferred therapy in this patient population.
Evaluation of thiazide diuretic use as preferred therapy in uncomplicated essential hypertension patients.
Greene RS,Escobar Quinones M,Edwards KL
Pharmacy Practice (Granada) , 2007,
Abstract: Thiazide diuretics are effective antihypertensive medications shown to reduce the risk of cardiovascular events and stroke. Despite being the preferred choice for uncomplicated essential hypertension, thiazide diuretics continue to be underutilized. Methods: Uncomplicated essential hypertension patients taking a single antihypertensive medication were evaluated upon enrollment, diagnosis after enrollment or initiation of therapy in treatment na ve patients. Clinician prescribing habits were determined for both pre-existing and newly diagnosed hypertensive patients. For the cost savings analysis, hydrochlorothiazide (HCTZ) 25mg daily was selected as the preferred conversion medication. Results: Four hundred seventy-eight patients were included. ACE inhibitors were the most prescribed at 35.4% (n=169), followed by dihydropyridine calcium channel blockers (DHP CCB) and thiazide diuretics, both at 20.3% (n=97). Only 12.9% (n=33) of patients with hypertension that were taking an antihypertensive medication upon enrollment were either continued or started on thiazide diuretic therapy. Newly diagnosed or treatment na ve patients were prescribed a thiazide diuretic 28.8% (n=64) of the time. DHP CCB accounted for 58.8% of the total medication cost per month with thiazide diuretics responsible for 0.8% of the cost. If all patients had been prescribed HCTZ 25mg daily, 95.8% of the total medication cost per month could have been saved. Conclusions: Thiazide diuretics were underutilized as preferred therapy in patients with pre-existing or newly diagnosed uncomplicated essential hypertension. While cost of therapy should not be the sole reason for medication selection, thiazide diuretics are an attractive option and should be considered as a preferred therapy in this patient population.
Calcium Channel Blockers, More than Diuretics, Enhance Vascular Protective Effects of Angiotensin Receptor Blockers in Salt-Loaded Hypertensive Rats  [PDF]
Eiichiro Yamamoto, Keiichiro Kataoka, Yi-Fei Dong, Nobutaka Koibuchi, Kensuke Toyama, Daisuke Sueta, Tetsuji Katayama, Osamu Yasuda, Hisao Ogawa, Shokei Kim-Mitsuyama
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0039162
Abstract: The combination therapy of an angiotensin receptor blocker (ARB) with a calcium channel blocker (CCB) or with a diuretic is favorably recommended for the treatment of hypertension. However, the difference between these two combination therapies is unclear. The present work was undertaken to examine the possible difference between the two combination therapies in vascular protection. Salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP) were divided into 6 groups, and they were orally administered (1) vehicle, (2) olmesartan, an ARB, (3) azelnidipine, a CCB, (4) hydrochlorothiazide, a diuretic, (5) olmesartan combined with azelnidipine, or (6) olmesartan combined with hydrochlorothiazide. Olmesartan combined with either azelnidipine or hydrochlorothiazide ameliorated vascular endothelial dysfunction and remodeling in SHRSP more than did monotherapy with either agent. However, despite a comparable blood pressure lowering effect between the two treatments, azelnidipine enhanced the amelioration of vascular endothelial dysfunction and remodeling by olmesartan to a greater extent than did hydrochlorothiazide in salt-loaded SHRSP. The increased enhancement by azelnidipine of olmesartan-induced vascular protection than by hydrochlorothiazide was associated with a greater amelioration of vascular nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, superoxide, mitogen-activated protein kinase activation, and with a greater activation of the Akt/endothelial nitric oxide synthase (eNOS) pathway. These results provided the first evidence that a CCB potentiates the vascular protective effects of an ARB in salt-sensitive hypertension, compared with a diuretic, and provided a novel rationale explaining the benefit of the combination therapy with an ARB and a CCB.
Efficacy of fixed combination of valsartan, amlodipine and hydrochlorothiazide in complex therapy of the patient of very high cardiovascular risk  [cached]
I.M. Sokolov,N.A. Zheleznyakova
Rational Pharmacotherapy in Cardiology , 2012,
Abstract: The high prevalence of arterial hypertension in association with high and very high cardiovascular risk requires widespread use of combined therapy. Current approaches to selection of combination components of antihypertensive drugs are based the efficacy of these drugs proven in multicenter randomized clinical trials. The triple combination of calcium antagonist, angiotensin II receptor blocker and thiazide diuretic is regarded as the best option for combined therapy in patients with arterial hypertension and ischemic heart disease to reduce cardiovascular risk.
Ambulatory blood pressure response to triple therapy with an angiotensin-receptor blocker (ARB), calcium-channel blocker (CCB), and HCTZ versus dual therapy with an ARB and HCTZ
Duprez D, Ferdinand K, Purkayastha D, Samuel R, Wright R
Vascular Health and Risk Management , 2011, DOI: http://dx.doi.org/10.2147/VHRM.S25743
Abstract: mbulatory blood pressure response to triple therapy with an angiotensin-receptor blocker (ARB), calcium-channel blocker (CCB), and HCTZ versus dual therapy with an ARB and HCTZ Original Research (3802) Total Article Views Authors: Duprez D, Ferdinand K, Purkayastha D, Samuel R, Wright R Published Date November 2011 Volume 2011:7 Pages 701 - 708 DOI: http://dx.doi.org/10.2147/VHRM.S25743 Daniel Duprez1, Keith Ferdinand2, Das Purkayastha3, Rita Samuel3, Richard Wright4 1University of Minnesota, Minneapolis, MN, 2Atlanta Clinical Research Centers, Atlanta, GA, 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, 4Pacific Heart Institute, Santa Monica, CA, USA Background: Stage 2 hypertension often requires combination antihypertensive therapy. Ambulatory blood pressure monitoring (ABPM) is a useful tool for assessing antihypertensive drugs and their combinations. Objective: To compare the effect of a moderate dose of angiotensin receptor blocker/calcium channel blocker (ARB/CCB) combined with a diuretic versus a maximal dose of ARB with a diuretic on 24-hour ambulatory blood pressure monitoring (ABPM) and other derived ambulatory blood pressure (ABP) parameters. Methods: The EXforge As compared to Losartan Treatment ABPM substudy was a randomized, double-blind, parallel-group, active-control, forced-titration study of patients with Stage 2 hypertension that compared the efficacy of initial treatment with valsartan/amlodipine 160/5 mg (n = 48) or losartan 100 mg (n = 36). At week 3, hydrochlorothiazide (HCTZ) 25 mg was added in both treatment groups. ABP was measured at baseline and at week 6. Additionaly, 24-hour ABP, nighttime (10 pm to 6 am) and daytime (6 am to 10 pm) ABP, and ABP load (percentage of readings above 140/90 mmHg) were determined. Results: Eighty-four patients (48 ARB/CCB/HCTZ, 36 ARB/HCTZ) had ABPM at baseline and at week 6. Reductions of systolic/diastolic ABP were greater in the ARB/CCB/HCTZ group than in the ARB/HCTZ group for 24-hour mean ABP (–22.0/–13.3 versus –17.4/–8.1 mmHg), as well as nighttime ABP (–22.2/–13.3 versus –16.2/–7.4 mmHg), daytime ABP (–21.9/–13.0 versus –18.1/–8.6 mmHg), ABP in the last 4 hours of the dosing period (–21.5/–13.5 versus –17.0/–7.7 mmHg), and ABP load (21.7%/12.8% versus 30.8%/20.0%). Conclusion: Initiating antihypertensive treatment with moderate doses of ARB/CCB with a diuretic is more effective in lowering nighttime and daytime ABP and reducing ABP load than a maximal dose of an ARB with a diuretic.
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