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Rationale for triple fixed-dose combination therapy with an angiotensin II receptor blocker, a calcium channel blocker, and a thiazide diuretic  [cached]
Volpe M,Tocci G
Vascular Health and Risk Management , 2012,
Abstract: Massimo Volpe,1,2 Giuliano Tocci21Division of Cardiology, Department of Clinical and Molecular Medicine, University of Rome, Sapienza, Sant'Andrea Hospital, Rome, 2IRCCS Neuromed, Pozzilli, ItalyAbstract: Hypertension is a growing global health problem, and is predicted to affect 1.56 billion people by 2025. Treatment remains suboptimal, with control of blood pressure achieved in only 20%–35% of patients, and the majority requiring two or more antihypertensive drugs to achieve recommended blood pressure goals. To improve blood pressure control, the European hypertension guidelines recommend that angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) are combined with calcium channel blockers (CCBs) and/or thiazide diuretics. The rationale for this strategy is based, in part, on their different effects on the renin-angiotensin system, which improves antihypertensive efficacy. Data from a large number of trials support the efficacy of ACEIs or ARBs in combination with CCBs and/or hydrochlorothiazide (HCTZ). Combining two different classes of antihypertensive drugs has an additive effect on lowering of blood pressure, and does not increase adverse events, with the ARBs showing a tolerability advantage over the ACEIs. Among the different ARBs, olmesartan medoxomil is available as a dual fixed-dose combination with either amlodipine or HCTZ, and the increased blood pressure-lowering efficacy of these two combinations is proven. Triple therapy is required in 15%–20% of treated uncontrolled hypertensive patients, with a renin-angiotensin system blocker, CCB, and thiazide diuretic considered to be a rational combination according to the European guidelines. Olmesartan, amlodipine, and HCTZ are available as a triple fixed-dose combination, and significant blood pressure reductions have been observed with this regimen compared with the possible dual combinations. The availability of these fixed-dose combinations should lead to improvement in blood pressure control and aid compliance with long-term therapy, optimizing the management of this chronic condition.Keywords: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, triple therapy, hypertension
Rationale for triple fixed-dose combination therapy with an angiotensin II receptor blocker, a calcium channel blocker, and a thiazide diuretic
Volpe M, Tocci G
Vascular Health and Risk Management , 2012, DOI: http://dx.doi.org/10.2147/VHRM.S28359
Abstract: tionale for triple fixed-dose combination therapy with an angiotensin II receptor blocker, a calcium channel blocker, and a thiazide diuretic Original Research (2712) Total Article Views Authors: Volpe M, Tocci G Published Date June 2012 Volume 2012:8 Pages 371 - 380 DOI: http://dx.doi.org/10.2147/VHRM.S28359 Received: 18 November 2011 Accepted: 23 December 2011 Published: 11 June 2012 Massimo Volpe,1,2 Giuliano Tocci2 1Division of Cardiology, Department of Clinical and Molecular Medicine, University of Rome, Sapienza, Sant'Andrea Hospital, Rome, 2IRCCS Neuromed, Pozzilli, Italy Abstract: Hypertension is a growing global health problem, and is predicted to affect 1.56 billion people by 2025. Treatment remains suboptimal, with control of blood pressure achieved in only 20%–35% of patients, and the majority requiring two or more antihypertensive drugs to achieve recommended blood pressure goals. To improve blood pressure control, the European hypertension guidelines recommend that angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) are combined with calcium channel blockers (CCBs) and/or thiazide diuretics. The rationale for this strategy is based, in part, on their different effects on the renin-angiotensin system, which improves antihypertensive efficacy. Data from a large number of trials support the efficacy of ACEIs or ARBs in combination with CCBs and/or hydrochlorothiazide (HCTZ). Combining two different classes of antihypertensive drugs has an additive effect on lowering of blood pressure, and does not increase adverse events, with the ARBs showing a tolerability advantage over the ACEIs. Among the different ARBs, olmesartan medoxomil is available as a dual fixed-dose combination with either amlodipine or HCTZ, and the increased blood pressure-lowering efficacy of these two combinations is proven. Triple therapy is required in 15%–20% of treated uncontrolled hypertensive patients, with a renin-angiotensin system blocker, CCB, and thiazide diuretic considered to be a rational combination according to the European guidelines. Olmesartan, amlodipine, and HCTZ are available as a triple fixed-dose combination, and significant blood pressure reductions have been observed with this regimen compared with the possible dual combinations. The availability of these fixed-dose combinations should lead to improvement in blood pressure control and aid compliance with long-term therapy, optimizing the management of this chronic condition.
Renin inhibition with aliskiren in hypertension: focus on aliskiren/hydrochlorothiazide combination therapy  [cached]
Kalathil K Sureshkumar
Vascular Health and Risk Management , 2008,
Abstract: Kalathil K SureshkumarDivision of Nephrology and Hypertension, Allegheny General Hospital, Pittsburgh, Pennsylvania, USAAbstract: Hypertension is a major risk factor for the development of cardiovascular and renal disease. The incidence of hypertension is increasing globally and the rate of blood pressure control remains inadequate. Renin-angiotensin-aldosterone system (RAAS) plays a crucial role in volume regulation and maintenance of blood pressure. Pathological activation of RAAS results in chronic hypertension and consequent end organ damage. Most patients with hypertension require combination therapy using agents with complimentary mechanisms of action. Hydrochlorothiazide (HCTZ) together with an agent blocking the RAAS such as an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) are widely used effective anti-hypertensive therapy. Aliskiren is an orally effective direct renin inhibitor that blocks the generation of angiotensin I from angiotensinogen, the rate limiting step of RAAS activation. Studies have shown equivalent antihypertensive efficacy of aliskiren when compared to existing medications such as HCTZ, ACE inhibitors and ARBs. Aliskiren has also been tested in combination therapies. The current review aims to look at the efficacy of aliskiren therapy in hypertension and the evidence for using aliskiren in combination with HCTZ.Keywords: hypertension, renin-angiotensin-aldosterone system, aliskiren, aliskiren-hydrochlorothiazide, combination therapy, renin inhibitors
Clinical efficacy and safety of olmesartan/hydrochlorothiazide combination therapy in patients with essential hypertension  [cached]
Luis M Ruilope
Vascular Health and Risk Management , 2008,
Abstract: Luis M RuilopeUnidad de Hipertensión, Hospital 12 de Octubre, Madrid, SpainAbstract: Hypertension is a major risk factor for cardiovascular disease that contributes to the premature death of millions of people each year, and identification and treatment of hypertension continues to be a challenge. Guidelines recommend that many patients will require two or more antihypertensive agents from different classes. Combining an angiotensin II receptor blocker (ARB) with hydrochlorothiazide (HCTZ) has been shown in clinical studies to increase the antihypertensive efficacy of both agents compared with either agent alone. This review covers several clinical trials and aims to examine several aspects of the efficacy of the combination of olmesartan and HCTZ, including dose-responsiveness, long-term efficacy, goal rate achievement, and efficacy in patients with moderate to severe hypertension. The results presented here demonstrate that olmesartan is effective when added to HCTZ monotherapy or when HCTZ is added to olmesartan monotherapy, both over the short and long term. Moderate to severe hypertension responds well to olmesartan/HCTZ combination therapy, and the great majority of patients are able to achieve recommended blood pressure targets. Thus olmesartan/HCTZ is a well-tolerated option for patients who fail to respond to monotherapy and as initial therapy in those who require large reductions in diastolic blood pressure or systolic blood pressure to achieve goal blood pressure.Keywords: hypertension, olmesartan medoxomil; hydrochlorothiazide, angiotensin II receptor blocker, thiazide diuretic
Triple drug combination of telmisartan, amlodipine and hydrochlorothiazide in the treatment of essential hypertension  [PDF]
Manish Maladkar, Vijay Kumar Verma, Keshav A. Narsikar, Rajan D. Walinjkar, W. R. Patil, N. J. S. Saggu, Suresh P. Kulkarni
Open Journal of Internal Medicine (OJIM) , 2012, DOI: 10.4236/ojim.2012.22014
Abstract: Background: Triple drug therapy comprising angiotensin receptor blocker (ARB), calcium channel blocker (CCB) and hydrochlorothiazide (HCT) effectively controls essential hypertension as evident from the literature. This study was undertaken to assess the efficacy and safety of triple combination compared to the dual drug therapy. Methodologies: A total of 220 male and female patients with essential hypertension were enrolled in the study. The patients were divided into two groups. Group A received a bilayer tablet of FDC of Telmisartan + Amlodipine + HCT and group B received FDC tablet of Telmisartan + HCT. Both the treatments were administered once daily for twelve weeks. The patients were asked to follow-up on week 1, 2, 4, 6, 8 and 10 for periodic efficacy and safety evaluations. Effect on systolic blood pressure (SBP), diastolic blood pressure (DBP) and quality of life (QOL) were recorded during the course of the trial. Results: Blood pressure reduction (BP) to the desired goals was observed with both the treatments. The SBP and DBP reductions were superior in triple combination therapy than double combination. Both treatments improved QOL of patients. Conclusion: Triple drug combination of telmisartan, amlodipine and HCT may serve a potential role in achieving desired BP goals, in patients with essential hypertension, which are otherwise poorly managed by either monotherapy or dual drug therapy.
A critical appraisal of the clinical effectiveness of a fixed combination of valsartan, amlodipine, and hydrochlorothiazide in achieving blood pressure goals  [cached]
Cheryl L Laffer,Fernando Elijovich
Integrated Blood Pressure Control , 2011,
Abstract: Cheryl L Laffer1, Fernando Elijovich21Section of Hypertension and Vascular Medicine, 2Division of General Internal Medicine, Department of Medicine, Texas A&M Health Sciences Center College of Medicine, Temple, TX USAAbstract: Recent guidelines for the treatment of hypertension have focused on the need for multiple medications to get most patients to goal blood pressure (BP). Two to three different classes of antihypertensive agents are frequently required, increasing the risk of poor compliance with therapy. Hence, the guidelines have recommended starting with combination therapy in patients with BP that is over 20 mm Hg systolic or 10 mm Hg diastolic above goal. The latest advance in treatment regimen has been the development of triple-therapy combinations of an angiotensin receptor blocker, amlodipine, and hydrochlorothiazide. We review the pathophysiologic rationale for such a combination and the efficacy, safety, and tolerability of the first triple therapy that has become available: valsartan + amlodipine + hydrochlorothiazide. Finally, we suggest that use of triple therapy could improve the accuracy of diagnosing resistant hypertension, an increasingly prevalent and severe condition, by enhancing adherence to treatment and weeding out patients with pseudoresistance. This would allow for implementation of expensive and invasive workup only in those truly resistant patients in whom it is justified.Keywords: combination therapy, compliance, hypertension control rates, resistant hypertension
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.
Severe hepatic encephalopathy in a patient with liver cirrhosis after administration of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker combination therapy: a case report
Sabine Oertelt-Prigione, Andrea Crosignani, Maurizio Gallieni, Emanuela Vassallo, Mauro Podda, Massimo Zuin
Journal of Medical Case Reports , 2010, DOI: 10.1186/1752-1947-4-141
Abstract: We administered this combination therapy to a 40-year-old Caucasian man with liver cirrhosis in our Hepatology Clinic, given the concomitant presence of glomerulopathy associated with severe proteinuria. While the administration of one single drug appeared to be well-tolerated, our patient developed severe acute encephalopathy after the addition of the second one. Discontinuation of the therapy led to the disappearance of the side-effect. A tentative rechallenge with the same drug combination led to a second episode of acute severe encephalopathy.We speculate that this adverse reaction may be directly related to the effect of angiotensin II on the excretion of blood ammonia. Therefore, we suggest that patients with liver cirrhosis and portal hypertension are at risk of developing clinically relevant encephalopathy when angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker combination therapy is administered, thus indicating the need for a careful clinical follow-up. In addition, the incidence of this serious side-effect should be rigorously evaluated in all patients with liver cirrhosis administered with this common treatment combination.A combination therapy of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) has been used to control proteinuria following initial demonstration of its efficacy [1]. However, recent concerns about the safety of this therapy have emerged, prompting several authors to urge for caution in its use [2]. In this case report, we describe the occurrence of a serious and unexpected adverse drug reaction after administration of the ACEI and ARB combination therapy to a patient with nephrotic syndrome and liver cirrhosis with severe portal hypertension. We suggest that the described adverse reaction is most likely related to the renal effects of the combination therapy and this should be taken into account in high-risk patients presenting with selected co-morbidities.A 40-year-old
RU28318, an Aldosterone Antagonist, in Combination with an ACE Inhibitor and Angiotensin Receptor Blocker Attenuates Cardiac Dysfunction in Diabetes  [PDF]
Ibrahim F. Benter,Fawzi Babiker,Ibrahim Al-Rashdan,Mariam Yousif,Saghir Akhtar
Journal of Diabetes Research , 2013, DOI: 10.1155/2013/427693
Abstract: Aims. We evaluated the effects of RU28318 (RU), a selective mineralocorticoid receptor (MR) antagonist, Captopril (Capt), an angiotensin converting enzyme inhibitor, and Losartan (Los), an angiotensin receptor blocker, alone or in combination with ischemia/reperfusion- (I/R-) induced cardiac dysfunction in hearts obtained from normal and diabetic rats. Methods. Isolated hearts were perfused for 30 min and then subjected to 30 min of global ischemia (I) followed by a period of 30 min of reperfusion (R). Drugs were administered for 30 min either before or after ischemia. Drug regimens tested were RU, Capt, Los, RU + Capt, RU + Los, Capt + Los, and RU + Capt + Los (Triple). Recovery of cardiac hemodynamics was evaluated. Results. Recovery of cardiac function was up to 5-fold worse in hearts obtained from diabetic animals compared to controls. Treatment with RU was generally better in preventing or reversing ischemia-induced cardiac dysfunction in normal hearts compared to treatment with Capt or Los alone. In diabetic hearts, RU was generally similarly effective as Capt or Los treatment. Conclusions. RU treatment locally might be considered as an effective therapy or preventative measure in cardiac I/R injury. Importantly, RU was the most effective at improving (a measure of diastolic function) when administered to diabetic hearts after ischemia. 1. Introduction In addition to the circulatory renin-angiotensin-aldosterone system (RAAS), there is now a significant body of evidence supporting the concept of a “local tissue or cellular RAAS” that has important roles in the pathology of cardiovascular diseases [1]. The local production of aldosterone and the discovery of mineralocorticoid receptor (MR) expression in the heart have led to a greater understanding of the role of aldosterone/mineralocorticoid receptor activation in the cardiovascular diseases, including hypertension and heart failure [2, 3]. Aldosterone activates its mineralocorticoid receptor (MR) in the nondiabetic heart and can cause structural and electrical remodelling, fibrosis, oxidative stress, inflammation, and arrhythmias [1, 4–7]. MR antagonists have shown significant benefit in patients with left ventricular dysfunction and myocardial infarction [8]. For example, the recent Eplerenone in Mild Patients Hospitalization And Survival Study in Heart Failure (EMPHASIS-HF) study has shown that eplerenone, an MR antagonist, has beneficial effects in patients with moderate heart failure (NYHA class II) [9]. However, beneficial effects of MR blockade in pathological states such as diabetes are
Organoprotective effects of the fixed combination of angiotensin-converting enzyme inhibitor lisinopril and diuretic hydrochlorothiazide  [cached]
E.A. Ryabikhin,M.E. Mozheiko
Rational Pharmacotherapy in Cardiology , 2009,
Abstract: Aim. To study effects of fixed drug combination of lisinopril and hydrochlorothiazide – Listril Plus (Dr. Reddy’s laboratories), on blood pressure (BP), morphofunctional indexes of left ventricle, elastic features of the main arteries and quality of life in patients with arterial hypertension (HT).Material and methods. 30 patients with HT of 1-3 degree (aged 70,5±2, y.o., HT duration 14,8±1,8 years) received the drug within 12 weeks.Results. Office BP reduced from 161,8±18,6/93,9±8,9 mm Hg to 137,3±12,2/84,1±6,5 mm Hg (p<0,05) after 12 weeks of treatment. The tendency to regression of left ventricle hypertrophy, arterial elasticity improvement and neutral effect on carbohydrate and lipid metabolism was also observed.Conclusion. Listril Plus is effective combined antihypertensive drug which reduces risk of vascular catastrophes and HT complications in patients of high cardiovascular risk.
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