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Role of triple fixed combination valsartan, amlodipine and hydrochlorothiazide in controlling blood pressure  [cached]
Monica Doménech,Antonio Coca
Patient Preference and Adherence , 2010,
Abstract: Monica Doménech, Antonio CocaHypertension Unit, Department of Internal Medicine, Institute of Internal Medicine and Dermatology, Hospital Clinic (IDIBAPS), University of Barcelona, SpainAbstract: Hypertension is one of the main risk factors for the development of cardiovascular diseases and the search for new therapeutic strategies aimed at optimizing its control remains an ongoing research and clinical challenge. In recent years, there has been a marked increase in the use of combinations of antihypertensive drugs with complementary mechanisms of action, with the aims of reducing blood pressure levels more rapidly and vigorously than strategies employing monotherapy and improving treatment compliance and adhesion. Therefore, as recommended by the 2009 reappraisal of the European Society of Hypertension/European Society of Cardiology Guidelines, the use of a triple combination that combines a calcium channel blocker, an angiotensin II receptor blocker and a thiazide diuretic seems a reasonable and efficacious combination for the management of hypertensive patients with moderate, high or very high risk. This article reviews the clinical trials carried out with the fixed combination of amlodipine/valsartan/hydrochlorothiazide at the doses recommended for each drug in monotherapy. The data show that this combination achieved greater reductions in mean sitting diastolic and systolic blood pressure than amlodipine, valsartan or hydrochlorothiazide in monotherapy, with favorable pharmacodynamic and pharmacokinetic profiles. The triple combination at high single doses should be used with caution in elderly patients and those with renal or liver failure. Although the tolerability and safety of the triple combination are good, the mostfrequently reported adverse effects were peripheral edema, headache and dizziness. Analytical alterations were consistent with the already-known biochemical effects of amlodipine, valsartan or hydrochlorothiazide in monotherapy. In summary, triple-therapy with amlodipine/valsartan/hydrochlorothiazide in a single pill contributes additional advantages to fixed -combinations of two drugs, achieving a greater and more rapid reduction in blood pressure levels in a safe, well-tolerated manner.Keywords: hypertension treatment, antihypertensive fixed-dose triple-therapy, blood pressure control
Role of triple fixed combination valsartan, amlodipine and hydrochlorothiazide in controlling blood pressure
Monica Doménech, Antonio Coca
Patient Preference and Adherence , 2010, DOI: http://dx.doi.org/10.2147/PPA.S6561
Abstract: le of triple fixed combination valsartan, amlodipine and hydrochlorothiazide in controlling blood pressure Review (5369) Total Article Views Authors: Monica Doménech, Antonio Coca Published Date April 2010 Volume 2010:4 Pages 105 - 113 DOI: http://dx.doi.org/10.2147/PPA.S6561 Monica Doménech, Antonio Coca Hypertension Unit, Department of Internal Medicine, Institute of Internal Medicine and Dermatology, Hospital Clinic (IDIBAPS), University of Barcelona, Spain Abstract: Hypertension is one of the main risk factors for the development of cardiovascular diseases and the search for new therapeutic strategies aimed at optimizing its control remains an ongoing research and clinical challenge. In recent years, there has been a marked increase in the use of combinations of antihypertensive drugs with complementary mechanisms of action, with the aims of reducing blood pressure levels more rapidly and vigorously than strategies employing monotherapy and improving treatment compliance and adhesion. Therefore, as recommended by the 2009 reappraisal of the European Society of Hypertension/European Society of Cardiology Guidelines, the use of a triple combination that combines a calcium channel blocker, an angiotensin II receptor blocker and a thiazide diuretic seems a reasonable and efficacious combination for the management of hypertensive patients with moderate, high or very high risk. This article reviews the clinical trials carried out with the fixed combination of amlodipine/valsartan/hydrochlorothiazide at the doses recommended for each drug in monotherapy. The data show that this combination achieved greater reductions in mean sitting diastolic and systolic blood pressure than amlodipine, valsartan or hydrochlorothiazide in monotherapy, with favorable pharmacodynamic and pharmacokinetic profiles. The triple combination at high single doses should be used with caution in elderly patients and those with renal or liver failure. Although the tolerability and safety of the triple combination are good, the mostfrequently reported adverse effects were peripheral edema, headache and dizziness. Analytical alterations were consistent with the already-known biochemical effects of amlodipine, valsartan or hydrochlorothiazide in monotherapy. In summary, triple-therapy with amlodipine/valsartan/hydrochlorothiazide in a single pill contributes additional advantages to fixed -combinations of two drugs, achieving a greater and more rapid reduction in blood pressure levels in a safe, well-tolerated manner.
Role of valsartan, amlodipine and hydrochlorothiazide fixed combination in blood pressure control: an update  [cached]
Maurizio Destro,Francesca Cagnoni,Antonio D’Ospina,et al
Vascular Health and Risk Management , 2010,
Abstract: Maurizio Destro1, Francesca Cagnoni1, Antonio D’Ospina1, Alessandra Rossi Ricci1, Elena Demichele1, Emmanouil Peros1, Augusto Zaninelli2, Paola Preti31Internal Medicine, Ospedale Unificato Broni-Stradella, Stradella (PV), Italy; 2General Medicine, School of Medicine, University of Florence, Florence, Italy; 3Internal Medicine, University of Pavia, Pavia, ItalyAbstract: The treatment of moderate or severe hypertension in most cases requires the contemporaneous use of multiple antihypertensive agents. The most available two-drug combinations have an agent that addresses renin secretion and another one that is statistically more effective in renin-independent hypertension. The practice of combining agents that counteract different mechanisms is the most likely explanation for the fact that most available two-drug combinations have an agent that addresses renin secretion (beta-blocker, angiotensin converting enzyme inhibitor, angiotensin II receptor blocker or direct renin inhibitor) and another one that is more effective in renin-independent hypertension (diuretic, dihydropyridine or non-dihydropyridine calcium channel blocker). Based on these considerations, addition of hydrochlorothiazide to the combination of an antagonist of the renin-angiotensin system with a calcium channel blocker would constitute a logical approach. Inclusion of a diuretic in the triple combination is based on the evidence that these agents are effective and cheap, enhance the effect of other antihypertensive agents, and add a specific effect to individuals with salt-sensitivity of blood pressure. The benefit of triple combination therapy with amlodipine, valsartan and hydrochlorothiazide over its dual component therapies has been demonstrated, and the use of a single pill will simplify therapy resulting in better blood pressure control.Keywords: valsartan, amlodipine, hydrochlorothiazide, HCTZ, blood pressure, hypertension
Role of valsartan, amlodipine and hydrochlorothiazide fixed combination in blood pressure control: an update
Maurizio Destro, Francesca Cagnoni, Antonio D’Ospina, et al
Vascular Health and Risk Management , 2010, DOI: http://dx.doi.org/10.2147/VHRM.S6805
Abstract: le of valsartan, amlodipine and hydrochlorothiazide fixed combination in blood pressure control: an update Review (6892) Total Article Views Authors: Maurizio Destro, Francesca Cagnoni, Antonio D’Ospina, et al Published Date April 2010 Volume 2010:6 Pages 253 - 260 DOI: http://dx.doi.org/10.2147/VHRM.S6805 Maurizio Destro1, Francesca Cagnoni1, Antonio D’Ospina1, Alessandra Rossi Ricci1, Elena Demichele1, Emmanouil Peros1, Augusto Zaninelli2, Paola Preti3 1Internal Medicine, Ospedale Unificato Broni-Stradella, Stradella (PV), Italy; 2General Medicine, School of Medicine, University of Florence, Florence, Italy; 3Internal Medicine, University of Pavia, Pavia, Italy Abstract: The treatment of moderate or severe hypertension in most cases requires the contemporaneous use of multiple antihypertensive agents. The most available two-drug combinations have an agent that addresses renin secretion and another one that is statistically more effective in renin-independent hypertension. The practice of combining agents that counteract different mechanisms is the most likely explanation for the fact that most available two-drug combinations have an agent that addresses renin secretion (beta-blocker, angiotensin converting enzyme inhibitor, angiotensin II receptor blocker or direct renin inhibitor) and another one that is more effective in renin-independent hypertension (diuretic, dihydropyridine or non-dihydropyridine calcium channel blocker). Based on these considerations, addition of hydrochlorothiazide to the combination of an antagonist of the renin-angiotensin system with a calcium channel blocker would constitute a logical approach. Inclusion of a diuretic in the triple combination is based on the evidence that these agents are effective and cheap, enhance the effect of other antihypertensive agents, and add a specific effect to individuals with salt-sensitivity of blood pressure. The benefit of triple combination therapy with amlodipine, valsartan and hydrochlorothiazide over its dual component therapies has been demonstrated, and the use of a single pill will simplify therapy resulting in better blood pressure control.
A critical appraisal of the clinical effectiveness of a fixed combination of valsartan, amlodipine, and hydrochlorothiazide in achieving blood pressure goals
Cheryl L Laffer, Fernando Elijovich
Integrated Blood Pressure Control , 2011, DOI: http://dx.doi.org/10.2147/IBPC.S6562
Abstract: critical appraisal of the clinical effectiveness of a fixed combination of valsartan, amlodipine, and hydrochlorothiazide in achieving blood pressure goals Review (3812) Total Article Views Authors: Cheryl L Laffer, Fernando Elijovich Published Date January 2011 Volume 2011:4 Pages 1 - 5 DOI: http://dx.doi.org/10.2147/IBPC.S6562 Cheryl L Laffer1, Fernando Elijovich2 1Section of Hypertension and Vascular Medicine, 2Division of General Internal Medicine, Department of Medicine, Texas A&M Health Sciences Center College of Medicine, Temple, TX USA Abstract: 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.
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
Critical appraisal and pooled analysis of telmisartan alone or in combination with hydrochlorothiazide for achieving blood pressure goals
Satoshi Morimoto, Nobuyuki Takahashi, Tatsuyori Morita, et al
Integrated Blood Pressure Control , 2010, DOI: http://dx.doi.org/10.2147/IBPC.S9325
Abstract: itical appraisal and pooled analysis of telmisartan alone or in combination with hydrochlorothiazide for achieving blood pressure goals Review (3420) Total Article Views Authors: Satoshi Morimoto, Nobuyuki Takahashi, Tatsuyori Morita, et al Published Date June 2010 Volume 2010:3 Pages 73 - 79 DOI: http://dx.doi.org/10.2147/IBPC.S9325 Satoshi Morimoto, Nobuyuki Takahashi, Tatsuyori Morita, Kazunori Someya, Nagaoki Toyoda, Toshiji Iwasaka Second Department of Internal Medicine, Kansai Medical University 2-3-1, Shinmachi, Hirakata, Osaka 573-1191, Japan Abstract: Rigid control of blood pressure (BP) is essential to prevent cardiovascular disease. However, only about 40% of hypertensive patients undergoing pharmacological intervention with a single agent achieve their BP goals in contemporary clinical practice. Combined therapy using currently available agents is effective in maximizing treatment outcome, although it raises medical costs and decreases the drug compliance rate. To overcome such negative consequences, a combination tablet containing an angiotensin II receptor blocker (ARB) with a small dose of hydrochlorothiazide (HCTZ) is now available on the international market, including Japan. This article briefly describes the unique properties of telmisartan, a highly selective ARB for the angiotensin II type 1 receptor, including its long-acting characteristics and recent prospective multicenter randomized clinical trials, followed by a description of a newly-introduced combination tablet in Japan, which contains telmisartan and HCTZ. This article also reviews its safety and efficacy based on currently available evidence. Finally, evidence comparing telmisartan/HCTZ with other combination therapies is presented.
Significance of initial blood pressure and comorbidity for the efficacy of a fixed combination of an angiotensin receptor blocker and hydrochlorothiazide in clinical practice
Roland E Schmieder, Markus Schwertfeger, Peter Bramlage
Vascular Health and Risk Management , 2009, DOI: http://dx.doi.org/10.2147/VHRM.S7756
Abstract: nificance of initial blood pressure and comorbidity for the efficacy of a fixed combination of an angiotensin receptor blocker and hydrochlorothiazide in clinical practice Original Research (4815) Total Article Views Authors: Roland E Schmieder, Markus Schwertfeger, Peter Bramlage Published Date November 2009 Volume 2009:5 Pages 991 - 1000 DOI: http://dx.doi.org/10.2147/VHRM.S7756 Roland E Schmieder1, Markus Schwertfeger2, Peter Bramlage3 1Department of Nephrology and Hypertension, University Hospital of Erlangen; Germany; 2Sanofi-Aventis Deutschland GmbH, Berlin, Germany; 3Institute of Cardiovascular Pharmacology and Epidemiology, Mahlow, Germany Background: Two-thirds of all patients with arterial hypertension need drug combinations to achieve blood pressure (BP) goals. Fixed combinations have high efficacy and result in high patient compliance. 300 mg irbesartan plus 25 mg hydrochlorothiazide (HCTZ) has been investigated only in clinical trials but not in daily practice. Methods: A multicenter, noninterventional, noncontrolled observational study with 8123 patients seen by 1604 physicians in daily practice. BP reduction (office measurements), co-morbid disease and tolerability were documented over a 6-month observational period. Results: At mean baseline BP of 161 ± 15/94 ± 10 mmHg, administering of fixed combination resulted in a substantial BP reduction averaging 28 ± 15/14 ± 10 mmHg (P < 0.001). Decrease of systolic BP ran parallel with increasing systolic baseline BP (Spearman’s Rho –0.731; P < 0.0001; diastolic BP vs diastolic baseline BP Rho 0.740; P < 0.0001), independent from patient characteristics (age, obesity, diabetes or nephropathy) but enhanced with short history of hypertension (P < 0.0001 vs long history), prior beta blockers (P = 0.001 vs prior angiotensin receptor blockers [ARBs]), prior calcium channel blockers (P = 0.046 vs prior ARBs) and no prior medication (P = 0.012 vs prior ARBs). High compliance (>98%) and low incidence of adverse events (0.66%) were documented. Conclusions: The fixed combination of 300 mg irbesartan with 25 mg HCTZ was efficacious and tolerable in an unselected patient population in primary care.
Critical appraisal and pooled analysis of telmisartan alone or in combination with hydrochlorothiazide for achieving blood pressure goals  [cached]
Satoshi Morimoto,Nobuyuki Takahashi,Tatsuyori Morita,et al
Integrated Blood Pressure Control , 2010,
Abstract: Satoshi Morimoto, Nobuyuki Takahashi, Tatsuyori Morita, Kazunori Someya, Nagaoki Toyoda, Toshiji IwasakaSecond Department of Internal Medicine, Kansai Medical University 2-3-1, Shinmachi, Hirakata, Osaka 573-1191, JapanAbstract: Rigid control of blood pressure (BP) is essential to prevent cardiovascular disease. However, only about 40% of hypertensive patients undergoing pharmacological intervention with a single agent achieve their BP goals in contemporary clinical practice. Combined therapy using currently available agents is effective in maximizing treatment outcome, although it raises medical costs and decreases the drug compliance rate. To overcome such negative consequences, a combination tablet containing an angiotensin II receptor blocker (ARB) with a small dose of hydrochlorothiazide (HCTZ) is now available on the international market, including Japan. This article briefly describes the unique properties of telmisartan, a highly selective ARB for the angiotensin II type 1 receptor, including its long-acting characteristics and recent prospective multicenter randomized clinical trials, followed by a description of a newly-introduced combination tablet in Japan, which contains telmisartan and HCTZ. This article also reviews its safety and efficacy based on currently available evidence. Finally, evidence comparing telmisartan/HCTZ with other combination therapies is presented.Keywords: angiotensin II receptor blocker, ARB, blood pressure, hypertension, diuretics, PPAR-γ
Significance of initial blood pressure and comorbidity for the efficacy of a fixed combination of an angiotensin receptor blocker and hydrochlorothiazide in clinical practice  [cached]
Roland E Schmieder,Markus Schwertfeger,Peter Bramlage
Vascular Health and Risk Management , 2009,
Abstract: Roland E Schmieder1, Markus Schwertfeger2, Peter Bramlage31Department of Nephrology and Hypertension, University Hospital of Erlangen; Germany; 2Sanofi-Aventis Deutschland GmbH, Berlin, Germany; 3Institute of Cardiovascular Pharmacology and Epidemiology, Mahlow, GermanyBackground: Two-thirds of all patients with arterial hypertension need drug combinations to achieve blood pressure (BP) goals. Fixed combinations have high efficacy and result in high patient compliance. 300 mg irbesartan plus 25 mg hydrochlorothiazide (HCTZ) has been investigated only in clinical trials but not in daily practice.Methods: A multicenter, noninterventional, noncontrolled observational study with 8123 patients seen by 1604 physicians in daily practice. BP reduction (office measurements), co-morbid disease and tolerability were documented over a 6-month observational period.Results: At mean baseline BP of 161 ± 15/94 ± 10 mmHg, administering of fixed combination resulted in a substantial BP reduction averaging 28 ± 15/14 ± 10 mmHg (P < 0.001). Decrease of systolic BP ran parallel with increasing systolic baseline BP (Spearman’s Rho –0.731; P < 0.0001; diastolic BP vs diastolic baseline BP Rho 0.740; P < 0.0001), independent from patient characteristics (age, obesity, diabetes or nephropathy) but enhanced with short history of hypertension (P < 0.0001 vs long history), prior beta blockers (P = 0.001 vs prior angiotensin receptor blockers [ARBs]), prior calcium channel blockers (P = 0.046 vs prior ARBs) and no prior medication (P = 0.012 vs prior ARBs). High compliance (>98%) and low incidence of adverse events (0.66%) were documented.Conclusions: The fixed combination of 300 mg irbesartan with 25 mg HCTZ was efficacious and tolerable in an unselected patient population in primary care.Keywords: hypertension, combination therapy, obesity, irbesartan, noninterventional study, diuretics
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