Targeting mechanisms of hypertensive vascular disease with dual calcium channel and renin–angiotensin system blockade

Weir, Matthew R.

doi:10.1038/sj.jhh.1002254

Cited by 26 publications

(18 citation statements)

References 105 publications

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“…The rationale for combination therapy with agents that block the RAAS and a CCB or diuretic is well founded [40]. However, the use of ARBs and CCBs has independent benefits beyond BP lowering, on morbidity and mortality in patients with hypertension and comorbid conditions.…”

Section: Reviewmentioning

confidence: 99%

Combination therapy in hypertension: An update

Kalra

Agrawal

2010

Diabetol Metab Syndr

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Meticulous control of blood pressure is required in patients with hypertension to produce the maximum reduction in clinical cardiovascular end points, especially in patients with comorbidities like diabetes mellitus where more aggressive blood pressure lowering might be beneficial. Recent clinical trials suggest that the approach of using monotherapy for the control of hypertension is not likely to be successful in most patients. Combination therapy may be theoretically favored by the fact that multiple factors contribute to hypertension, and achieving control of blood pressure with single agent acting through one particular mechanism may not be possible. Regimens can either be fixed dose combinations or drugs added sequentially one after other. Combining the drugs makes them available in a convenient dosing format, lower the dose of individual component, thus, reducing the side effects and improving compliance. Classes of antihypertensive agents which have been commonly used are angiotensin receptor blockers, thiazide diuretics, beta and alpha blockers, calcium antagonists and angiotensin-converting enzyme inhibitors. Thiazide diuretics and calcium channel blockers are effective, as well as combinations that include renin-angiotensin-aldosterone system blockers, in reducing BP. The majority of currently available fixed-dose combinations are diuretic-based. Combinations may be individualized according to the presence of comorbidities like diabetes mellitus, chronic renal failure, heart failure, thyroid disorders and for special population groups like elderly and pregnant females.

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Section: Reviewmentioning

confidence: 99%

Combination therapy in hypertension: An update

Kalra

Agrawal

2010

Diabetol Metab Syndr

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“…9 One such approach involves the use of an ARB plus the CCB amlodipine, a combination supported both by clinical evidence [11][12][13][14][15][16][17][18][19] and mechanism of action considerations. 20 Recently, a single-dose combination of the ARB telmisartan and amlodipine was approved in the United States for the treatment of HTN and as initial therapy for patients likely to require multiple antihypertensive agents to reach BP targets. This single-dose therapy is available in the following combinations: 40 mg telmisartan/5 mg amlodipine equivalent (40/5), 40 mg telmisartan/10 mg amlodipine equivalent (40/10), 80 mg telmisartan/5 mg amlodipine equivalent (80/5), and 80 mg telmisartan/10 mg amlodipine equivalent (80/10).…”

Section: Introductionmentioning

confidence: 99%

Review: A Single-Pill Combination of Telmisartan plus Amlodipine for the Treatment of Hypertension

Guthrie

2011

Postgraduate Medicine

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Despite an increased proportion of patients with hypertension achieving recommended blood pressure (BP) targets, BP control remains suboptimal in many patients. A range of combination therapies utilizing medications with differing mechanisms of action have been shown to provide superior BP-lowering efficacy than monotherapy with individual components. Single-pill combinations deliver improved convenience and may help to improve patient compliance. A single-pill combination of the angiotensin receptor blocker (ARB) telmisartan and the calcium channel blocker (CCB) amlodipine has recently been approved in 4 different doses (telmisartan/amlodipine 40 mg/5 mg, 40 mg/10 mg, 80 mg/5 mg, and 80 mg/10 mg) for antihypertensive use in the United States. In an 8-week clinical study (N = 1461), these combinations were superior to monotherapy with telmisartan or with amlodipine with respect to the primary endpoint, change in diastolic BP (DBP) from baseline (mean baseline BP, 153.2 [± 12.1]/101.7 [± 4.3] mm Hg) to study end (placebo-corrected reductions of 10.3, 14.0, 12.0, and 13.9 mm Hg, respectively), as well as in multiple secondary endpoints, including change in systolic BP (SBP), DBP response, SBP response, BP control (< 140/< 90 mm Hg), and DBP control (< 90 mm Hg). The telmisartan plus amlodipine combinations were well tolerated, with the incidence of adverse events similar to placebo; the incidence of peripheral edema was lower with the 40 mg/10 mg and 80 mg/10 mg combinations than with amlodipine 10 mg alone. In another study (N = 858), the highest-dose combination (80 mg/10 mg) demonstrated superior BP-lowering efficacy than same-dose monotherapy with either telmisartan or amlodipine in patients with severe hypertension (SBP ≥ 180 and DBP ≥ 95 mm Hg). Single-pill telmisartan plus amlodipine combination therapy appears to be an effective and well-tolerated treatment as initial therapy for patients likely to require > 1 antihypertensive agent to reach BP targets.

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Section: 2mentioning

confidence: 99%

“…There are published data suggesting that the combination of a calcium channel blocker (CCB) with an angiotensin II receptor blocker (ARB) is beneficial. 5,[7][8][9][10][11][12][13][14][15][16][17] Furthermore, such a combination approach involving adding a blocker of the renin-angiotensin system (RAS) to a CCB appears to be associated with a reduction in the incidence of CCB-related edema;18 the exact mechanism for this attenuation of edema remains to be established but appears to involve the ability of RAS blockers to counteract the microcirculatory changes induced by CCBs and dilate venous capacitance vessels. 19,20 The aim of the current study was to evaluate the efficacy and safety of two different strengths of singlepill combinations (SPCs) of telmisartan 40 or 80 mg (T40 or T80) and amlodipine 5 mg (A5) compared with that of monotherapy with A5 and amlodipine 10 mg (A10) in a hypertensive patient population whose BP is not controlled by A5 alone.…”

mentioning

confidence: 99%

Telmisartan and Amlodipine Single‐Pill Combinations vs Amlodipine Monotherapy for Superior Blood Pressure Lowering and Improved Tolerability in Patients With Uncontrolled Hypertension: Results of the TEAMSTA‐5 Study

Neldam

Lang

Jones

2011

J of Clinical Hypertension

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An 8-week, randomized, double-blind, controlled study with single-pill combinations of telmisartan 40 mg or 80 mg ⁄ amlodipine 5 mg (T40 ⁄ A5 or T80 ⁄ A5) vs monotherapy with amlodipine 5 mg or 10 mg (A10) in 1097 patients with uncontrolled hypertension (diastolic blood pressure [BP] !90 mm Hg). T40 ⁄ A5 and T80 ⁄ A5 resulted in significantly greater (P<.0001) reductions in seated trough systolic ⁄ diastolic BP vs A5 ()7.4 mm Hg ⁄ )3.6 mm Hg; )8.8 mm Hg ⁄ )4.9 mm Hg) and a significantly greater (P<.001) proportion of patients achieving systolic ⁄ diastolic BP goal rate (60.0% ⁄ 56.7%; 65.7% ⁄ 63.8%) vs A5 (39.2% ⁄ 42.0%). Superior BP reductions were also seen with T40-T80 ⁄ A5 vs A10, with BP goal rates at least as high as with A10; however, there was significantly more peripheral edema with A10 (27.2% vs 4.3% for pooled T40-T80 ⁄ A5; P<.0001). Switching patients with uncontrolled BP to a single-pill combination of T40 ⁄ A5 or T80 ⁄ A5 is a better treatment option than up-titration to full-dose monotherapy with A10. J Clin Hypertens (Greenwich). 2011;13:459-466. Ó2011 Wiley Periodicals, Inc.Current European and US guidelines emphasize the need for aggressive pharmacologic treatment of hypertension to reduce cardiovascular (CV) risk.1,2 Large clinical studies suggest that more than 50% of hypertensive patients receiving monotherapy with amlodipine 5 mg do not have their blood pressure (BP) controlled adequately, 3,4 and the 2007 guidelines from the European Society of Hypertension ⁄ European Society of Cardiology (ESH ⁄ ESC) emphasizes that the ability of any antihypertensive agent used alone to achieve target BP values (<140 ⁄ 90 mm Hg) does not exceed 20% to 30% of the overall hypertensive population except in patients with grade 1 hypertension.1 When initial monotherapy with an antihypertensive agent does not have the desired BP-lowering effect, the dose of the antihypertensive agent is often increased. Uptitrating amlodipine from 5 mg to 10 mg may improve BP response rates but typically also increases the incidence of side effects such as edema, which, in turn, may lead to reduced patient compliance and possibly to treatment discontinuation. To achieve the specified BP goals and to reduce the risk of CV morbidity and mortality, the majority of patients with hypertension will require !2 antihypertensive medications. 1,2Two drugs from different classes with complimentary mechanisms of action may result in additional BP decreases compared with either agent used alone.5 In a recent meta-analysis, Wald and colleagues 6 showed that the combination of drugs from two different antihypertensive drug classes was up to 5 times more effective in lowering BP than increasing the dose of one drug. Hypertensive patients whose BP is not controlled adequately by monotherapy amlodipine 5 mg may therefore benefit from combination therapy by adding an antihypertensive agent with a distinct and complementary mechanism of action. There are published data suggesting that the combination of a calcium channel blocker (CCB) with an ang...

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Targeting mechanisms of hypertensive vascular disease with dual calcium channel and renin–angiotensin system blockade

Cited by 26 publications

References 105 publications

Combination therapy in hypertension: An update

Combination therapy in hypertension: An update

Review: A Single-Pill Combination of Telmisartan plus Amlodipine for the Treatment of Hypertension

Telmisartan and Amlodipine Single‐Pill Combinations vs Amlodipine Monotherapy for Superior Blood Pressure Lowering and Improved Tolerability in Patients With Uncontrolled Hypertension: Results of the TEAMSTA‐5 Study

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