High-dose monotherapy vs low-dose combination therapy of calcium channel blockers and angiotensin receptor blockers in mild to moderate hypertension

Andreadis, Emmanuel A.; Tsourous, G I; Marakomichelakis, G.; Katsanou, Panagiota; Fotia, M E; Vassilopoulos, Charalambos; Diamantopoulos, E J

doi:10.1038/sj.jhh.1001843

Cited by 38 publications

(30 citation statements)

References 16 publications

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“…Our separate results for compliance (21% improvement: Pϭ0.02) and persistence (54% improvement: Pϭ0.07) with FDCs of antihypertensive medications are in keeping with the findings of other lessspecific reviews. 14,28 The 20% reduction in adverse events associated with the use of an FDC reported in our review is perhaps surprising but is consistent with studies published previously 33,34 and a meta-analysis 11 of 82 studies comparing FDCs of 2 antihypertensive agents with various first-line antihypertensive agents as monotherapy. This earlier meta-analysis 11 showed that the use of FDCs had a comparable or even better safety profile than single agents.…”

Section: Discussionsupporting

confidence: 75%

Compliance, Safety, and Effectiveness of Fixed-Dose Combinations of Antihypertensive Agents

2010

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Abstract-Two or more antihypertensive agents are increasingly used to control blood pressure (BP) in hypertensive patients. However, it is unclear whether fixed-dose combinations (FDCs) of 2 antihypertensive agents in a single tablet provide greater benefits than the corresponding free-drug components given separately. A meta-analysis was performed to assess compliance, persistence, BP control, and safety associated with FDCs in comparison with their free-drug components. Fifteen included studies (nϭ32331) reported on Ն1 of the evaluated outcomes. In 3 cohort studies and 2 trials reporting on drug compliance (nϭ17 999), the use of FDCs was associated with significantly better compliance (odds ratio: Pϭ0.19). In 9 trials (nϭ1671) with BP data, use of an FDC was associated with nonsignificant changes in systolic and diastolic BPs of 4.1 mm Hg (95% CI: Ϫ9.8 to 1.5; Pϭ0.15) and 3.1 mm Hg (95% CI: Ϫ7.1 to 0.9; Pϭ0.13), respectively. In these BP-lowering comparisons, there was heterogeneity associated with differences in study design but no publication bias. In conclusion, compared with free-drug combinations, FDCs of antihypertensive agents are associated with a significant improvement in compliance and with nonsignificant beneficial trends in BP and adverse effects. (Hypertension. 2010;55:399-407.)

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Section: Discussionsupporting

confidence: 75%

Compliance, Safety, and Effectiveness of Fixed-Dose Combinations of Antihypertensive Agents

2010

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“…12 Combining agents that target compensatory pathways lowers BP more effectively than monotherapy. [13][14][15][16][17] Rationally selected combination therapy has the potential to mitigate adverse events, such as edema or hypokalemia, that are commonly encountered with monotherapeutic approaches. 14,18,19 The rationale for combining a CCB with a renin-angiotensin-aldosterone system (RAAS) blocker, such as an ACE inhibitor or ARB, is based on their respective mechanisms of action and subsequent vascular effects.…”

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confidence: 99%

Managing Peripheral Edema in Patients With Arterial Hypertension

Epstein¹,

Roberts²

2009

American Journal of Therapeutics

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Calcium channel blockers (CCBs) play a vital role in the management of hypertension. Peripheral edema is the most common side effect reported with CCB monotherapy, especially with high-dose dihydropyridine CCBs. CCB-related peripheral edema is a dose-limiting effect that is usually medically benign but can compromise patient adherence. CCB-related peripheral edema may cause considerable discomfort and patient concern. Patients presenting with peripheral edema should undergo assessment for drug and nondrug causes. Rather than lowering the CCB dose or switching to another monotherapy, combination therapy (e.g, CCB plus a renin-angiotensin-aldosterone system inhibitor) can enhance blood pressure control, generally with lower doses of individual agents, and lessen the risk of adverse events. As recommended by consensus guidelines, addition of a renin-angiotensin-aldosterone system inhibitor as part of combination therapy may accelerate the time to goal blood pressure as well as help alleviate peripheral edema in affected patients. Successful management of CCB-related peripheral edema with lifestyle changes and rational combination therapy is likely to improve blood pressure control and patient outcomes.

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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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High-dose monotherapy vs low-dose combination therapy of calcium channel blockers and angiotensin receptor blockers in mild to moderate hypertension

Cited by 38 publications

References 16 publications

Compliance, Safety, and Effectiveness of Fixed-Dose Combinations of Antihypertensive Agents

Compliance, Safety, and Effectiveness of Fixed-Dose Combinations of Antihypertensive Agents

Managing Peripheral Edema in Patients With Arterial 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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