Amlodipine and Valsartan Combined and as Monotherapy in Stage 2, Elderly, and Black Hypertensive Patients: Subgroup Analyses of 2 Randomized, Placebo‐Controlled Studies

Abstract

Patients with difficult to control hypertension typically require 2 or more agents to achieve goal blood pressure (BP) levels. Fixed-dose combination therapies with lower doses generally are well tolerated and more effective than higher-dose monotherapy. The authors performed prespecified and post hoc subgroup analyses of 2 double-blind, randomized, placebo-controlled trials that assessed the efficacy and safety of amlodipine and valsartan, alone and in combination, in patients with mild to moderate hypertension. Patients were randomized to amlodipine (study 1: 2.5 or 5 mg/d; study 2: 10 mg/d), valsartan (study 1: 40, 80, 160, or 320 mg/d; study 2: 160 or 320 mg/d), combination therapy across the same dose ranges, or placebo. Analyses were performed on changes from baseline in mean sitting systolic and diastolic BP and the occurrence of adverse events in specific subgroups of patients (ie, those with stage 2 hypertension [post hoc], the elderly [65 years or older], and blacks [both prespecified]). Amlodipine + valsartan combination therapy was associated with greater BP-lowering effects in the subgroups compared with each respective monotherapy and placebo. These findings were consistent with the primary efficacy analysis results from the overall study populations. Combination regimens were generally well tolerated by all patient subgroups.

Mitigation of calcium channel blocker-related oedema in hypertension by antagonists of the renin–angiotensin system

“…First, as CCBs and RAS inhibitors effect vasodilation by different mechanisms, their antihypertensive effects are additive when used in combination. [5][6][7][8]64,65 This effect is exemplified by data from a recent trial involving amlodipine and olmesartan medoxomil, which showed that both the absolute BP reductions achieved and the rate of target BP attainment were significantly greater in patients who received combination therapy than in those who received amlodipine monotherapy. 5 It is important to note that, in contrast to many other studies, the target BP in this trial was defined using both diastolic blood pressure and systolic blood pressure (o140/90 mm Hg for the majority of patients; o130/80 mm Hg for those with diabetes).…”

“…This combination, which is recommended for use by the current guidelines, 2,3 is highly effective in reducing BP in hypertensive patients. [4][5][6][7][8] When used as monotherapy, CCBs are associated with a substantial risk of peripheral oedema, 9-12 a side effect that may reduce patient compliance or necessitate switching to a different drug. 13,14 The incidence of oedema in CCB-treated patients can be substantially reduced by addition of an inhibitor of the renin-angiotensin system (RAS), that is, an ARB or an angiotensin-converting enzyme inhibitor (ACEI).…”

Nifedipine GITS/Candesartan Combination Therapy Lowers Blood Pressure Across Different Baseline Systolic and Diastolic Blood Pressure Categories: DISTINCT Study Subanalyses

“…The nifedipine GITS formulation offers, in addition, the advantage of controlled drug release, making it suitable for once‐daily administration, and an observational study suggests that candesartan reduces the risk of cardiovascular disease and heart failure in comparison with another angiotensin receptor blocker (ARB), losartan 16, 18. A placebo arm was included in DISTINCT in accordance with the International Conference on Harmonisation guideline for evaluation of fixed‐dose combination products for the treatment of hypertension and similar to other multifactorial trials of combination antihypertensive therapies 20, 21, 22, 23. DISTINCT demonstrated that initial combination therapy with nifedipine GITS/candesartan cilexetil was more effective in lowering BP and meeting target BP goals (SBP <140 and DBP <90 mm Hg) vs respective monotherapies at the same doses in participants with hypertension.…”

Results of Pharmacoepidemiologic Study of Arterial Hypertension Pifagor Iv: Physicians Compliance

“…Так, получила обоснования комбинация антагонистов кальция с ингибиторами АПФ, в результате взаимо-действия более значительно уменьшается пульсовое АД и максимально снижается риск развития сердечно-сосудистых осложнений (результаты исследования ASCOT-BPLA). Особое значение получила комбина-ция антагонистов кальция и АРАII, фармакодинами-ческое взаимодействие которых позволяет почти в 2 раза уменьшать частоту развития отеков лодыжек, связанных с применением антагонистов кальция [14].…”