Triple Antihypertensive Therapy With Amlodipine, Valsartan, and Hydrochlorothiazide

Abstract

Abstract-Many patients with hypertension require Ն3 agents to achieve target blood pressure (BP). The efficacy/safety of the dual combinations of valsartan (Val)/hydrochlorothiazide (HCTZ) and amlodipine (Aml)/Val in hypertension are well established. This randomized, double-blind study evaluated the efficacy/safety of triple therapy with Aml/Val/ HCTZ for moderate or severe hypertension (mean sitting systolic BP: Ն145 mm Hg; mean sitting diastolic BP: Ն100 mm Hg). The study included a single-blind, placebo run-in period, followed by double-blind treatment for 8 weeks; patients were randomly assigned to 1 of 4 groups titrated to Aml/Val/HCTZ 10/320/25 mg, Val/HCTZ 320/25 mg, Aml/Val 10/320 mg, or Aml/HCTZ 10/25 mg once daily. Dual-therapy recipients received half of the target doses of both agents for the first 2 weeks, titrating to target doses during week 3. Those on triple therapy received Val/HCTZ 160.0/12.5 mg during week 1, Aml/Val/HCTZ 5.0/160.0/12.5 mg during week 2, and target doses of all 3 of the agents during week 3. Of the 4285 patients enrolled, 2271 were randomly assigned to treatment, and 2060 completed the study. Key Words: amlodipine Ⅲ valsartan Ⅲ hydrochlorothiazide Ⅲ hypertension Ⅲ triple therapy H ypertension treatment guidelines recommend a target blood pressure (BP) goal of Ͻ140/90 mm Hg for uncomplicated hypertension. Target goals are lower (Ͻ130/ 80 mm Hg) for patients with hypertension complicated by diabetes mellitus or renal disease or for those considered at high risk (eg, history of stroke or myocardial infarction). 1,2 To facilitate attainment of these target goals in at-risk patients, the guidelines recommend dual therapy as the initial treatment. 1,2 However, despite extensive evidence of the negative effects of poorly controlled BP and the numerous antihypertensive agents available, only approximately one third of hypertensive patients achieve adequate BP control in the United States. 3 Because of the multifactorial nature of hypertension, most patients require treatment with Ͼ1 antihypertensive agent to achieve target pressure, 4 with many patients requiring Ն3 agents. 5,6 Antihypertensive regimens that include Ն2 agents with complementary mechanisms of action may result in greater reductions in BP than the single-agent components. For example, the use of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic represents a logical choice for combination therapy. A calcium channel blocker inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle, an angiotensin receptor blocker inhibits angiotensin II-mediated vasoconstriction and renal sodium retention, and a thiazide diuretic reduces intravascular volume and total body sodium. In addition to potential efficacy benefits when used in combination, one antihypertensive agent may attenuate certain adverse effects of another. 7,8 For example, in addition to valsartan (Val) and hydrochlorothiazide (HCTZ) providing a greater antihypertensive effect in combination over ...

Effectiveness and safety of high-dose valsartan monotherapy in hypertension treatment: the ValTop study

“…20,21 Although additional reductions up to 2-3 mm Hg have been reported for valsartan/hydrochlorothiazide combination, in most studies, the maximal antihypertensive effect was typically seen within 4 weeks. [20][21][22] This is reflected in the current prescribing information for valsartan and valsartan/HCTZ, which states that the antihypertensive effect is substantially present within 2 weeks, and maximal effects are attained within 4 weeks and persist during long-term therapy.…”

Angiotensin Receptor Blockers: Pharmacology, Efficacy, and Safety

“…Two of the ARBs, valsartan 45 and olmesartan, 46 are now available as part of 3-drug combinations that also include amlodipine and HCTZ. It is noteworthy that combinations that contain all 3 drugs are more effective than a combination that includes any 2 of the 3 drugs.…”

Achieving blood pressure goal: initial therapy with valsartan/hydrochlorothiazide combination compared with monotherapy

“…8,[24][25][26] In moderate and severe hypertensive patients, triple therapy with the combination of amlodipine/Val/HCTZ has been shown to produce significantly greater BP reductions than dual therapy with amlodipine/Val, Val/HCTZ or amlodipine/ HCTZ. 27 In a previously reported study by Calhoun et al, 28 the primary objective was to compare initial therapy with Val/HCTZ combination therapy with Val monotherapy in patients with severe hypertension. Patients initiated therapy with either Val 160 mg or Val/HCTZ 160/12.5 mg and were force-titrated to Val 320 mg and Val/HCTZ 320/25 mg, respectively.…”