Triple Antihypertensive Therapy With Amlodipine, Valsartan, and Hydrochlorothiazide A Randomized Clinical Trial

Sleep/Wake Disorders Center, University of Alabama at Birmingham, 35294, USA.
Hypertension (Impact Factor: 7.63). 08/2009; 54(1):32-9. DOI: 10.1161/HYPERTENSIONAHA.109.131300
Source: PubMed

ABSTRACT Many patients with hypertension require > or =3 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: > or =145 mm Hg; mean sitting diastolic BP: > or =100 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. Triple therapy was significantly superior to all of the dual therapies in reducing mean sitting systolic BP and mean sitting diastolic BP from baseline to end point (all P<0.0001). Significantly more patients on triple therapy achieved overall BP control (<140/90 mm Hg; P<0.0001) and systolic and diastolic control (P< or =0.0002) compared with each dual therapy. Aml/Val/HCTZ was well tolerated. The benefits of triple therapy over dual therapy were observed regardless of age, sex, race, ethnicity, or baseline mean sitting systolic BP. In conclusion, this study demonstrates the efficacy/safety of treating moderate and severe hypertension with Aml/Val/HCTZ 10/320/25 mg.

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    • "In the BP-CRUSH trial [26], a treatment algorithm in which patients were titrated to triple therapy with amlodipine, olmesartan, and hydrochlorothiazide, 90% of patients achieved BP control. In another trial [27], a 3-drug combination of valsartan, hydrochlorothiazide, and amlodipine resulted in Table 1 Hints of nonadherence to pharmacologic therapy. "
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    • "In 2009, the US Food and Drug Administration (FDA) and the European Medicines Agency approved a triple fixed-dose combination of AML, VAL and HCT. It was found that the use of this triple combination was generally more effective in reducing blood pressure and providing overall blood pressure control than the dual combination therapies regardless of age, race, gender, ethnicity, or hypertension severity (Calhoun et al., 2009 and Chrysant, 2011). "
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