Triple Antihypertensive Therapy With Amlodipine, Valsartan, and Hydrochlorothiazide A Randomized Clinical Trial
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.
- SourceAvailable from: Massimo Volpe
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- "In the BP-CRUSH trial , 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 , a 3-drug combination of valsartan, hydrochlorothiazide, and amlodipine resulted in Table 1 Hints of nonadherence to pharmacologic therapy. "
ABSTRACT: Although the blood pressure (BP) of many patients can be controlled using standard combinations, treatment of hypertension frequently represents a clinical challenge to the primary care physician. This article will review best practices for managing patients with easy- and difficult-to-treat hypertension, including preferred antihypertensive combinations, optimizing adherence and persistence, recognizing white-coat hypertension, and intensifying therapy for treatment-resistant patients. Each physician must decide based on his or her own level of experience at what point a patient becomes too challenging and would benefit from referral to a hypertension specialist for more intensive management and to complete the exclusion of secondary forms of arterial hypertension. With intensive pharmacotherapy, many patients with difficult-to-treat hypertension can achieve BP control. If it fails, interventional strategies (e.g., renal denervation) are a valid option to get BP controlled.International journal of cardiology 01/2014; 172(1). DOI:10.1016/j.ijcard.2013.12.125 · 6.18 Impact Factor
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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). "
ABSTRACT: A simple and selective HPLC-DAD stability indicating method was developed for the simultaneous determination of the three antihypertensive drugs amlodipine besylate (AML), valsartan (VAL) and hydrochlorothiazide (HCT) in their combined formulation. Effective chromatographic separation was achieved using Zorbax SB-C8 column (4.6 × 250 mm, 5 μm ps) with gradient elution of the mobile phase composed of 0.025 M phosphoric acid and acetonitrile at a flow rate of 1 mL/min. The multiple wavelength detector was set at 238 nm for measurement of AML and 225 nm for both VAL and HCT. Quantification was based on measuring the peak areas. The three compounds were resolved with retention times of 4.9, 6.4 and 8.3 min for HCT, AML and VAL respectively. Analytical performance of the proposed HPLC procedure was statistically validated with respect to system suitability, linearity, ranges, precision, accuracy, specificity, robustness, detection and quantification limits. The linearity ranges were 5–200, 5–200 and 10–200 μg/mL for AML, VAL and HCT respectively with correlation coefficients >0.9993. The three drugs were subjected to stress conditions of acidic and alkaline hydrolysis, oxidation, photolysis and thermal degradation. The proposed method proved to be stability-indicating by resolution of the analytes from their forced-degradation products. The validated HPLC method was applied to the analysis of the cited antihypertensive drugs in their combined pharmaceutical tablets (Exforge HCT). The proposed method made use of DAD as a tool for peak identity and purity confirmation.Arabian Journal of Chemistry 04/2013; 84. DOI:10.1016/j.arabjc.2013.04.012 · 2.68 Impact Factor
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ABSTRACT: A 7 kHz-band speech CODEC using an advanced digital signal processor is developed. The coding algorithm for this CODEC requires greater processing power due to its complexity and high sampling rate. A high-performance digital signal processor VLSI, "DSSP-1", is applied to this CODEC. Arithmetic word-length, arithmetic operation speed, and memory capacity required for this CODEC is evaluated. DSSP-1 can satisfy these requirements; this CODEC has been built with two DSSP-1 chips and several memory chips.Acoustics, Speech, and Signal Processing, IEEE International Conference on ICASSP '86.; 05/1986