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Introducing candesartan 32 mg plus hydrochlorothiazide 25 mg in previously untreated patients with severe essential hypertension.

ABSTRACT: PURPOSE:To investigate the efficacy of candesartan 32 mg and hydrochlorothiazide (HCTZ) 25 mg combination in patients with severe essential hypertension. PATIENTS AND METHODS:In this prospective, open-label, single-group study, 106 previously untreated patients with a baseline systolic blood pressure (SBP) of 150-200 mmHg, and a diastolic blood pressure (DBP) of 110 to 120 mmHg, started with candesartan 16 mg during the first week. HCTZ 12.5 mg was added at week 2 and from fourth week onwards candesartan 32 mg plus HCTZ 25 mg was given over 6 weeks. The primary efficacy endpoint was mean reduction in SBP and DBP after 9 weeks. Response was defined as a decrease in SBP to <140 mmHg and/or by ?20 mmHg and in DBP to <90 mmHg and/or by ?10 mmHg. A second response criterion defined blood pressure reduction below 140/90 mmHg. RESULTS:Blood pressure was lowered from 180.0 ± 11.7/114.7 ± 3.1 mmHg by SBP 44.4 ± 16.8 and DBP 32.0 ± 11.3 mmHg (P < 0.0001). Response was 92.4% and 64.8% achieved <140/90 mmHg. Each titration step produced a statistically significant and clinically relevant decrease in SBP and DBP, but a level below 140/90 mmHg was achieved by >50% of the patients only after the third titration step. Adverse reactions were reported by 3.8% of the patients. The disorders were in line with the known safety profile of the study drugs. CONCLUSION:A stepped treatment approach with candesartan/HCTZ combinations is effective and safe to achieve a swift blood pressure reduction in newly diagnosed, severe hypertension. The target of <140/90 mmHg was reached by >50% of the patients only after taking the full dose of candesartan 32 mg and HCTZ 25 mg.

SUBMITTER: Baumgart P

PROVIDER: S-EPMC5045001 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Introducing candesartan 32 mg plus hydrochlorothiazide 25 mg in previously untreated patients with severe essential hypertension.

Baumgart Peter P Naudts Ingomar I Kiel Gerhard G

Pragmatic and observational research 20110429

<h4>Purpose</h4>To investigate the efficacy of candesartan 32 mg and hydrochlorothiazide (HCTZ) 25 mg combination in patients with severe essential hypertension.<h4>Patients and methods</h4>In this prospective, open-label, single-group study, 106 previously untreated patients with a baseline systolic blood pressure (SBP) of 150-200 mmHg, and a diastolic blood pressure (DBP) of 110 to 120 mmHg, started with candesartan 16 mg during the first week. HCTZ 12.5 mg was added at week 2 and from fourth ...[more]

PMID: 27774009

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Project description:IntroductionIn most treated patients with hypertension, a two or more drug combination is required to achieve adequate blood pressure (BP) control. In our study we assessed whether the combination of zofenopril + hydrochlorothiazide (HCTZ) was at least as effective as irbesartan + HCTZ in essential hypertensives with at least one additional cardiovascular risk factor, uncontrolled by a previous monotherapy.MethodsAfter a 2-week placebo washout, 361 treated hypertensive patients [office sitting diastolic BP (DBP), ≥90 mmHg], aged 18-75 years, were randomized double blind to 18-week treatment with zofenopril 30 mg plus HCTZ 12.5 mg or irbesartan 150 mg plus HCTZ 12.5 mg once daily, in an international, multicenter study. After the first 6 and 12 weeks, zofenopril and irbesartan doses could be doubled in non-normalized subjects. The primary study end point was the office sitting DBP reduction after 18 weeks of treatment. Secondary end points included office systolic BP (SBP), ambulatory BP and high sensitivity C-reactive protein (hs-CRP).ResultsThe between-treatment difference for office DBP averaged to +1.0 (95% CI -0.4, +0.8) mmHg (P = 0.150), the upper limit of the 95% confidence interval being inferior to the protocol-defined non-inferiority limit (3 mmHg). In the subset of patients with valid ambulatory BP, no difference in 24-h average DBP [n = 181; 6.7 (8.7, 4.6) zofenopril + HCTZ vs. 6.3 (8.8, 3.7) mmHg irbesartan + HCTZ, P = 0.810] and SBP reductions [11.7 (15.4, 8.0) vs. 12.6 (17.2, 8.0) mmHg, P = 0.758] were observed between the two treatment groups. hs-CRP was reduced by zofenopril + HCTZ [-0.52 (-1.05, 0.01) mg/L], while it was increased by irbesartan plus HCTZ [0.97 (0.29, 1.65) mg/L, P = 0.001 between treatments].ConclusionIn previously monotherapy-treated, uncontrolled patients with hypertension, zofenopril 30-60 mg + HCTZ 12.5 mg is as effective as irbesartan 150-300 mg plus HCTZ 12.5 mg, with the added value of a potential protective effect against vascular inflammation.

Project description:BackgroundThe purpose of this work was to describe the efficacy and safety of a telmisartan 80 mg + hydrochlorothiazide 25 mg (T80/H25) single-pill combination therapy in patients with moderate-severe hypertension (mean seated trough cuff systolic blood pressure [BP] ≥ 160 mmHg and diastolic BP ≥ 100 mmHg) in specific patient subpopulations.MethodsThis was a planned analysis of a double-blind, multicenter, parallel-group trial that demonstrated the superiority of a single-pill combination of T80/H25 versus T80 monotherapy in terms of systolic BP change from baseline to week 7. Subpopulations included older (aged ≥ 65 years) versus younger, gender, race, hypertension severity, and prior antihypertensive therapy. Endpoints were change from baseline in mean seated trough cuff systolic and diastolic BP, proportion of patients achieving their BP goal (systolic/diastolic BP < 140/90 mmHg), and proportion of patients attaining systolic BP reductions of >30 mmHg and >40 mmHg.ResultsAcross all subgroups, the T80/H25 single-pill combination provided consistently greater systolic and diastolic BP reductions than T80 and more patients had systolic BP reductions of >30 mmHg. In the T80 and T80/H25 groups, BP control was achieved in 34.1% and 48.8% of men, 35.5% and 62.7% of women, 34.5% and 56.6% of Asians, 22.6% and 38.6% of blacks, 36.7% and 57.8% of whites, 36.9% and 57.5% of patients < 65 years, 29.3% and 49.3% ≥65 years, 44.2% and 66.2% of those with grade 2 hypertension, 20.4% and 39.4% of those with grade 3 hypertension, 38.9% and 53.2% of previously untreated patients, 38.1% and 62.5% of patients previously treated with one antihypertensive, and 29.7% and 48.9% of patients previously treated with two or more antihypertensive agents respectively. Treatment was generally well tolerated across the patient subgroups.ConclusionThe T80/H25 single-pill combination provides consistent BP reductions and higher goal attainment rates versus T80 across a range of hypertensive patient subgroups, which are likely to have a positive impact on patients' cardiovascular risk.

Project description:BACKGROUND:Bevacizumab, a VEGF-A inhibitor, in combination with chemotherapy, has proven to increase progression-free survival (PFS) and overall survival in multiple lines of therapy of metastatic colorectal cancer (mCRC). The angiogenic factor angiopoetin-2 (Ang-2) is associated with poor prognosis in many cancers, including mCRC. Preclinical models demonstrate improved activity when inhibiting both VEGF-A and Ang-2, suggesting that the dual VEGF-A and Ang-2 blocker vanucizumab (RO5520985 or RG-7221) may improve clinical outcomes. This phase II trial evaluated the efficacy of vanucizumab plus modified (m)FOLFOX-6 (folinic acid (leucovorin), fluorouracil (5-FU) and oxaliplatin) versus bevacizumab/mFOLFOX-6 for first-line mCRC. PATIENTS AND METHODS:All patients received mFOLFOX-6 and were randomized 1:1 to also receive vanucizumab 2,000 mg or bevacizumab 5 mg/kg every other week. Oxaliplatin was given for eight cycles; other agents were continued until disease progression or unacceptable toxicity for a maximum of 24 months. The primary endpoint was investigator-assessed PFS. RESULTS:One hundred eighty-nine patients were randomized (vanucizumab, n =?94; bevacizumab, n =?95). The number of PFS events was comparable (vanucizumab, n = 39; bevacizumab, n =?43). The hazard ratio was 1.00 (95% confidence interval, 0.64-1.58; p = .98) in a stratified analysis based on number of metastatic sites and region. Objective response rate was 52.1% and 57.9% in the vanucizumab and bevacizumab arm, respectively. Baseline plasma Ang-2 levels were prognostic in both arms but not predictive for treatment effects on PFS of vanucizumab. The incidence of adverse events of grade ?3 was similar between treatment arms (83.9% vs. 82.1%); gastrointestinal perforations (10.8% vs. 8.4%) exceeded previously reported rates in this setting. Hypertension and peripheral edema were more frequent in the vanucizumab arm. CONCLUSION:Vanucizumab/mFOLFOX-6 did not improve PFS and was associated with increased rates of antiangiogenic toxicity compared with bevacizumab/mFOLFOX-6. Our results suggest that Ang-2 is not a relevant therapeutic target in first-line mCRC. IMPLICATIONS FOR PRACTICE:This randomized phase II study demonstrates that additional angiopoietin-2 (Ang-2) inhibition does not result in superior benefit over anti-VEGF-A blockade alone when each added to standard chemotherapy. Moreover, the performed pharmacokinetic and pharmacodynamic analysis revealed that vanucizumab was bioavailable and affected its intended target, thereby strongly suggesting that Ang-2 is not a relevant therapeutic target in the clinical setting of treatment-naïve metastatic colorectal cancer. As a result, the further clinical development of the dual VEGF-A and Ang-2 inhibitor vanucizumab was discontinued.

Dataset Information

Introducing candesartan 32 mg plus hydrochlorothiazide 25 mg in previously untreated patients with severe essential hypertension.

Publications

Introducing candesartan 32 mg plus hydrochlorothiazide 25 mg in previously untreated patients with severe essential hypertension.

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