Comparison of long-term safety of fixed-dose combinations azilsartan medoxomil/chlorthalidone vs olmesartan medoxomil/hydrochlorothiazide.

This 52-week, randomized, open-label study evaluated long-term safety/tolerability of fixed-dose combination azilsartan medoxomil/chlorthalidone (AZL-M/CLD) vs fixed-dose combination olmesartan medoxomil/hydrochlorothiazide (OLM/HCTZ) in patients with essential hypertension (stage 2; clinic systolic blood pressure 160-190 mm Hg). Initial AZL-M/CLD 40/12.5 mg/d (n=418) or OLM/HCTZ 20/12.5 mg/d (n=419) could be uptitrated during weeks 4 to 52 (AZL-M/CLD to 80/25 mg; OLM/HCTZ to 40/25 mg [United States] or 20/25 mg [Europe]) to meet blood pressure targets. Treatment-emergent adverse events/serious adverse events occurred in 78.5%/5.7% of patients taking AZL-M/CLD vs 76.4%/6.2% taking OLM/HCTZ. The most frequent adverse events were dizziness (16.3% vs 12.6%), blood creatinine increase (21.5% vs 8.6%), headache (7.4% vs 11.0%), and nasopharyngitis (12.2% vs 11.5%). Hypokalemia was uncommon (1.0% vs 0.7%). Greater blood pressure reductions with AZL-M/CLD by week 2 were maintained throughout the study, despite less uptitration (32.3% vs 48.9% with OLM/HCTZ). Fixed-dose combination AZL-M/CLD showed an encouraging benefit-risk profile when used per standard clinical practice in a titrate-to-target strategy.

Evaluation of the angiotensin II receptor blocker azilsartan medoxomil in African-American patients with hypertension.

The efficacy and safety of azilsartan medoxomil (AZL-M) were evaluated in African-American patients with hypertension in a 6-week, double-blind, randomized, placebo-controlled trial, for which the primary end point was change from baseline in 24-hour mean systolic blood pressure (BP). There were 413 patients, with a mean age of 52 years, 57% women, and baseline 24-hour BP of 146/91 mm Hg. Treatment differences in 24-hour systolic BP between AZL-M 40 mg and placebo (-5.0 mm Hg; 95% confidence interval, -8.0 to -2.0) and AZL-M 80 mg and placebo (-7.8 mm Hg; 95% confidence interval, -10.7 to -4.9) were significant (P≤.001 vs placebo for both comparisons). Changes in the clinic BPs were similar to the ambulatory BP results. Incidence rates of adverse events were comparable among the treatment groups, including those of a serious nature. In African-American patients with hypertension, AZL-M significantly reduced ambulatory and clinic BPs in a dose-dependent manner and was well tolerated.

Safety and tolerability of azilsartan medoxomil in subjects with essential hypertension: a one-year, phase 3, open-label study.

This 56-week phase 3, open-label, treat-to-target study, involving 2 consecutive, non-randomized cohorts, evaluated the safety and tolerability of azilsartan medoxomil (AZL-M) in essential hypertension (mean baseline blood pressure [BP] 152/100 mmHg). All subjects (n = 669) initiated AZL-M 40 mg QD, force-titrated to 80 mg QD at week 4, if tolerated. From week 8, subjects could receive additional medications, starting with chlorthalidone (CLD) 25 mg QD (Cohort 1) or hydrochlorothiazide (HCTZ) 12.5-25 mg QD (Cohort 2), if required, to reach BP targets. Adverse events (AEs) were reported in 75.9% of subjects overall in the two cohorts (73.8% Cohort 1, 78.5% Cohort 2). The most common AEs were dizziness (14.3%), headache (9.9%) and fatigue (7.2%). Transient serum creatinine elevations were more frequent with add-on CLD. Clinic systolic/diastolic BP (observed cases at week 56) decreased by 25.2/18.4 mmHg (Cohort 1) and 24.2/17.9 mmHg (Cohort 2). These results demonstrate that AZL-M is well tolerated over the long term and provides stable BP improvements when used in a treat-to-target BP approach with thiazide-type diuretics.

Meet the reformer.

When Elizabeth Tysoe accepted a secondment in the prison service she had no idea what to expect.

Recruitment network.

An innovative campaign developed on social media has helped an NHS trust to attract and recruit more than 150 qualified nurses.

A solid basis for improvement.

A two-day training plan delivered to ward-based staff at a West Midlands trust has had a major effect on the care of patients with cognitive impairment and dementia.

Calling on some foreign aid.

Hospitals are becoming increasingly reliant on overseas nurses, according to figures showing that the UK imports more nurses than it exports for the first time in eight years.

Safety, tolerability, and efficacy of azilsartan medoxomil with or without chlorthalidone during and after 8 months of treatment for hypertension.

A phase 3, 26-week, open-label, titrate-to-target study (n=418) assessed the safety of azilsartan medoxomil (AZL-M) alone and with chlorthalidone (CLD), followed by a 6-week, double-blind, placebo-controlled reversal phase with change in clinic diastolic blood pressure (DBP) as the primary endpoint. Target blood pressure (BP) was <140/90 mm Hg (<130/80 mm Hg with diabetes/chronic kidney disease). AZL-M was initiated at 40 mg once a day (QD), force-titrated to 80 mg at week 4. CLD 25 mg QD could be added (weeks 8-22), if required, to reach target, followed by additional antihypertensives from week 12. At the end of the open-label phase, mean change in systolic BP (SBP)/DBP from baseline was -23/-16 mm Hg. The most common adverse events, irrespective of treatment, were dizziness (8.9%) and headache (7.2%). Serious AEs were reported in eight patients (1.9%). Consecutive creatinine elevations ≥50% with values exceeding the upper limit of normal (ULN) were reported in nine (2.2%) patients. All returned to below the 50% threshold; most also returned to below the ULN after drug discontinuation. Mean DBP was maintained through the reversal phase in patients receiving AZL-M, but increased with placebo (difference: -7.8 mm Hg, 95% confidence interval, -9.8 to -5.8; P<.001). AZL-M alone or with CLD showed good long-term safety and stable BP improvements in a titrate-to-target approach. BP improvements caused by AZL-M therapy were safely reversible upon AZL-M withdrawal.

Investing in wellbeing.

A trust in the West Midlands has introduced wellbeing apprentices to offer one-to-one support to patients with dementia of at high risk of falls. As well as providing companionship to ease patients' stress during hospital stays, the young apprentices receive training that can set them on the path to a nursing career.

Wards in good cheer.

Over the past year a West Midlands trust has introduced activities to improve the experience of patients in a co-ordinated and sustainable way. The initiative is spreading to other settings across the country.

Antihypertensive efficacy of hydrochlorothiazide vs chlorthalidone combined with azilsartan medoxomil.

BACKGROUND: Chlorthalidone has proven efficacy to reduce cardiovascular morbidity and mortality, yet it is infrequently used in practice. This study provides a direct comparison of chlorthalidone with hydrochlorothiazide, each combined with the angiotensin receptor blocker azilsartan medoxomil, on blood pressure reduction and control rates. METHODS: This is a randomized, double-blind, titrate-to-target blood pressure trial comparing the single-pill combination of azilsartan medoxomil and chlorthalidone versus co-administration of azilsartan medoxomil and hydrochlorothiazide in participants with stage 2 primary hypertension. After 2 weeks of treatment with azilsartan medoxomil 40 mg alone, all participants also received 12.5 mg of diuretic for 4 weeks (up to week 6) and were titrated to 25 mg for another 4 weeks (up to week 10) if they failed to achieve target blood pressure. The primary end point was change in clinic systolic blood pressure. Target blood pressure was defined as clinic blood pressure <140/90 mm Hg for participants without diabetes or chronic kidney disease or <130/80 mm Hg for participants with diabetes or chronic kidney disease. RESULTS: The mean age of the 609 participants was 56.4 years, and the mean baseline clinic blood pressure was 164.6/95.4 mm Hg. The primary end point analysis at week 6 demonstrated a greater reduction of clinic systolic blood pressure for the chlorthalidone (-35.1 mm Hg) versus hydrochlorothiazide combination (-29.5 mm Hg) (mean difference, -5.6 mm Hg; 95% confidence interval, -8.3 to -2.9; P <.001). The mean difference in 24-hour ambulatory systolic blood pressure at week 6 was -5.8 mm Hg (95% confidence interval, -8.4 to -3.2; P <.001), favoring the azilsartan medoxomil/chlorthalidone group. The percentage of participants achieving target clinic blood pressure at week 6 was greater for the chlorthalidone versus hydrochlorothiazide combination (64.1% vs 45.9%, P <.001). Drug discontinuations due to adverse events were not statistically significantly different between groups (9.3% vs 7.3%, P = .38), and hypokalemia was uncommon in both groups. CONCLUSIONS: Chlorthalidone combined with azilsartan medoxomil provides better blood pressure reduction and a higher likelihood of achieving blood pressure control than hydrochlorothiazide combined with azilsartan medoxomil. This benefit occurred without a difference in safety measurements.