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.

Hypothyroidism Prevalence in the United States: A Retrospective Study Combining National Health and Nutrition Examination Survey and Claims Data, 2009-2019.

Previous estimates determined prevalence of hypothyroidism (HT) to be 4.6% of the US population. This study aimed to update estimates of HT prevalence in the United States by retrospective analysis of 2 datasets. Data on HT type (overt or subclinical HT) and treatment were collected from the 2009-2010 and 2011-2012 National Health and Nutrition Examination Survey (NHANES) cycles. From the Optum administrative claims database, medical and pharmacy claims were collected between January 1, 2012, and December 31, 2019. Patients were defined as having HT if, per given year, they had >1 prescription for HT treatment, >1 claim indicating an HT diagnosis, or thyroid-stimulating hormone levels >4.0 mIU/L (NHANES arm). For both studies, treatment was defined as any evidence of synthetic or natural thyroid hormone replacement, identified by pharmacy claims or patient surveys. Data are reported as percentage of patients with HT and treatments received. Between 2009 and 2012, HT prevalence remained around 9.6% of the US population. The administrative claims dataset showed that HT prevalence grew from 9.5% in 2012 to 11.7% in 2019 and that >78% of patients received thyroxine (T4) monotherapy. Similarly, the NHANES dataset showed that T4 replacement therapy was the most common treatment for HT. From 2012-2019, patients with untreated HT grew from 11.8% to 14.4%. The prevalence of HT in the United States has steadily increased since 2009. Likewise, the percentage of hypothyroid-diagnosed patients not receiving treatment also increased, suggesting that the increased prevalence may be due to increased cases of subclinical HT.

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.

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.