Significance of estimated salt excretion as a possible predictor of the efficacy of concomitant angiotensin receptor blocker (ARB) and low-dose thiazide in patients with ARB resistance

Abstract

The purpose of this study was to assess the factors affecting the efficacy of combination therapy with losartan and thiazide, with a focus on the significance of salt excretion, via a multicenter observational study. Adult patients with essential hypertension showing therapy resistance to angiotensin receptor blocker (ARB) as a monotherapy or in combination with Ca channel blockers (CCB) were enrolled, and their previously administered ARBs were replaced with the combination tablet containing losartan (50 mg per day) and hydrochlorothiazide (12.5 mg per day). Blood pressure and biochemical parameters were monitored for a year. The baseline blood pressure (153.4±14.8/86.4±11.3 mm Hg) was significantly lowered at the 3rd month (137.3±17.4/78.2±11.1 mm Hg, n=93) and was maintained at this lower level until the 12th month (135.3±14.0/76.4±11.1 mm Hg, n=74). The baseline value of estimated salt excretion (eSE), calculated using Tanaka's formula, differed significantly between the high and low treatment response groups, which were defined by the average change in mean blood pressure (MBP-C, -11.3 mm Hg; eSE=10.8±2.9 g per day in high responders vs. 9.2±2.3 g per day in low responders, P=0.004). Univariate and multivariate analyses showed a significant correlation between eSE and MBP-C (R=-0.288, P=0.007) and indicated the clinical effectiveness of eSE as a possible predictor for MBP-C (P=0.021). In addition, the urine Na-to-Cr ratio (NCR) demonstrated significant correlations with eSE (R=0.848, P<0.001) and MBP-C (R=-0.344, P<0.001). These results suggest that eSE or NCR could, to a certain extent, predict the efficacy of combination therapy with losartan and low-dose thiazide in patients demonstrating ARB resistance. Combination therapy with losartan and thiazide might thus be suitable for patients with a large amount of salt excretion.

Release From Glomerular Overload by the Addition of Low-dose Thiazide in Patients With Angiotensin Receptor Blocker-Resistant Hypertension

“…The results showed that estimated salt excretion (eSE) at baseline was significantly correlated with the magnitude of blood pressure decrease, and that eSE could predict the efficacy of the combination therapy [10]. The study also demonstrated a significant decrease in the estimated glomerular filtration rate (eGFR) during the first 3 months after the switch to ARB/thiazide combination therapy [10]. …”

“…The main outcomes and complete study design, organization, clinical measures, exclusion criteria, and baseline characteristics have been published [10]. The study was conducted in accordance with the principles of the Declaration of Helsinki.…”

“…At the 3rd- and 12th-month visits, each patient provided blood and urine samples using methods similar to those used for the baseline sample collection. As described [10], 93 and 74 participants completed the 3-month and 12-month observations, respectively. At the baseline, the patients' mean age was 67.7 ± 12.6 years and their mean body mass index (BMI) was 24.6 ± 3.6 kg/m 2 [10].…”

“…We included patients aged 38-85 years with essential hypertension who were administered an ARB with or without the concomitant administration of a CCB over a 1-month period (May 2008 to April 2010). Patients who did not meet the target blood pressure levels described in the 2004 Japanese Society of Hypertension Guidelines for the Management of Hypertension (≤130/85 mmHg for young and middle-aged adults, ≤ 140/90 mmHg for adults aged > 75 years) [13] after this antihypertension therapy and who provided informed consent were enrolled in the SALT study As described [10], patients were excluded from the study if they had been administered any type of diuretic or thiazolidinedione agent or if they exhibited advanced renal insufficiency (serum Cr > 2.00 mg/dL or eGFR < 30 mL/min), heart failure (New York Heart Association functional class III or IV for dyspnea at exertion), or severe liver dysfunction.…”

“…We recently conducted a multicenter, prospective, observational study in the Saitama Prefecture of Japan (the Saitama Anti-hypertension Losartan-hydrochlorothiazide Trial: SALT study), wherein we studied the clinical effectiveness of losartan/thiazide combination therapy in patients with hypertension that was resistant to either ARB monotherapy or concomitant ARB + calcium channel blocker (CCB) therapy [10]. The results showed that estimated salt excretion (eSE) at baseline was significantly correlated with the magnitude of blood pressure decrease, and that eSE could predict the efficacy of the combination therapy [10].…”