Efficacy and Safety of the Losartan-Hydrochlorothiazide Combination Tablet in Patients with Hypertension Uncontrolled by Angiotensin II Receptor Antagonist Therapy: The Aichi Research on Combination Therapy for Hypertension (ARCH) Study

Abstract

Background The guidelines recommend combination therapy for patients who are unable to achieve target BP with monotherapy; some fixed dose therapies including an angiotensin II receptor blocker (ARB) and diuretics are available in Japan. However, to date there have been few reports on this long-term treatment and the patient profiles suited for this combination remain ambiguous. Method The Aichi Research on Combination therapy for Hypertension Study was a multicenter, open-label, prospective observational study that investigated the efficacy and safety of 1-year treatment with the losartanhydrochlorothiazide (HCTZ) combination tablet in patients with hypertension uncontrolled by either ARB monotherapy or combination therapy with a calcium channel blocker (CCB). An ARB was switched to a losartan-HCTZ tablet after a pre-observation period. Results A total of 614 of 648 patients were evaluable (mean age, 66.3 years; 52.8% men; mean baseline blood pressure, BP, 157.7/87.9 mmHg). The BP had decreased significantly to 138.0/78.2 mmHg by month 3 (p<0.001, t-test), and 36.2% of the patients had achieved their target BP. The hypotensive effect lasted for 1 year and was found equally in the losartan-HCTZ arm and the losartan-HCTZ plus CCB arm. A stratified analysis showed significant hypotensive effects in patients with higher baseline BP, women, and patients who did not drink alcohol (p<0.001, unpaired t-test). Conclusion The losartan-HCTZ combination tablet was found to have an early hypotensive effect, good tolerability, and stable long-term benefits in patients with hypertension uncontrolled by ARB monotherapy or combination therapy with a CCB.

Persistent olmesartan-based blood pressure–lowering effects on morning hypertension in Asians: the HONEST study

“…In a previous study that investigated the antihypertensive effect of combined losartan–hydrochlorothiazide, 35 there was a difference in the BP-lowering effect of ⩾4 mm Hg in female or elderly patients compared with other patient groups at the baseline BP of approximately 160 mm Hg. By contrast, in the present study, although there was an interaction between baseline BP and sex or age, the difference in the BP-lowering effect at baseline BP of approximately 160 mm Hg was small—that is, there was no clinically significant difference in the antihypertensive effect of olmesartan by patient background factors.…”

Low Salt Intake and Changes in Serum Sodium Levels in the Combination Therapy of Low-Dose Hydrochlorothiazide and Angiotensin II Receptor Blocker

“…The ARCH study, which examined the antihypertensive effect of 12.5 mg HCTZ plus 50 mg losartan for 1 year, reported that none of the study participants (n=651) had hyponatremia. 18 Thus, hyponatremia is thought to be uncommon in 12.5 mg HCTZ treatment. Of all of the present study participants, only 1 patient demonstrated hyponatremia (srNa <130 mEq/dl).…”