Losartan/hydrochlorothiazide combination vs. high-dose losartan in patients with morning hypertension—a prospective, randomized, open-labeled, parallel-group, multicenter trial

Abstract

on behalf of the MAPPY Study InvestigatorsThe treatment of morning hypertension has not been established. We compared the efficacy and safety of a losartan/ hydrochlorothiazide (HCTZ) combination and high-dose losartan in patients with morning hypertension. A prospective, randomized, open-labeled, parallel-group, multicenter trial enrolled 216 treated outpatients with morning hypertension evaluated by home blood pressure (BP) self-measurement. Patients were randomly assigned to receive a combination therapy of 50 mg losartan and 12.5 mg HCTZ (n¼109) or a high-dose therapy with 100 mg losartan (n¼107), each of which were administered once every morning. Primary efficacy end points were morning systolic BP (SBP) level and target BP achievement rate after 3 months of treatment. At baseline, BP levels were similar between the two therapy groups. Morning SBP was reduced from 150.3 ± 10.1 to 131.5 ± 11.5 mm Hg by combination therapy (Po0.001) and from 151.0 ± 9.3 to 142.5 ± 13.6 mm Hg by high-dose therapy (Po0.001). The morning SBP reduction was greater in the combination therapy group than in the high-dose therapy group (Po0.001). Combination therapy decreased evening SBP from 141.6±13.3 to 125.3±13.1 mm Hg (Po0.001), and high-dose therapy decreased evening SBP from 138.9 ± 9.9 to 131.4 ± 13.2 mm Hg (Po0.01). Although both therapies improved target BP achievement rates in the morning and evening (Po0.001 for both), combination therapy increased the achievement rates more than high-dose therapy (Po0.001 and Po0.05, respectively). In clinic measurements, combination therapy was superior to high-dose therapy in reducing SBP and improving the achievement rate (Po0.001 and Po0.01, respectively). Combination therapy decreased urine albumin excretion (Po0.05) whereas high-dose therapy reduced serum uric acid. Both therapies indicated strong adherence and few adverse effects (Po0.001). In conclusion, losartan/HCTZ combination therapy was more effective for controlling morning hypertension and reducing urine albumin than high-dose losartan.

Reduction in Morning Blood Pressure Is a Key Factor for Ameliorating Urinary Albumin Excretion in Patients With Morning Hypertension Irrespective of Treatment Regimen

“…Thus, it is suggested that morning SBP reduction is important for UAE reduction, irrespeccacy of these treatments in patients with morning hypertension. 1 The MAPPY study has shown that a losartan/HCTZ combination induces a greater morning SBP reduction, the primary endpoint, than high-dose losartan (-18 mmHg vs. -8 mmHg, P<0.001). With regard to the secondary endpoints, the combination regimen decreased UAE (P<0.05), whereas the high-dose regimen lowered serum uric acid (P<0.001).…”

“…1 The institutional review boards or ethics committees of all participating institutions approved the study protocol. All patients gave written informed consent.…”

“…1 Briefly, an anti-hypertensive drug was randomly switched to a 50-mg losartan/12.5-mg HCTZ combination tablet (combination regimen) or 100-mg losartan (high-dose regimen) without washout period. If patients had been given an ARB or ACEI, the ARB or ACEI was switched to losartan/HCTZ combination or 100-mg losartan.…”

Impact of the combination of an angiotensin II receptor blocker and low-dose hydrochlorothiazide on patients with morning hypertension

“…5 Previous studies have documented that the combination of losartan (50 mg) with lowdose HCTZ (12.5 mg) successfully reduced BP in patients with essential hypertension. 6,7 However, there has been no study that tested the hypothesis that selective suppression of an exaggerated morning BP surge leads to a regression of target organ damage and a reduction in subsequent CV events.In this issue of Hypertension Research, Ueda et al 8 reported an interesting clinical study, in which they compared the efficacy and safety of a losartan (50 mg)/HCTZ (12.5 mg) combination and high-dose losartan (100 mg) in patients with morning hypertension or a morning BP surge. 9 Combination therapy induced a greater reduction in the morning systolic BP than did high-dose losartan therapy (131.5±11.5 vs. 142.5 ± 13.6 mm Hg, Po0.001).…”

“…In this issue of Hypertension Research, Ueda et al 8 reported an interesting clinical study, in which they compared the efficacy and safety of a losartan (50 mg)/HCTZ (12.5 mg) combination and high-dose losartan (100 mg) in patients with morning hypertension or a morning BP surge. 9 Combination therapy induced a greater reduction in the morning systolic BP than did high-dose losartan therapy (131.5±11.5 vs. 142.5 ± 13.6 mm Hg, Po0.001).…”