Soon Yong Suh1, Taehoon Ahn2, Jang-Ho Bae3, Do-Sun Lim4, Seoung Uk Lee5, Young Kwon Kim6, Min Su Hyon7, Won Ho Kim8, Kyoo Rok Han9, Hoon Ki Park10. 1. Gachon University Gil Hospital, Incheon, Republic of Korea. 2. Gachon University Gil Hospital, Incheon, Republic of Korea. Electronic address: encore@gilhospital.com. 3. Konyang University Hospital, Daejeon, Republic of Korea. 4. Korea University Anam Hospital, Seoul, Republic of Korea. 5. Kwangju Christian Hospital, Kwangju, Republic of Korea. 6. Dongguk University Ilsan Hospital, Ilsan, Republic of Korea. 7. Soonchunhyang University Hospital, Seoul, Republic of Korea. 8. Chungbuk National University Hospital, Jeonju, Republic of Korea. 9. Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea. 10. VHS Medical Center, Seoul, Republic of Korea.
Abstract
PURPOSE: The aim of this study was to determine whether the efficacy and tolerability of amlodipine camsylate/losartan 5/100 mg/d (AML/LOS) are noninferior to those of losartan/hydrochlorothiazide 100/12.5 mg/d (LOS/HCTZ) fixed-dose combination in hypertensive patients unresponsive tolosartan 100-mg/d monotherapy. METHODS:Male and female patients aged ≥ 18 years with hypertension despite 4-week, stable treatment withlosartan 100-mg/d monotherapy were eligible for inclusion in this multicenter, randomized, double-blind study. Patients were randomly assigned to receive AML/LOS or LOS/HCTZ once daily for 8 weeks. The primary end point was the change from baseline to week 8 in sitting diastolic blood pressure (ΔsiDBP), and the secondary end points were the changes from baseline to 4 weeks in siDBP and sitting systolic BP (ΔsiSBP) and changes from baseline to 4 and 8 weeks in BP response rate. Tolerability was evaluated by physical examination, including vital sign measurement; laboratory analysis; and ECG. FINDINGS: Of 275 patients screened at 9 cardiovascular centers, 199 were enrolled (AML/LOS, n = 101; LOS/HCTZ, n = 98), and 183 completed the study. The demographic characteristics were similar between the 2 groups (mean age, 51.56 [9.97] years; men, 70.53%). At 8 weeks, the mean ΔsiDBP values were -11.54 (7.89) and -9.05 (6.57) mm Hg in the AML/LOS and LOS/HCTZ groups, respectively (both, P < 0.0001 vs baseline). The mean difference between the 2 groups was -2.57 mm Hg, a nonsignificant difference, meaning that AML/LOS was noninferior to LOS/HCTZ with regard to the primary end point. At 8 weeks, the mean uric acid level was changed significantly from baseline in the LOS/HCTZ group (+0.41 [0.80] mg/dL; P < 0.0001) but not in the AML/LOS group (-0.12 [0.82] mg/dL), representing a significant intergroup difference (P < 0.0001). Nineteen patients each in the AML/LOS (18.81%) and LOS/HCTZ (20.00%) groups experienced ≥ 1 adverse event, with 4 (3.96%) and 3 (3.16%) patients, respectively, experiencing 1 or more events considered by the investigators to have been treatment related. IMPLICATIONS: The efficacy and tolerability of AML/LOS 5/100 mg/d was found to have been noninferior to those of LOS/HCTZ 100/12.5 mg/d in these hypertensive patients nonresponsive to losartan 100-mg/d monotherapy.
RCT Entities:
PURPOSE: The aim of this study was to determine whether the efficacy and tolerability of amlodipine camsylate/losartan 5/100 mg/d (AML/LOS) are noninferior to those of losartan/hydrochlorothiazide 100/12.5 mg/d (LOS/HCTZ) fixed-dose combination in hypertensivepatients unresponsive to losartan 100-mg/d monotherapy. METHODS: Male and female patients aged ≥ 18 years with hypertension despite 4-week, stable treatment with losartan 100-mg/d monotherapy were eligible for inclusion in this multicenter, randomized, double-blind study. Patients were randomly assigned to receive AML/LOS or LOS/HCTZ once daily for 8 weeks. The primary end point was the change from baseline to week 8 in sitting diastolic blood pressure (ΔsiDBP), and the secondary end points were the changes from baseline to 4 weeks in siDBP and sitting systolic BP (ΔsiSBP) and changes from baseline to 4 and 8 weeks in BP response rate. Tolerability was evaluated by physical examination, including vital sign measurement; laboratory analysis; and ECG. FINDINGS: Of 275 patients screened at 9 cardiovascular centers, 199 were enrolled (AML/LOS, n = 101; LOS/HCTZ, n = 98), and 183 completed the study. The demographic characteristics were similar between the 2 groups (mean age, 51.56 [9.97] years; men, 70.53%). At 8 weeks, the mean ΔsiDBP values were -11.54 (7.89) and -9.05 (6.57) mm Hg in the AML/LOS and LOS/HCTZ groups, respectively (both, P < 0.0001 vs baseline). The mean difference between the 2 groups was -2.57 mm Hg, a nonsignificant difference, meaning that AML/LOS was noninferior to LOS/HCTZ with regard to the primary end point. At 8 weeks, the mean uric acid level was changed significantly from baseline in the LOS/HCTZ group (+0.41 [0.80] mg/dL; P < 0.0001) but not in the AML/LOS group (-0.12 [0.82] mg/dL), representing a significant intergroup difference (P < 0.0001). Nineteen patients each in the AML/LOS (18.81%) and LOS/HCTZ (20.00%) groups experienced ≥ 1 adverse event, with 4 (3.96%) and 3 (3.16%) patients, respectively, experiencing 1 or more events considered by the investigators to have been treatment related. IMPLICATIONS: The efficacy and tolerability of AML/LOS 5/100 mg/d was found to have been noninferior to those of LOS/HCTZ 100/12.5 mg/d in these hypertensivepatients nonresponsive to losartan 100-mg/d monotherapy.