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Purpose The objective of this study was to evaluate the efficacy and tolerability of a triple combination of amlodipine/losartan/rosuvastatin in patients with hypertension and hypercholesterolemia. Methods A randomized, multicenter, double-blind, placebo-controlled study was conducted. Eligible patients with hypertension and a sitting diastolic blood pressure (SiDBP) of >90 mm Hg and LDL-C levels <250 mg/dL were screened. After a 4-week run-in period with therapeutic lifestyle changes and losartan potassium 100 mg once daily, patients who met both blood pressure criteria (80 mm Hg ≤ SiDBP < 110 mm Hg) and the LDL-C level criteria (defined in the National Cholesterol Education Program Adult Treatment Panel III cardiovascular risk categories) were randomized to 1 of 3 groups and treated once daily for 8 weeks: losartan potassium 100 mg + rosuvastatin 20 mg treatment (L/R 100/20) group, amlodipine camsylate 5 mg + losartan potassium 100 mg treatment (A/L 5/100) group, and amlodipine 5 mg + losartan potassium 100 mg + rosuvastatin 20 mg (A/L/R 5/100/20) group. The primary efficacy variables were the percent change in LDL-C in the A/L/R 5/100/20 and A/L 5/100 groups and the mean change of SiDBP in the A/L/R 5/100/20 and L/R 100/20 groups after 8 weeks of treatment, relative to baseline values. Findings A total of 146 patients were enrolled and the demographic characteristics were similar among the 3 treatment groups. After 8 weeks of treatment, the mean (SD) percent change in LDL-C was significantly greater in the A/L/R group than in the A/L group (–48.40% [2.77%] vs –6.70% [3.00%]; P < 0.0001). Moreover, the mean change in SiDBP was significantly greater in the A/L/R group than in the L/R group (–9.75 [0.92] mm Hg vs –1.73 [1.03] mm Hg; P < 0.0001). SiDBP and LDL-C reductions in the A/L/R group were comparable to reductions in the A/L and L/R groups, respectively. Ten adverse events were reported in 7 patients (4.83%), and 1 patient from the A/L group (0.69%) experienced 2 adverse drug reactions (tachycardia and face edema), which were mild and resolved without specific treatment. There were no clinically significant tolerability issues during the treatment period. Implications Triple combination therapy with amlodipine/losartan/rosuvastatin can be an effective therapeutic strategy in patients with hypertension combined with dyslipidemia. These findings will form the foundation of the future development of a single-pill triple combination. ClinicalTrials.gov identifier: NCT02899455. [ABSTRACT FROM AUTHOR]

Purpose A new antihypertensive drug that selectively blocks angiotensin II receptor type 1, fimasartan, has a potent and rapidly acting antihypertensive effect. We investigated the antihypertensive effects of fimasartan 60 and 120 mg and its safety in comparison to 8 mg of candesartan. Methods This clinical trial is a multicenter, randomized, double-blind, active comparator, and parallel group study. Three hundred sixty-two individuals were screened, and 290 patients aged 19 to 75 years with mild to moderate hypertension (diastolic blood pressure [DBP], 90–110 mm Hg) were randomly assigned to 60 to 120 mg/d of fimasartan or 8 mg/d of candesartan after a 2-week placebo run-in period. Treatments were administered for 12 weeks without dosage adjustment. The primary end point was the differences in DBP changes at week 12. Findings After 12 weeks of treatment, DBP and systolic blood pressure (SBP) decreased significantly in all 3 groups. The decrease in DBP at week 12 was larger but not statistically significant in the fimasartan 60 mg compared with the candesartan 8 mg group with a mean (SD) difference of 1.72 (8.32) mm Hg (95% CI, −0.71 to 4.15 mm Hg; P = 0.17). The lower margin of the CI (−0.71 mm Hg) exceeded the noninferiority margin (−3.5 mm Hg). The DBP-lowering effect of fimasartan 120 mg was also nonsignificantly larger than candesartan 8 mg (difference, 1.58 [8.27] mm Hg; P = 0.20). The decrease in SBP was also nonsignificantly larger in the fimasartan 60 mg group compared with the candesartan 8 mg group (difference, 3.50 [12.63] mm Hg; P = .06). The SBP-lowering effect of fimasartan 120 mg was statistically larger than candesartan 8 mg (difference, 4.98 [13.99] mm Hg; P = .02). Response rate (DBP <90 mm Hg or DBP lowering >10 mm Hg at week 12) was also nonsignificantly greater in both fimasartan groups (Fimasartan 60 mg, 81%; fimasartan 120 mg, 72%; candesartan 8 mg, 71%). The safety profile of the fimasartan 60 mg and 120 mg was similar to candesartan 8 mg, with a slightly higher, but statistically not significant, incidence of hepatic enzyme elevation in fimasartan 120 mg. Implications The antihypertensive effect of fimasartan, a newly available angiotensin II receptor type 1 blocker, is comparable, although not superior, to candesartan with a good safety profile. ClinicalTrials.gov identifier: NCT01135212. [ABSTRACT FROM AUTHOR]

Purpose Doubling the dose of antihypertensive drugs is necessary to manage hypertension in patients whose disease is uncontrolled. However, this strategy can result in safety issues. This study compared the safety and efficacy of up-titration of the nifedipine gastrointestinal therapeutic system (GITS) with up-titration of valsartan monotherapy; these were also compared with low-dose combinations of the two therapies. Methods This prospective, open-label, randomized, active-controlled, multicenter study lasted 8 weeks. If patients did not meet the target blood pressure (BP) after 4 weeks of treatment with low-dose monotherapy, they were randomized to up-titration of the nifedipine GITS dose from 30 mg (N30) to 60 mg or valsartan from 80 mg to 160 mg or they were randomized to receive a low-dose combination of N30 and valsartan 80 mg for another 4 weeks. BP variability was assessed by using the SD or the %CV of the short-term BP measured at clinic. Findings Of the 391 patients (20~70 years with stage II or higher hypertension) screened for study inclusion, 362 patients who had 3 BP measurements were enrolled. The reduction in the mean systolic/diastolic BP from baseline to week 4 was similar in both low-dose monotherapy groups with either N30 or valsartan 80 mg. BP variability (SD) was unchanged with either therapy, but the %CV was slightly increased in the N30 group. There was no significant difference in BP variability either in SD or %CV between responders and nonresponders to each monotherapy despite the significant difference in the mean BP changes. The up-titration effect of nifedipine GTS from 30 to 60 mg exhibited an additional BP reduction, but this effect was not shown in the up-titration of valsartan from 80 to 160 mg. Although the difference in BP was obvious between high-dose nifedipine GTS and valsartan, the BP variability was unchanged between the 2 drugs and was similar to the low-dose combinations. There was a low rate of adverse events in all treatment groups. In addition, escalating the dose of either nifedipine GITS or valsartan revealed a similar occurrence of adverse effects with low-dose monotherapy or the low-dose combination. Implications Compared with up-titration of the angiotensin receptor blocker valsartan, up-titration of the calcium channel blocker nifedipine GITS provided no additional increased safety concerns and revealed better mean reductions in BP without affecting short-term BP variability. ClinicalTrials.gov identifier: NCT01071122. [ABSTRACT FROM AUTHOR]

Background: Fimasartan, a selective angiotensin II type 1 receptor blocker, was approved in Korea for the treatment of patients with mild to moderate hypertension. Objective: The aim of this study was to evaluate the 24-hour blood pressure (BP) profiles before and after 8-week treatment with fimasartan and to compare them with those of valsartan. Methods: A multicenter, randomized, double-blind, active-controlled, parallel-group study was conducted using ambulatory BP monitoring (ABPM). Korean patients with mild to moderate essential hypertension were enrolled and randomly received once-daily oral fimasartan 60 or 120 mg or valsartan 80 mg for 8 weeks. ABPM was performed before and after 8-week treatment, and clinic BP was also measured. Based on ABPM data, trough-to-peak ratio and smoothness index were derived. Tolerability was monitored throughout the study. Results: Ninety-two patients were enrolled (mean [SD] age, 54.1 [8.2] years; weight, 67.9 [10.2] kg). After 8 weeks, 24-hour, daytime, and nighttime mean ambulatory systolic and diastolic BPs (SBP and DBP, respectively) were significantly decreased in all 3 treatment groups (range: SBP, -9.2 to -15.6 mm Hg; DBP, -5.0 to -10.7 mm Hg; P <0.0001-<0.05). The global trough-to-peak ratios of ambulatory DBP in the fimasartan groups were 0.74 (60 mg/d) and 0.81 (120 mg/d)--45.1% and 58.8% higher, respectively, than the ratio of 0.51 in the valsartan group. Fima-sartan 60 mg/d was associated with 53.5% (SBP) and 68.3% (DBP) greater smoothness index scores com-pared with those with valsartan 80 mg/d (SBP, 1.52 vs. 0.99; DBP, 1.38 vs. 0.82). The decrease in clinic-measured DBP was significantly greater in the fima-sartan 60-mg/d group compared with that in the valsartan 80-mg/d group (-14.0 vs -8.7 mm Hg; P = 0.0380). Fimasartan was well tolerated; headache was the most common adverse event. Conclusion: Once-daily fimasartan effectively main-tained a BP-reduction profile over the full 24-hour dosing interval; this profile was comparable to or slightly better than that of once-daily valsartan. Fimasartan was well tolerated; headache was the most common adverse event. ClinicalTrials.gov identifier: NCT00922441. [ABSTRACT FROM AUTHOR]

Background: Both combination therapies of an an-giotensin II receptor blocker (ARB) with the thiazide diuretic hydrochlorothiazide (HCTZ) and an ARB with a calcium channel blocker (CCB) are recommended to achieve blood pressure (BP) goals in antihy-pertensive treatment. However, although HCTZ is known to have unfavorable effects on lipid metabolism, the effects of HCTZ in the ARB + HCTZ combination on lipid metabolism have not been fully elucidated. Objective: The aim of this study was to compare the effects on lipid metabolism of combination treatment with the ARB losartan + HCTZ and losartan + the CCB amlodipine and to assess the efficacy in BP lowering of these 2 combination therapies. The metabolism of glucose, uric acid (UA), and high-sensitivity C- reactive protein (hs-CRP), an inflammation marker of atherosclerosis, were also assessed in association with lipid metabolism. Methods: This 48-week, prospective, randomized, open-label trial was conducted at 2 clinics and 2 hospitals in Tokorozawa City (Saitama, Japan) and Shin-juku- ku Ward (Tokyo, Japan). Eligible patients had a systolic BP (SBP) >140 mm Hg and/or diastolic BP (DBP) >90 mm Hg despite a > 1-month history of monotherapy with an ARB. Patients were randomly assigned to receive losartan 50 mg/d + HCTZ 12.5 mg/d (LOS + HCTZ) or losartan 50 mg/d + amlodipine 5 mg/d (LOS + CCB) for 48 weeks. Follow-up visits were scheduled at 4, 8, 12, 24, and 48 weeks. Biochemical measurements were centrally measured at a single institute. Tolerability and treatment compliance were assessed by physicians every 4 weeks. Results: A total of 112 patients were enrolled; 26 were excluded from the final analysis, leaving 42 and 44 patients in the LOS + HCTZ and LOS + CCB groups, respectively, included in the final analysis. At 48 weeks, SBP and DBP were significantly decreased in the 2 treatment groups (both, P < 0.0001). The decrease in SBP was significantly greater in the LOS + HCTZ group than in the LOS + CCB group (P < 0.001). The difference in the decrease in DBP between the 2 groups was nonsignificant. There were no significant differences in the changes from baseline (Δ) in any of the lipid parameters between the 2 groups. The decreases at 8 and 12 weeks in LDL-C, TC, and apolipo-protein (apo) B were significantly greater in the LOS + CCB group compared with those in the LOS + HCTZ group. The between-group differences in ΔTG, ΔHDL-C, ΔapoA- 1, and AapoE throughout the study were nonsignificant. Changes in fasting plasma glucose (FPG), hemoglobin A1c, and hs-CRP were not significantly different between the 2 groups. The between-group difference in ΔUA in men was not significant, but a significant difference was found in women (LOS + HCTZ, 0.74 mg/dL; LOS + CCB, 0.28 mg/dL [P = 0.0017]). No clinically significant adverse events were reported with either treatment throughout the study. Conclusions: The findings from the present study suggest that LOS + HCTZ was more efficacious in decreasing SBP than was LOS + CCB in the management of hypertension refractory to ARB monotherapy. Unfavorable effects on lipid metabolism were not observed with either combination therapy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Azilsartan medoxomil is an angiotensin receptor blocker, approved on February 25, 2011 by the US Food and Drug Administration (FDA) for hypertension management. Objective: The purpose of this study was to review the pharmacology, pharmacokinetics, efficacy, safety profile, and role of azilsartan for hypertension management. Methods: Peer-reviewed clinical trials, review articles, and relevant treatment guidelines were identified from MEDLINE and Current Contents (both 1966 to August 31, 2011) using the search terms azilsartan, TAK-491, TAK-536, pharmacology, pharmacokinetics, pharmacodynamics, pharmacoeconomics, and cost-effectiveness. The FDA Web site and manufacturer prescribing information were also reviewed to identify other relevant information. Results: Compared with olmesartan 40 mg daily, azilsartan 80 mg reduced mean systolic blood pressure (SBP) by an additional 2.1 mm Hg (P = 0.038), whereas azilsartan 40 mg was noninferior to olmesartan 40 mg. Azilsartan 40 mg or 80 mg added to chlorthalidone 25 mg daily significantly reduced SBP to a greater extent than did chlorthalidone alone (P < 0.05), but there was no difference between azilsartan 40 mg and 80 mg (40 mg: –31.72 mm Hg; 80 mg: –31.3 mm Hg [P > 0.05]). When coadministered with amlodipine 5 mg daily, both azilsartan 40 mg and 80 mg + amlodipine decreased SBP significantly more than amlodipine alone (amlodipine: –13.6 mm Hg; with azilsartan 40 mg: –24.79 mm Hg; with azilsartan 80 mg: –24.51 mm Hg [P < 0.05]). Compared with ramipril 10 mg daily, both azilsartan 40 mg and 80 mg resulted in significantly (P < 0.001) greater reductions in mean SBP (–20.63 and –21.24 mm Hg, respectively; ramipril: –12.22 mm Hg). The most common adverse events reported were dizziness (4%), dyslipidemia (3.3%), and diarrhea (2%). Conclusions: At the recommended dose of 80 mg once daily, azilsartan is reported to be an efficacious BP-lowering agent. With once-daily dosing and a favorable side-effect profile, azilsartan is an attractive option for the treatment of hypertension. There is a lack of data supporting the use of azilsartan for improvement in cardiovascular outcomes; therefore, azilsartan is not approved for indications other than the treatment of hypertension. [Copyright &y& Elsevier]

The goal of this study was to evaluate the concurrent control rate of hypertension and dyslipidemia by fimasartan and rosuvastatin in patients who were concomitantly prescribed both drugs. : This single-center, cross-sectional study was conducted in 536 patients with hypertension and dyslipidemia who were taking fimasartan and rosuvastatin together for at least 12 weeks. Patients were enrolled from October 2016 to March 2018 at a tertiary hospital in the Republic of Korea. The primary end point was the concurrent control rate of blood pressure (<140/90 mm Hg) and LDL-C. As a secondary end point, the target blood pressure <130/80 mm Hg was adopted in all patients or in high-risk patients with atherosclerotic cardiovascular diseases. Target LDL-C and non–HDL-C levels followed the domestic guidelines. Correlation between blood pressure control and lipid profile was also evaluated. All parameters were assessed in a clinic by board-certified physicians. Of the total 536 patients, 69% (n = 368) had very high (n = 308) or high (n = 60) cardiovascular risk, with an average age of 65 years; 57% were male. When the target blood pressure was set at 140/90 mm Hg, the proportion of patients meeting the targeting LDL-C level was 40.3% (95% CI, 36.2–44.5; P < 0.001). When applied to the revised blood pressure criteria targeting 130/80 mm Hg, the concurrent control rate dropped by one half to 20.3% (95% CI, 17.2–24.0; P < 0.001). To apply the new blood pressure criteria, more intensive management is mandatory in patients with high or very high cardiovascular risk. There was no positive correlation between the controlled rate of hypertension and dyslipidemia. Fimasartan and rosuvastatin were shown to have effects on target diseases, but there was no synergistic effect when administered in combination. The higher the cardiovascular risk of the patients, the lower the rate of concurrent control when fimasartan and rosuvastatin were administered simultaneously. More active treatment is therefore required in high-risk patients. [ABSTRACT FROM AUTHOR]

Purpose Oxaliplatin-induced peripheral neuropathy has remained an unresolved issue in clinical practice. Our previous study hypothesized that inhibition of the renin-angiotensin system (RAS) may produce a preventive effect on oxaliplatin-induced neuropathy. The aim of this study was to clarify whether RAS inhibitors prevent oxaliplatin-induced peripheral neuropathy. Methods This study retrospectively analyzed data from cancer patients who had received chemotherapy including oxaliplatin and were treated with or without RAS inhibitors. This retrospective observational study was conducted at Ehime University Hospital using electronic medical records from May 2009 to December 2016. The primary end point was the incidence of severe peripheral neuropathy during or after oxaliplatin treatment, according to the Common Terminology Criteria for Adverse Events, version 4.0. A multivariate Cox proportional hazards model analysis was used to identify risk factors. Findings A total of 150 patients were included in the study. The estimated incidence of peripheral neuropathy was 36.9% and 91.7% in the RAS inhibitor group and the non–RAS inhibitor group, respectively. The multivariate analysis using a Cox proportional hazards model showed that the RAS inhibitor group was slightly associated with a decreased risk of neurotoxicity (adjusted hazard ratio, 0.42 [95% CI, 0.18–0.99]; P  = 0.048). Implications The present findings suggest that RAS inhibitors have the ability to prevent oxaliplatin-induced peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Purpose The objective of this study was to evaluate the efficacy and safety of a fimasartan/amlodipine combination in patients with hypertension and to determine the optimal composition for a future single-pill combination formulation. Methods This Phase II study was conducted by using a randomized, multicenter, double-blind, placebo-controlled, 3 × 3 factorial design. After a 2-week placebo run-in period, eligible hypertensive patients (with a sitting diastolic blood pressure [SiDBP] between 90 and 114 mm Hg) were randomized to treatment. They received single or combined administration of fimasartan at 3 doses (0, 30, and 60 mg) and amlodipine at 3 doses (0, 5, and 10 mg) for 8 weeks. The primary efficacy end point was the change in SiDBP from baseline and at week 8; secondary end points included the change in SiDBP from baseline and at week 4 and the changes in sitting systolic blood pressure from baseline and at weeks 4 and 8. Treatment-emergent adverse events (AEs) were also assessed. Findings 420 Korean patients with mild to moderate hypertension were randomly allocated to the 9 groups. Mean (SD) SiDBP changes in each group after 8 weeks were as follows: placebo, –6.0 (8.5) mm Hg; amlodipine 5 mg, –10.6 (9.2) mm Hg; amlodipine 10 mg, –15.9 (7.2) mm Hg; fimasartan 30 mg, –10.1 (9.1) mm Hg; fimasartan 60 mg, –13.0 (10.0) mm Hg; fimasartan 30 mg/amlodipine 5 mg, –16.2 (8.5) mm Hg; fimasartan 30 mg/amlodipine 10 mg, –19.5 (7.5) mm Hg; fimasartan 60 mg/amlodipine 5 mg, –16.6 (6.9) mm Hg; and fimasartan 60 mg/amlodipine 10 mg, –21.5 (8.3) mm Hg. All treatment groups produced significantly greater reductions in blood pressure compared with the placebo group. In addition, all combination treatment groups had superior reductions in blood pressure compared with the monotherapy groups. In the combination treatment groups, doubling fimasartan dose in the given dose of amlodipine did not show further BP reduction, whereas doubling amlodipine dose showed significantly further BP reduction in the given dose of fimasartan. During the study period, 75 (17.9%) of 419 patients experienced 110 AEs. Ninety-five AEs were mild, 9 were moderate, and 6 were severe in intensity. Eight patients discontinued the study due to AEs. There was no significant difference in incidence of AEs among groups ( P = 0.0884). The most common AE was headache (12 patients [2.9%]), followed by dizziness (11 patients [2.6%]) and elevated blood creatine phosphokinase levels (6 patients [1.4%]). Implications Fimasartan combined with amlodipine produced superior blood pressure reductions and low levels of AEs compared with either monotherapy. Therefore, a single-pill combination with fimasartan 60 mg/amlodipine 10 mg will be developed. ClinicalTrials.gov: NCT01518998. [ABSTRACT FROM AUTHOR]

Abstract: Background: Angiotensin receptor blockers (ARBs) is an effective and well tolerated first-line antihypertensive drug. Fimasartan is a newly developed ARB that has not been compared with other ARBs with regard to its efficacy and tolerability. Objective: The goal of this study was to determine the noninferiority of fimasartan to losartan with regard to its efficacy and tolerability in adult Korean patients with mild-to-moderate hypertension. Methods: This was a randomized, multicenter, double-blind, parallel group, dose escalation, Phase III, noninferiority clinical trial. Patients aged 18 to 70 years with mild-to-moderate hypertension were randomized to receive either fimasartan 60/120 mg daily or losartan 50/100 mg daily with optional titration. Antihypertensive efficacy and tolerability were evaluated for 12 weeks. The primary end point was noninferiority of improvement in mean siDBP from baseline to week 12 for fimasartan compared with losartan. The incidence and severity of adverse events (AEs) and adverse drug reactions (ADRs) were evaluated to assess their tolerability. In addition, some patients whose blood pressure reached goal levels participated in a 24-week extension study for additional assessment of tolerability and efficacy. Results: Five hundred six patients were randomly allocated to receive fimasartan (n = 256) or losartan (n = 250). There was no significant difference in baseline demographic characteristics between the 2 treatment groups (fimasartan-treated group—mean age, 53.96 [8.79] years; mean weight, 70.58 [11.73] kg; male, 68.02%; losartan-treated group—mean age, 53.58 [9.61] years; mean weight, 69.80 [11.08] kg; male, 70.17%). At week 12, siDBP was significantly decreased from baseline in both groups (−11.26 [7.53] mm Hg in the fimasartan group and −8.56 [7.72] mm Hg in the losartan group [P < 0.0001]). The between-group difference was 2.70 mm Hg (P = 0.0002), and the lower limit of the 2-sided 95% CI (1.27 mm Hg) was higher than the prespecified noninferiority margin (−2.5 mm Hg). The incidence of ADRs were 7.84% and 10.40% in the fimasartan and losartan groups, respectively (χ2 test, P = 0.3181). The efficacy of fimasartan was maintained over 24 weeks, and its tolerability was comparable with losartan in the extension study. Conclusions: In this study with eligible adult Korean patients who had mild-to-moderate hypertension, the reduction of siDBP after 12 weeks of treatment with fimasartan 60/120 mg was noninferior to that of losartan 50/100 mg. By post hoc comparison, between-group differences in siDBP were significant in favor of fimasartan, suggesting superiority to losartan. There was no statistically significant difference in tolerability between the groups. This efficacy and tolerability were maintained throughout the additional 12-week extension study. ClinicalTrials.gov identifier: NCT00922480. [Copyright &y& Elsevier]

Background: Fimasartan, a selective angiotensin II type 1 receptor blocker, was approved in Korea for the treatment of patients with mild to moderate hypertension., Objective: The aim of this study was to evaluate the 24-hour blood pressure (BP) profiles before and after 8-week treatment with fimasartan and to compare them with those of valsartan., Methods: A multicenter, randomized, double-blind, active-controlled, parallel-group study was conducted using ambulatory BP monitoring (ABPM). Korean patients with mild to moderate essential hypertension were enrolled and randomly received once-daily oral fimasartan 60 or 120 mg or valsartan 80 mg for 8 weeks. ABPM was performed before and after 8-week treatment, and clinic BP was also measured. Based on ABPM data, trough-to-peak ratio and smoothness index were derived. Tolerability was monitored throughout the study., Results: Ninety-two patients were enrolled (mean [SD] age, 54.1 [8.2] years; weight, 67.9 [10.2] kg). After 8 weeks, 24-hour, daytime, and nighttime mean ambulatory systolic and diastolic BPs (SBP and DBP, respectively) were significantly decreased in all 3 treatment groups (range: SBP, -9.2 to -15.6 mm Hg; DBP, -5.0 to -10.7 mm Hg; P <0.0001-<0.05). The global trough-to-peak ratios of ambulatory DBP in the fimasartan groups were 0.74 (60 mg/d) and 0.81 (120 mg/d)--45.1% and 58.8% higher, respectively, than the ratio of 0.51 in the valsartan group. Fimasartan 60 mg/d was associated with 53.5% (SBP) and 68.3% (DBP) greater smoothness index scores compared with those with valsartan 80 mg/d (SBP, 1.52 vs. 0.99; DBP, 1.38 vs. 0.82). The decrease in clinic-measured DBP was significantly greater in the fimasartan 60-mg/d group compared with that in the valsartan 80-mg/d group (-14.0 vs -8.7 mm Hg; P = 0.0380). Fimasartan was well tolerated; headache was the most common adverse event., Conclusion: Once-daily fimasartan effectively maintained a BP-reduction profile over the full 24-hour dosing interval; this profile was comparable to or slightly better than that of once-daily valsartan. Fimasartan was well tolerated; headache was the most common adverse event., (© 2013 Elsevier HS Journals, Inc. All rights reserved.)