<p>Effect of Fimasartan versus Valsartan and Olmesartan on Office and Ambulatory Blood Pressure in Korean Patients with Mild-to-Moderate Essential Hypertension: A Randomized, Double-Blind, Active Control, Three-Parallel Group, Forced Titration, Multicenter, Phase IV Study (Fimasartan Achieving Systolic Blood Pressure Target (FAST) Study)</p>

Abstract

Purpose: Head-to-head comparison of the blood pressure (BP) lowering effect of fimasartan versus valsartan, with olmesartan as a reference, on office blood pressure and ambulatory BP. Patients and Methods: Of the 369 randomly assigned patients in this study, 365 hypertensive patients were referred as the full analysis set and divided into 3 groups with a 3:3:1 ratio (fimasartan group: 155, valsartan group: 157, olmesartan group: 53). After the 2-week single-blind placebo run-in period, initial standard doses of 60-mg fimasartan, 80-mg valsartan, and 10-mg olmesartan were administered for 2 weeks, then forcibly up-titrated higher doses (fimasartan 120 mg, valsartan 160 mg, olmesartan 20 mg) were given for 4 weeks. ABP was measured before and after the 6-week treatment. Primary endpoint was reduction of sitting office systolic BP (SiSBP) of fimasartan compared to valsartan after 6 weeks. Secondary endpoints were reduction of sitting office diastolic BP (SiDBP) and 24 hrs, daytime, and night-time mean systolic and diastolic ABP (ASBP, ADBP) after 6 weeks. Results: Patients' mean age was 58.34±7.68 years, and 289 patients were male (79.18%). After the 6-week treatment, SiSBP reduction of fimasartan and valsartan were −16.26±15.07 and −12.81±13.87 (p=0.0298) and SiDBP were −7.63±9.67 and −5.14±8.52 (p=0.0211). Reductions in 24 hrs mean ASBP were −15.22±13.33 and −9.45±12.37 (p=0.0009), and ADBPs were −8.74±7.55 and −5.98±7.85 (p=0.0140). Reductions of night-time ASBPs were −16.80±15.81 and −10.32±14.88 (p=0.0012), and those of night-time ADBPs were −8.89 ±9.93 and −5.55±9.70 (p=0.0152). Reduction of BP in olmesartan group did not demonstrate significant difference with fimasartan group in all end-points. Conclusion: Fimasartan 120-mg treatment demonstrated superior efficacy in reduction of SiSBP, SiDBP, and 24 hrs ASBP and ADBP compared to valsartan 160 mg. Reduction of night-time ASBP from baseline was largest in fimasartan group, suggesting that fimasartan may be effective for recovering dipping pattern. NCT number: NCT02495324 (Fimasartan Achieving SBP Target (FAST) study).

Long‐term mortality and cardiovascular events of seven angiotensin receptor blockers in hypertensive patients: Analysis of a national real‐world database: A retrospective cohort study

“… 32 , 33 Many head‐to‐head studies have revealed more potent antihypertensive effects, particularly when compared with losartan or valsartan. 22 , 34 , 35 However, these newer ARBs do not have compelling evidence of long‐term cardiovascular outcomes, and the clinical use of these drugs is limited. Our study demonstrates that newer ARBs have similar long‐term clinical outcomes to those of earlier ARBs, based on the data of many patients in the real world.…”

“… 37 Several studies comparing the antihypertensive effect of ARBs have shown differences in the magnitude of BP reduction. 34 , 35 This difference in BP control may affect patients' prognoses. In patients with acute myocardial infarction, comparative analysis revealed that insurmountable ARBs, which have a longer and more stable duration of action, were more effective on long‐term clinical outcomes compared with surmountable ARBs.…”

“…For example, the number of hydrogen bonds that affect binding affinity is different among ARBs, and this can translate into various antihypertensive effects 37 . Several studies comparing the antihypertensive effect of ARBs have shown differences in the magnitude of BP reduction 34,35 . This difference in BP control may affect patients' prognoses.…”

Incidence and Pattern of Aminotransferase Elevation During Anti-Hypertensive Therapy With Angiotensin-II Receptor Blockers

“… 7 Fimasartan is mainly excreted unchanged through bile by multiple cytochrome p450s, mainly CYP3A, and less than 3% is excreted in urine. Fimasartan has excellent efficacy in controlling hypertension, 8 but the pharmacokinetics of the drug have raised concerns regarding the increased possibility of drug-induced liver injury (DILI). To date, few case reports have described ARB-induced liver injury.…”

“…9 10 11 12 Most cohort studies have not reported detailed liver injury incidence and outcomes related to ARB-related DILI, instead only the overall, severe adverse drug-related reaction rates have been reported. 8 …”