Fimasartan noninferior to perindopril in older adults with essential hypertension

In the treatment of older patients with essential hypertension, fimasartan alone or combined with hydrochlorothiazide demonstrates comparable safety and efficacy to perindopril monotherapy or in combination with indapamide, as shown in the results of a phase IIIb trial.

“Fimasartan is a nonpeptide angiotensin II receptor blocker (ARB) with a selective blocking effect on the angiotensin type 1 receptor, and it has been proven to be clinically effective in many randomized controlled trials,” the investigators noted. [Drugs 2016;76:1015-1022]

On the other hand, “perindopril arginine is an angiotensin-converting enzyme (ACE) inhibitor used in HYVET (Hypertension in the Very Elderly Trial), a representative clinical study evaluating the effects of hypertension treatment in [older] patients aged >80 years,” they added. [N Engl J Med 2008;358:1887-1898]

The current analysis included 238 older Korean patients (mean age 74.3 years, 79 percent male) with a mean sitting systolic blood pressure (BP) ≥140 mm Hg. They were randomized to receive fimasartan 30 mg or perindopril arginine 2.5 mg once daily. If BP was uncontrolled after 4 weeks, the dose was doubled. At week 8, patients who still did not achieve BP control received a diuretic combination (fimasartan 60 mg/hydrochlorothiazide 12.5 mg or perindopril arginine 5 mg/indapamide 1.25 mg).

After 16 weeks of the double-blind treatment, all patients with controlled BP participated in an 8-week open-label extension study.

The primary outcome of mean systolic BP at week 8 significantly dropped from baseline in the two treatment arms (–14.2 mm Hg with fimasartan and –9.0 mm Hg with perindopril; least squares mean difference, 5.4 mm Hg), indicating the noninferiority of fimasartan to perindopril. Of note, fimasartan exhibited a higher BP-lowering effect than perindopril (p=0.0108). [Clin Ther 2021;43:1746-1756]

Furthermore, fimasartan produced greater reductions in systolic and diastolic BP from baseline to weeks 4, 8, and 16 compared with perindopril, although there was no difference in the systolic BP reduction recorded at week 16.

Treatment compliance through week 16 was high in both groups (97.4 percent). In terms of safety, 82 adverse events (AEs) occurred in 52 patients, including 40 in the fimasartan arm and 42 in the perindopril arm. Dizziness was the most common AE, and only one case of orthostatic hypotension in a perindopril-treated patient was reported.

“It is recommended that [older] hypertensive patients without comorbidities be treated with ACE inhibitors, ARBs, calcium channel blockers, and diuretic agents… For strict BP control, combination therapy with two or more drugs should be considered if BP is not controlled with monotherapy,” they pointed out. [Clin Hypertens 2019;25:19]

The low incidence of AEs and orthostatic hypotension, according to the investigators, might be related to the slow titration schedule based on the repetitive BP measurement combined with BP measurement in the standing position.

“ARBs are known to have a flat dose–response relationship in BP-lowering efficacy, and a lower dose was reported to decrease the duration of the antihypertensive effect… However, in the population [of patients] aged ≥65 years [in the HYVET trial], the bioavailability of fimasartan was higher than that in young healthy control [participants], making it available as a once-daily medication. The trial also used a slow titration schedule to minimize TEAEs,” the investigators explained. [N Engl J Med 2008;358:1887-1898]

“As a result, at the end of the dose titration period, >70 percent of patients successfully uptitrated the initial dose, and diuretic combination was possible for further BP reduction,” they added.