Pharmacological Profiles of a Highly Potent and Long-Acting Angiotensin II Receptor Antagonist, Fimasartan, in Rats and Dogs after Oral Administration

Paik, Soo Heui; Ha, Yong; Lee, Joo Han; Han, Hee-Soo; Lee, Kyung‐Tae

doi:10.1248/bpb.b16-00987

Cited by 8 publications

(4 citation statements)

References 30 publications

(51 reference statements)

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“…Newer ARBs, including olmesartan, fimasartan, and azilsartan, are known to have higher potency compared with previous ARBs. 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.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, claims data enable analysis of the data of many patients. Newer ARBs, including olmesartan, fimasartan, and azilsartan, are known to have higher potency compared with previous ARBs 32,33 . Many head‐to‐head studies have revealed more potent antihypertensive effects, particularly when compared with losartan or valsartan 22,34,35 .…”

Section: Discussionmentioning

confidence: 99%

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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

Lee

Kang

Park

et al. 2023

Health Science Reports

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Background and Aims Although many angiotensin receptor blockers (ARBs) are widely used, comparative data regarding their impact on clinical outcomes are limited. We aimed to compare the clinical effectiveness of seven ARBs on long‐term cardiovascular outcomes in Korean patients with hypertension. Methods Using the Korean National Health Insurance Service database, the data of 780,785 patients with hypertension without cardiovascular disease (CVD) who initiated ARB treatment (candesartan, fimasartan, irbesartan, losartan, olmesartan, telmisartan, or valsartan) in 2014 and underwent this treatment for more than 6 months, were analyzed. Cox‐regression analysis was performed using Losartan as a comparator, as it was the most widely used drug, by adjusting age, sex, diabetes, dyslipidemia, smoking, alcohol drinking, exercise, body mass index, systolic blood pressure, albuminuria, estimated glomerular filtration rate, and concomitant medications. The occurrence of mortality and the rate of major adverse cardiovascular events (MACEs) of the six ARBs was compared with that of losartan. Results The median follow‐up duration was 5.94 (interquartile range, 5.87–5.97) years. In the crude analysis of all‐cause mortality and MACEs, fimasartan exhibited the lowest event rates. In the Cox‐regression analysis with adjustment, there was no significant difference in all‐cause mortality among ARBs. The risk of MACEs with ARBs was similar to that with losartan, although the risks with irbesartan (hazard ratio [HR], 1.079; 95% confidence interval [CI], 1.033–1.127; p = 0.007) and candesartan (HR: 1.066; 95% CI, 1.028–1.106; p = 0.015) were slightly higher. Conclusion In a Korean population of patients with hypertension without CVD, six different ARBs showed similar efficacy to losartan in terms of long‐term mortality and MACEs. Further well‐designed prospective studies are required to confirm our findings.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Lee

Kang

Park

et al. 2023

Health Science Reports

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“…Fimasartan, a pyrimidin-4(3H)-one derivative of losartan with the imidazole ring replaced, which enables higher potency and longer duration than losartan. With a strong binding affinity to AT 1 receptor, fimasartan had the highest association rate compared to other ARBs 28 and better efficacy on blood pressure lowering. 29 30 31 In addition, fimasartan has the cardioprotective effects against myocardial ischemia and reperfusion injury, 32 or heart failure progression 12 in preclinical studies.…”

Section: Discussionmentioning

confidence: 99%

Comparison Between Fimasartan Versus Other Angiotensin Receptor Blockers in Patients With Heart Failure After Acute Myocardial Infarction

et al. 2023

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Backgrounds Fimasartan is the most recently developed, potent, and long-acting angiotensin II receptor blocker (ARB). However, data are limited regarding treatment effects of fimasartan in patients with heart failure. Methods Between 2010 and 2016, patients who underwent coronary revascularization for myocardial infarction (MI) with heart failure and prescription of ARB at hospital discharge were enrolled from the Korean nationwide medical insurance data. Clinical outcomes were compared between patients receiving fimasartan and those receiving other ARBs (candesartan, valsartan, losartan, telmisartan, olmesartan, and irbesartan). The primary outcome was a composite of all-cause death, recurrent MI, hospitalization for heart failure, and stroke. Results Of 2,802 eligible patients, fimasartan was prescribed to 124 patients (4.4%). During a median follow-up of 2.2 years (interquartile range, 1.0–3.9), 613 events of the primary outcome occurred. There was no significant difference in the primary outcome between patients receiving fimasartan and those receiving other ARBs (adjusted hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.46–1.45). Compared with patients receiving other ARBs, those receiving fimasartan had comparable incidence of all-cause death (adjusted HR, 0.70; 95% CI, 0.30–1.63), recurrent MI (adjusted HR, 1.28; 95% CI, 0.49–3.34), hospitalization for heart failure (adjusted HR, 0.70; 95% CI, 0.27–1.84), and stroke (adjusted HR, 0.59; 95% CI, 0.18–1.96). Conclusion In this nationwide cohort, fimasartan, compared with other ARBs, had comparable treatment effects for a composite of all-cause death, recurrent MI, hospitalization for heart failure, and stroke in patients with heart failure after MI.

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“…Fimasartan was also reported to reduce ischemic cell death when used to treat transient focal ischemia in rats [31], and to prevent unilateral ureteral obstruction-induced apoptosis in mice [32]. Although fimasartan has not been previously studied for the treatment of HF, it is expected to exert similar effects to other ARBs, and potentially greater efficacy because of its higher affinity for angiotensin II type 1 (AT1) receptors compared with other drugs of its class in preclinical studies [33]. The AT1 receptor is involved in the classical physiological actions of angiotensin II: the regulation of blood pressure, electrolytes, and water balance; thirst; hormone secretion, and the regulation of renal function [34].…”

Section: Discussionmentioning

confidence: 99%

Fimasartan, an angiotensin II receptor antagonist, ameliorates an in vivo zebrafish model of heart failure

Quan

Seok

et al. 2020

Korean J Intern Med

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Background/Aims: Angiotensin II in the failing heart initially helps to maintain cardiac output and blood pressure, but ultimately accelerates its deterioration. In this study, we established a model of arrhythmia-induced heart failure (HF) in zebrafish and investigated the role of renin-angiotensin-aldosterone system (RAAS) modulation by using an angiotensin II type 1 receptor blocker, fimasartan, through the assessment of cellular and physiologic responses, morbidity, and mortality. Methods: HF was induced in zebrafish larvae by exposure to 20 μM terfenadine.Morphologic, physiologic, and functional parameters were assessed in the presence or absence of fimasartan treatment. Results: Zebrafish exposed to terfenadine showed marked dilatation of the ventricle and reduced systolic function. Treatment with terfenadine was associated with 10-fold higher expression of atrial natriuretic peptide (p < 0.001 vs. vehicle), increased p53 mRNA expression, and chromatin fragmentation in the TUNEL assay, all of which were significantly reduced by fimasartan treatment. Moreover, fimasartan improved fractional shortening (terfenadine + fimasartan 16.9% ± 3.1% vs. terfenadine + vehicle 11.4% ± 5.6%, p < 0.05) and blood flow (terfenadine + fimasartan 479.1 ± 124.1 nL/sec vs. terfenadine + vehicle 273.0 ± 109.0 nL/sec, p < 0.05). Finally, treatment with fimasartan remarkably reduced mortality (terfenadine + fimasartan 36.0% vs. terfenadine + vehicle 96.0%, p < 0.001). Conclusions: Fimasartan effectively protected against the progression of HF in zebrafish by improving hemodynamic indices, which improved survival. A reduction in apoptotic cell death and an improvement in hemodynamics may be the mechanisms behind these effects. Further human studies are warranted to evaluate the possible role of fimasartan in the treatment of HF.

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Pharmacological Profiles of a Highly Potent and Long-Acting Angiotensin II Receptor Antagonist, Fimasartan, in Rats and Dogs after Oral Administration

Cited by 8 publications

References 30 publications

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

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

Comparison Between Fimasartan Versus Other Angiotensin Receptor Blockers in Patients With Heart Failure After Acute Myocardial Infarction

Fimasartan, an angiotensin II receptor antagonist, ameliorates an in vivo zebrafish model of heart failure

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