|Year : 2019 | Volume
| Issue : 7 | Page : 2184-2188
Fimasartan: A new armament to fight hypertension
Akshyaya Pradhan, Vikas Gupta, Rishi Sethi
Department of Cardiology, King George Medical University, Lucknow, Uttar Pradesh, India
|Date of Submission||10-Apr-2019|
|Date of Decision||10-Apr-2019|
|Date of Acceptance||22-May-2019|
|Date of Web Publication||31-Jul-2019|
Dr. Akshyaya Pradhan
Department of Cardiology, King George's Medical University, Lucknow - 226 003, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Hypertension is a major public health problem of modern era. Fimasartan is a new Angiotensin Receptor Blocker approved for treatment of hypertension. It is more potent and longer acting angiotensin receptor blocker with effects lasting over 24 hours. Many clinical studies have affirmed its role in pharmacotherapy of hypertension. Further, it is renoprotective and has proven beneficial in diabetes also. This article briefly discusses the pharmacology and clinical evidence with fimasartan with a short summary of previous angiotensin receptor blockers.
Keywords: Angiotensin receptor blocker, clinical studies, fimasartan, hypertension, pharmacokinetics
|How to cite this article:|
Pradhan A, Gupta V, Sethi R. Fimasartan: A new armament to fight hypertension. J Family Med Prim Care 2019;8:2184-8
| Introduction|| |
Hypertension is a major public health problem of modern era. Up to 28% of the world's adult population had uncontrolled hypertension in a study published in 2011. Anchala et al. reported an overall hypertension prevalence of 29.8% in India in their meta-analysis. The prevalence of hypertension in this study was significantly higher in urban Indians than in rural Indians (33.8% vs. 27.6%, respectively).
Hypertension if left untreated can lead to end organ damage, such as retinopathy, chronic kidney disease, cerebrovascular disease, heart failure, coronary artery disease, and atrial fibrillation. Various classes of drugs are available for treatment of hypertension. Among these angiotensin receptor blockers (ARBs) are most widely used antihypertensive drugs and have maximal patient acceptability profile. ARBs hold class I recommendation for pharmacological management of hypertension in various guidelines including European and American guidelines.,,
| Mechanism of Action of ARBs|| |
The ARBs selectively inhibit angiotensin II by competitive antagonism of the angiotensin receptors [Figure 1]. Thereby, they antagonize angiotensin II-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, and water retention. These mechanisms reduce adverse effects and possibly improve clinical efficacy in comparison to angiotensin convertase enzyme inhibitors (ACEIs). The currently available ARBs are summarized briefly in [Table 1].
|Figure 1: Mechanism of action of angiotensin convertase enzyme inhibitors and angiotensin receptor blockers|
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|Table 1: Brief description of currently available ARBs (“Sartans”),,,|
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| Fimasartan - the Latest “sartan”|| |
Fimasartan is a latest  angiotensin II receptor antagonist with selectivity for the AT(1) receptor subtype, developed by a korean company Boryung Pharmaceutical as an oral antihypertensive drug. [Figure 2] demonstrates journey of ARBs from first marketed ARB molecule to recently introduced fimasartan. Fimasartan has been approved for use in patients with hypertension by FDA of Korea. Boryung has also got approval for this molecule in many other countries such as China, Singapore, and Russia. Fimasartan has also been approved in India by CDSCO (Central Drugs Standard Control Organization) recently.
Fimasartan is a biochemical derivative of losartan in which the imidazole ring has been replaced. This change provides higher potency and longer duration of action to this molecule. Fimasartan is selective angiotensin II type 1 (AT1) receptor antagonist. In contrast to other ARBs, it did not show agonistic action to AT2 receptor in animal models.
| Pharmacokinetics and Dynamics|| |
The pharmacokinetics and pharmacodynamics of fimasartan are highlighted in [Table 2]. It is a long acting drug, requiring once daily dosing. It is usually given in dosage of 60–120 mg OD. The onset of action of fimasartan is faster that it's congeners. It is usually well tolerated in mild to moderate renal dysfunction, but dose reduction is required in severe renal dysfunction (<30 mL/min creatinine clearance starting dose is 30 mg OD). It is safe in mild hepatic dysfunction. Fimasartan should be avoided in severe hepatic dysfunction, patients on hemodialysis, pregnant or nursing mothers, and patients with hypersensitivity reaction.
|Table 2: Pharmacokinetics and pharmacodynamics of fimasartan,,|
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The drug has been well tolerated in clinical studies. Most adverse reactions were transient and not dose related. Headache and dizziness were the most common ones reported. Other reported side effects include nausea, pain abdomen, cough, pruritus, hot flushes, increased liver enzymes, etc.
| Clinical Evidence for Use in Hypertension|| |
We have now accumulated data for fimasartan use in close to 20,000 patients. Fimasartan was found to have an excellent efficacy and tolerability profile in a large-scale observational population study - Safe-KanArb. In this study, a total of 14,151 patients with mean age of 59 ± 12 years were evaluated. This study established the safety, efficacy, and compliance of this molecule. The Systolic blood pressure (SBP) fell by an average of -18.65 mm of Hg and Diastolic blood pressure by - 9.73 mm of Hg with drug therapy at 2 months. Interestingly, the pulse rate declined from 74.4 to 71.9 beats per min in the treatment arm. The benefits were attained irrespective of age, sex, comorbidities and background antihypertensive therapy. It should be noted that more than half of the study population (63%) was on background anti-hypertensive therapy underscoring the potency and efficacy of the drug. The drug was found to be excellent in patients potentially at higher risk for adverse events.
The K-MetS study of 10601 patients was planned to evaluate long-term effects of fimasartan on major adverse cardiovascular outcomes. The study also evaluated long-term metabolic effects of fimasartan. Three-year follow-up was planned in this study. At 1-year follow-up, in a sub group analysis published in 2017, fimasaratn significantly decreased the albumin/creatinine ratio. The systolic blood pressure fell from 143.7 ± 17.2 mm of Hg to 126.7 ± 12.6 mm of Hg at 1 year (a fall of around 17 mm of Hg). On a similar note, the diastolic BP decreased from 88.4 ± 11.48 at baseline to 78.6 ± 8 mm of Hg. Waist circumference and triglyceride levels were also diminished simultaneously.
In another study, the drug was associated with reduction in day to day BP variability independent of absolute BP reduction. Fimasartan was similarly effective in reducing Systolic as well as diastolic BP in hypertensive elderly patients compared with nonelderly patients in a sub group analysis of K-MetS study. It also resulted in better pulse pressure reduction with similar home blood pressure reduction efficacy and safety in hypertensive elderly patients.
One recent study evaluated the effects of fimasartan and amlodipine therapy on carotid atherosclerotic plaque inflammation using 18F-fluorodeoxyglucose positron emission tomography imaging. Both drugs were found to decrease carotid atherosclerotic plaque inflammation similarly in patients with acute coronary syndrome. The major studies done with fimasartan so far are depicted in [Table 3].
|Table 3: Major studies establishing the clinical role of fimasartan in hypertension.,,,,,,,,,[BP-Blood Pressure; FMS- Fimasartan; HCTZ-Hydrochlorthiazide]|
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| Implications for Clinical Practice|| |
The prevalence of hypertension is continuously rising, yet the proportion of patient's with their blood pressures under target remains low. The ACC/AHA 2017 hypertension guidelines suggest that most of the hypertensive patients will need combination therapy for attaining BP goals. In real world, primary care physician (not the cardiologist) is usually the first contact of a patient for hypertension consultation. So longer acting, potent antihypertensive drugs with least side effect profile are needed to make the task of hypertension control easy. ARBs have proven their efficacy in treatment of hypertension for past two decades. They have most favorable side effect profile among current antihypertensive portfolio. Fimasartan is newer longer acting and potent ARB. So, it can be safely used by primary care physician in an efficient manner for management of hypertension.
| Future Directions|| |
FANTASTIC study will assess renoprotective effect of fimasartan and the target blood pressure to reduce adverse outcomes in hypertensive diabetic chronic kidney disease patients with overt proteinuria.
The safety and efficacy of drug in elderly patients (>70 years) against perindopril is being evaluated in FITNESS study (NCT 03246555). The FRESH (FimasaRtan-basEd BP Targets After Drug SwitcHing) study aimed to find proportion of patients achieving BP goals after switching to fimasartan-based regimens in patients with uncontrolled hypertension (NCT 03649646).
| Conclusion|| |
A good number of clinical evidences support the use of this newer, potent, longer acting ARB- Fimasartan [See [Figure 3]]. Fimasartan achieved clinically significant blood pressure reduction in various studies with effect persisting over 24 h dosing interval. It was also shown to be renoprotective too. Apart from being efficacious, it has also demonstrated safety in elderly and high risk populations. So, this newer ARB has shown promising results in terms of efficacy, safety, and tolerability in clinical studies. The molecule is currently being used in number of countries in treatment of hypertension. In India, it has been launched recently. Fimasartan appears as a promising drug for management of hypertension for future in our country.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]