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

Choi, W.J.; Kim, Gi‐Ae; Park, Jaewon; Jang, Sangmi; Jung, Woo Jin; Shim, Jae‐Jun; Sinn, Dong Hyun; Choi, Gwang Hyeon; Kim, Jin‐Wook; Jeong, Sook‐Hyang; Jang, Eun Sun

doi:10.3346/jkms.2022.37.e255

Cited by 4 publications

(3 citation statements)

References 18 publications

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“…Moreover, valsartan administered at 160 or 320 mg is more effective at lowering BP than losartan 100 mg, irbesartan 150 mg and candesartan 16 mg [ 15 ]. Valsartan has good tolerability with a side-effect profile indistinguishable from placebo and superior to some other ARBs (e.g., olmesartan and losartan), which improved patient compliance, resulting in increased drug efficacy [ 16 , 17 , 18 , 19 ]. One study showed total discontinuations in olmesartan, losartan and valsartan during treatment of 16.9%, 13.5% and 10.3%, respectively [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Two-Drug Combinations Therapy of Different Doses of Valsartan Existing Diverse Significance for Hypertensive Patients

Wang¹,

Shixiong²,

Zhang³

et al. 2023

Rev. Cardiovasc. Med.

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Background:The incidence of hypertension and clinical complications (e.g., heart, cerebrovascular and kidney injury) is increasing worldwide. It is widely known that a relatively large dose of valsartan (320 mg) could alleviate clinical complications. The current network meta-analysis assessed which drug could be combined with a relatively large dose of valsartan to control blood pressure (BP) more effectively. And which combination therapy with different dosages of valsartan did not induce excessive BP reduction with increasing dosages of valsartan. Methods: The PubMed, Embase, Medline, Cochrane Library, CNKI, Wanfang, and CSTJ databases were searched from inception to October 2022 for relevant randomized controlled trials (RCTs). The search strategies included concepts related to hypertension and two-drug combination therapy of different doses of valsartan, and there were no language or data restrictions. The outcomes included adverse effects and changes in systolic BP and diastolic BP. Permanent discontinuations related to treatment were the most accurate and objective measure of adverse effects. The common adverse effects of most studies (i.e., dizziness, headache, nasopharyngitis, asthenia and urticaria) were also included. A Bayesian network meta-analysis was performed, and mean differences with 95% confidence intervals were calculated. ADDIS and STATA were used for Bayesian model network meta-calculation. Results: Thirty-four RCTs were included involving 26,752 patients, and the interventions included different doses of valsartan combined with various types and doses of drugs. Among many combination therapies, the combination of valsartan 320 mg with amlodipine 10 mg (p < 0.01) had the best antihypertensive effect without significant adverse effects. Compared with valsartan 80 mg and 160 mg, valsartan 320 mg combined with hydrochlorothiazide 25 mg (p > 0.05) did not further reduce BP and was not shown to increase the incidence of adverse effects. Conclusions: Combination therapy with a relatively large dose of valsartan could control BP and improve clinical complications effectively. However, for hypertensive patients with different treatment requirements, specific choices should be made regarding whether to control BP, treat clinical complications, or both.

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Section: Discussionmentioning

confidence: 99%

Two-Drug Combinations Therapy of Different Doses of Valsartan Existing Diverse Significance for Hypertensive Patients

Wang¹,

Shixiong²,

Zhang³

et al. 2023

Rev. Cardiovasc. Med.

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“… 3 , 11 The balance between the achievement of goal BP and the reduced risk of side effects has become a key concern for clinicians. 12 – 14 Few randomized controlled studies have evaluated geriatric high BP patients of varying ages, disease stages, and degrees of susceptibility, particularly in the Chinese elderly population. It is essential to reduce the safety risk and maximize the efficacy-to-safety ratio of candesartan in geriatric patients.…”

Section: Introductionmentioning

confidence: 99%

Physiologically based pharmacokinetic modeling of candesartan to predict the exposure in hepatic and renal impairment and elderly populations

Guo,

Zhu,

Zhang

et al. 2023

Therapeutic Advances in Drug Safety

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Background: Candesartan cilexetil is a widely used angiotensin II receptor blocker with minimal adverse effects and high tolerability for the treatment of hypertension. Candesartan is administered orally as the prodrug candesartan cilexetil, which is wholly and swiftly converted to the active metabolite candesartan by carboxylesterase during absorption in the intestinal tract. In populations with renal or hepatic impairment, candesartan’s pharmacokinetic (PK) behavior may be altered, necessitating dosage adjustments. Objectives: This study was conducted to examine how the physiologically based PK (PBPK) model characterizes the PKs of candesartan in adult and geriatric populations and to predict the PKs of candesartan in elderly populations with renal and hepatic impairment. Design: After developing PBPK models using the reported physicochemical properties of candesartan and clinical data, these models were validated using data from clinical investigations involving various dose ranges. Methods: Comparing predicted and observed blood concentration data and PK parameters was used to assess the fit performance of the models. Results: Doses should be reduced to approximately 94% of Chinese healthy adults for the Chinese healthy elderly population; approximately 92%, 68%, and 64% of that of the Chinese healthy adult dose in elderly populations with mild, moderate, and severe renal impairment, respectively; and approximately 72%, 71%, and 52% of that of the Chinese healthy adult dose in elderly populations with Child–Pugh-A, Child–Pugh-B, and Child–Pugh-C hepatic impairment, respectively. Conclusion: The results suggest that the PBPK model of candesartan can be utilized to optimize dosage regimens for special populations.

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“…In the current issue of the Journal of Korean Medical Science , Choi et al 5 reported the incidence and pattern of aminotransferase elevation during antihypertensive therapy with ARBs. In this retrospective study, significant alanine transaminase (ALT) elevation (ALT > 120 IU/L) and severe ALT elevation (ALT > 200 IU/L) among patients treated with either fimasartan, candesartan, valsartan, or losartan occurred in about 2% and 0.6% of patients, respectively.…”

mentioning

confidence: 99%

Are Angiotensin II Receptor Blockers Really Safe From Aminotransferase Elevation or Drug-Induced Liver Injury?

Jang

2022

J Korean Med Sci

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

Cited by 4 publications

References 18 publications

Two-Drug Combinations Therapy of Different Doses of Valsartan Existing Diverse Significance for Hypertensive Patients

Two-Drug Combinations Therapy of Different Doses of Valsartan Existing Diverse Significance for Hypertensive Patients

Physiologically based pharmacokinetic modeling of candesartan to predict the exposure in hepatic and renal impairment and elderly populations

Are Angiotensin II Receptor Blockers Really Safe From Aminotransferase Elevation or Drug-Induced Liver Injury?

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