Efficiency of Combined Antihypertensive Therapy in Patients With Arterial Hypertension and Obesity Depending on the Polymorphism of Cyp2c9 Gene

Kovalenko, F. A.; Skibitsky, V. V.; Фендрикова, А. В.; Lazarev, K. Yu.; Lukonin, I. A.

doi:10.25207/1608-6228-2018-25-2-94-100

Cited by 3 publications

(4 citation statements)

References 9 publications

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“…The articles selected for the final analysis are presented in Table 1 . 22 articles [ 10 – 14 , 16 – 19 , 21 – 24 , 26 – 31 , 33 – 35 ] of the 26 reported the results of unauthorised clinical trials. Moreover, one of the 22 unauthorised trials was conducted in children aged from 6 to 29 months [ 10 ], and two were conducted in children aged 7–18 years [ 14 , 33 ].…”

Section: Resultsmentioning

confidence: 99%

“…In yet another trial, different treatments were allocated to patients according to the estimated risk of cardiovascular disease [ 22 ]. In two cases [ 28 , 35 ] of the 26 studies, the described randomisation process was not in line with the objectives of the study and further analysis because the study conclusions were based on comparisons of other treatment arms that were not envisaged by the randomisation scheme.…”

Section: Resultsmentioning

confidence: 99%

“…We assume that in some cases, the clinical studies were so-called ‘marketing trials’ [ 34 , 35 , 37 ], i.e. they were conducted not to answer a scientific question but to boost sales by publishing articles in professional journals.…”

Section: Discussionmentioning

confidence: 99%

“…We sequentially reviewed each publication until 20 articles that met our inclusion criteria were accrued [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. When we replicated the search a few months later, the results in eLIBRARY were different, in that six additional articles that met the inclusion criteria were found; these were also added to our analysis [30][31][32][33][34][35]. Having consulted the eLIBRARY staff, we could not reliably determine the cause of discrepancy in the search results at different times.…”

Section: Methodsmentioning

confidence: 99%

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Unapproved clinical trials in Russia: exception or norm?

Talantov

Niyazov²,

Viryasova

et al. 2021

BMC Med Ethics

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Background In modern Russia, any clinical investigation of a pharmaceutical for use in humans is subject to prior evaluation and approval by the Ministry of Health and its Central Ethics Committee. Despite this, some researchers and trial sponsors fail to comply, this is particularly true in case of the studies initiated by domestic sponsors or sponsor-investigators and published in Russian language medical journals. This exploratory research aims to discover whether it is a sporadic non-compliance with regulations or a common practice. Methods We searched the Russian language database eLIBRARY for the phrase ‘results of a randomised trial’. We selected publications reporting clinical trials and conducted in Russia. For each of the selected studies, we searched the state register of the approved clinical trials. We assessed whether (1) the investigational medicinal product was approved for marketing in Russia; (2) the therapeutic indications, posology, and administration method in the clinical trial were consistent with the approved labelling; (3) the issue of the journal included an advertisement of the medicinal product in question; and (4) the full description of the methodology corroborated that the clinical trial was randomised, as was stated in the title or abstract. Results Of the 26 selected articles, 22 reported the results of unauthorised clinical trials. Three of those trials were conducted in children. Twenty-one studies reported on data from unauthorised trials for investigational products approved for marketing in Russia. However, in nine cases, the therapeutic indications, posology, or administration method did not match the conditions indicated in the labelling. Moreover, in one case, the unauthorised trial included a drug therapy intervention where the active substance was not approved for use in any medicinal product marketed in Russia. In 14 of the 26 articles, the issue of the journal or the article itself contained an advertisement for the same medicinal product or, in one case, its manufacturer. All publications accompanied by advertisements claimed that the medicinal product in question was efficacious. Conclusions A substantial fraction of the clinical trials initiated by domestic sponsors and reported in Russian medical journals failed to obtain the mandatory prior evaluation and approval from the regulator. This can affect the rights and well-being of the study participants and the scientific validity of the studies.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Unapproved clinical trials in Russia: exception or norm?

Talantov

Niyazov²,

Viryasova

et al. 2021

BMC Med Ethics

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Personalized pharmacotherapy of arterial hypertension patients with musculoskeletal system diseases based on pharmacogenetic aspects

2021

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Pharmacotherapy in patients with comorbidity is a current issue for clinical practice. Combination of hypertension and musculoskeletal diseases can be found in 40% of outpatients, which requires simultaneous administration of different drugs. The main mechanisms of drug interactions are associated with pharmacokinetics or pharmacodynamics alterations. It has been proven that changes in drugs pharmacokinetics can be due to cytochromes P450 activity. The main symptom of musculoskeletal diseases is chronic pain, which requires long-term therapy with non-steroidal anti-inflammatory drugs (NSAIDs). The 2C19 isoenzyme takes part in metabolism of some NSAIDs. Losartan, the inhibitor of renin-angiotensinaldosterone system (RAAS), is also metabolized by the 2C9 isoenzyme and is quite often prescribed to outpatients to treat hypertension. Hence, an influence of genetic factors on efficacy and safety of antihypertensive drugs and NSAIDs combinations requires further studies.

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Efficiency of combined antihypertensive pharmacotherapy in patients with arterial hypertension, combined with type 2 diabetes mellitus and non-alcoholic fatty liver disease

Lukonin

Skibitsky

Фендрикова

et al. 2022

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Background. Treatment of patients with arterial hypertension (AH) associated with type 2 diabetes mellitus (DM2) and non-alcoholic fatty liver disease (NAFLD) is a complex clinical challenge. The complementary and aggravating effect of these comorbidities often prevents the realization of the antihypertensive potential of the drugs used and their combinations, and therefore it is necessary to search for additional ways to intensify therapy.Aim. To assess the efficiency of combined pharmacotherapy in patients with AH associated with DM2 and NAFLD, depending on the CYP2C9 gene polymorphism.Materials and methods. The study included 68 patients with uncontrolled AH associated with DM2 and NAFLD (Fatty Liver Index (FLI) > 60) who received prior antihypertensive therapy. All subjects were prescribed a combination of azilsartan medoxomil with amlodipine at doses of 40/5 mg/day. The duration of therapy was 24 weeks. Those included in the study underwent control of office blood pressure (BP) at the initial visit, after 4, 8 and 24 weeks of treatment; 24-hour BP monitoring (ABPM) — initially and after 24 weeks. Venous blood samples were taken from patients, followed by DNA isolation from leukocytes by phenol- chloroform extraction. Determination of polymorphic variants of the CYP2C9 gene was carried out on an amplifier Rotor Gene — Q. The TaqMan method (allele discrimination) and a set of primers and probes were used.Results. As a result of genetic testing, the following distribution of polymorphic variants of the CYP2C9 gene was revealed: *1/*1 was found in 73,5% of patients, *1/*2 in 14,7%, *1/*3 in 11,8%. It was shown that after 4 weeks of therapy with a polymorphic variant of the *1/*1 CYP2C9 gene, the achievement of the target level (TL) of BP was registered in 62% of patients, with polymorphisms *1/*2 and *1/*3 — in 30% and 25%. After increasing the dose of azilsartan medoxomil and amlodipine to 80/10 mg/day, respectively, and 8 weeks from the start of treatment in the *1/*1 group, the number of BP targets achieved increased to 88%, in the *1/*2 groups and *1/*3 — up to 60% and 62,5%. Antihypertensive therapy was intensified with prolonged release indapamide at a dose of 1,5 mg/day, and according to the results of 24 weeks of therapy, patients with a polymorphic variant of the CYP2C9 *1/*1 gene achieved the TLBP in 96% of cases, with *1/*2 and *1/*3 — In 90% and 87,5%, respectively. At the same time, in patients with polymorphism of the CYP2C9 gene *1/*1, *1/*2 and *1/*3, positive dynamics of all ABPM parameters was revealed. However, in the *1/*1 variant, more pronounced positive changes were observed in the systolic BP time index during the day and the diastolic BP time index during the day, and the diastolic BP time index at night.Conclusions. As a result of a 24-week study, the majority of patients who had the polymorphic variant *1/*1 of the CYP2C9 gene showed a more pronounced efficacy of the studied combination of drugs. Patients with *1/*2 and *1/*3 polymorphisms often required triple therapy to achieve TLBP. At the same time, further studies are needed to study the dependence of the antihypertensive effects of drugs on polymorphisms of the corresponding genes, which may help identify groups of patients who need more intensive antihypertensive therapy already at the start of treatment.

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Efficiency of Combined Antihypertensive Therapy in Patients With Arterial Hypertension and Obesity Depending on the Polymorphism of Cyp2c9 Gene

Cited by 3 publications

References 9 publications

Unapproved clinical trials in Russia: exception or norm?

Unapproved clinical trials in Russia: exception or norm?

Personalized pharmacotherapy of arterial hypertension patients with musculoskeletal system diseases based on pharmacogenetic aspects

Efficiency of combined antihypertensive pharmacotherapy in patients with arterial hypertension, combined with type 2 diabetes mellitus and non-alcoholic fatty liver disease

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