Bisoprolol In Patients Research Articles

Bisoprolol in Patients With Chronic Obstructive Pulmonary Disease

Bisoprolol in Patients With Chronic Obstructive Pulmonary Disease

Bisoprolol in Patients With Chronic Obstructive Pulmonary Disease—Reply

Bisoprolol in Patients With Chronic Obstructive Pulmonary Disease—Reply

Bisoprolol in Patients With Chronic Obstructive Pulmonary Disease at High Risk of Exacerbation

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Observational studies report that β-blocker use may be associated with reduced risk of COPD exacerbations. However, a recent trial reported that metoprolol did not reduce COPD exacerbations and increased COPD exacerbations requiring hospital admission. To test whether bisoprolol decreased COPD exacerbations in people with COPD at high risk of exacerbations. The Bisoprolol in COPD Study (BICS) was a double-blind placebo-controlled randomized clinical trial conducted in 76 UK sites (45 primary care clinics and 31 secondary clinics). Patients with COPD who had at least moderate airflow obstruction on spirometry (ratio of forced expiratory volume in the first second of expiration [FEV1] to forced vital capacity <0.7; FEV1 <80% predicted) and at least 2 COPD exacerbations treated with oral corticosteroids, antibiotics, or both in the prior 12 months were enrolled from October 17, 2018, to May 31, 2022. Follow-up concluded on April 18, 2023. Patients were randomly assigned to bisoprolol (n = 261) or placebo (n = 258). Bisoprolol was started at 1.25 mg orally daily and was titrated as tolerated during 4 sessions to a maximum dose of 5 mg/d, using a standardized protocol. The primary clinical outcome was the number of patient-reported COPD exacerbations treated with oral corticosteroids, antibiotics, or both during the 1-year treatment period. Safety outcomes included serious adverse events and adverse reactions. Although the trial planned to enroll 1574 patients, recruitment was suspended from March 16, 2020, to July 31, 2021, due to the COVID-19 pandemic. Two patients in each group were excluded postrandomization. Among the 515 patients (mean [SD] age, 68 [7.9] years; 274 men [53%]; mean FEV1, 50.1%), primary outcome data were available for 514 patients (99.8%) and 371 (72.0%) continued taking the study drug. The primary outcome of patient-reported COPD exacerbations treated with oral corticosteroids, antibiotics, or both was 526 in the bisoprolol group, with a mean exacerbation rate of 2.03/y, vs 513 exacerbations in the placebo group, with a mean exacerbation rate of 2.01/y. The adjusted incidence rate ratio was 0.97 (95% CI, 0.84-1.13; P = .72). Serious adverse events occurred in 37 of 255 patients in the bisoprolol group (14.5%) vs 36 of 251 in the placebo group (14.3%; relative risk, 1.01; 95% CI, 0.62-1.66; P = .96). Among people with COPD at high risk of exacerbation, treatment with bisoprolol did not reduce the number of self-reported COPD exacerbations requiring treatment with oral corticosteroids, antibiotics, or both. isrctn.org Identifier: ISRCTN10497306.

EFFECT OF SEQUENTIAL NEPHRON BLOCKADE X DUAL RENIN-ANGIOTENSIN SYSTEM BLOCKADE + BISOPROLOL IN THE TREATMENT OF RESISTANT HYPERTENSION, A RANDOMIZED CONTROLLED TRIAL (RESHYPOT)

Objective: The primary aim was to compare sequential nephron blockade (SNB) versus dual renin-angiotensin system blockade (DRASB) plus bisoprolol in patients with resistant hypertension to observe reductions in systolic and diastolic blood pressure (SBP and DBP) levels after 20 weeks of treatment. Design and method: This trial was an open-label, prospective, randomized, parallel-group, clinical study with optional drug uptitration. Participants were evaluated during five visits at 28-day intervals. Results: The mean age was 55.5 years in the SNB and 58.4 years in the DRASB + bisoprolol group (p=NS). Significant office BP reductions were observed in both groups. SNB group, SBP decreased from 174.5±21.0 to 127.0±14.74 mmHg (p&lt;0.0001), and DBP decreased from 105.3±15.5 to 78.11±9.28 mmHg (p&lt;0.0001). DRASB group, SBP decreased from 178.4±21.08 to 134.4 ± 23.25 mmHg (p&lt;0.0001) and DBP decreased from 102.7±11.07 to 77.33±13.75 mmHg (p&lt;0.0001). Ambulatory blood pressure monitoring (ABPM) showed also significant SBP and DBP reductions in both groups (p&lt;0.0001). Central systolic blood pressure had a greater reduction in the SNB group pre x post-intervention (128.8± 22.1 x 117.4± 17.9) (p = 0.03). Conclusions: In patients with RHTN adherent to treatment, SNB and DRASB plus bisoprolol showed excellent therapeutic efficacy, although SNB was associated with earlier SBP reduction and a greater reduction in Central systolic blood pressure.

Efficacy and Safety of Bisoprolol in Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

To evaluate the clinical efficacy and safety of bisoprolol in patients with chronic obstructive pulmonary disease (COPD). This systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statements. The primary outcome measures analyzed included: Pulmonary function(FEV1, FEV1%, FVC), 6-minute walking distance (6MWD), adverse events and inflammatory cytokines(IL-6, IL-8, CRP). Thirty-five studies were included with a total of 3269 study participants, including 1650 in the bisoprolol group and 1619 in the control group. The effect of bisoprolol on lung function in patients with COPD, FEV1, MD (0.46 [95% CI, 0.27 to 0.65], P=0.000), FEV1%, MD (-0.64 [95% CI, 0.42 to 0.86], P=0.000), FVC, MD (0.20 [95% CI, 0.05 to 0.34], P=0.008), the results all showed a statistically significant result. The effect of bisoprolol on 6MWD in COPD patients, MD (1.37 [95% CI, 1.08 to 1.66], P=0.000), which showed a statistically significant result. The occurrence of adverse events in COPD patients treated with bisoprolol, RR (0.83 [95% CI, 0.54 to 1.26], P=0.382), resulted in no statistical significance. The effect of bisoprolol on inflammatory cytokines in COPD patients, IL-6, MD (-1.16 [95% CI, -1.67 to -0.65], P=0.000), IL-8, MD (-0.94 [95% CI, -1.32 to -0.56], P=0.000), CRP, MD (-1.74 [95% CI, -2.40 to -1.09], P=0.000), the results were statistically significant. We performed a subgroup analysis of each outcome indicator according to whether the patients had heart failure or not, and the results showed that the therapeutic effect of bisoprolol on COPD did not change with the presence or absence of heart failure. Bisoprolol is safe and effective in the treatment of COPD, improving lung function and exercise performance in patients with COPD, and also reducing inflammatory markers in patients with COPD, and this effect is independent of the presence or absence of heart failure.

Features of management of patients with cardiometabolic polymorbidity phenotype: focus on the efficacy and safety of bisoprolol

The presence of coexisting chronic non-infectious diseases is associated with reduced quality of life and increased risk of early disability and mortality. The coexistence of two or more diseases in a patient is defined by the term polymorbidity. Currently, there is an increase in polymorbid pathology not only among elderly patients, but also among young and middle-aged people, which entails significant health care costs and has a negative impact on the economy of the country as a whole. Therefore, the problem of polymorbidity and the management of such patients in real clinical practice is urgent and key in the field of public health. According to major foreign and domestic studies, the most common polymorbidity phenotype is the cardiometabolic phenotype. Taking into account the fact that in our country almost every second patient with arterial hypertension has metabolic disorders and, therefore, polymorbid pathology, approaches to the management of such patients should be personalized already from the beginning of drug therapy. In this regard, this review reviews some key pathophysiological mechanisms of the relationship between arterial hypertension and metabolic disturbances occurring in patients with the cardiometabolic phenotype of polymorbidity, presents features of antihypertensive therapy in such patients, in particular, describes in more detail the class of beta-blockers with pathogenetic validity of use in this case. Also, a review of the available clinical trial data concerning the effects of the highly selective beta-adrenoblocker bisoprolol in patients with arterial hypertension is presented, emphasizing its effect on metabolic status and its importance for comprehensive clinical management.

The early use of bisoprolol in patients with severe sepsis and its impact on the patients outcome

Objectives To explore the hypothesis that beta 1 adrenergic receptor blockage might be protective through attenuation of destructive sympathetic activity and catecholaminergic inflammatory effects in severe sepsis patients. Design Prospective, randomized, controlled study. Settings Critical care department in Alexandria main university hospital. Patients and methods The study was conducted on 50 adult patients who were admitted to the Department of Critical Care Medicine in the Alexandria Main University Hospital who fulfilled the criteria for severe sepsis according to The American College Of Chest Physicians, patients were randomly assigned into two groups, group I: Included 25 patients receiving Bisoprolol 2.5 to 10 mg enterally for a target heart rate 80–90 beat/minute within the first 24 h according to the effect on hemodynamic stabilization and group II: Included 25 patients, as a control group, who received routine management of severe sepsis. Both groups were followed up and compared regarding the primary end points (discharge from the intensive care unit after recovery, septic shock or death) and the secondary end points (length of ICU stay, days of mechanical ventilation and need for inotropes). Results The heart rate at the end of the study was significantly lower in survived patients in group I with mean value of 80.06+9.05 beats/minute compared to mean value of 102.22+7.58 beats/minute in the died patients in the same group (P=0.003). The mean arterial blood pressure (mmHg) in studied patients, was not significantly different between the two groups on admission (P=0.099) and on the 1st day (P=0.172) the significant differences started to appear on the 2nd day (P=0.003), and over the whole period of observation till the end point of the study as the mean value of 83.31+16.90 in group I compared to mean value of 72.0+16.07 in group II (P=&lt;0.021), regarding the comparison between the survived and died patients in group I, on admission there was no statistically significant difference between them (p 0.213) while by the end point of the study, there was a statistically significant difference being higher in survived patients with mean value of 95.38+3.38 compared to mean value of 61.44+2.70 in died patients (P&lt;0.001). Regarding the occurrence of septic shock, it was less in group I as 40% compared to 72% in group II (P=0.023), group I had longer ICU stay (5.0 to 24.0 days) compared to group II (7.0 to 20.0 days), with a statistically significant difference (P=0.029). The duration of mechanical ventilation days (P=0.001), as longer in group II compared group I (group I= 8.37±3.43 days, group II=12.0±3.21 days). The mortality was lower in group I about 36% compared to 68% in group II with a statistically significant difference between the two groups (P= 0.024). Conclusion The administration of bisoprolol to patients with severe sepsis decrease the mortality, length of stay in ICU, days of mechanical ventilation and improves tissue perfusion without significant effect on hemodynamics.

A Comparative Study to Investigate the Effects of Bisoprolol in Patients with Chronic Heart Failure and Hypertension When Switched from Tablets to Transdermal Patches.

Oral beta-blockers are effective for heart failure and hypertension. Here, we conducted a prospective study to investigate the efficacy of the beta-blocker bisoprolol in patients switching from the oral tablet to the transdermal patch. We studied 50 outpatients receiving oral bisoprolol for chronic heart failure and hypertension. After patients switched treatments, we measured heart rate (HR) over 24 h by Holter echocardiography as the primary endpoint. Secondary endpoints were (1) HR at 00:00, 06:00, 12:00, and 18:00, (2) the total number of premature atrial contractions (PACs) over 24 h and the incidence rate per time segment, and the total number of premature ventricular contractions (PVCs) over 24 h and the incidence rate per time segment, (3) blood pressure, (4) atrial natriuretic peptide and B-type natriuretic peptide, and (5) echocardiography. Minimum, maximum, mean, and total HR over 24 h was not significantly different between the two groups. Mean and maximum HR at 06:00, total PACs, total PVCs, and PVCs at 00:00 to 05:59 and 06:00 to 11:59 were significantly lower in the patch group. Compared with oral bisoprolol, the bisoprolol transdermal patch lowers HR at 06:00 and inhibits the onset of PVCs during sleep and in the morning.

ME-1: ROLE OF MINERALOCORTICOID RECEPTOR BLOCKERS IN RESISTANT AND REFRACTORY HYPERTENSION

Resistant hypertension is defined as blood pressure (BP) that remains above goal in spite of compliance with full doses of 3 or more antihypertensive medications of different classes. Ideally, a thiazide-like diuretic should be included in this 3 drug regimen. Classically, the recommendation has been to add a mineralocorticoid receptor antagonist such as spironolactone or eplerenone to the regimen of these resistant hypertensive patients to gain BP control. The study that deserves major credit for establishing this practice is the Prevention And Treatment of Hypertension With Algorithm based therapY (PATHWAY) study (Williams B, et al. Lancet. 386:2059–2068, 2015). PATHWAY compared the mineralocorticoid receptor antagonist spironolactone to doxazosin and bisoprolol in patients with resistant hypertension and demonstrated that spironolactone was overwhelmingly more successful in controlling the patient's BP and was also very well tolerated. The results of PATHWAY established aldosterone antagonists as the best add-on therapy for patients with resistant hypertension. However, spironolactone and other steroidal mineralocorticoid receptor antagonists such as eplerenone do have major adverse effects which can limit their use. These include sex hormone-related adverse effects such as gynecomastia and breast tenderness in women and erectile dysfunction and feminization in men. A solution to this problem, which is currently under active development, is use of non-steroidal mineralocorticoid receptor antagonists such as esaxerenone and finerenone (Figure 1). These non-steroidal mineralocorticoid receptor antagonists are bulky molecules which bind to the mineralocorticoid receptors and effectively prevent their activation. Specifically, esaxerenone has been shown to be as effective as eplerenone in lowering BP and to be well tolerated in Japanese patients with essential hypertension. Esaxerenone also has no sex hormone-dependent adverse effects. The question now is whether the non-steroidal mineralocorticoid receptor antagonists are to be the answer for resistant and refractory hypertension. Figure 1. Molecular Structures of Steroids and MR Blockers Adapted from: Tezuka Y, Ito S. The time to reconsider mineralocorticoid receptor blocking strategy: Arrival of nonsteroidal mineralocorticoid receptor blockers. Curr Hypertens Rep. 2022 Jul;24(7):215–224. doi: 10.1007/s11906-022-01177-6.

The effect of rs776746 polymorphism in the &lt;i&gt;CYP3A5&lt;/i&gt; gene on heart rate when using bisoprolol in patients with acute coronary syndrome

Aim. The aim of this work was to study the occurrence of the rs776746 allelic variant of the CYP3A5 gene and its effect on heart rate (HR) when using bisoprolol in patients hospitalized with acute coronary syndrome (ACS).Materials and methods. The study included patients with ACS who were prescribed bisoprolol for clinical indications. All patients underwent molecular genetic testing. In order to evaluate the effectiveness of the therapy with bisoprolol, all patients underwent Holter electrocardiogram (ECG) monitoting on days 10, the following parameters were assessed: minimum, average, maximum heart rate and heart rate during an exercise test. The stress test was performed as a ladder test.Results. The study involved 97 patients (63,5±10,5 years), including 60 men and 37 women. The frequency of occurrence of the desired alleles of the CYP3A5 gene was: CYP3A5*3 - 93%, and CYP3A5*1 - 7%, which corresponds to its prevalence in the European population. 84 carriers of the CYP3A5*3*3 genotype (87%), 12 heterozygous carriers of the *1 allele (12%) and one patient with the *1*1 genotype (1%) were identified. In order to search for differences in the effects of bisoprolol depending on the genetically predetermined activity of CYP3A5, we divided the general group of patients into two subgroups: subgroup 1 (CYP3A5*3*3), represented by carriers of the genotype associated with the synthesis of the inactive form of CYP3A5, and subgroup 2 (CYP3A5*1*3 and CYP3A5*1*1), represented by carriers of at least one allele encoding the synthesis of a fully functional protein CYP3A5, coupled with an increased metabolic rate. Patients did not differ in clinical and demographic characteristics. By the time of daily ECG monitoring, both groups reached comparable heart rate values. In carriers of at least one CYP3A5*1 allele (n = 13), associated with an increased metabolic rate, the daily dose of bisoprolol on the 10th day of hospitalization was significantly higher (p &lt;0.05). The only carrier of the homozygous CYP3A5 *1*1 variant receives bisoprolol at a daily dose of 10 mg. Taking into account the close to significant differences in glomerular filtration rate (GFR) in patients in the groups with the studied genetic variants, and the known eliminating role of the kidneys for bisoprolol, a linear regression model was built with the inclusion of factors that could affect the dose of bisoprolol: GFR, functional class of chronic heart failure, gender, age, number of simultaneously assigned CYP3A5 substrates. Of the parameters listed, only the CYP3A5 genotype significantly predicted the dose of bisoprolol (F=8.5; p&lt;0.005; R2=0.096).Conclusion. In this study, it was demonstrated for the first time that patients with different genetic variants of CYP3A5, in particular with respect to the rs776746 polymorphism, may differ in individual requirements for the dose of bisoprolol.

Effect of Enalapril Combined with Bisoprolol on Cardiac Function and Inflammatory Indexes in Patients with Acute Myocardial Infarction.

Objective The use of enalapril in combination with bisoprolol in patients with acute myocardial infarction (AMI) was studied for its effect on cardiac function and inflammatory parameters. Methods Sixty-two cases of AMI patients admitted to our clinic from November 2019 to November 2021 were selected for the study and grouped according to the random number table method, those enrolled were given conventional treatment such as oxygenation, absolute bed rest, and sedation, and administered low molecular heparin, aspirin, atorvastatin calcium tablets, clopidogrel, and nitrates. The control group (31 cases) was treated with enalapril maleate folic acid tablets, and the treatment group (31 cases) was treated with bisoprolol fumarate tablets on top of the control group, and the efficacy, adverse effects, cardiac function, inflammatory indexes, and oxidative stress indexes of the two arms were contrasted. Results The incidence of adverse reactions in the therapy cohort was 12.90% higher than that in the controlled arm, but the discrepancy was not medically relevant (P < 0.05). The SOD level was larger than the concentration in the corresponding drug therapy group, and the MDA level was lower than the concentration in the respective test cases (P < 0.05); the incidence of 12.90% adverse reactions in the treatment period was lower than that of 16.13% in the specific drug therapy group, but the variance was not scientifically evident (P > 0.05). Conclusion Enalapril application combined with bisoprolol in AMI patients is beneficial to boost the efficacy, promote the improvement of cardiac function, reduce the inflammatory response, and improve the oxidative stress with fewer adverse effects, which can ensure the therapeutic security.

Lack of Effects of Renin-Angiotensin-Aldosterone System Activity and Beta-Adrenoceptor Pathway Polymorphisms on the Response to Bisoprolol in Hypertension.

PurposeThis study examined the effects of plasma renin activity (PRA), angiotensin II (Ang II) and aldosterone (PAC) concentrations as well as common polymorphisms in the β1-Adrenoceptor gene (ADRB1) and the G-protein α-Subunit (Gαs) protein gene the G protein α-Subunit 1 gene (GNAS) on the blood pressure (BP) and heart rate (HR) response to bisoprolol in Chinese patients with hypertension.MethodsPatients with sitting clinic systolic BP (SBP) 140–169 mmHg and/or diastolic BP (DBP) 90–109 mmHg after placebo run-in were treated with open-label bisoprolol 2.5 mg daily for 6 weeks. Patients diagnosed as having primary aldosteronism or renal artery stenosis were excluded. PRA, Ang II and PAC concentrations were measured after the placebo run-in and after 6 weeks of treatment. The Ser49Gly and Arg389Gly polymorphisms in ADRB1 and the c.393C > T polymorphism in GNAS were genotyped by the TaqMan® assay.ResultsIn 99 patients who completed the study, baseline PAC levels were significantly associated with baseline DBP and plasma potassium on univariate but not on multivariate linear regression analysis. PRA, Ang II, and PAC concentrations at baseline were not associated with changes in BP with bisoprolol treatment, but the values were all significantly reduced (PRA −0.141 ± 0.595 ng/mL/h, Ang II −2.390 ± 5.171 pmol/L and aldosterone −51.86 ± 119.1 pg/mL; all P < 0.05) following 6 weeks of bisoprolol treatment. There were no significant differences in BP or HR responses in patients with baseline PRA above or below the PRA cut-point of 0.65 ng/mL/h or the median value of 0.9 ng/ml/hour. There were no significant associations of the ADRB1 and GNAS polymorphisms with the clinic and ambulatory BP and HR responses to bisoprolol.ConclusionBaseline PRA, PAC and Ang II concentrations showed no significant association with the BP response to bisoprolol treatment, but all these parameters were reduced after 6 weeks of treatment with bisoprolol. The two common polymorphisms in ADRB1 and the c.393C > T polymorphism in GNAS had no significant association with the BP and HR response to bisoprolol in these patients.

The possibilities of using beta-blocker bisoprolol in patients with stable angina with concomitant bronchial asthma.

Aim To compare efficacy and safety of treatments with the calcium antagonist (CA) verapamil, the cardioselective β-blocker (BB) bisoprolol, and a combination therapy with bisoprolol and amlodipine in patients with stable angina (SA) with concurrent mild and moderate, persistent bronchial asthma (BA).Material and methods This open, prospective, randomized, comparative study included 120 patients with an IHD+BA comorbidity. Of these patients, 60 had mild persistent BA and 60 had moderate persistent BA. Each group was divided into 3 subgroup, each including 20 patients, based on the used regimen of antianginal therapy. Stepwise dose titration was performed every 2 weeks (subgroup 1 received the BB bisoprolol 2.5 mg - 5 mg - 10 mg; subgroup 2 received the CA verapamil 240 mg - 240 mg - 240 mg; subgroup 3 received bisoprolol 2.5 mg followed by the combination treatment with bisoprolol and amlodipine as a fixed combination 5+5 mg). All patients underwent a complete clinical and instrumental examination at baseline and at 2, 4, and 6 weeks of treatment. The antianginal effectivity and the effect on bronchial patency were evaluated.Results In patients with SA and mild persistent BA, the study of external respiration function (ERF) at 2, 4, and 6 weeks of treatment did not detect any significant difference in the forced expiratory volume in 1 second (FEV1) between the treatment subgroups. In patients with SA and moderate persistent BA receiving the treatment, a significant decrease in FEV1 (р=0.022) was observed in subgroup 1 receiving bisoprolol 10 mg at 6 weeks of treatment. In subgroups 2 and 3 during the treatment, significant differences were absent. In patients with SA and mild or moderate persistent BA, the heart rate was significantly decreased in all three subgroups; however, in subgroup 2 receiving verapamil, the changes were considerably smaller than in other subgroups.Conclusion The study results showed that the BB bisoprolol with dose titration every two weeks from 2.5 to 10 mg or the combination treatment with the BB bisoprolol and the CA amlodipine can be used as the antianginal therapy in patients with SA and mild persistent BA. The BB bisoprolol may be used in patients with SA and moderate persistent BA as the antianginal therapy, but only at doses not exceeding 5 mg to avoid the development of bronchial obstruction. The combination therapy with the BB bisoprolol 5 mg and the CA amlodipine 5 mg is indicated to enhance antianginal and vasoprotective effects.

Influence of CYP2D6 and CYP3A5 Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Bisoprolol in Hypertensive Chinese Patients

Purpose: This study was performed to investigate the effects of common polymorphisms in CYP2D6 and CYP3A5 on the plasma concentrations and antihypertensive effects of bisoprolol in hypertensive Chinese patients.Methods: One hundred patients with essential hypertension were treated with open-label bisoprolol 2.5 mg daily for 6 weeks. Clinic blood pressure (BP) and ambulatory BP (ABP) were measured after the placebo run-in and after 6 weeks treatment. Peak plasma concentrations of bisoprolol were measured at 3 h after the first dose and 3 h after the dose after 6 weeks treatment. Trough levels were measured before the dose after 6 weeks treatment. Bisoprolol plasma concentrations were measured with a validated liquid chromatography tandem mass spectrometry method. Six common polymorphisms in CYP2D6 and the CYP3A5*3 polymorphism were genotyped by TaqMan® assay.Results: After 6 weeks of treatment, clinic BP and heart rate were significantly reduced by 14.3 ± 10.9/8.4 ± 6.2 mmHg (P < 0.01) and 6.3 ± 7.6 BPM (P < 0.01), respectively. Similar reductions were seen in ABP values. Bisoprolol plasma concentration at 3 h after the first dose and 3 h post-dose after 6 weeks of treatment were significantly associated with baseline body weight (P < 0.001) but there was no significant effect of the CYP2D6 and CYP3A5 polymorphisms on these or the trough plasma concentrations. There was no significant association of the CYP2D6 and CYP3A5 polymorphisms or plasma bisoprolol concentrations with the clinic BP or ABP responses to bisoprolol.Conclusion: Bisoprolol 2.5 mg daily effectively reduced BP and HR. The common polymorphisms in CYP2D6 that were examined and the CYP3A5*3 polymorphism appear to have no benefit in predicting the hemodynamic response to bisoprolol in these patients.

Influence of carriage of genetic variants CYP2D6 * 4 / CYP2D6 * 3 on maximum heart rate when using bisoprolol in patients with acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Bisoprolol is one of the most effective and frequently prescribed beta-blockers. The widespread use of bisoprolol is due to its high efficiency in the treatment of patients with various cardiological pathologies: arterial hypertension, ischemic heart disease, chronic heart failure. Bisoprolol, like all members of the group of beta-adrenergic blockers, is effective in the treatment of patients with acute myocardial infarction, reducing the risk of complications such as rhythm disturbances and sudden cardiac death. In vitro studies indicate that bisoprolol is a substrate for two isoforms of cytochrome P450 - 3A4 and 2D6. Purpose The purpose of this work was to analyze the effect of CYP2D6 activity on the chronotropic effect of bisoprolol therapy in patients with acute coronary syndrome (ACS). Materials and methods The study included patients with ACS who was assigned bisoprolol according to clinical indications. All patients included in the study were Holter monitor on the 10th day of hospitalization - the minimum, mean, maximum heart rate during the day and the maximum heart rate were assessed at the time of exercise was evaluated against the background of the current therapy. All patients included in the study also underwent molecular genetic testing. The detection of polymorphic variants of СYP2D6 (*3/*4) gene was carried out by real-time PCR. Results A total of 93 patients, 58 males and 35 females were included in the study. The average age of patients is 63 years. In the studied population, CYP2D6 * 3 was not detected. The CYP2D6 * 4 mutation occurred with a frequency of 15%, which is comparable to previously published data on the Russian population. The distribution of alleles corresponded to the Hardy-Weinberg law (Chi square, p&amp;gt; 0.05). In order to determine the effect of genetically determined CYP2D6 activity on the effectiveness of bisoprolol therapy in patients with ACS, we identified a group of patients - carriers of the allelic CYP2D6 * 4 variant in homozygous or heterozygous form (AA / AG) (group with a reduced metabolic rate), and a group with the CYP2D6 genotype GG (group with normal and increased metabolic rate). In the correlation analysis, carriage of CYP2D6 * 4 in heterozygous or homozygous form was associated with a lower maximum heart rate during exercise (r-0.21; p &amp;lt;0.05). Maximum heart rate during exercise in carriers of CYP2D6 * 4 was 107 [105; 119], in the comparison group - 114 [108; 120]. The difference was significant with p &amp;lt;0.05 (values are expressed as median [25%; 75%]). Conclusion In this study, for the first time, the role of the influence of allelic variants of the CYP2D6 gene on the achievement of maximum heart rate during exercise was revealed when using bisoprolol in patients with ACS. These data may have promising implications for maximizing the personalization of therapy for patients, including those with ACS.

Effects of trimetazidine in combination with bisoprolol in patients with chronic heart failure and concomitant chronic obstructive pulmonary disease: A protocol for systematic review and meta-analysis.

Background:To the best of our knowledge, there is no study that has conducted a review investigating the clinical efficacy and safety of bisoprolol combined with trimetazidine on chronic heart failure (CHF) patients with chronic obstructive pulmonary disease (COPD). Therefore, in order to provide new evidence-based medical evidence for clinical treatment, we undertook a systematic review and meta-analysis to assess the effectiveness and safety of bisoprolol combined with trimetazidine on CHF patients with COPD.Methods:Seven electronic databases including Web of Science, Embase, PubMed, Wanfang Data, Scopus, Science Direct, Cochrane Library will be searched in April 2021 by 2 independent reviewers. For search on PubMed, the following search terms will be used: “trimetazidine, bisoprolol, chronic heart failure, chronic obstructive pulmonary disease.” In order to achieve a consistency of extracted items, the data extractors will extract data from a sample of eligible studies. The outcomes include all-cause mortality and hospitalization for cardiac or/and respiratory causes; left ventricular structure and function; and functional scores. Review Manager software (v 5.4; Cochrane Collaboration) will be used for the meta-analysis. Two independent reviewers will assess the risk of bias of the included studies at study level. Any disagreements will be discussed and resolved in discussion with a third reviewer.Results:The results of our review will be reported strictly following the PRISMA criteria.Conclusions:The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings.OSF registration number:10.17605/OSF.IO/ZWPRB.

An attempt at administering a transdermal formulation of bisoprolol in patients with acute cardiac symptoms.

Bisono® is the world's first transdermal formulation of a bisoprolol, which is approved for the treatment of hypertension in Japan. We aimed to investigate the usefulness of this formulation in patients who were admitted to our hospital with cardiac symptoms suggestive of acute coronary syndrome or an acute exacerbation of heart failure. This study involved a retrospective survey of medical records from September 1, 2017 to April 30, 2018 obtained from the Cardiovascular Center of Kyoto Katsura Hospital. The clinical data of patients on admission who had received a transdermal formula of bisoprolol (Bisono® tape) were retrieved; their blood pressure and heart rate data were analyzed in relation to the doses of Bisono® tape administered. Sixty-three patients received the Bisono® tape. Their final diagnoses included acute myocardial infarction, an exacerbation of heart failure, and atrial fibrillation. While there was no significant correlation observed between the administered doses of the drug and reduction in blood pressure achieved within 24h after admission, there was a significant (p<0.05) correlation between the doses of Bisono®tnd reduction in the heart rate within 24h after admission (ΔHR0-24 h). Only one patient who received 8mg of Bisono® exhibited temporal bradycardia (heart rate<50bpm). The transdermal formulation of bisoprolol may be useful for the early introduction of β-blockers in patients admitted with cardiac symptoms associated with myocardial ischemia or heart failure. However, caution should be exercised because of the possible risk of hypotension.

Association Between Dose and Plasma Concentration of Bisoprolol in Patients with Heart Failure (CVI ARO 6).

Although bisoprolol is used widely to treat patients with heart failure (HF), little information is available regarding the association between the dose of bisoprolol administered and the bisoprolol plasma concentration (Bis-PC) in real-world clinical practice.This was a single-center, observational study in 114 patients with HF receiving once-daily bisoprolol. After determination of trough Bis-PC, the relationship between the dose of bisoprolol and Bis-PC was analyzed. In a multiple linear regression model, the dose of bisoprolol and estimated creatinine clearance (reciprocal number) were identified as independent predictors. HF severity and hepatic function were not associated with Bis-PC.Bis-PC was increased by renal dysfunction, which explained most of the discrepancy between the dose of bisoprolol administered and Bis-PC.

THE EFFECT OF VARIOUS VARIANTS OF ANTIARRHYTHMIC THERAPY ON THE STRUCTURAL AND FUNCTIONAL STATE OF THE LEFT VENTRICULAR MYOCARDIUM IN PATIENTS WITH ARTERIAL HYPERTENSION AND FREQUENT ATTACKS OF ATRIAL FIBRILLATION DURING 6 MONTHS OF TREATMENT

The aim - to determine the effect of various antiarrhythmic therapy on the structural and functional state of the left ventricular myocardium in patients with arterial hypertension (AH) and frequent attacks of atrial fibrillation (AF) during 6 months of treatment.Materials and methods. There were examined 146 patients aged from 37 to 86 years with AH stage II complicated by frequent recurrences of AF. All examined patients received permanent antiarrhythmic therapy. All patients underwent echocardiography (EchoCG) according to the standard protocol at the beginning of the study and after 6 months of treatment.Results. 6-month treatment with propafenone and etatsizin, as well as a combination of etatsizin with bisoprolol in patients with AH and frequent attacks of AF without severe structural damage of the myocardium showed significant decreasing of end-diastolic dimension and end-systolic dimension of the left ventricle, left ventricular mass index, the size and the volume of the left atrium, right ventricular size, E/e' average ratio and increased left ventricular ejection fraction, and Ve/Va ratio.Conclusions. 6-month treatment with 1C class of propaphenone and etatsizin, as well as a combination of etatsizin with bisoprolol in patients with arterial hypertension and frequent attacks of atrial fibrillation without severe structural damage of the myocardium has not adversely affect on the structural and functional state of the myocardium and it is accompanied by significant decreasing of end-diastolic dimension and end-systolic dimension of the left ventricle, left ventricular mass index, the size and the volume of the left atrium, right ventricular size, ratio E/e'average and increased left ventricular ejection fraction and Ve/Va ratio.

Population Pharmacokinetic Analysis of Bisoprolol in Patients With Acute Coronary Syndrome.

To date, many questions about the extent and cause of pharmacokinetic (PK) variability of even the most widely studied and prescribed β1-adrenergic receptor blockers, such as metoprolol and bisoprolol, remain unanswered. Given that there are still no published population pharmacokinetic (PopPK) analyses of bisoprolol in routinely treated patients with acute coronary syndrome (ACS), the aim of this study was to determine its PK variability in 71 Serbian patients with ACS. PopPK analysis was conducted using a nonlinear mixed-effects model (NONMEM), version 7.3.0 (Icon Development Solutions). In each patient, the same formulation of bisoprolol was administered once or twice daily at a total daily dose of 0.625-7.5 mg. We separately assessed the effects of 31 covariates on the PKs of bisoprolol, and our results indicated that only 2 covariates could have possible influence on the variability of the clearance of bisoprolol: the mean daily dose of the drug and smoking habits of patients. These findings suggest that possible autoinduction of drug metabolism by higher total daily doses and induction of cytochrome P450 isoform 3A4 (CYP3A4) by cigarette smoke in liver could be the potential causes of increased total clearance of bisoprolol in patients with ACS.