Bisoprolol Treatment Research Articles

β1-adrenergic receptor polymorphisms: a possible genetic predictor of bisoprolol response in acute coronary syndrome.

To investigate the association between beta1-adrenergic receptor (ADRB1) polymorphisms and response to bisoprolol treatment in beta-blocker naive patients with acute coronary syndrome (ACS). Seventy-seven patients received bisoprolol for four weeks. Blood pressure and heart rate were measured at baseline and during treatment. TaqMan allelic discrimination method was utilized for ADRB1 Ser49Gly and Arg389Gly genotyping. Arg389Arg carriers showed greater reductions in systolic and diastolic blood pressure (-8.5%±7.8% vs -0.76%±8.7%, p=0.000218), and (-9.5%±9.7% vs -0.80%±11.5%, p=0.000149), respectively, compared with Gly389 carriers. No statistical difference was found for study's outcomes based on codon 49. Arg389Gly polymorphism is a promising bisoprolol response predictor in ACS patients.

Targeting adrenergic receptors to activate brown fat without cardiovascular effects

Background: We previously revealed that oral administration of the β3-adrenergic receptor (AR) agonist mirabegron only elicited small increases in brown adipose tissue (BAT) thermogenesis when ingested at the maximal allowable dose (200 mg). This led to off-target binding of the β1- and β2-AR, thereby increasing cardiovascular responses and white adipose tissue lipolysis, respectively. We hypothesize that a balanced activation between β1- and β3-AR is key to stimulating metabolic benefits without cardiovascular side effects. Method: We performed a randomized crossover trial in 8 lean men over two study days. The intervention consisted of oral administration of mirabegron (200 mg) with or without the cardio selective β1-AR antagonist bisoprolol (10 mg). Dynamic [11C]-acetate and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET/CT scans were performed sequentially starting at 210 min after oral administration of mirabegron ± bisoprolol. Results: Compared to baselines measures, mirabegron alone or with bisoprolol increased energy expenditure (EE) by 27% (+18.2±6.7 kcal/h) and 11% (7.4±8.1 kcal/h), respectively. However, EE was significantly lower when mirabegron was co-ingested with bisoprolol (P=0.0402) Compared to room temperature, mirabegron alone increased BAT oxidative metabolism (0.631±0.267 vs 1.695±1.097 min-1 from the [11C]-acetate, P=0.0421), but was not different from mirabegron with bisoprolol (1.273±0.651 min-1). Metabolic rate of glucose in BAT, measured using [18F]FDG PET, was significantly higher with mirabegron than mirabegron combined with bisoprolol (24±10 vs 16±8 nmol/g/min, P=0.0284). Mirabegron also increased systolic blood pressure (+5±5 vs -6±10 mmHg, P=0.0252) and heart rate (6±7 vs -5±6 beats·min-1, P=0.0081) relative to baseline levels, which was prevented with bisoprolol. The glycerolipid-fatty acid cycling was not different between mirabegron without or with bisoprolol treatment (total cycling: 118.1±346.9 vs 168.5±439.5 μmol·min-1, P=0.8023). Conclusion: The administration of a β1-AR antagonist decreases the adverse cardiovascular effects of mirabegron. However, at the provided dose, it also restricts the stimulating effects of mirabegron on the thermogenesis. Public foundation grants This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

To Evaluate the ‘Real World’ Clinical Performance of Bisoprolol in Post-Myocardial Infarction with Left-Ventricular Dysfunction: TENACITY Study

Beta-blockers are the cornerstone in management of heart failure and are well studied in Acute Coronary Syndromes (ACS). There is paucity of data of Bisoprolol in acute ICU setting in patients admitted with left ventricular systolic dysfunction (LVSD) with recent ACS, especially amongst Asian Indians. We evaluated the impact of Bisoprolol on Heart Rate (HR) and Left Ventricular Ejection Fraction (LVEF) along with metabolic indicators of HbA1C and lipid profile in post-ACS patients with LVSD at 1 year as compared to baseline.This non-interventional, retrospective, single center, secondary data collection study captured demographics, comorbidities, hemodynamics, concomitant medications and assessed the effectiveness of oral Bisoprolol (1.25, 2.5 mg, 5 mg and 10mg) treatment over a 1-year follow up period, in post-ACS patients with LVSD (i.e., HFmrEF and HFrEF; LVEF <50%). Data-records of 400 patients hospitalized between August 1, 2016 to November 30, 2018 were evaluated for change in LVEF as primary endpoint and change in HR and Lipid profile, HBA1C and ST segment deviation of J point at 1 year as compared to baseline as secondary outcomes.The mean age of 400 patients was 55.28±7.9 years of which 29.75% were female. Significant improvement in LVEF (41.45±5.1% vs 48.73±5.5%) with significant reduction in heart rate (85.06±5.64 bpm vs 76.73±4.6 bpm) was observed at the end of 1-year treatment as compared to baseline (p=0.0001 and p=0.0001 respectively) on treatment with Bisoprolol (mean 4.15 + 1.4 mg). NYHA class improved from 1.6 + 0.5 to 1.11 + 0.31 at the end of 1 year. Bisoprolol along with GDMT was neutral for HbA1C (6.2±0.6 % vs 6.1±0.7%; p=0.64), while serum lipids (Total Cholesterol: 199.7 + 7.6 vs 127.6 + 4.85 mg% p=0.001; TG: 196.2 +12.1 vs 111.7 + 6.88 mg%, p=0.001; LDL: 126.9 + 9.1 vs 62.4 + 5.51 p=0.001; HDL: 33.7 + 3 vs 42.8 +1.9 p=0.001) improved at 1 year due to statins. Maximum ST deviation at J point in resting ECG was also lesser at 1 year as compared to baseline (0.29 + 1.5 mm vs 0.05 + 0.22 mm; p=0.0001).Bisoprolol administered along with GDMT to patients post-ACS with LVSD significantly improved LVEF with significant reduction in heart rate and ST segment deviation at J point at 1 year without adverse effect on lipid and HBA1C.

Chinese Classical Music Lowers Blood Pressure and Improves Left Ventricular Hypertrophy in Spontaneously Hypertensive Rats.

High blood pressure (BP) plays an important role in the pathogenesis and development of cardiovascular diseases and multi-organ damages. Music has been well known to elicit emotional changes, such as anxiolytic effects. However, whether music therapy lowers BP in spontaneously hypertensive rats (SHR) and the potential mechanism remains unknown. SHRs were, respectively exposed to white noise (WN), Western classical music (WM), Chinese classical music (CCM), rock music (RM), and bisoprolol treatment. WN and WM did not lower systemic BP, but CCM and RM significantly lowered BPs in SHRs. The effects of CCM therapy on lowering systemic BPs is comparable to that of bisoprolol at the dose of low to medium. Combination of CCM treatment with bisoprolol further improved systemic BPs and myocardial hypertrophy in SHRs, compared to CCM treatment or bisoprolol alone. Furthermore, IHC and WB analysis indicated that CCM therapy inhibited the β1/cAMP/PKA and α1/PLC/PKC signalings, but didn’t alter the β2/PI3K/Akt signaling. Above all, CCM therapy lowers systemic BPs and alleviates myocardial hypertrophy in hypertensive rats, which may be caused by the inhibitions of β1/cAMP/PKA and α1/PLC/PKC signalings.

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.

Molecular interactions of polyvinyl chloride microplastics and beta-blockers (Diltiazem and Bisoprolol) and their effects on marine meiofauna: Combined in vivo and modeling study

The ecotoxicological effects of beta-blockers (i.e. Diltiazem and Bisoprolol) and their interactions with the microplastic polyvinyl chloride on marine meiofauna were tested in laboratory microcosms. An experimental factorial design was applied, using meiobenthic fauna collected from the Old Harbor of Bizerte (NE Tunisia), but with a main focus on the nematode communities. The meiobenthic invertebrates were exposed to two concentrations of Diltiazem and Bisoprolol, of 1.8 µg.L-1 and 1.8 mg.L-1, respectively, and one concentration of polyvinyl chloride (i.e. 20 mg.kg-1), separately and mixed. The overall meiofauna abundance was significantly reduced in all treatments, mainly that of polychaetes and amphipods. Moreover, the juveniles-gravid female ratios of the nematode communities were the lowest in the 1.8 µg.L-1 Bisoprolol treatment and for the 1.8 mg.L-1 mixture of Diltiazem and microplastics, suggesting that different dosages influence the maturity status of the examined species. The demographic results were also supported by in silico approach. The simulation of molecular interactions revealed acceptable binding affinities (up to −8.1 kcal/mol) and interactions with key residues in the germ line development protein 3 and sex-determining protein from Coenorhabditis elegans. Overall, the experimental outcome strongly indicates synergistic interactions among the beta-blockers Diltiazem and Bisoprolol and the microplastic polyvinyl chloride on marine nematode communities.

The double anaerobic threshold in heart failure

BackgroundCardiopulmonary exercise test (CPET) has an important role in assessing heart failure (HF) patients. Among CPET parameters, a pivotal role is attributed to the anaerobic threshold (AT), normally determined by V-slope, ventilatory equivalent and end-tidal methods. In about 10% of healthy subjects, a lack of concordance between these methods has been reported. This event was named double AT (DT). We hypothesized that DT was due to a delay in chemoreflex response. MethodsWe reanalyzed CPET data of two cross-over studies in which we compared CPET in stable HF patients treated for two months with bisoprolol and carvedilol. In chronic HF, carvedilol has a greater sympathetic inhibition than bisoprolol, as shown by a lower chemoreflex response. ResultsIn 87 patients, we identified DT in 46% and 66% of cases during bisoprolol and carvedilol treatment, respectively (p < 0.01). Compared with bisoprolol, carvedilol treatment was associated to a lower peak oxygen uptake (from 17.4 ± 4.3 to 16.4 ± 4.1 mL/min/kg) and oxygen pulse (from 11.8 ± 2.9 to 11.1 ± 2.9 mL/min/kg) suggestive of lower peak cardiac output. ConclusionsDT is frequent in HF and more often with carvedilol than bisoprolol treatment, may be due to a greater inhibition of sympathetic tone and prolonged circulatory time. These findings open an unexplored research field.

Efficacy and safety of bisoprolol compared to other selective beta-1 blockers in the treatment of hypertension: a systematic review and meta-analysis of randomized parallel clinical trials

Abstract Background Bisoprolol, a highly cardioselective beta-1 blocker (s-BB) has theoretical advantage over other cardio selective betablockers by way of better potency and tolerability in treating hypertension (HT). Individual published trials comparing s-BB are typically small. Meta-analysis of such trials clarifies the issue and position of bisoprolol in HT therapy. Purpose This meta-analysis compares bisoprolol with other s-BBs (Atenolol, Betaxolol, Esmolol, Acebutolol, Metoprolol, Nebivolol) for their efficacy and safety in patients with HT. Methods Literature databases PubMed, Embase, Cochrane Library, Clinicaltrials.gov, Surveillance, Epidemiology and End Results Program and 12 PV databases were searched systematically to identify randomized, parallel clinical trials published from inception to October 2019. Studies which compared bisoprolol with other s-BBs in HT patients were evaluated in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Random effects meta-analyses were conducted to assess mean difference (MD) and 95% confidence interval (95% CI) for blood pressure (BP), heart rate (HR) and lipid profile. Results 13 studies compared bisoprolol with other s-BBs (metoprolol, atenolol) were included in this meta-analysis. Bisoprolol reported significant reduction in aortic systolic BP [MD: −8.00; 95% CI: −11.57, −4.43; P&amp;lt;0.01] and diastolic BP [MD: −2.90; 95% CI: −4.98, −0.82; P&amp;lt;0.01] during 8 weeks (w) treatment compared to other s-BBs. Bisoprolol treatment for 12w showed significant change in ambulatory heart rate (AHR) [MD: −5.22; 95% CI: −8.37, −2.07; P&amp;lt;0.01], daytime AHR [MD: −5.75; 95% CI: −9.16, 2.34; P&amp;lt;0.01] and nighttime AHR [MD: −3.22; 95% CI: −6.18, −0.26; P=0.03] in comparison to other s-BBs. Significant increase in low frequency HR variability [MD: 100.79; 95% CI: 16.66, 184.91; P=0.02] was reported with bisoprolol treated for 8w compared to other s-BBs. Baroreflex sensitivity significantly favored bisoprolol treated for 8w [MD: 1.01; 95% CI: 0.03, 1.98; P=0.04] in comparison to other s-BBs. HDL-C significantly increased with bisoprolol treated for 52w [MD: 6.80; 95% CI: 3.01, 10.60; P&amp;lt;0.01], 104w [MD: 12.00; 95% CI: 5.04, 18.96; P&amp;lt;0.01] and 156w [MD: 8.00; 95% CI: 0.58, 15.42; P=0.03]. There were no significant changes in total cholesterol [MD: −3.06; P=0.38], LDL-C [MD: −3.60; P=0.18] and triglyceride [MD: −21.00; P=0.26] on treatment with bisoprolol. Serious adverse events did not differ significantly on treatment with bisoprolol compared to other s-BBs. Conclusion The results of this meta-analysis reveal that bisoprolol showed a significant reduction of BP, HR, baroreflex sensitivity and improved HDL cholesterol levels compared to other s-BBs. Our results highlight the heterogeneity amongst the s-BBs and highlights the benefit of choosing bisoprolol in comparison to other s-BB in the management of HT. Funding Acknowledgement Type of funding sources: None.

Effectiveness of bisoprolol versus selective beta-1 blockers in the management of hypertension: a systematic review and meta-analysis of randomized cross-over trials

Abstract Background Cross-over trials carry a higher weightage in choosing a therapeutic agent in clinical practice. A meta-analysis of cross-over trials involving the use of bisoprolol in hypertension (HT) would bring about clarity in positioning this drug. Purpose The present study aimed to clarify the underlying benefits of bisoprolol in the reduction of blood pressure (BP) in HT patients when compared to selective beta-1 blockers (s-BBs - Atenolol, Betaxolol hydrochloride, Esmolol, Acebutolol hydrochloride, Metoprolol succinate, Nebivolol) by performing a meta-analysis of “cross-over” trials published in literature. Methods Systematic search was undertaken in PubMed, Embase, Cochrane Library, Clinicaltrials.gov registry, Surveillance, Epidemiology and End Results Program and 12 pharmacovigilance databases. Randomized, cross-over studies published up to October 2019 which compared bisoprolol with other s-BBs in HT patients were evaluated in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A meta-analysis was performed using random effects model in terms of mean difference (MD) and 95% confidence intervals (95% CI) for BP, heart rate (HR) and lipid profile. Results Nine randomized cross-over studies which compared bisoprolol with other s-BBs (atenolol and nebivolol) were included in this meta-analysis. Bisoprolol reported significant reduction of sitting BP [MD: −3.35, 95% CI: −6.75, 0.05; P=0.05] and reduction of diastolic BP [MD: −2.00; 95% CI: −8.04, 4.04; P=0.52, non-significant] among patients with HT when compared to other s-BBs. Heart rate (HR) decreased significantly among HT patients in bisoprolol group treated for 2 w [MD: −6.00; 95% CI: −11.30, −0.70; P=0.03] when compared to those treated with other s-BBs. Analysis of lipid profile showed non-significant reduction of serum cholesterol [MD: −7.74; 95% CI: −17.18, 1.70; P=0.11] and triglyceride [MD: −26.57; 95% CI: −64.34, 11.20; P=0.17] levels in the bisoprolol group compared to other s-BBs. Bisoprolol treatment for 8 w resulted in a slight but statistically significant change in potassium levels [MD: −0.10; 95% CI: −0.16, −0.04; P&amp;lt;0.01] among HT patients. Conclusion The results of this meta-analysis reported significant efficacy of bisoprolol on BP and HR in comparison to other s-BBs in a meta-analysis of cross-over trials. Our findings show that use of bisoprolol as a therapeutic option is efficacious and safe compared to other s-BBs in this patient population. Funding Acknowledgement Type of funding sources: None.

Bisoprolol and/or hyperoxic breathing do not reduce hyperventilation in pulmonary arterial hypertension patients.

Hyperventilation is common in pulmonary arterial hypertension and may be related to autonomic imbalance. Patients underwent exercise testing and hyperoxic breathing before and after bisoprolol treatment. We found that neither beta blocker treatment nor hyperoxic breathing in patients reduced hyperventilation at rest and during exercise, although it reduced heart rate.

Temporal haemodynamic changes after bisoprolol treatment in patients with uncontrolled hypertension.

BackgroundAnti-hypertensive drugs are widely used to control blood pressure, yet their effects on haemodynamics, especially in Chinese populations, and the potential for non-invasive methods to monitor these changes, are poorly understood. This study aimed to determine the early and late effects of bisoprolol treatment on blood pressure, cardiac output (CO), stroke volume (SV), heart rate (HR), systematic vascular resistance (SVR), and inotropy measured in Chinese patients with hypertension.MethodsTwelve Chinese subjects (median age: 55 years, interquartile range: 52–58 years; 33% male) with uncontrolled hypertension were recruited at the Prince of Wales Hospital in Hong Kong and haemodynamic measurements were assessed using a non-invasive Ultrasonic Cardiac Output Monitor (USCOM). Seven hourly measurements were taken before and after bisoprolol 2.5 mg on day 1 (T0 to T6), and in nine patients this was repeated six weeks later (TF0 to TF6). Any BP change of 5 mmHg was considered clinically significant and P<0.05 was considered statistically significant.ResultsOn day 1 (N=12), there was a significant drop in median CO [4.9 (4.7–5.6) vs. 3.8 (3.3–4.7) L/m2, P<0.0001] associated with a compensatory increase in SVR [1,698.1 (1,584.6–1,894.3) vs. 2,222.6 (1,777.4–2,712.5) d·s·cm−5, P<0.0001] at T2. The median dBP {92 [87–95] vs. 86 [79–89] mmHg, P=0.0002} and MAP {110 [104–114] vs. 104 [101–109] mmHg, P=0.038} reduced significantly 6 hours after bisoprolol treatment. Except for HR, all other measured haemodynamics returned to baseline at T6. On week 6 (N=9), SVR was generally reduced, but major parallel swings in CO and SVR were still evident. All patients showed a trend to lower blood pressure, SVR, and inotropy (P<0.05), but HR, SV, and CO returned to baseline values after 6 weeks treatment (P>0.05).ConclusionsThe acute haemodynamic changes between 6 hours of the first dose and the dose after 6 weeks of bisoprolol treatment are similar. Long-term therapy can effectively reduce blood pressure by reducing SVR.

THE POSITIVE EFFECT OF MOXONIDINE ON TELOMERASE ACTIVITY

Objective: To estimate the effect of moxonidine versus bisoprolol on cellular senescence processes in postmenopausal women with arterial hypertension (AH). Design and method: There was an open randomized control study. The study group was represented by 56 women with AH and a mean age of 63 ± 9.217 years, with SBP of 146.72 ± 7.127 mm Hg and DBP of 84.38 ± 7.941 mm Hg, who received moxonidine treatment (average dose 0.515 mg/day [0.4; 0.6]) for 12 months. The control group was comprised of 59 female patients with AH and a mean age of 61 ± 9.117 years, with SBP of 145.59 ± 6.102 mm Hg and DBP of 86.18 ± 6.682 mm Hg, who received treatment with bisoprolol (average dose 5.0 mg/day [5.0; 7.5]) for 12 months. For all patients, the measurement of telomerase activity was performed using genomic DNA real-time PCR at baseline and after 12 months of treatment. Statistical analysis was carried out using the SPSS/PASW Statistics software (version 18, SPSS Inc., Chicago, Illinois, USA). Results: In both groups there was a substantial and significant BP reduction, in the moxonidine treatment group: SBP – 126.93 ± 8.086 mm Hg (p &lt; 0.001), DBP – 73.64 ± 7.522 mm Hg (p &lt; 0.001); in the bisoprolol treatment group: SBP – 125.83 ± 8.097 mm Hg (p &lt; 0.001), DBP – 73.31 ± 7.964 mm Hg (p &lt; 0.001). Patients from the moxonidine treatment group demonstrated a significant reduction of body weight, on average, by 1.89% (from 75.7 ± 12.77 kg to 74.5 ± 11.7 kg,p &lt; 0.001) and of BMI (from 29.359 ± 4.7 kg/m2 to 28.6 ± 4.4 kg/m2, p &lt; 0.001). By contrast, in the bisoprolol treatment group patients’ average body weight increased by 2.22% (from 76.655 ± 13.754 kg to 78.13 ± 13.728 kg, p &lt; 0.001) as well as BMI (from 29.037 ± 4.6 kg/m2 to 29.609 ± 4.7 kg/m2, p &lt; 0.001). TA in the moxonidine treatment group increased from 0.87 [0.16; 1.18] to 1.1 [0.74; 1.5] (p &lt; 0.001), and, conversely in the bisoprolol treatment group TA decreased from 1.1 [0.5; 1.6] to 0.94 [0.56; 1.5] (p &lt; 0.001). Conclusions: The preliminary data suggests that moxonidine can be used as telomerase activator and effective geroprotective agent. Increased TA against the backdrop of moxonidine treatment may be explained by increased insulin sensitivity, decreased body weight, and, consequently, lower intensity of chronic inflammation.

THE INFLUENCE OF RENAL DENERVATION ON BLOOD PRESSURE VARIABILITY IN PATIENTS WITH RESISTANT HYPERTENSION

Objective: Comparative evaluation of the impact of renal denervation versus pharmacological treatment with sympathetic nervous system (SNS) blockers on blood pressure variability in patients with resistant hypertension. Design and method: 75 patients with resistant hypertension without comorbidities after a 3-week standardized treatment with Losartan, Amlodipine and Indapamide and confirmation of their resistance were randomized into three groups, depending on medication supplimented to the previously administred: group I M - selective I1-imidazoline agonist Moxonidine, group II B – cardioselective beta-blocker Bisoprolol, group III D – renal artery denervation (RDN). Blood pressure variability assessed by ambulatory blood pressure monitoring (ABPM) were determined at baseline, 3 and 6 months follow-up. Results: The media/day and media/night systolic blood pressure (SBP) variability increased at the baseline in all three groups was reduced statistically significant from 3 months of monitoring, reaching the maximum effect towards the end of the study, when its normal values were recorded in all observational groups. Although treatment group supplimented with Moxonidine demonstrated an effect superior to that with Bisoprolol, and RDN - superiority to both, all three schemes had an authentic dynamics in improving SBP at 6 months of evaluation (p &lt; 0,001) (Fig.1). The evolution of diastolic blood pressure (DBP) media/day and media/night variability noted a beneficial effect, starting with 3 months, the improvement of this parameter being maintained until the end of the study. Although the reduction of DBP variability was statistically authentic in all three groups at all stages of evaluation, the Bisoprolol treatment group noted a smaller effect in improving this parameter, the higher net effect being manifested by the RDN patients group (p &lt; 0,001) (Fig.2). Conclusions: RDN in patients with resistant hypertension reduced statistically significant SBP and DBP variability starting with 3 months of follow-up and reaching maximum effect at the end of the study, simultaneously demonstrating superiority over treatment with SNS blockers.

Ivabradine for Treatment of Heart Failure with Preserved Ejection Fraction

Aim To evaluate the effect of combination ivabradine-containing therapy for chronic heart failure (CHF) with preserved ejection fraction on quality of life (QoL) and the primary composite endpoint during a one-year follow-up.Material and methods This study included 160 patients aged 45 to 65 years with NYHA functional class (FC) II-III CHF with preserved left ventricular ejection fraction (CHF-PEF) and grade I and II diastolic dysfunction associated with FC III stable angina with sinus rhythm and a heart rate (HR) higher than 70 bpm. Presence of CHF-PEF was confirmed by results of echocardiography and myocardial tissue Doppler imaging. During one year of prospective observation, effects of bisoprolol and ivabradine as a part of the combination therapy on the primary composite endpoint, including death from cardiovascular complications (CVC) and hospitalizations for myocardial infarction (MI) or CHF, were evaluated in patients with CHF-PEF. Patients were randomized to three groups: A, bisoprolol with dose titration from 2.5 to 10 mg; В, combination of bisoprolol 2.5-10 mg and ivabradine 10-15 mg/day; and С, ivabradine 10-15 mg/day. All patients were on a chronic background therapy, including angiotensin-converting enzyme inhibitors (lisinopril) or, if not tolerated, angiotensin II receptor blockers (valsartan), antiaggregants, statins (atorvastatin, rosuvastatin), and short-acting nitrates as required. If edema developed diuretics were added. The follow-up duration was one year.Results After 12 weeks of follow-up, the achievement of goal HR in group A was associated with a tendency to increased distance in the 6-min walk test from 279±19 to 341±21 m (р&gt;0,05); in group B the distance increased from 243±25 to 319±29 m (р&lt;0.05); and in group C the distance increased from 268±21 to 323±22 m (р&lt;0.05). In the combination ivabradine and bisoprolol treatment group, results of the 24-h electrocardiogram monitoring showed a more pronounced anti-ischemic effect associated with a decrease in the number of myocardial ischemic episodes (p&lt;0.05). QoL was evaluated with the Minnesota questionnaire against the background of treatment. At 12 weeks of observation, the total score decreased from 44.5±2.6 to 38.4±2.1 in group A; from 45±2.9 to 38±2.2 in group B; and from 50.9±3.2 to 42.7±2.8 in group C (р&lt;0.05). The risk of acute MI and repeated hospitalization for CHF during the year of observation, as evaluated according to the Kaplan-Meier method, decreased in both bisoprolol and ivabradine combination treatment groups.Conclusion The inclusion of bisoprolol and ivabradine into the background therapy of CHF-PEF patients with stable IHD provided an improvement of QoL and a decrease in the risk of hospitalization for acute MI and CHF during the year of observation.

ПРОГНОСТИКА ГЕМОДИНАМИЧЕСКОЙ ЭФФЕКТИВНОСТИ У БОЛЬНЫХ АРТЕРИАЛЬНОЙ ГИПЕРТОНИЧЕСКОЙ БОЛЕЗНЬЮ ПРИ РАЗЛИЧНОЙ ГЕЛИОТРОПНОЙ РЕАКЦИИ

The article is dedicated to the study of the position of hemodynamic figure in patients with II-stage of arterial hypotension disease with the help of moxonidin and bisoprolol treatment. 49 patients aged from 32 to 60 years old with arterial hypotension disease were examined. All the patients were provided with echocardiography. It is proved that moxonidin has more positive impaction in hemodynamic figure rather than bisoprolol.

Bisoprolol therapy does not reduce right ventricular sympathetic activity in pulmonary arterial hypertension patients.

Right ventricular (RV) function and autonomic dysfunction are important determinants of morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Although successful in animal studies, effects of beta-blocker therapy on RV function in clinical trials were disappointing. To understand this discrepancy, we studied whether beta-blocker therapy changes RV sympathetic activity. Idiopathic PAH (IPAH) patients received beta-blocker therapy (uptitrated to a maximal tolerated dose) and underwent cardiac magnetic resonance imaging, right heart catheterization, and a [11C]-hydroxyephedrine positron emission tomography ([11C]HED PET) scan at baseline to determine, respectively, RV ejection fraction (RVEF), RV pressures, and sympathetic activity. [11C]HED, a norepinephrine analogue, allows determination of sympathetic innervation of the RV. [11C]HED retention index reflects norepinephrine transporter activity. As a consequence of excessive catecholamine levels in the synaptic cleft, this transporter may be downregulated. Therefore, low [11C]HED retention index indicates high sympathetic activity. 13 IPAH patients underwent [11C]HED PET scans at baseline and after bisoprolol treatment. Although heart rate was reduced, systemic modulation of autonomic activity by bisoprolol did not affect local RV sympathetic nerve activity, RV function, or RV wall tension. In PAH patients, RV [11C]HED retention index was lower compared to LV tracer uptake (p<0.01) and was related to systolic wall tension (R2 = 0.4731, p<0.01) and RV function (R2 = 0.44, p = 0.01). In RV failure, the tolerated dosage of bisoprolol did not result in an improvement of RV function nor in a reduction in RV sympathetic activity.

Protective effect of propranolol and nadolol on social defeat-induced behavioral impairments in rats

Benzodiazepines and SSRIs are considered as standard treatment options for anxiety and depression, hallmarks of Post-Traumatic Stress Disorder (PTSD), although their use is often limited by adverse effects. While promising evidence emerged with β-adrenergic receptor (β-AR) antagonists (or ‘β-blockers’) and PTSD relief, efficacy issues dampened the excitement. However, we believe it is premature to completely eliminate a beneficial role of β-blockers. Our previous work has suggested that social defeat (SD) results in anxiety-like and depression-like behaviors in rats. Here, using the SD paradigm, we examined the effect of several β-adrenergic receptor antagonists (propranolol, nadolol, bisoprolol) on these behaviors in rats. Following acclimatization, Sprague-Dawley rats received no treatment (for control groups) or treated with ; propranolol (50 mg/kg/day in water), or nadolol (18 mg/kg/day in rats’ chow), or bisoprolol (15 mg/kg/day in water). The treatment lasted for 36 days, following which rats were subjected to SD/control exposures (1 week). Later, anxiety-like and depression-like behaviors, social interaction and learning-memory function tests were conducted. SD rats exhibited anxiety- and depression-like behavior as well as learning-memory impairment. Propranolol and nadolol protected SD rats from exhibiting anxiety-or depression-like behaviors. Bisoprolol treatment did not mitigate SD-induced behavioral impairments in rats. Nadolol, propranolol or bisoprolol have no effect in attenuating SD-induced memory function tests. These results suggest that certain ‘β-blockers’ have the potential to mitigate the negative psychological effects of traumatic events.

Bisoprolol transdermal patch treatment for patients with atrial fibrillation after noncardiac surgery: A single-center retrospective study of 61 patients.

Objectives:Atrial fibrillation after surgery is associated with increased rates of heart failure and ischemic stroke, and extension of hospitalization. Bisoprolol is a β-blocker used to reduce heart rate and manage arrhythmias during atrial fibrillation. However, the safety and efficacy of bisoprolol transdermal patch treatment in patients with postoperative atrial fibrillation remain unclear.Methods:We retrospectively assessed the electronic health records of our hospital between September 2013 and July 2018 and identified patients with postoperative atrial fibrillation who had been treated with a bisoprolol transdermal patch. We excluded patients with sinus rhythm using bisoprolol transdermal patch to prevent atrial fibrillation recurrence and those with sustained atrial fibrillation before surgery. Data on heart rhythm, heart rate, and blood pressure at the baseline and after 24 h of treatment were obtained from the electronic health records.Results:Of the 603 patients treated with the bisoprolol transdermal patch, 61 patients with postoperative atrial fibrillation after noncardiac surgery were included. The bisoprolol transdermal patch was discontinued due to bradycardia in two patients (3.3%). In both cases, the heart rate increased after the removal of the bisoprolol transdermal patch and no additional treatment was necessary. Among the 61 patients, sinus rhythm was restored within 24 h of bisoprolol treatment in 47 patients (77.0%). The heart rate significantly decreased from 124.8 ± 26.3 bpm at the baseline to 78.9 ± 16.6 bpm at 24 h after treatment (p < 0.001). There were no significant differences in the systolic and diastolic blood pressures between patients before and at 24 h after treatment.Conclusion:The results of this study indicate that the bisoprolol transdermal patch is well tolerated and effective in patients with atrial fibrillation after noncardiac surgery.

Effect of indapamide and bisoprolol monotherapy on cerebrovascular reactivity in hypertensive patients with rheumatoid arthritis

Aim. To investigate the effect of indapamide and bisoprolol monotherapy on cerebrovascular reactivity (CVR) in patients with combined hypertension (HT) and rheumatoid arthritis (RA).Materials and Methods. A total of 66 patients with HT grade 1-2 and RA (average age of 59.0 ± 7.5 years) were included in an open-controlled randomized study in parallel groups. Group 1 included 33 patients treated with indapamide 2.5 mg/day. Group 2 included 33 patients treated with bisoprolol 6.0 ± 2.6 mg/day. We performed 24-h blood pressure monitoring and transcranial Doppler ultrasound of the middle cerebral arteries (MCA) with assessment of CVR during hyperoxia and hypercapnia tests before and after 24 weeks of treatment.Results. Indapamide treatment improved CVR parameters during hypercapnia test. The MCA peak systolic velocity increased significantly from 53.7 [34.8; 67.8] to 55.8 [37.6; 69.0] сm/s (p = 0.017). Bisoprolol treatment worsened CVR parameters during hypercapnia test. The speed modification of MCA blood flow velocity decreased significantly from 0.10 [0.05; 0.19] to 0.08 [-0.01; 017] cm/s2 (p = 0.032). The index of recovery of MCA blood flow velocity decreased significantly from 1.11 [0.95; 1.27] to 0.84 [0.78; 1.08] (p = 0.006)Conclusion. Indapamide treatment improved CVR parameters, but bisoprolol treatment worsened CVR parameters during hypercapnia test in patients with combined HT and RA.

Adverse influence of bisoprolol on central blood pressure in the upright position: a double-blind placebo-controlled cross-over study

Treatment with beta-blockers is characterized by inferior reduction of central versus peripheral blood pressure. We examined changes in blood pressure, cardiac function, and vascular resistance after 3 weeks of bisoprolol treatment (5 mg/day) during passive head-up tilt in 16 never-treated Caucasian males with grade I–II primary hypertension. A double-blind, randomized, placebo-controlled cross-over design was applied, and hemodynamics were recorded using continuous tonometric pulse wave analysis and whole-body impedance cardiography. Bisoprolol decreased blood pressure in the aorta (~8/10 mmHg, p ≤ 0.032) and radial artery (~10/9 mmHg, p ≤ 0.037), but upright aortic systolic blood pressure was not significantly reduced (p = 0.085). Bisoprolol reduced heart rate and left cardiac work, and increased subendocardial viability index in supine and upright positions (p ≤ 0.044 for all). Bisoprolol increased stroke volume in the supine (~11 ml, p = 0.02) but not in the upright position, while only upright (~1 l/min, p = 0.007) but not supine cardiac output was reduced. Upright elevation in systemic vascular resistance was increased 2.7-fold (p = 0.002), while upright pulse pressure amplification was decreased by ~20% (p = 0.002) after bisoprolol. Aortic augmentation index, augmentation pressure, and pulse pressure were not changed in the supine position but were increased in the upright position (from 9% to 17%, 3–6 mmHg, and 30–34 mmHg, respectively, p ≤ 0.016 for all). In conclusion, although bisoprolol treatment reduced peripheral blood pressure, central systolic blood pressure in the upright position was not decreased. Importantly, the harmful influences of bisoprolol on central pulse pressure and pressure wave reflection were manifested in the upright position.