Comparison of the efficacy, safety, and tolerability of the FDC of telmisartan + bisoprolol with telmisartan + metoprolol succinate ER combination therapy for stage 1 and stage 2 hypertension: A double-blind, multicentric, phase-III clinical study.

AIM: The present study compared the safety, efficacy, and tolerability of the new fixed-dose combination (FDC) of telmisartan 40 mg + bisoprolol 5 mg (TBP) tablets with the existing comparator FDC telmisartan 40 mg + metoprolol succinate ER 50 mg (TMS) tablets in patients with stage 1 and stage 2 hypertension. METHODOLOGY: The multicentric, double-blind, parallel-group, comparative, prospective, phase-III clinical study involved 264 subjects with stage 1 and stage 2 hypertension from 10 centres across India. The selected subjects were randomized into two groups: group A received the TMS and group B received the new FDC TBP. The primary endpoint was the mean change in seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) from baseline to week 12 in both the control and study arms. The secondary endpoint was achieving the target of SeSBP <140 mmHg and SeDBP <90 mmHg from baseline to week 12 in both groups. Safety and tolerability parameters were evaluated in both groups based on adverse effects (AEs) reported by the patients and the physician. RESULTS: Both treatment groups exhibited a reduction in BP after 2 weeks of treatment, which was sustained until 12 weeks. The mean change in SeSBP and SeDBP at weeks 2, 6, and 12 compared to the previous visit showed statistical significance (p < 0.001) in all cases for both groups A and B. The mean changes in SeSBP and SeDBP from baseline to study end were numerically higher in group B than in group A. The mean difference in SeSBP from baseline to study end was significantly higher in group B compared to group A (p = 0.029). By week 12, 88.28 % and 89.84 % of subjects in group B achieved SeSBP <140 mmHg and SeDBP <90 mmHg respectively, while 86.71 % and 91.40 % of subjects in group A achieved the same targets. Reported AEs were mostly mild to moderate in both treatment groups, and no serious AEs or deaths were reported. Tolerability was rated as 'excellent' by 93.75 % of subjects in group B and 91.40 % of subjects in group A. CONCLUSION: Both the new FDC TBP and the existing comparator TMS combination therapy have comparable efficacy, tolerability, and safety for the management of stage 1 and stage 2 hypertension. TRIAL REGISTRY NAME: Clinical Trials Registry of India (CTRI) TRIAL REGISTRATION NO: CTRI/2021/11/037,926 PROTOCOL NO: MLBTL/05/2021 PROTOCOL URL: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=62069&EncHid=&userName=bisoprolol.

Impact of CYP2D6*2A, CYP2D6*4 and CYP3A5*3 genetic polymorphisms on Bisoprolol peak concentration and clinical response in acute coronary syndrome patients.

AIMS: Acute coronary syndrome (ACS) represents a major cause of death. Bisoprolol is commonly used in the management of ACS. This study aims to investigate the impact of CYP2D6*2A, CYP2D6*4 and CYP3A5*3 genetic polymorphisms on pharmacokinetics and clinical response of bisoprolol in ACS patients. METHODS: This is an open-label cohort study that included 127 ACS patients and studied the effect of CYP3A5*3, CYP2D6*2A and CYP2D6*4 genotyping using real-time polymerase chain reaction on steady state bisoprolol plasma peak concentration analysed by high performance liquid chromatography-fluorescence detector. RESULTS: Regarding CYP3A5*3, the mean peak bisoprolol concentration for CC, CT and TT genotypes were 4.25 ± 1.20, 3.93 ± 1.10 and 1.79 ± 0.69 ng/mL, respectively (P < .001). Higher systolic (126 ± 5.47 mmHg), diastolic blood pressure (82 ± 2.73 mmHg) and heart rate (97.80 ± 3.03 beats/min) were also observed in CYP3A5*3 TT carriers (P < .05). In CYP2D6*2A, the peak concentration of bisoprolol was lower in CC carriers (3.54 ± 1 ng/mL) compared to GG (4.38 ± 1.25 ng/mL) and GC carriers (4.07 ± 1.29 ng/mL, P = .019). In CYP2D6*4, the mean bisoprolol peak concentration in CC carriers was 3.98 ± 1.31 ng/mL, which was lower than T allele carriers (4.5 ± 0.8, P = .02). No differences in heart rate, systolic, diastolic blood pressure or bisoprolol dose were observed among CYP2D6*2A or CYP2D6*4 variants. Smokers exhibited lower bisoprolol peak concentration (3.96 ± 1.2 ng/mL) compared to nonsmokers (4.55 ± 1.34 ng/mL, P = .037). CONCLUSION: There is an association between CYP3A5*3, CYP2D6*4, CYP2D6*2A variants and bisoprolol peak concentration, which may serve as a guide in the future in choosing the optimum dose of bisoprolol in ACS patients.

ß-blockers are not all the same: pharmacologic similarities and differences, potential combinations and clinical implications.

ß-blockers are a heterogeneous class, with individual agents distinguished by selectivity for ß1- vs. ß2- and α-adrenoceptors, presence or absence of partial agonist activity at one of more ß-receptor subtype, presence or absence of additional vasodilatory properties, and lipophilicity, which determines the ease of entry the drug into the central nervous system. Cardioselectivity (ß1-adrenoceptor selectivity) helps to reduce the potential for adverse effects mediated by blockade of ß2-adrenoceptors outside the myocardium, such as cold extremities, erectile dysfunction, or exacerbation of asthma or chronic obstructive pulmonary disease. According to recently updated guidelines from the European Society of Hypertension, ß-blockers are included within the five major drug classes recommended as the basis of antihypertensive treatment strategies. Adding a ß-blocker to another agent with a complementary mechanism may provide a rational antihypertensive combination that minimizes the adverse impact of induced sympathetic overactivity for optimal blood pressure-lowering efficacy and clinical outcomes benefit.

Sympathetic overactivity, hypertension and cardiovascular disease: state of the art.

Cardiovascular disease (CVD) remains the most prevalent cause of premature death worldwide. It had been suspected for decades that increased activity of the sympathetic nervous system (SNS) might play a pathogenetic role in the development and progression of hypertension, heart failure (HF) and CVD. The use of microneurographic techniques to directly assess the SNS has allowed this field to advance considerably in recent years. We now have compelling evidence for a key role of sympathetic overactivity in the pathogenesis and progression of hypertension and associated hypertension-mediated organ damage (such as endothelial dysfunction, arterial stiffness and left ventricular hypertrophy), HF (with or without reduced left ventricular ejection fraction). Sympathetic overactivity also drives increased cardiovascular risk in the settings of obesity, metabolic syndrome, chronic kidney disease and obstructive sleep apnoea, among other conditions. Thus, sympathetic overactivity is an important factor that drives patients through the CVD continuum, from the early appearance of cardiovascular risk factors, to impairments of the structure and function of components of the heart and arteries, to established CVD, and ultimately to a life-threatening cardiovascular event. A deeper understanding of the role of sympathetic overactivity in the pathogenesis of CVD and HF will support the optimization of therapeutic interventions for these conditions.

Heart failure management with ß-blockers: can we do better?

Heart failure (HF) is associated with disabling symptoms, poor quality of life, and a poor prognosis with substantial excess mortality in the years following diagnosis. Overactivation of the sympathetic nervous system is a key feature of the pathophysiology of HF and is an important driver of the process of adverse remodelling of the left ventricular wall that contributes to cardiac failure. Drugs which suppress the activity of the renin-angiotensin-aldosterone system, including ß-blockers, are foundation therapies for the management of heart failure with reduced ejection fraction (HFrEF) and despite a lack of specific outcomes trials, are also widely used by cardiologist in patients with HF with preserved ejection fraction (HFpEF). Today, expert opinion has moved away from recommending that treatment for HF should be guided solely by the LVEF and interventions should rather address signs and symptoms of HF (e.g. oedema and tachycardia), the severity of HF, and concomitant conditions. ß-blockers improve HF symptoms and functional status in HF and these agents have demonstrated improved survival, as well as a reduced risk of other important clinical outcomes such as hospitalisation for heart failure, in randomised, placebo-controlled outcomes trials. In HFpEF, ß-blockers are anti-ischemic and lower blood pressure and heart rate. Moreover, ß-blockers also reduce mortality in the setting of HF occurring alongside common comorbid conditions, such as diabetes, CKD (of any severity), and COPD. Higher doses of ß-blockers are associated with better clinical outcomes in populations with HF, so that ensuring adequate titration of therapy to their maximal (or maximally tolerated) doses is important for ensuring optimal outcomes for people with HF. In principle, a patient with HF could have combined treatment with a ß-blocker, renin-angiotensin-aldosterone system inhibitor/neprilysin inhibitor, mineralocorticoid receptor antagonist, and a SGLT2 inhibitor, according to tolerability.

Cu-Co Bimetallic Catalyst-based Electrochemical Sensing Platform for Determination of Bisoprolol in Clinical Samples.

BACKGROUND: Bisoprolol (BIS) is a selective beta-blocker. It has been successfully used to treat hypertension and angina pectoris. An overdose of BIS can lead to serious complications. An overdose is a medical emergency that requires immediate medical attention to overcome the adverse effects of the overdose. Hence, sensitive, reliable, and cost-effective methods are required for the determination of BIS. METHODS: In this work, a new electrochemical sensing platform based on a bimetallic catalyst was developed for the determination of BIS. The Cu-Co nanocatalyst was easily synthesized by galvanic displacement onto a carbon paste electrode (CPE). Then, field emission scanning electron microscopy (FESEM), energy dispersive spectroscopy (EDS), and cyclic voltammetry (CV) were utilized for the characterization of the Cu-Co catalyst. RESULTS: The galvanic displacement of Cu metal significantly affected the electro-catalytic behavior of the Cu-Co catalyst and the Cu-Co/CPE electrode displayed a very sensitive and accurate response towards BIS. Under optimized conditions, the response was linear in the 3 to 120 µM concentration range, sensitivity of 631.1 µA mM-1 and a detection limit of as low as 0.4 µM using cyclic voltammetry. The simple proposed method was also successfully employed in the analysis of BIS in biological and pharmaceutical samples. The advantages of Cu-Co/CPE are its fast and simple manufacturing and the possibility of a repeated surface regeneration of the sensing platform, as well as its application for the detection of BIS in tablets and biological samples, making Cu-Co significant promise for use in clinical diagnostics. Besides, the synthesized catalysts showed excellent reusability and stability. CONCLUSION: The presence of Cu metal due to galvanic displacement increased the sensitivity. These findings suggest that the new nanocatalyst has potential applications in sensors and electronics.

Beta-blocker therapy in heart failure with preserved ejection fraction (B-HFpEF): A systematic review and meta-analysis.

INTRODUCTION: While beta-blockers are considered the cornerstone of treatment for heart failure with reduced ejection fraction, the same may not apply to patients with heart failure with preserved ejection fraction (HFpEF). To date, the benefit of beta-blockers remains uncertain, and there is no current consensus on their effectiveness. This study sought to evaluate the efficacy of beta-blockers on mortality and rehospitalization among patients with HFpEF. METHODS: A systematic review and meta-analysis of randomized or observational cohort studies examined the efficacy of beta-blocker therapy in comparison with placebo, control, or standard medical care in patients with HFpEF, defined as left ventricular ejection fraction ≥50 %. The main endpoints were mortality (i.e., all-cause and cardiovascular), rehospitalization (i.e., all-cause and for heart failure) and a composite of the two. RESULTS: Out of the 13,189 records initially identified, 16 full-text records met the inclusion criteria and were analyzed recruiting a total of 27,188 patients. The mean age range was 62-84 years old, predominantly female, with HFpEF in which 63.4 % of patients received a beta-blocker and 36.6 % did not. The pooled analysis of included cohort studies, of variable follow-up durations, showed a significant reduction in all-cause mortality by 19 % (odds ratio (OR) 0.81; 95 % confidence interval (CI): 0.65-0.99, p = 0.044) whereas rehospitalization for heart failure (OR 1.13; 95 % CI: 0.91-1.41, p = 0.27) or its composite with all-cause mortality (OR 1.01; 95 % CI: 0.78-1.32, p = 0.92) were similar between the beta-blocker and control groups. CONCLUSION: This meta-analysis showed that beta-blocker therapy has the potential to reduce all-cause mortality in patients with HFpEF based on observational studies. Nevertheless, it did not affect rehospitalization for heart failure or its composite with all-cause mortality. Large scale randomized trials are needed to clarify this uncertainty.

Immediate Reaction to Propranolol: An Extremely Rare but Important Condition. A Case Report.

INTRODUCTION: Beta-blockers involve a group of drugs widely used nowadays. Propranolol was the first beta-blocker available in the market. It is the most prescribed first-generation betablocker and is commonly used. Beta-blocker allergy is extremely unusual. Only an isolated case of an urticaria reaction to propranolol has been published in 1975. CASE PRESENTATION: We present a 44-year-old man. In 2016, he was treated with a daily dose of 5 mg of propranolol prescribed for a diagnosis of essential tremor. On the third day of medical treatment, he experienced an episode of generalized urticaria directly related to the administration of propranolol. He continued with his habitual treatment and he had no other urticaria episodes. A drug provocation test was carried out with gradually increasing doses of the culprit drug. Thirty minutes after a total cumulative dose of 5 mg, the patient had several hives on the chest, abdominal region and arms. Two weeks later, a new drug provocation test was performed to bisoprolol as an alternative beta-blocker, with good tolerance. CONCLUSION: We describe a new case of urticaria secondary to propranolol, presenting as an immediate hypersensitivity reaction. Bisoprolol has been succesfully proved to be a safe option. Bisoprolol is a second-generation beta-blocker, it is available and commercialized worldwide, which makes it a good alternative.

The improvement of routine drug quality control analysis of some antihypertensive drugs using high-performance thin-layer chromatography densitometry method with greenness profile evaluation.

The common antihypertensive drugs are B-blockers and diuretics. For the determination of beta-blocker medicines (bisoprolol fumarate and carvedilol) and diuretic drug (Furosemide), new and accurate chromatographic method has been developed. The separation was achieved using a developing system that includes chloroform:methanol:ethyl acetate:ammonia (6:2:2:0.2 by volume) as a mobile phase and the bands were detected at 240 nm. The concentration ranges were 5-25, 1-7, and 1-3.5 µg/band for bisoprolol fumarate, carvedilol, and furosemide, respectively. This chromatographic approach is the first methodology for simultaneously determining bisoprolol fumarate, carvedilol, and furosemide in their pure forms and in their pharmaceutical dosage forms. The advantages of using known analytical procedures are their simplicity, speed, cost effectiveness, lack of laboriousness, and ability to save time as the three tablets are determined in one step and can be used for routine analysis of the investigated combinations in quality control laboratories. According to International Conference of Harmonization guidelines, the established procedures have been validated, and the results were statistically compared to those obtained by the reported reversed-phase-high-performance liquid chromatography methods using Student's t-test and F-test, with no significant difference between them, indicating that the proposed methods can be used for routine drug quality control analysis.

A Retrospective Observational Real-Word Analysis of the Adherence, Healthcare Resource Consumption and Costs in Patients Treated with Bisoprolol/Perindopril as Single-Pill or Free Combination.

INTRODUCTION: The present real-world analysis aims to compare the drug utilization, hospitalizations and direct healthcare costs related to the use of single-pill combination (SPC) or free-equivalent combination (FEC) of perindopril and bisoprolol (PER/BIS) in a large Italian population. METHODS: This observational retrospective analysis was based on administrative databases covering approximately 7 million subjects across Italy. All adult subjects receiving PER/BIS as SPC or FEC between January 2017-June 2020 were included. Subjects were followed for 1 year after the first prescription of PER/BIS as FEC (± 1 month) or SPC. Before comparing the SPC and FEC cohorts, propensity score matching (PSM) was applied to balance the baseline characteristics. Drug utilization was investigated as adherence (defined by the proportion of days covered, PDC) and persistence (evaluated by Kaplan-Meier curves). Hospitalizations and mean annual direct healthcare costs (due to drug prescriptions, hospitalizations and use of outpatient services) were analyzed during follow-up. RESULTS: The original cohort included 11,440 and 6521 patients taking the SPC and FEC PER/BIS combination, respectively. After PSM, two balanced SPC and FEC cohorts of 4688 patients were obtained (mean age 70 years, approximately 50% male, 24% in secondary prevention). The proportion of adherent patients (PDC ≥ 80%) was higher for those on SPC (45.5%) than those on FEC (38.6%), p < 0.001. The PER/BIS combination was discontinued by 35.8% of patients in the SPC cohort and 41.7% in the FEC cohort (p < 0.001). The SPC cohort had fewer cardiovascular (CV) hospitalizations (5.3%) than the free-combination cohort (7.4%), p < 0.001. Mean annual total healthcare costs were lower in the SPC (1999€) than in the FEC (2359€) cohort (p < 0.001). CONCLUSION: In a real-world setting, patients treated with PER/BIS SPC showed higher adherence, lower risk of drug discontinuation, reduced risk of CV hospitalization, and lower healthcare costs than those on FEC of the same drugs.

Patients with cardiovascular conditions often need to take many pills. This may result in patients not taking their pills as prescribed (i.e., low adherence) and compromise the potential benefits derived from prescription of cardiovascular protective drugs. Simplifying treatment by combining drugs into a single pill can improve adherence and, consequently, patient outcomes. In this analysis using data from real clinical practice, we explored whether using a single pill of perindopril and bisoprolol is associated with higher levels of adherence, lower proportion of patients with hospitalizations and lower economic costs than using the same drugs prescribed as free-equivalent combination in a large sample of the Italian population of approximately 7 million people. We identified two groups of patients taking single pill or free-equivalent combination of perindopril and bisoprolol (4688 patients in each cohort). Over 1-year follow-up, patients taking single pill were more likely to be adherent and were less likely to stop taking their treatment. They also had fewer cardiovascular hospitalizations with shorter hospital admission and had lower healthcare direct costs. In conclusion, simplifying treatment by combining perindopril and bisoprolol in a single pill instead of two may have a positive effect on adherence, outcomes and healthcare costs already after 1 year.

Meta-analysis about ADRB1 Arg389Gly polymorphism on the efficacy of bisoprolol / 中国药房

OBJECTIVE To explore the effects of ADRB1 Arg389Gly polymorphisms on the efficacy of bisoprolol， thus providing some information for individualized drug therapy. METHODS A systematic search was conducted in PubMed， Embase， Cochrane Library， CBM， CNKI， and Wanfang Data to retrieve and find out all relevant literature about bisoprolol and ADRB1 Arg389Gly polymorphism from the inception to May 2023. The retrieved literature was screened and selected according to the inclusive and exclusive criteria， thereafter quality assessment was conducted. RevMan 5.4 software was utilized to perform the meta- analysis for the outcome index. RESULTS Overall 7 literature with 1 339 cases were included. Among them， 4 studies provided the changes in systolic blood pressure （SBP）， diastolic blood pressure （DBP） （ΔSBP and ΔDBP）； 4 involving the change （ΔLVEF） of left ventricular ejection fraction （LVEF）. Results of the study showed that there was no statistical significance in the improvement of blood pressure between wild-type group （AA） and mutation group （AG+GG） of ADRB1 Arg389Gly treated with bisoprolol {ΔSBP [SMD＝0.17，95%CI （－0.97，1.31）， P＝0.77]， ΔDBP [SMD＝－0.01，95%CI （－0.65，0.62）， P＝0.97]}； there was no statistical significance in the improvement of ΔLVEF [SMD＝－0.61， 95%CI （－2.74，1.53）， P＝0.58] between 2 groups. CONCLUSIONS ADRB1 Arg389Gly gene polymorphism has no significant influence on the improvement of SBP， DBP， and LVEF in cardiovascular patients who use bisoprolol.

Potential application of bisoprolol derivative compounds as antihypertensive drugs: synthesis and in silico study.

Two bisoprolol derivatives, N-acetyl bisoprolol and N-formyl bisoprolol, belonging to the beta-blocker class of antihypertensive drugs, were synthesized using acetylation and formylation reactions. The yields of the reactions were determined to be 32.40% for N-acetyl bisoprolol and 20.20% for N-formyl bisoprolol. In silico methods such as molecular docking, molecular dynamics simulation and SwissADME prediction were employed to evaluate the potential of these bisoprolol derivatives as antihypertensive drugs. These methods were used to assess the interaction between the bisoprolol derivatives and various receptors associated with hypertension, including human angiotensin I-converting enzyme (PDB ID: 1O8A), renin (PDB ID: 2V0Z), beta-1 adrenergic receptors (PDB ID: 4BVN, 7BVQ), voltage-dependent L-type calcium channel subunit alpha-1S (PDB ID: 6JP5) and mineralocorticoid receptor (PDB ID: 6L88). Our results demonstrated the highest binding energy when bisoprolol and its derivatives bound to 4BVN, with binding energy values of 6.74 kcal mol-1, 7.03 kcal mol-1 and 7.63 kcal mol-1 for bisoprolol, N-acetyl bisoprolol and N-formyl bisoprolol, respectively. The stability of these complexes was confirmed by molecular dynamics simulations, with a root-mean-square deviation value of approximately 2. Furthermore, the SwissADME results indicated that both derivatives exhibited similar properties to the reference drug bisoprolol.

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

Purpose: To evaluate the clinical efficacy and safety of bisoprolol in patients with chronic obstructive pulmonary disease (COPD). Research Methods: 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). Results: 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. Conclusion: 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.

Identifying multi-target drugs for prostate cancer using machine learning-assisted transcriptomic analysis.

Prostate cancer is a leading cause of cancer death in men, and the development of effective treatments is of great importance. This study explored to identify the candidate drugs for prostate cancer by transcriptomic data and CMap database analysis. After integrating the results of omics analysis, bisoprolol is confirmed as a promising drug. Moreover, cell experiment reveals its potential inhibitory effect on the proliferation of prostate cancer cells. Importantly, machine learning methods are employed to predict the targets of bisoprolol, and the dual-target ADRB3 and hERG are explored by dynamic simulation. The findings of this study demonstrate the potential of bisoprolol as a multi-target drug for prostate cancer treatment and the feasibility of using beta-adrenergic receptor inhibitors in prostate cancer treatment. In addition, the proposed research approach is promising for discovering potential drugs for cancer treatment by leveraging the concept of drug side effects leading to anticancer effects. Further research is necessary to investigate the pharmacological action, potential toxicity, and underlying mechanisms of bisoprolol in treating prostate cancer with ADRB3.Communicated by Ramaswamy H. Sarma.

Genetic polymorphisms in ADRB1, ADRB2 and CYP2D6 genes and response to beta-blockers in patients with acute coronary syndrome.

Betablockers (BBs) are prescribed for ischaemia in patients with acute coronary syndrome (ACS). In Spain, bisoprolol and carvedilol are the most prescribed BBs, but patients often had to discontinue them due to adverse effects. Single nucleotide polymorphisms (SNPs) in ADRB1, ADRB2 and CYP2D6 genes have strong evidence of pharmacogenetic association with BBs in heart failure or hypertension, but the evidence in ACS is limited. Therefore, our study focuses on investigating how these genes influence the response to BBs in ACS patients. We analysed the association between SNPs in ADRB1 Gly389Arg (rs1801253) and Ser49Gly (rs1801252), ADRB2 Gly16Arg (rs1042713) and Glu27Gln (rs1042714), and CYP2D* 6 (*2- rs1080985, *4- rs3892097, *10 - rs1065852) and the occurrence of bradycardia/hypotension events during one year of follow-up. We performed an observational study and included 285 ACS-PCI-stent patients. A first analysis including patients treated with bisoprolol and a second analysis including patients treated with other BBs were performed. We found that the presence of the G allele (Glu) of the ADRB2 gene (rs1042714; Glu27Gln) conferred a protective effect against hypotension-induced by BBs; OR (CI 95%) = 0,14 (0,03-0,60), p < 0.01. The ADRB2 (rs1042713; Gly16Arg) GG genotype could also prevent hypotensive events; OR (CI 95%) = 0.49 (0.28-0.88), p = 0015. SNPs in ADRB1 and CYP2D6 * 2, CYP2D6 * 4 weren´t associated with primary events. The effect of CYP2D6 * 10 does not seem to be relevant for the response to BBs. According to our findings, SNPs in ADRB2 (rs1042713, rs1042714) could potentially affect the response and tolerance to BBs in ACS-patients. Further studies are necessary to clarify the impact of ADRB2 polymorphisms.

Comparison between the ECG Outcomes of Metoprolol and Bisoprolol.

BACKGROUND: Beta-blockers are essential agents in the management of cardiovascular diseases, such as heart failure, acute myocardial infarction (MI), and cardiac arrhythmias. However, there are diurnal variations in the cardioprotective effects of the subgroups as a result of their different pharmacokinetic, pharmacodynamic, and pharmacogenetic profiles. OBJECTIVE: We aimed to compare metoprolol and bisoprolol in terms of electrocardiogram (ECG) outcomes. METHODS: A retrospective cross-sectional study was conducted at Prince Sultan Cardiac Center. The trial included 404 patients who met the inclusion criteria (204 in the metoprolol arm and 200 in the bisoprolol arm). Using case record forms that had already been created, information, such as patient demographics, medical histories, and treatment histories, was taken from their medical files. The most recent ECG records were also gathered. The ethical approval for this study was obtained from Qassim ethical committee (approval number: 45-44-902). RESULTS: There was no significant difference found between the patients in both arms in terms of baseline characteristics, age, or sex. CONCLUSION: In this retrospective cross-sectional study, we have compared the effects of metoprolol and bisoprolol beta blockers on ECG changes. The findings have indicated no difference between metoprolol and bisoprolol groups in terms of all ECG readings, particularly PR/ms, QTC-ms, and ventricular rate. Further studies are required to confirm these findings.

Role of ß-blockers in the cardiovascular disease continuum: a collaborative Delphi survey-based consensus from Asia-Pacific.

OBJECTIVE: This Delphi method of consensus was designed to develop scientific statements for ß-blockers in the continuum of cardiovascular diseases with a special focus on the role of bisoprolol. METHODS: Eleven experienced cardiologists from across the Asia-Pacific countries participated in two rounds of the survey. In the first round, experts were asked to rate agreement/disagreement with 35 statements across seven domains regarding the use of ß-blockers for treating hypertension, heart failure, coronary artery diseases, co-morbidities, as well as their safety profile, usage pattern, and pharmacokinetic variability. A consensus for a statement could be reached with >70% agreement. RESULTS: Except for seven statements, all attained consensus in the first round. In the second round that was conducted virtually, the experts re-appraised their ratings for the seven statements along with a critical appraisal of two additional statements that were suggested by experts in the preceding round. At the end of the second round, the final version included 36 statements (34 original statements, two statements suggested by experts, and the omission of one statement that did not attain consensus). The final version of statements in the second round was disseminated among experts for their approval followed by manuscript development. CONCLUSION: Attainment of consensus for almost all statements reconfirms the clinical benefits of ß-blockers, particularly ß1-selective blockers for the entire spectrum of cardiovascular diseases.

ß1-adrenergic receptor polymorphisms: a possible genetic predictor of bisoprolol response in acute coronary syndrome.

Aim: 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). Patients & methods: 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. Results: 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. Conclusion: Arg389Gly polymorphism is a promising bisoprolol response predictor in ACS patients.

Pharmacogenetics is a field of study that explores how our genes can affect how well certain medicines work. In this study, scientists looked at a specific gene called beta1-adrenergic receptor to see how it can influence a drug called bisoprolol. They wanted to find out if some people's genes made bisoprolol work better for them. They studied 77 patients with a heart problem called acute coronary syndrome (ACS) who were taking bisoprolol for 4 weeks. The researchers discovered that people with a particular gene piece called Arg389Arg responded better to bisoprolol. They had bigger reductions in their blood pressure compared with those who had a different gene called Gly389. This finding suggests that by looking at a person's genes, doctors might be able to predict how well bisoprolol will work for them. This way, doctors can choose the best treatment for each patient, making sure they get the most benefit from the medicine.