Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction.

BACKGROUND: Most trials that have shown a benefit of beta-blocker treatment after myocardial infarction included patients with large myocardial infarctions and were conducted in an era before modern biomarker-based diagnosis of myocardial infarction and treatment with percutaneous coronary intervention, antithrombotic agents, high-intensity statins, and renin-angiotensin-aldosterone system antagonists. METHODS: In a parallel-group, open-label trial performed at 45 centers in Sweden, Estonia, and New Zealand, we randomly assigned patients with an acute myocardial infarction who had undergone coronary angiography and had a left ventricular ejection fraction of at least 50% to receive either long-term treatment with a beta-blocker (metoprolol or bisoprolol) or no beta-blocker treatment. The primary end point was a composite of death from any cause or new myocardial infarction. RESULTS: From September 2017 through May 2023, a total of 5020 patients were enrolled (95.4% of whom were from Sweden). The median follow-up was 3.5 years (interquartile range, 2.2 to 4.7). A primary end-point event occurred in 199 of 2508 patients (7.9%) in the beta-blocker group and in 208 of 2512 patients (8.3%) in the no-beta-blocker group (hazard ratio, 0.96; 95% confidence interval, 0.79 to 1.16; P = 0.64). Beta-blocker treatment did not appear to lead to a lower cumulative incidence of the secondary end points (death from any cause, 3.9% in the beta-blocker group and 4.1% in the no-beta-blocker group; death from cardiovascular causes, 1.5% and 1.3%, respectively; myocardial infarction, 4.5% and 4.7%; hospitalization for atrial fibrillation, 1.1% and 1.4%; and hospitalization for heart failure, 0.8% and 0.9%). With regard to safety end points, hospitalization for bradycardia, second- or third-degree atrioventricular block, hypotension, syncope, or implantation of a pacemaker occurred in 3.4% of the patients in the beta-blocker group and in 3.2% of those in the no-beta-blocker group; hospitalization for asthma or chronic obstructive pulmonary disease in 0.6% and 0.6%, respectively; and hospitalization for stroke in 1.4% and 1.8%. CONCLUSIONS: Among patients with acute myocardial infarction who underwent early coronary angiography and had a preserved left ventricular ejection fraction (≥50%), long-term beta-blocker treatment did not lead to a lower risk of the composite primary end point of death from any cause or new myocardial infarction than no beta-blocker use. (Funded by the Swedish Research Council and others; REDUCE-AMI ClinicalTrials.gov number, NCT03278509.).

Safety and tolerability of ß-blockers: importance of cardioselectivity.

Cardioselective ß-blockade is generally well tolerated in practice and contraindications to this therapy are uncommon. ß-blockers are a diverse therapeutic class, and their individual tolerability profiles are influenced strongly by their pharmacodynamic effects across different adrenergic receptors. Bisoprolol, probably the ß-blocker with the highest selectivity for blockade of ß1- vs. ß2-adrenoceptors, does not block ß2-adrenoceptors to an appreciable extent at doses in therapeutic use. Side-effects often attributed to ß-blockers, such as erectile dysfunction and adverse metabolic effects are uncommon with bisoprolol and other ß-blockers used at doses which only block ß1-adrenoceptors. Cautious use of a cardioselective ß-blocker is not contraindicated in people with chronic obstructive pulmonary disease or asthma and the outcomes benefits of ß-blockers in patients with coronary heart disease or heart failure are also apparent in patients with concurrent COPD. Starting with a low dose and titrating upwards carefully is important for optimising the tolerability of a ß-blocker. Most people with hypertension will receive combination antihypertensive therapy in practice, and the low-dose combination therapy approach provides a useful strategy for optimising the efficacy and tolerability of a regimen that includes a ß-blocker, compared with up-titrating an existing monotherapy.

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.

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.

Bisoprolol versus celiprolol on dynamic hyperinflation, cardiopulmonary exercise and domiciliary safety in COPD: a single-centre, randomised, crossover study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is frequently associated with cardiovascular disease. The utility of beta-blockers for treating patients with COPD may be beneficial, but their safety remains uncertain, including worsening of dynamic hyperinflation (DH) during exercise. We hypothesised that among cardioselective beta-blockers celiprolol, due to its partial beta-2 agonist activity, may be safer than bisoprolol on exercise DH. METHODS: We measured isotime inspiratory capacity (IC) during cycle endurance testing in eleven moderate-severe COPD subjects, alongside other non-invasive cardiopulmonary exercise, bioreactance cardiac output, pulmonary function, biomarkers and daily domiciliary measures. Participants received titrated doses of either bisoprolol (maximim 5 mg) or celiprolol (maximum 400 mg) in randomised crossover fashion, each over 4 weeks. RESULTS: Clinically relevant DH occurred between resting and exercise isotime IC but showed no significant difference with either beta-blocker compared with post-run-in pooled baseline or between treatments. There were no other significant differences observed for remaining exercise ventilatory; non-invasive cardiac output; resting pulmonary function; beta-2 receptor and cardiac biomarkers; domiciliary pulmonary function, oxygen saturation and symptom outcomes, either between treatments or compared with baseline. No significant adverse effects occurred. CONCLUSIONS: Significant DH in moderate-severe COPD subjects was no different between bisoprolol or celiprolol or versus baseline. A broad spectrum of other non-invasive cardiopulmonary and domiciliary safety outcomes was equally reassuring. Bronchoprotection with a concomitant long-acting muscarinic antagonist might be an important safety measure in this context. TRIAL REGISTRATION NUMBER: NCT02380053.

Efficacy and safety of bisoprolol 5 mg plus amlodipine 5 mg in patients with hypertension uncontrolled on monotherapy with 5 mg of amlodipine, a phase III multicenter, randomized, double-blind, placebo-controlled clinical trial - the AMCOR study.

OBJECTIVE: To evaluate the antihypertensive effect and safety of bisoprolol 5 mg (BISO5mg) and amlodipine 5 mg (AMLO5mg) combination in comparison to AMLO5mg in hypertensive subjects uncontrolled with AMLO5mg. METHODS: Phase III, prospective, randomized, double-blind, placebo-controlled, 8-week trial with parallel design (EudraCT Number: 2019-000751-13). RESULTS: 367 patients aged 57.58 ± 14.62 years were randomized to BISO5mg once daily on top of AMLO5mg (n = 181) or placebo on top of AMLO5mg (n = 186). Systolic/diastolic blood pressure (SBP/DBP) in the bisoprolol-treated group was reduced by 7.2 ± 12.74/3.95 ± 8.85 mmHg at 4 weeks (both p < .0001) and by 5.5 ± 12.44/3.84 ± 9.46 mmHg at 8 weeks (p < .0001/p < .0002) compared to placebo control. Bisoprolol-treated group had lower heart rate than placebo control (difference -7.23 ± 9.84/-6.25 ± 9.26 beats per minute at 4 and 8 weeks, respectively, both p < .0001). Both target SBP and DBP was achieved at 4 weeks by 62 vs. 41% (p = .0002) and at 8 weeks by 65 vs. 46% (p = .0004) of bisoprolol-treated patients and placebo group patients, respectively. SBP <140 mmHg was achieved at 4 and 8 weeks in 68 and 69% of bisoprolol-treated patients and 45 and 50% of placebo group patients, respectively. No deaths and serious adverse events were reported. Adverse events occurred in 34 bisoprolol-treated patients vs. 22 patients in the placebo group (p = .064). Bisoprolol was withdrawn due to adverse events in 7 patients, mostly (n = 4) due to asymptomatic bradycardia. CONCLUSIONS: Addition of bisoprolol to patients uncontrolled with amlodipine monotherapy significantly improves blood pressure control. We can expect additional 7.2/3.95 mmHg SBP/DBP lowering effect by adding bisoprolol 5 mg to amlodipine 5 mg.

Managing postoperative atrial fibrillation after open-heart surgery using transdermal ß1 blockers.

BACKGROUND: Postoperative atrial fibrillation (POAF) after open-heart surgery is a non-negligible complication. We aimed to describe the efficacy of a transdermal patch of bisoprolol for managing POAF and flutter in thoracic surgical procedures. METHODS: We analyzed the data of 384 patients who underwent open-heart surgery at our hospital and received oral bisoprolol to prevent POAF. Among them, 65 patients (16.9%) also received a 4-mg transdermal patch of bisoprolol to control the heart rate due to POAF. We applied the bisoprolol transdermal patch when the heart rate was > 80 bpm and removed it at ≤ 60 bpm; an additional patch was applied when the heart rate was > 140 bpm. Heparin calcium injections were administered twice daily for anticoagulation between 2 and 6 days postoperatively. RESULTS: The average number of prescriptions for transdermal patches of bisoprolol during hospitalization was 1.8 ± 1.1 (1-5). The median first prescription date was on postoperative day 2 (range: days 0-37). Sinus rhythm recovered within 24 h in 18 patients (27.7%). Eight patients (12.3%) were switched to continuous landiolol infusion because of persistent tachycardia. In three patients, the transdermal patch was removed owing to severe bradycardia. Fifteen patients experienced persistent atrial fibrillation and were treated with electrical cardioversion during hospitalization. We did not observe any serious complications that could be directly attributed to bisoprolol transdermal patch use. CONCLUSIONS: Single-use bisoprolol transdermal patch may help control the heart rate during the initial treatment of POAF after open-heart surgery.

Effectiveness and Tolerability of Bisoprolol/Perindopril Single-Pill Combination in Patients with Arterial Hypertension and a History of Myocardial Infarction: The PRIDE Observational Study.

INTRODUCTION: This study assessed the real-life effectiveness of a single-pill combination (SPC) of bisoprolol/perindopril for controlling blood pressure (BP) and symptoms of angina in patients with hypertension and a history of myocardial infarction (MI). METHODS: Eligible patients with arterial hypertension and a history of MI were aged 18-79 years and had initiated bisoprolol/perindopril SPC within 3 months of study enrollment as part of routine Russian clinical practice. The primary endpoint was mean change in systolic and diastolic BP (SBP/DBP) at week 12 compared with baseline (data collected retrospectively). Secondary endpoints were assessed at weeks 4 and 12 and included mean change in resting heart rate (HR), proportion of patients reaching target level of resting HR, antianginal effectiveness of the SPC, and proportion of patients reaching target BP levels. RESULTS: A total of 504 patients were enrolled, of whom 481 comprised the full analysis set (mean age 61.4 ± 8.9 years, 68% men). Mean baseline SBP/DBP and HR values were 148.9 ± 16.8/87.7 ± 11.0 mmHg and 77.4 ± 10.5 bpm, respectively. Mean durations of hypertension and CAD were 12.8 ± 8.4 and 6.1 ± 6.3 years, respectively, and time since MI was 3.8 ± 5.3 years. At week 12, SBP/DBP had decreased by 24.9/12.2 mmHg (P < 0.001 vs baseline). Target BP (< 140/90 mmHg) was achieved by 69.8% and 95.9% of patients at weeks 4 and 12, respectively, and target HR (55-60 bpm) by 17.3% and 34.5% at weeks 4 and 12 versus 3.1% at baseline (P < 0.001). Reductions in angina attacks, nitrate consumption, and improvements in HR were statistically significant. Treatment was well tolerated. CONCLUSION: Treatment of symptomatic patients with CAD, hypertension, and a history of MI with a bisoprolol/perindopril SPC was associated with significant decreases in SBP/DBP and a high proportion of patients achieving BP treatment goals. This was accompanied by improvements in angina symptoms and reductions in HR in a broad patient population representative of those seen in everyday clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04656847.

The Effect of Bisoprolol on Premature Ventricular Complex in Vietnamese Patients with Hypertension and Left Ventricular Hypertrophy.

BACKGROUND: Premature ventricular contraction (PVC) is a common arrhythmia that causes a large number of clinical symptoms, adversely impacts the quality of life, and can even initiate serious arrhythmias, such as ventricular tachycardia or ventricular fibrillation. The incidence of premature ventricular contraction is higher in hypertensive patients, particularly if concomitant left ventricular hypertrophy (LVH) is present. OBJECTIVES: This study was conducted on the characteristics of PVC in hypertensive patients with left ventricular hypertrophy and aimed to evaluate the effect of bisoprolol on PVC in Vietnamese patients with hypertension and LVH. MATERIALS AND METHODS: We conducted a study to determine how bisoprolol potency affected PVC management in the group with both high blood pressure and LVH. We selected a convenient sample of all patients who came to the Medical Examination Department at the Can Tho University of Medicine and Pharmacy Hospital and met sampling criteria with hypertension, LVH on echocardiography, and PVC on 12-leads electrocardiogram. Over 2 years, we collected 76 patients who satisfied the above conditions. Out of which, 50 patients were indicated for management with bisoprolol, and 26 patients were excluded from the study, including 7 patients with asthma and 19 patients who had simple PVC on a 24-hour Holter ECG. Data were analyzed with SPSS version 22. RESULTS: Fifty patients participated in the study, of whom 70% were female. It is clear that palpitation was the most prevalent symptom (66%), and 38% of patients had complicated PVC (Lown III-V). When treating PVC with bisoprolol, 50% of patients achieved the treatment goal with a decrease in the number of PVCs of more than 70%, accompanied by symptom relief and eradication of dangerous PVCs. After 4 weeks of treatment, bisoprolol decreased the number of PVCs, heart rate, and blood pressure while also easing PVC-related symptoms (p < 0.05). CONCLUSION: Low-dose bisoprolol effectively reduces the number of PVCs in hypertensive patients with LVH.

Effect of Sequential Nephron Blockade versus Dual Renin-Angiotensin System Blockade Plus Bisoprolol in the Treatment of Resistant Hypertension, a Randomized Controlled Trial (Resistant Hypertension on Treatment - ResHypOT).

Introduction: Hypertension is the most important modifiable risk factor for cardiovascular disease and a leading public health concern. Objectives: 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. Material and Methods: This trial was an open-label, prospective, randomized, parallel-group, clinical study with optional drug up-titration. 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<0.0001), and DBP decreased from 105.3±15.5 to 78.11±9.28 mmHg (p<0.0001). DRASB group, SBP decreased from 178.4±21.08 to 134.4 ± 23.25 mmHg (p<0.0001) and DBP decreased from 102.7±11.07 to 77.33±13.75 mmHg (p<0.0001). Ambulatory blood pressure monitoring (ABPM) showed also significant SBP and DBP reductions in both groups (p<0.0001). Conclusion: In patients with RHTN adherent to treatment, SNB and DRASB plus bisoprolol showed excellent therapeutic efficacy, although SNB was associated with earlier SBP reduction.

The Efficacy and Safety of Bisoprolol in the Treatment of Myocardial Infarction with Cardiac Insufficiency.

Background: Bisoprolol is commonly used to treat moderate or severe chronic stable heart failure, coronary heart disease, and hypertension. This study is aimed at analyzing the efficacy of bisoprolol in the treatment of myocardial infarction with cardiac insufficiency and its effect on cardiac function, Hcy, and CRP through meta-analysis. Methods: A total of 120 patients with myocardial infarction and cardiac insufficiency from February 2020 to February 2021 were selected and randomly divided into two groups (control and the observation, n = 60) according to the random number table method. The control group was given conventional treatment. The observation group was given bisoprolol on the basis of control group. The clinical efficacy, systolic blood pressure, diastolic blood pressure, heart rate, cardiac function indexes, homocysteine (Hcy), and C-reactive protein (CRP) levels were compared between the two groups before and after treatment through data analysis. Adverse reactions were observed during treatment. Results: Compared with the control group, the total effective rate of the observation group was significantly increased (p < 0.05). After treatment, the levels of heart rate, left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV) and serum Hcy and CRP levels in the observation group were significantly lower than those in the control group (p < 0.05). Meanwhile, left ventricular ejection fraction (LVEF) level in the observation group after treatment was higher than that of the control group (p < 0.05). Conclusion: Bisoprolol combined with conventional treatment can reduce serum Hcy and CRP levels in patients with myocardial infarction and cardiac insufficiency and improve cardiac function. Moreover, there are no obvious adverse reactions during the treatment.

A growing evidence base for the fixed-dose combination of bisoprolol and amlodipine to manage hypertension.

OBJECTIVES: Hypertension is a major cause of morbidity and mortality worldwide. Although current drug therapies can be effective, management of hypertension is closely linked to patient adherence to therapy. A fixed-dose combination (FDC) of bisoprolol and amlodipine has shown to be effective and convenient, and to significantly improve patient adherence. METHODS: This narrative review evaluates recent evidence from four studies which explore the efficacy, safety, and adherence of FDC bisoprolol and amlodipine in patients with hypertension: one observational study; two randomized clinical trials (RCTs); and one indirect comparison analysis. RESULTS: All four studies support the efficacy of FDC bisoprolol and amlodipine in the management of hypertension, highlighting clinically meaningful reductions in systolic and diastolic blood pressure (BP), and high adherence. In a large cohort study exploring FDC bisoprolol and amlodipine in daily practice, high adherence improved BP and heart rate control versus baseline. In a Phase 3 RCT, FDC bisoprolol and amlodipine demonstrated superiority over monotherapies in BP control and a positive tolerability profile, further supporting its use to manage hypertension in second line following monotherapy. In another Phase 3 RCT, the combination of bisoprolol and amlodipine led to significant BP reductions versus monotherapy with amlodipine with a comparable safety profile. Finally, in the indirect treatment comparison, a low dose combination of bisoprolol and amlodipine showed a similar decrease in systolic BP compared with a maximum dose of amlodipine. CONCLUSIONS: This review adds to growing evidence supporting the efficacy, safety, and tolerability of FDC bisoprolol and amlodipine in managing hypertension.

Use of the oral beta blocker bisoprolol to reduce the rate of exacerbation in people with chronic obstructive pulmonary disease (COPD): a randomised controlled trial (BICS).

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity, mortality and healthcare costs. Beta blockers are well-established drugs widely used to treat cardiovascular conditions. Observational studies consistently report that beta blocker use in people with COPD is associated with a reduced risk of COPD exacerbations. The bisoprolol in COPD study (BICS) investigates whether adding bisoprolol to routine COPD treatment has clinical and cost-effective benefits. A sub-study will risk stratify participants for heart failure to investigate whether any beneficial effect of bisoprolol is restricted to those with unrecognised heart disease. METHODS: BICS is a pragmatic randomised parallel group double-blind placebo-controlled trial conducted in UK primary and secondary care sites. The major inclusion criteria are an established predominant respiratory diagnosis of COPD (post-bronchodilator FEV1 < 80% predicted, FEV1/FVC < 0.7), a self-reported history of ≥ 2 exacerbations requiring treatment with antibiotics and/or oral corticosteroids in a 12-month period since March 2019, age ≥ 40 years and a smoking history ≥ 10 pack years. A computerised randomisation system will allocate 1574 participants with equal probability to intervention or control groups, stratified by centre and recruitment in primary/secondary care. The intervention is bisoprolol (1.25 mg tablets) or identical placebo. The dose of bisoprolol/placebo is titrated up to a maximum of 4 tablets a day (5 mg bisoprolol) over 4-7 weeks depending on tolerance to up-dosing of bisoprolol/placebo-these titration assessments are completed by telephone or video call. Participants complete the remainder of the 52-week treatment period on the final titrated dose (1, 2, 3, 4 tablets) and during that time are followed up at 26 and 52 weeks by telephone or video call. The primary outcome is the total number of participant reported COPD exacerbations requiring oral corticosteroids and/or antibiotics during the 52-week treatment period. A sub-study will risk stratify participants for heart failure by echocardiography and measurement of blood biomarkers. DISCUSSION: The demonstration that bisoprolol reduces the incidence of exacerbations would be relevant not only to patients and clinicians but also to healthcare providers, in the UK and globally. TRIAL REGISTRATION: Current controlled trials ISRCTN10497306 . Registered on 16 August 2018.

Pharmacological differences between beta-blockers and postoperative mortality following colon cancer surgery.

ß-blocker therapy has been positively associated with improved survival in patients undergoing oncologic colorectal resection. This study investigates if the type of ß-blocker used affects 90-day postoperative mortality following colon cancer surgery. The study was designed as a nationwide retrospective cohort study including all adult (≥ 18 years old) patients with ongoing ß-blocker therapy who underwent elective and emergency colon cancer surgery in Sweden between January 1, 2007 and December 31, 2017. Patients were divided into four cohorts: metoprolol, atenolol, bisoprolol, and other beta-blockers. The primary outcome of interest was 90-day postoperative mortality. A Poisson regression model with robust standard errors was used, while adjusting for all clinically relevant variables, to determine the association between different ß-blockers and 90-day postoperative mortality. A total of 9254 patients were included in the study. There was no clinically significant difference in crude 90-day postoperative mortality rate [n (%)] when comparing the four beta-blocker cohorts metoprolol, atenolol, bisoprolol and other beta-blockers. [97 (1.8%) vs. 28 (2.0%) vs. 29 (1.7%) vs. 11 (1.2%), p = 0.670]. This remained unchanged when adjusting for relevant covariates in the Poisson regression model. Compared to metoprolol, there was no statistically significant decrease in the risk of 90-day postoperative mortality with atenolol [adj. IRR (95% CI): 1.45 (0.89-2.37), p = 0.132], bisoprolol [adj. IRR (95% CI): 1.45 (0.89-2.37), p = 0.132], or other beta-blockers [adj. IRR (95% CI): 0.92 (0.46-1.85), p = 0.825]. In patients undergoing colon cancer surgery, the risk of 90-day postoperative mortality does not differ between the investigated types of ß-adrenergic blocking agents.

Effects of short-term bisoprolol on perioperative myocardial injury in patients undergoing non-cardiac surgery: a randomized control study.

The protective role of preoperative beta-blocker in patients undergoing non-cardiac surgery is unknown. We aimed to evaluate the effects of beta-blocker on perioperative myocardial injury in patients undergoing non-cardiac surgery. We consecutively enrolled 112 patients undergoing non-cardiac surgery. They were randomly allocated to receive bisoprolol or placebo given at least 2 days preoperatively and continued until 30 days after surgery. The primary outcome was incidence of perioperative myocardial injury defined by a rise of high-sensitive troponin-T (hs-TnT) more than 99th percentile of upper reference limit or a rise of hs-TnT more than 20% if baseline level is abnormal. Baseline characteristics were comparable between bisoprolol and placebo in randomized cohort Mean age was 62.5 ± 11.8 years and 76 (67.8%) of 112 patients were male. Among 112 patients, 49 (43.8%) underwent vascular surgery and 63 (56.2%) underwent thoracic surgery. The median duration of assigned treatment prior to surgery was 4 days (2-6 days). We did not demonstrate the significant difference in the incidence of perioperative myocardial injury [52.6% (30 of 57 patients) vs. 49.1% (27 of 55 patients), P = 0.706]. In addition, the incidence of intraoperative hypotension was higher in bisoprolol group than placebo group in patients undergoing non-cardiac surgery [70.2% (40 of 57 patients) vs. 47.3% (26 of 55 patients), P = 0.017]. We demonstrated that there was no statistically significant difference in perioperative myocardial injury observed between patients receiving bisoprolol and placebo who had undergone non-cardiac surgery.

[Chronic use of the unfixed combination of ACE-inhibitors and beta-blockers in Italy from 2013 to 2019 through the healthcare administrative data.] / Uso cronico dell'associazione estemporanea ACE-inibitori e beta-bloccanti in Italia dal 2013 al 2019 attraverso i dati amministrativi sanitari.

INTRODUCTION: The association between an ACE-inhibitor and a beta-blocker is recommended in case of complicated arterial hypertension and heart failure with reduced ejection fraction. This retrospective drug-utilization study has described its chronic use from the Italian National Healthcare Service perspective. METHODS: From the ReS (Ricerca e Salute) database, collecting Italian healthcare administrative data, patients receiving an ACE-inhibitor or a beta-blocker from 2013 to 2019 were selected. The prevalence of use (patients treated/1000 inhabitants) and of continuous treatment (patients treated for ≥80% period from the supply to the end of the same year - by means of dosage units - per 1000 inhabitants) of each single active substance were assessed. Among patients continuously treated, those supplied with an ACE-inhibitor and a beta-blocker (unfixed and fixed combinations) were analyzed in terms of prevalence of continuous treatment. Subjects treated with the unfixed combination ramipril-bisoprolol in 2019 were characterized by gender and age. RESULTS: The prevalence of ACE-inhibitors' use increased from 49.7/1000 inhab. in 2013 to 50.2 in 2019: ramipril was the most supplied each year (28.9 to 31.6/1000 inhab.). The prevalence of continuous treatment increased from 27.4 to 28.3/1000 inhab.: ramipril the most continuously dispensed (16 to 18/1000 inhab.). The prevalence of beta-blockers' use increased from 61.0 to 90.4/1000 inhab.: bisoprolol the most supplied and with the highest increase (27.1 to 52.2/1000 inhab.). The prevalence of continuous treatment increased from 33.1 to 55.8/1000 inhab.: bisoprolol the most continuously dispensed (18 to 37/1000 inhab.). Among patients with continuous supplies, from 49,843 a 51,496 were treated with associations between an ACE-inhibitor and a beta-blocker on an ongoing basis. Half of them were continuously treated with the unfixed combination ramipril-bisoprolol (4.3 to 4.8/1000 inhab.). In 2019, subjects with continuous supplies of ramipril-bisoprolol were mainly males (63.4%) and elderly (mean age 71±12), and the prevalence of use increased with age. CONCLUSIONS: These findings, together with recommendations from the main international guidelines encourage to make available also ramipril and bisoprolol as fixed dose combination, in order to simplify the therapy administration and improve the adherence, especially among elderly and patients with multimorbidity.

Impact of the COVID-19 pandemic on the management of chronic heart failure.

The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented challenge. Meeting this has resulted in changes to working practices and the impact on the management of patients with heart failure with reduced ejection fraction (HFrEF) is largely unknown. We performed a retrospective, observational study contrasting patients diagnosed with HFrEF attending specialist heart failure clinics at a UK hospital, whose subsequent period of optimisation of medical therapy was during the COVID-19 pandemic, with patients diagnosed the previous year. The primary outcome was the change in equivalent dosing of ramipril and bisoprolol at 6-months. Secondary outcomes were the number and type of follow-up consultations, hospitalisation for heart failure and all-cause mortality. In total, 60 patients were diagnosed with HFrEF between 1 December 2019 and 30 April 2020, compared to 54 during the same period of the previous year. The absolute number of consultations was higher (390 vs 270; p = 0.69), driven by increases in telephone consultations, with a reduction in appointments with hospital nurse specialists. After 6-months, we observed lower equivalent dosing of ramipril (3.1 ± 3.0 mg vs 4.4 ± 0.5 mg; p = 0.035) and similar dosing of bisoprolol (4.1 ± 0.5 mg vs 4.9 ± 0.5 mg; p = 0.27), which persisted for ramipril (mean difference 1.0 mg, 95% CI 0.018-2.09; p = 0.046) and bisoprolol (mean difference 0.52 mg, 95% CI -0.23-1.28; p = 0.17) after adjustment for baseline dosing. We observed no differences in the proportion of patients who died (5.0% vs 7.4%; p = 0.59) or were hospitalised with heart failure (13.3% vs 9.3%; p = 0.49). Our study suggests the transition to telephone appointments and re-deployment of heart failure nurse specialists was associated with less successful optimisation of medical therapy, especially renin-angiotensin inhibitors, compared with usual care.

Do beta-adrenergic blocking agents increase asthma exacerbation? A network meta-analysis of randomized controlled trials.

Beta-adrenergic blocking agents (abbreviated as beta-blockers) have been used for treating various cardiovascular diseases. However, the potential for asthma exacerbation is one of the major adverse effects of beta-blockers. This study aimed to compare the level of risk for an asthma attack in patients receiving various beta-blockers. We searched for randomized controlled trials (RCTs) of either placebo-controlled or active-controlled design. The current network meta-analysis (NMA) was conducted under a frequentist model. The primary outcome was the incidence of asthmatic attack. A total of 24 RCTs were included. Overall NMA revealed that only oral timolol [risk ratio (RR) = 3.35 (95% confidence interval (CI) 1.04-10.85)] and infusion of propranolol [RR = 10.19 (95% CI 1.29-80.41)] were associated with significantly higher incidences of asthma attack than the placebo, whereas oral celiprolol [RR = 0.39 (95% CI 0.04-4.11)], oral celiprolol and propranolol [RR = 0.46 (95% CI 0.02-11.65)], oral bisoprolol [RR = 0.46 (95% CI 0.02-11.65)], oral atenolol [RR = 0.51 (95% CI 0.20-1.28)], infusion of practolol [RR = 0.80 (95% CI 0.03-25.14)], and infusion of sotalol [RR = 0.91 (95% CI 0.08-10.65)] were associated with relatively lower incidences of asthma attack than the placebo. In participants with a baseline asthma history, in addition to oral timolol and infusion of propranolol, oral labetalol, oxprenolol, propranolol, and metoprolol exhibited significantly higher incidences of asthma attack than did the placebo. In conclusion, oral timolol and infusion of propranolol were associated with a significantly higher risk of developing an asthma attack in patients, especially in those with a baseline asthma history, and should be avoided in patients who present a risk of asthma.Trial registration: PROSPERO CRD42020190540.

Effect of Digoxin vs Bisoprolol for Heart Rate Control in Atrial Fibrillation on Patient-Reported Quality of Life: The RATE-AF Randomized Clinical Trial.

Importance: There is little evidence to support selection of heart rate control therapy in patients with permanent atrial fibrillation, in particular those with coexisting heart failure. Objective: To compare low-dose digoxin with bisoprolol (a ß-blocker). Design, Setting, and Participants: Randomized, open-label, blinded end-point clinical trial including 160 patients aged 60 years or older with permanent atrial fibrillation (defined as no plan to restore sinus rhythm) and dyspnea classified as New York Heart Association class II or higher. Patients were recruited from 3 hospitals and primary care practices in England from 2016 through 2018; last follow-up occurred in October 2019. Interventions: Digoxin (n = 80; dose range, 62.5-250 µg/d; mean dose, 161 µg/d) or bisoprolol (n = 80; dose range, 1.25-15 mg/d; mean dose, 3.2 mg/d). Main Outcomes and Measures: The primary end point was patient-reported quality of life using the 36-Item Short Form Health Survey physical component summary score (SF-36 PCS) at 6 months (higher scores are better; range, 0-100), with a minimal clinically important difference of 0.5 SD. There were 17 secondary end points (including resting heart rate, modified European Heart Rhythm Association [EHRA] symptom classification, and N-terminal pro-brain natriuretic peptide [NT-proBNP] level) at 6 months, 20 end points at 12 months, and adverse event (AE) reporting. Results: Among 160 patients (mean age, 76 [SD, 8] years; 74 [46%] women; mean baseline heart rate, 100/min [SD, 18/min]), 145 (91%) completed the trial and 150 (94%) were included in the analysis for the primary outcome. There was no significant difference in the primary outcome of normalized SF-36 PCS at 6 months (mean, 31.9 [SD, 11.7] for digoxin vs 29.7 [11.4] for bisoprolol; adjusted mean difference, 1.4 [95% CI, -1.1 to 3.8]; P = .28). Of the 17 secondary outcomes at 6 months, there were no significant between-group differences for 16 outcomes, including resting heart rate (a mean of 76.9/min [SD, 12.1/min] with digoxin vs a mean of 74.8/min [SD, 11.6/min] with bisoprolol; difference, 1.5/min [95% CI, -2.0 to 5.1/min]; P = .40). The modified EHRA class was significantly different between groups at 6 months; 53% of patients in the digoxin group reported a 2-class improvement vs 9% of patients in the bisoprolol group (adjusted odds ratio, 10.3 [95% CI, 4.0 to 26.6]; P < .001). At 12 months, 8 of 20 outcomes were significantly different (all favoring digoxin), with a median NT-proBNP level of 960 pg/mL (interquartile range, 626 to 1531 pg/mL) in the digoxin group vs 1250 pg/mL (interquartile range, 847 to 1890 pg/mL) in the bisoprolol group (ratio of geometric means, 0.77 [95% CI, 0.64 to 0.92]; P = .005). Adverse events were less common with digoxin; 20 patients (25%) in the digoxin group had at least 1 AE vs 51 patients (64%) in the bisoprolol group (P < .001). There were 29 treatment-related AEs and 16 serious AEs in the digoxin group vs 142 and 37, respectively, in the bisoprolol group. Conclusions and Relevance: Among patients with permanent atrial fibrillation and symptoms of heart failure treated with low-dose digoxin or bisoprolol, there was no statistically significant difference in quality of life at 6 months. These findings support potentially basing decisions about treatment on other end points. Trial Registration: ClinicalTrials.gov Identifier: NCT02391337 and clinicaltrialsregister.eu Identifier: 2015-005043-13.