Cardioselective Beta-blocker Research Articles

Non-cardiac comorbidities in heart failure: an update on diagnostic and management strategies.

Managing non-cardiac comorbidities in heart failure (HF) requires a tailored approach that addresses each patient's specific conditions and needs. Regular communication and coordination among healthcare providers is crucial to providing the best possible care for these patients. Poorly controlled hypertension contributes to left ventricular remodeling and diastolic dysfunction, emphasizing the importance of optimal blood pressure control while avoiding adverse effects. Among HF patients with diabetes, SGLT2 inhibitors and mineralocorticoid receptor antagonists have shown promise in reducing HF-related morbidity and mortality. Chronic kidney disease exacerbates HF and vice versa, forming the vicious cardiorenal syndrome, so disease-modifying therapies should be maintained in HF patients with comorbid CKD, even with transient changes in kidney function. Anemia in HF patients may be multifactorial, and there is growing evidence for the benefit of intravenous iron supplementation in HF patients with iron deficiency with or without anemia. Obesity, although a risk factor for HF, paradoxically offers a better prognosis once HF is established, though developing treatment strategies may improve symptoms and cardiac performance. In HF patients with stroke and atrial fibrillation, anticoagulation therapy is recommended. Among HF patients with sleep-disordered breathing, continuous positive airway pressure may improve sleep quality. Chronic obstructive pulmonary disease often coexists with HF, and many patients can tolerate cardioselective beta-blockers. Cancer patients with comorbid HF require careful consideration of cardiotoxicity risks associated with cancer therapies. Depression is underdiagnosed in HF patients and significantly impacts prognosis. Cognitive impairment is prevalent in HF patients and impacts their self-care and overall quality of life.

Hypertension Management in Pre- and Post Percutaneous Coronary Intervention Patients: An Expert Opinion of Cardiologists from India

Introduction: Despite recent advancements in hypertension management, a significant portion of the population in India still has uncontrolled blood pressure (BP), particularly post percutaneous coronary intervention (PCI). This paper fulfils the gap between post-PCI and hypertension management, ensuring hypertension is well-controlled before, during, and after PCI. Methods: Cardiologists (interventional, n = 256; noninterventional, n = 336) throughout India who treated hypertensive patients, post PCI were invited to participate in a survey and virtual meetings. The perception and practices in managing these patients and strategies to improve BP control were captured. Results: Out of 593 cardiologists, 57.5% opined that heart failure (HF) was more common in patients with hypertension indicated for PCI. The target BP after PCI for patients aged <65 years and >65 years was recommended to be 121–130/80 mmHg by 39% of experts while 131–140/90 mmHg by 33.2% of experts, respectively, with a target heart rate of 60–80 bpm. Angiotensin II receptor blockers (ARBs) were considered the most effective antihypertensive agent in different comorbid conditions. Metoprolol and bisoprolol were the most preferred cardio-selective beta-blockers for both post-PCI and HF. A combination of ARBs and beta-blockers after the intervention was suggested in hypertensive patients with coronary artery disease and diabetes mellitus (57.0%), stroke (41.1%), and HF (44.9%). Conclusions: Managing BP and heart rate in patients with hypertension post-PCI is important. In monotherapy, ARBs followed by beta-blockers and angiotensin-converting enzyme inhibitors, were the most preferred antihypertensive agents in these patients with different comorbid conditions. While a combination of ARB and beta-blocker was preferred in patients with PCI and multiple comorbidities.

Current Knowledge of Beta-Blockers in Chronic Hemodialysis Patients.

Beta-blockers include a large spectrum of drugs with various specific characteristics, and a well-known cardioprotective efficacy. They are recommended in heart failure, hypertension and arrhythmia. Their use in chronic hemodialysis patients is still controversial, mainly because of the lack of specific randomized clinical trials. Large observational studies and two important clinical trials have reported almost unanimously their efficacy in chronic hemodialysis patients, which seems to be related to their levels of dialyzability and cardioselectivity. A recent meta-analysis suggested that high dialyzable beta-blockers are correlated to a reduced risk of all-cause mortality and cardiovascular complications compared with low dialyzable beta-blockers. Despite their benefits, beta-blockers may have adverse effects, such as intradialytic hypotension with low dialyzability beta-blockers or the risk of sub-therapeutic plasma concentration of high dialyzable ones during dialysis sessions. Both cases are linked to adverse cardiovascular events. A solution for both high and low dialyzable drugs could be their administration after dialysis sessions. Futhermore, the bulk of existing literature seems to favor cardioselective beta-blockers with moderate-to-high dialyzability as the ideal agents in dialysis patients, but further, larger studies are needed. This review aims to analyze beta-blockers' characteristics, indications and evidence-based role in chronic hemodialysis patients.

Differential Effects of the Betablockers Carvedilol, Metoprolol and Bisoprolol on Cardiac Kv4.3 (Ito) Channel Isoforms.

Cardiac Kv4.3 channels contribute to the transient outward K+ current, Ito, during early repolarization of the cardiac action potential. Two different isoforms of Kv4.3 are present in the human ventricle and exhibit differential remodeling in heart failure (HF). Cardioselective betablockers are a cornerstone of HF with reduced ejection fraction therapy as well as ventricular arrhythmia treatment. In this study we examined pharmacological effects of betablockers on both Kv4.3 isoforms to explore their potential for isoform-specific therapy. Kv4.3 isoforms were expressed in Xenopus laevis oocytes and incubated with the respective betablockers. Dose-dependency and biophysical characteristics were examined. HEK 293T-cells were transfected with the two Kv4.3 isoforms and analyzed with Western blots. Carvedilol (100 µM) blocked Kv4.3 L by 77 ± 2% and Kv4.3 S by 67 ± 6%, respectively. Metoprolol (100 µM) was less effective with inhibition of 37 ± 3% (Kv4.3 L) and 35 ± 4% (Kv4.3 S). Bisoprolol showed no inhibitory effect. Current reduction was not caused by changes in Kv4.3 protein expression. Carvedilol inhibited Kv4.3 channels at physiologically relevant concentrations, affecting both isoforms. Metoprolol showed a weaker blocking effect and bisoprolol did not exert an effect on Kv4.3. Blockade of repolarizing Kv4.3 channels by carvedilol and metoprolol extend their pharmacological mechanism of action, potentially contributing beneficial antiarrhythmic effects in normal and failing hearts.

Understanding the Position of Beta-blockers in the Management of Hypertension among Patients with Different Clinical Comorbidities: An Expert Opinion of Cardiologists from India

Abstract Background: Elevated blood pressure (BP) increases the risk of cardiovascular mortality, underscoring the vital importance of effective management in individuals with hypertension (HTN) and cardiovascular disease. However, lack of clear guidance on the utilization of the new beta-blockers has caused hesitation among doctors in using them effectively. The objective of this expert opinion was to understand the role and current position of beta-blockers in the management of patients with HTN and different clinical comorbidities. Methods: A collective of 828 cardiologists throughout India were invited to participate in an online survey and virtual meetings. Their clinical insights were gathered on approaches in managing these patients and their understanding of the role of beta-blockers. Results: The panel of experts recommended that in patients with HTN and angina, the BP target should be 130/80 mmHg (40.70%), and the use of a combination of telmisartan and cardio-selective beta-blockers should be used to lower BP (63.29%). A combination of telmisartan and a beta-1 blocker was recommended for effective BP control and structural regression of left ventricular hypertrophy (52.78%). For intensive BP control, combination therapy of telmisartan and beta-blockers should be used in patients with HTN and atrial fibrillation (59.18%). The panel of experts opined (60.02%) that different BP targets should be considered for different stroke subtypes. Telmisartan (44.44%) and selective beta-1 blockers (29.35%) are recommended to manage BP variability in patients with HTN and recurrent stroke. Conclusion: In patients with HTN and cardiovascular disease, individualized decision-making is necessary for beta-blocker use in HTN management. Selective beta-blockers should be considered first-line therapy or combined with telmisartan when indicated.

Mortality and ventricular arrhythmias in patients on d,l-sotalol for rhythm control of atrial fibrillation: A nationwide cohort study

Use of d,l-sotalol for rhythm control in patients with atrial fibrillation (AF) has raised safety concerns. Previous randomized studies are few and not designed for mortality outcome. The purpose of this study was to compare the incidences of mortality and ventricular arrhythmias in AF patients treated with d,l-sotalol for rhythm control vs matched control patients treated with cardioselective beta-blockers. This population-based cohort study included AF patients from the Swedish National Patient Registry (2006-2017) who underwent rhythm control after a second cardioversion. Incidence rates (IRs) and adjusted hazard ratios (aHRs) for mortality and a composite endpoint of cardiac arrest/death and ventricular arrhythmias were calculated for the overall cohort and a 1:1 propensity score matched cohort of d,l-sotalol vs beta-blocker treatment. Among patient treated with d,l-sotalol (n = 4987) and beta-blocker (n = 27,078) (mean follow-up 458 days), all-cause mortality was lower in patients treated with d,l-sotalol: IR 1.21; 95% confidence interval 0.95-1.52 vs 2.42 (2.26-2.60) deaths per 100 patient-years; aHR 0.66 (0.52-0.83). The difference in mortality persisted in the propensity score matched comparison (n = 4953 in each group): aHR 0.63 (0.48-0.86). No differences were observed in the composite outcome: IR in propensity cohorts 2.13 (1.78-2.52) vs 2.07 (1.73-2.53) events per 100 years; aHR 1.01 (0.78-1.29). There was no excess mortality with d,l-sotalol compared with cardioselective beta-blockers in patients undergoing rhythm control treatment for AF after a second cardioversion. Our results indicate that the risk associated with d,l-sotalol treatment for AF can be mitigated by careful patient selection and strict adherence to follow-up protocols.

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

BackgroundChronic 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...

IMPACT OF RENAL DENERVATION TREATMENT ON LEFT VENTRICLE REMODELING IN RESISTANT HYPERTENSIVE PATIENTS: THREE YEARS FOLLOW-UP

Objective: Evaluation of effects of RDN on left ventricle remodeling in patients with resistant hypertension and heart failure with preserved ejection fraction. Design and method: The study enrolled 125 hypertensive patients, who after 3-week of standardized treatment with Losartan, Amlodipine and Indapamide and confirmation of their drug resistance, were randomly assigned into three groups depending on medication supplemented to previously administered: group I - selective I1-imidazoline agonist Moxonidine, group II - cardioselective beta-blocker Bisoprolol and group III - renal denervation. All patients underwent a transthoracic echocardiogram at baseline, one, two and three years follow-up. Renal denervation was performed in the main renal arteries and their branches. Results: Transthoracic echocardiography at baseline revealed LV hypertrophy in all patients. The majority of patients in all three research groups had concentric hypertrophy (52% versus 60% and 56% in group I, II and III, respectively), the normal pattern not being recorded in any group. An authentic reduction in LV mass index was noted from 1-year follow-up in all three observational groups, the progressive reduction being maintained until the end of the study, the group of patients undergoing renal denervation manifested a net superior effect to both pharmacological groups. So, at 3-years follow-up LV mass index was 128,57±4,91 g/m2 in Moxonidine group versus 126,0±5,34 g/m2 in Bisoprolol group and 94,44±3,90 g/m2 in RDN group, p < 0.001. Analyzing the impact of various therapeutic regimes on the geometric pattern of the LV, we can note the fact that both treatment schemes with SNS blockers and RDN favored LV reverse remodeling, its normal pattern being regained by 5 (10%) patients from group I and 7 (28%) patients from group III. This time as well RDN demonstrated absolute superiority over both pharmacological treatment regimens (Figure 1). Conclusions: The obtained data confirm the benefit of RDN treatment on the reverse remodeling of the LV by significantly reduction in LV mass index and inducing the recovery of its normal physiological pattern in practically a third of treated patients at 3 years post-procedurally.

Comparing the Effectiveness of Propranolol versus Atenolol in Inducing Clinical Clearance in the Treatment of Infantile Haemangioma: A Randomised Controlled Trial.

Despite the excellent clinical efficacy of oral propranolol in the management of infantile haemangiomas (IHs), there is a need to further evaluate other beta blockers that may be equally efficacious but result in lesser adverse effects. We compared the efficacy and short-term safety of atenolol, a hydrophilic cardio-selective beta blocker, with propranolol, in the treatment of IHs. Sixty patients with complicated and/or cosmetically significant IHs were randomised into two groups, oral propranolol group (2 mg/kg/day) and the oral atenolol (1 mg/kg/day) group, respectively, for 9 months. Patients were assessed clinically, by the use of Doppler ultrasonography (USG) and measurement of serum hypoxia-inducible factor 1 alpha (HIF-1α). Twenty-two of 30 patients achieved complete clearance in the propranolol group (0.73; 95% CI = 0.54 to 0.87) compared with 13 of 25 patients in the atenolol group (0.52; 95% CI = 0.31 to 0.72). The mean time to achieve Physician Global Assessment Score 5 (PGA5) (25.00 ± 8.87 weeks) was significantly lesser in the propranolol group versus the atenolol group (31.69 ± 7.01 weeks; log-rank = 0.04). The two groups were comparable in terms of adverse effect profile, degree of volume reduction in USG and reduction in HIF-1α levels. Propranolol (2 mg/kg/day) is better than atenolol (1 mg/kg/day) in inducing complete clinical clearance of IH although the results need to be reproduced in larger studies.

Effect of Prunus Amagdalis (Almonds) on testosterone in Atenolol-induced derangements in the hormonal profile of male Balb-c mice

Background: Infertility is a very common health problem among middle-aged hypertensive individuals on beta-blocker therapy. With advancing research, it is observed that almonds can enhance the fertility index. Aim: To find that how almonds (prunus Amygdalus), cardioselective beta blocker and combined preparation of both these can affect serum testosteronein mice. Methods: This study was done in the Physiology Department, Shifa College of Medicine, Islamabad. Some part of this project was done inNational Institute of Health, Islamabad along with the Centre for Research in Experimental and Applied Medicine (CREAM) Laboratory, Army Medical College, Rawalpindi, and Shifa International Hospital, Islamabad. It was an Animal based experimental study. This study was conducted from December2014 to March 2015. 120 Balb-c mice were selected for our study according to the predefined setcriteria and four groups were made, each group consisting of 30 mice. Group A was the control group, atenolol was given to group B, almonds to group C, and atenolol plus almonds to group D. Serumtestosterone was measured after 3 months. Data was analyzed using SPSS version 17 and mean±standard deviation was determined. For difference, statistical significance was calculated after applying one way ANOVA. The p-value < 0.05 was considered significant. Results: In group A serving as control mean testosterone was found to be 1.58±0.69IU/L. Mean serum testosterone in B-group (Atenolol) was 0.43±0.27 IU/L. In group C (Almonds) it was 3.77±2.64 IU/Lwhich was significantly increased. In group D (almond+Atenolol) serum testosterone level was1.82±1.00 IU/L that is elevated but non-significantly in comparison to the control group. Conclusion: Almonds increase mean testosterone and atenolol lead to adecrease init. It is thus concluded that almondscan revert the changes induced by atenolol. Keywords: Almonds, Testosterone, Atenolol, Hypertension, Infertility.

Abstract 10954: Average Annual Out-of-Pocket Cost of Guideline Directed Medical Therapy for Heart Failure

Introduction: The 2022 multi-society heart failure guidelines underscore the importance of initiating and maintaining patients on Guideline Directed Medical Therapy (GDMT). Cost transparency plays a key role in the shared-decision making process, however, national estimates of out-of-pocket (OOP) cost for GDMT for Heart Failure (HF) are lacking Methods: Using data from the Medical Expenditure Panel Survey (MEPS) 2019, we estimated the average annual OOP cost for each GDMT drug class: cardio-selective Beta-Blockers (BB), Angiotensin-converting enzyme inhibitors (ACEi)/Angiotensin II receptor blockers (ARB)/Angiotensin Receptor-Neprilysin Inhibitor (ARNi), Mineralocorticoid Receptor Antagonists (MRA), and Sodium-glucose cotransporter-2 inhibitors (SGLT2i). We also estimated average annual OOP costs for recommended GDMT combinations: Quadruple therapy, quadruple with ARNI alone, and various combinations of triple therapy. Cost estimates were also stratified by insurance status. Results: Of 28,512 MEPS participants, we found 1,954 with a prescription for a BB, 3,642 with at least 1 script for an ACEi/ARB, 42 participants on ARNI, 280 with at least 1 script for an MRA, and 140 with at least 1 script for an SGLT2i. Average annual OOP costs for each GDMT drug class was: $41 (95%CI $34-$48) for BB, $29 (95%CI $26-$32) for ACEi/ARB, ARNi alone estimated at $192 (95%CI $111-$274), $32 (95%CI $25-$39) for MRA, and $151 (95%CI $110-$191) for SGLT2i. The average annual OOP cost for quadruple therapy in 2019 was $253, $292 for privately insured, $159 for those on public insurance, and $975 for the uninsured. Quadruple therapy with ARNI alone on average added ~$200 to the annual OOP cost. For triple therapies, a combination of MRA, BB, and ACEi/ARB was $282 less compared to a combination of BB, ARNI, and SGLT2i. Conclusions: The average annual OOP for GDMT was substantially mitigated by insurance coverage. Including estimates of GDMT cost and the protective role of health insurance coverage in the shared decision-making process might increase the proportion of heart failure patients initiated and maintained on GDMT.

Long-term antihypertensive effect of renal denervation in resistant hypertension: three years follow-up

Abstract Background Recent studies have shown proven efficacy of renal denervation in arterial hypertension, but there is a continuing need to assess the duration of antihypertensive effect. Purpose Evaluation of the long-term antihypertensive effect of renal denervation in patients with resistant hypertension. Methods 125 apparently resistant patients without comorbidities after a 3-week standardized treatment with Losartan 100 mg, Amlodipin 10 mg and Indapamid 1.5 mg and confirmation of their resistance were randomly assigned into three groups depending on treatment supplemented to previously administered: group I - selective I1-imidazoline agonist Moxonidine, group II - cardioselective beta-blocker Bisoprolol and group III – renal artery denervation. The compliance to treatment was confirmed using 8-item Morisky Medication Adherence Scale. Renal denervation was performed in the main renal arteries and their branches. Patients were assessed by ambulatory blood pressure monitoring at baseline, 3, 12, 24 and 36 months follow-up. Results The mean 24 hour systolic blood pressure (SBP) at baseline were 179.0±2.02 mmHg in group I versus 177.96±2.44 mmHg in group II and 176.92±1.97 mmHg in group III, p>0.05. A statistically significant reduction in SBP m/24 h was noted in all three groups starting at 3 months, the group of patients undergoing renal denervation showing superiority over both groups of pharmacological treatment: −6.48±0.81 mmHg in group I versus −6.2±0.88 mmHg in group II and −23.28±1.9 mmHg in group III, p<0.001. The progressive improvement continued until the end of the study, so at 3 years of evaluation in observational group supplemented with Moxonidine SBP m/24 h were 146.36±1.36 mmHg with a total reduction of −32.64±1.56 mmHg from baseline, in Bisoprolol group −152.88±1.56 mmHg with a reduction of −25.08±1.65 mmHg and 133.16±0.73 mmHg in renal denervation group with a total reduction of −282±1.30 mmHg in group III, p<0.001. The mean 24 hour diastolic blood pressure (DBP) increased at baseline in all three observational groups (105.52±1.28 mmHg in group I versus 108.6±1.6 mmHg in group II and 107.24±0.92 mmHg in group III, p>0.05) similar with SBP m/24 h noted an authentic reduction at 3 months follow-up. The maximum reduction in DBP m/24 h were registered at 3 years of evaluation, a comparative analyses of dynamics between groups showing a presence of statistical difference due to superiority of renal denervation in amelioration of this parameter: −18.36±1.88 mmHg in group I versus −16.84±1.76 mmHg in group II and −28.2±1.30 mmHg in group III, p<0.001. Conclusions All three regimens have been shown to be effective in reducing SBP and DBP m/24 h in patients with resistant hypertension, with a superior but comparable effect of Moxonidine to Bisoprolol and the absolute superiority of renal denervation treatment, the beneficial effect being maintained for a period of 3 years. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Agency for Research and Development

Short acting intravenous beta-blocker as a first line of treatment for atrial fibrillation after cardiac surgery: a prospective observational study.

Post-operative atrial fibrillation (POAF) defined as a new-onset of atrial fibrillation (AF) following surgery occurs frequently after cardiac surgery. For non-symptomatic patients, rate control strategy seems to be as effective as rhythm control one in surgical patients. Landiolol is a new highly cardio-selective beta-blocker agent with interesting pharmacological properties that may have some interest in this clinical situation. This is a prospective, monocentric, observational study. All consecutive adult patients (age >18 years old) admitted in the intensive care unit following cardiac surgery with a diagnosed episode of AF were eligible. Success of landiolol administration was defined by a definitive rate control from the beginning of infusion to the 72th h. We also evaluated rhythm control following landiolol infusion. Safety analysis was focused on haemodynamic, renal and respiratory side effects. From 1 January 2020 to 30 June 2021, we included 54 consecutive patients. A sustainable rate control was obtained for 49 patients (90.7%). Median time until a sustainable rate control was 4 h (1, 22). Median infusion rate of landiolol needed for a sustainable rate control was 10 µg/kg/min (6, 19). Following landiolol infusion, median time until pharmacological cardioversion was 24 h. During landiolol infusion, maintenance of mean arterial pressure target requires a concomitant very low dose of norepinephrine. We did not find any other side effects. Low dose of landiolol used for POAF treatment was effective and safe for a rapid and sustainable rate and rhythm control after cardiac surgery.

CONCOMITANT USE OF SULFONYLUREAS AND BETA-BLOCKERS AND THE RISK OF SEVERE HYPOGLYCEMIA: POPULATION-BASED COHORT STUDY

Objective: Evidence suggests that beta-blockers increase the risk of hypoglycemia. However, their effects among users of sulfonylureas, drugs that also cause hypoglycemia, are not well understood. Thus, our study assessed the potential association between concomitant use of sulfonylureas and beta-blockers and the risk of severe hypoglycemia. Design and method: This retrospective cohort study used the United Kingdom Clinical Practice Research Datalink linked to hospitalization and vital statistics data. It included patients with type 2 diabetes initiating sulfonylurea treatment between 1998 and 2020. Patients with use of beta-blockers in the 6 months prior to cohort entry were excluded. Time-dependent Cox proportional hazards models estimated confounder-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of severe hypoglycemia associated with concomitant use of sulfonylureas and beta-blockers compared to sulfonylurea use alone. To account for residual confounding, we also performed an analysis using an active comparator, where the reference category was current concomitant use of sulfonylureas and thiazide diuretics. To explore the role of cardioselectivity in the hypoglycemic risk of beta-blockers, we further compared head-to-head current concomitant use of sulfonylureas and non-cardioselective beta-blockers (i.e., propranolol, carvedilol, sotalol, labetalol) versus current concomitant use of sulfonylureas and cardioselective beta-blockers (i.e., acebutolol, atenolol, bisoprolol, metoprolol, nebivolol, esmolol). Results: Our cohort included 252,869 patients initiating sulfonylureas. During a mean (standard deviation) follow-up of 8.6 (5.7) years, there were 16,857 events of severe hypoglycemia (crude incidence rate, 7.8 [95% CI, 7.6–7.9] per 1000 person-years). Compared to sulfonylurea use alone, concomitant use of sulfonylureas and beta-blockers was associated with a 53% increased risk of severe hypoglycemia (adjusted HR, 1.53; 95% CI, 1.42–1.65). The use of an active comparator led to consistent findings (adjusted HR, 1.69; 95% CI, 1.42–2.01). When comparing concomitant use of sulfonylureas and non-cardioselective beta-blockers to concomitant use of sulfonylureas and cardioselective beta-blockers, we were not able to detect an increased risk of severe hypoglycemia (adjusted HR, 0.95; 95% CI, 0.74–1.24). Conclusions: Our population-based study showed an increased risk of severe hypoglycemia associated with concomitant use of sulfonylureas and beta-blockers. Cardioselectivity of beta-blockers did not seem to play a major role in this regard.

1135-P: Concomitant Use of Sulfonylureas and Beta-Blockers and the Risk of Severe Hypoglycemia: A Population-Based Cohort Study

Background: Beta-blockers may interact with sulfonylureas (SU) and increase their hypoglycemic risk. Our study assessed the potential association between concomitant use of SU and beta-blockers and the risk of severe hypoglycemia. Methods: We used the UK's Clinical Practice Research Datalink linked to hospitalization and vital statistics data of patients with type 2 diabetes initiating SU between 1998 and 2020, excluding those with beta-blocker use in the past 6 months. Time-dependent Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of severe hypoglycemia associated with current concomitant use of SU and beta-blockers compared to current SU use alone, adjusted for baseline confounders. To address potential residual confounding, we repeated the analysis with current concomitant use of SU and thiazide diuretics as reference group. We also compared current concomitant use of SU and non-cardioselective (propranolol, carvedilol, sotalol, labetalol) vs. cardioselective beta-blockers (acebutolol, atenolol, bisoprolol, metoprolol, nebivolol, esmolol) to explore the role of beta-blocker cardioselectivity in this association. Results: Our cohort included 252,869 SU initiators. The crude incidence rate of severe hypoglycemia was 7.8 per 1000/year. Concomitant use of SU and beta-blockers was associated with an increased risk of severe hypoglycemia compared to SU use alone (HR, 1.53; 95% CI, 1.42-1.65) . Changing the reference group led to consistent findings (HR, 1.69; 95% CI, 1.42-2.01) . There was no difference in the risk when comparing concomitant use of SU and non-cardioselective beta-blockers to concomitant use of SU and cardioselective beta-blockers (HR, 0.95; 95% CI, 0.74-1.24) . Conclusion: Our large cohort study showed an increased risk of severe hypoglycemia associated with concomitant use of SU and beta-blockers compared to SU use alone. This association did not vary with beta-blocker cardioselectivity. Disclosure J.Dimakos: None. Y.Cui: None. R.W.Platt: Consultant; Amgen Inc., Biogen, Merck & Co., Inc., Nant Pharma, Pfizer Inc. C.Renoux: None. K.B.Filion: None. A.Douros: None. Funding Canadian Institutes of Health Research (PJT-165882)

Effects of Beta‐Blockers on Thermal and Cardiovascular Strain of Adults With Coronary Artery Disease During Extreme Heat Events

IntroductionExtreme heat is associated with a greater risk of adverse cardiovascular events, especially in people with cardiovascular disease. Many patients with cardiovascular disease are prescribed beta‐blockers. Some research suggests that in young healthy adults, cardio‐selective beta‐blockers may alter heat loss capacity. However, the effects of beta‐blockers on temperature regulation in older adults during an extreme heat event are unknown. The objective of this study was to compare thermal and cardiovascular responses during simulated extreme heat events between older adults with coronary artery disease (CAD) who use and do not use beta‐blockers. It was hypothesised that the increase in heart rate and skin blood flow would be smaller in CAD patients who use beta‐blockers compared to those who do not use beta‐blockers.Method25 older adults (23 males/2 females) with stable CAD, 18 taking cardio‐selective beta‐blockers (BB: 66±8 y; 85.7±13.3 kg; 28.0±4.6 kg/m2) and 7 not taking beta‐blockers (NBB: 66±7 y; 77.1±14.6 kg; 26.1±3.9 kg/m2), were exposed to two 3‐hour simulated extreme heat events; one hot and humid (38°C, 60% relative humidity) and one hot and dry (45°C, 10% relative humidity). Rectal and mean skin temperatures, heart rate, and skin blood flow were continuously recorded. Whole body sweat losses were calculated from changes in nude body weight.ResultsAt the end of the 3‐h hot and humid heat exposure, relative to pre‐exposure baseline the change in heart rate (BB: +7±5 bpm; NBB: +11±9 bpm, p=0.20), rectal (BB: +0.57±0.27°C; NBB: +0.60±0.31°C, p=0.76) and mean skin (BB: +5.1±1.2°C; NBB: +5.1±1.1°C, P=0.91) temperatures, and whole body sweat losses (BB: 771±480 g; NBB: 798±172 g, p=0.88) did not differ between groups. The change in skin blood flow from baseline was greater in the NBB (+32±23 arbitrary units) compared to the BB (+9±7 arbitrary units; p=0.01) group. At the end of the 3‐h hot and dry heat exposure, the increase in heart rate (BB: +9±8 bpm; NBB: +9±5 bpm, p=0.93), rectal (BB: +0.61±0.40°C; NBB: +0.62±0.22°C, p=0.91) and mean skin (BB: +5.9±0.9°C; NBB: +5.7±1.3°C; p=0.79) temperatures, whole body sweat losses (BB: 1252±174 g; NBB: 1207±169, p=0.56) and skin blood flow (BB: +26±22 arbitrary units; NBB: +26±39 arbitrary units; p=0.98) from baseline did not differ between groups.ConclusionOur preliminary evidence indicates that cardio‐selective beta‐blocker use does not alter thermal or cardiovascular strain in adults with stable coronary artery disease during simulated hot and humid or hot and dry extreme heat events.

Clinical study evaluating β-blockers use and fracture risk in patients with primary osteoporosis Running title

Background and objectives: In osteoporosis, low bone mass and growing fragility are main symptoms. BB users had greater BMD and/or decreased fracture risk, according to observational studies. Other studies found no effect of BB on fracture risk and osteoporosis disease. In this study, the effect of selective and non-selective BB on fracture risk in osteoporotic individuals was studied. Methods: A total of fifty osteoporotic patients of both genders were included in this randomized controlled, parallel, and prospective trial. Osteoporotic subjects were divided into three groups: a control group (CG), a non-selective beta-blocker group (NSBB), and a cardio-selective beta-blocker group (CSBB). T-score, fracture risk (FR), bone mineral density (BMD), and bone turnover markers were studied as a result of this investigation. Results: After six months of follow-up, it was discovered that the T-score mean values of the three groups varied significantly. BMD was significantly higher in the group receiving non-selective beta-blockers (NSBB) than in the control group (CG). In the three categories of fracture risk region, the fracture risk was statistically decreased in both the NSBB and CSBB groups. Additionally, both the NSBB and CSBB groups demonstrated a decrease in bone turnover markers (BTM), as contrasted to the control group.

IDF21-0398 Arterial Hypertension and Type 2 Diabetes Mellitus. Have we achieved the goals in patients treated by specialists?

Background: In patients with Type 2 Diabetes (DT2), arterial hypertension (HTN) is twice more frequent. Coexistence of HTN and DT2 increases the risk of coronary artery disease (CAD), heart failure (HF), cerebrovascular accident (CVA), cardiovascular disease mortality (CVD), and the risk of nephropathy, retinopathy and neuropathy. Blood pressure (BP) control reduces the rate of DT2 complications. Objectives: Quantify the frequency of HTN in patients with DT2 in Argentina. Know the rate that achieves the BP goal and identify the factors related to higher and lower levels of the goal. Determine therapeutic tools and adherence to treatment. Materials and Method: A descriptive, observational, cross-sectional, multicenter study was designed in 28 centers in Argentina specialized in Diabetes (FRADYC III Group). Patients older than 18 years with DT2 were included. Medical history, clinical examination, laboratory, complications, cardiovascular risk factors and HTN medication were considered. BP target was < 140/90 mmHg. Morisky-Green-Levine test was used to evaluate adherence and the WHO 5 test for quality of life (low well-being less than 50 points). STATA intercooler software. Results: In 1329 patients with DT2, women 46.6%, mean age 61.7 ± 11.6 years, with mean HbA1c 7.0 ± 1.4%, age of DM2 9.6 ± 7.4 years, BMI 31.7 ± 5.7 kg/m2, with waist circumference (WC) > 88 cm in women and > 102 cm in men 76.7%, HTN 81%, during 12.7 ± 9.4 yrs, dyslipidemia (DLP) 81.4%, CVD 37.2%, neuropathy 19%, nephropathy 12.6%, retinopathy 10%, depression 11.7%, smoked 11.6% and physical activity ≥ 150 minutes/week 29.8%. Adherence to treatment was 68.37%, with low well-being 21%. Treatment of HTN: no drugs 9.9%, 1 drug 42.9%, 2 drugs 29.6%, and 3 or more drugs 14.2%. HTN drugs were: ARA II 35%, ACEI 31.9%, cardioselective beta-blockers 19.5%, amlodipine 14.6%, thiazides 12.7%, non-cardioselective beta-blocker 6%, loop diuretics 3.2%, indapamide 2%, spironolactone 1.7%, nifedipine 0.9%. The goal was achieved by 62.4% of DT2 with HTN with no differences by age or gender. The older, more than 65 years (p = 0.0001) the greater the adherence to treatment. Reaching the goal was associated with less HTN time (p = 0.0091), higher education (p = 0.0001), private insurance (p = 0.0001), physical activity (p = 0.028), no nephropathy (p = 0.010), and no neuropathy (p = 0.023). Lower achievement no HTN drugs (p = 0.0001) and low well-being (p = 0.027). Multiple logistic regression: reaching the goal was associated with no cardiometabolic risk waist (OR: 0.67, p = 0.021), no nephropathy (OR: 0.69, p = 0.045), and private insurance (OR: 1.9, p = 0.0001). Conclusions: In this study, 81% of DT2 patients had HTN, well controlled in 62.4%. Higher education, physical activity, private insurance, and HTN drug treatment were associated with BP goal, while abdominal obesity, nephropathy, no health insurance, not taking HTN medications and less well-being had a negative association. The youngest, despite less adherent and with shorter HTN time, reached the goal with the same statistical significance as the older ones. We should assess welI-being and optimize adherence in the youngest.

Relationships Between Bronchodilators, Steroids, Antiarrhythmic Drugs, Antidepressants, and Benzodiazepines and Heart Disease and Ischemic Stroke in Patients With Predominant Bronchiectasis and Asthma.

ObjectiveWe investigated the effects of medication on heart disease and ischemic stroke (HDS) risk in patients with predominant bronchiectasis-asthma combination (BCAS).MethodsBCAS and non-BCAS cohorts (N = 588 and 1,118, respectively) were retrospectively enrolled. The cumulative incidence of HDS was analyzed using Cox proportional regression; propensity scores were estimated using non-parsimonious multivariable logistic regression. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for HDS were calculated, adjusting for sex, age, comorbidities, and medication {long- and short-acting β2 agonists and muscarinic antagonists (LABAs/SABAs and LAMAs/SAMAs), steroids [inhaled corticosteroid steroids (ICSs), oral steroids (OSs)], antiarrhythmics, antidepressants (fluoxetine), benzodiazepines (alprazolam, fludiazepam), statins and antihypertensive drugs (diuretics, cardioselective beta blockers, calcium channel blockers (CCBs) and angiotensin converting enzyme inhibitors (ACEi), angiotensin II blockers)}.ResultsCompared with the non-BCAS cohort, the BCAS cohort taking LABAs, SABAs, SAMAs, ICSs, OSs, antiarrhythmics, and alprazolam had an elevated HDS risk [aHRs (95% CIs): 2.36 (1.25–4.33), 2.65 (1.87–3.75), 2.66 (1.74–4.05), 2.53 (1.61–3.99), 1.76 (1.43–2.18), 9.88 (3.27–30.5), and 1.73 (1.15–2.58), respectively except fludiazepam 1.33 (0.73–2.40)]. The aHRs (95% CIs) for LABAs ≤ 30 days, DDDs <415, ICSs ≤ 30 days were 1.10 (0.38–3.15), 2.95 (0.22–38.8), 1.45 (0.76–2.77). The aHRs (95% CIs) for current and recent alprazolam were 1.78 (1.09–2.93) and 777.8 (1.34–451590.0); for current and past fludiazepam were 1.39 (0.75–2.59) and 1.29 (0.42–4.01) and for past alprazolam was 1.57 (0.55–4.46); respectively. The aHRs (95% CIs) for alprazolam >30 DDDs, fludiazepam >20 DDDs, ICSs ≦415 DDDs, and OSs DDDs ≦15 were 1.60 (0.78–3.29), 2.43 (0.90–6.55), 5.02 (1.76–14.3), and 2.28 (1.43–3.62), respectively.ConclusionThe bronchodilators, steroids, and antiarrhythmics were associated with higher risk of HDS, even low dose use of steroids. However, the current use of LABAs/ICSs were not associated with HDS. Benzodiazepines were relatively safe, except for current or recent alprazolam use. Notably, taking confounders into account is crucial in observational studies.

Outcomes of beta blockers (BB) in hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICIs).

399 Background: Portal hypertension increases intestinal permeability, dysbiosis, and bacterial translocation, leading to a pro-inflammatory state, which can in turn promote progression of liver disease. However, multiple studies have shown that BB use in patients with cirrhosis can reduce the risk of developing HCC, and in patients with HCC, BB can improve overall survival (OS). In recent years, ICIs have become first-line therapy for patients with unresectable HCC, and we aimed to evaluate whether BB use conferred survival benefits in patients treated with ICIs using real-world data. Methods: We conducted a retrospective chart review of HCC patients treated with ICI from 2017 to 2019 at 13 institutions across North America, Europe, and Asia in order to evaluate the association between BB use and OS, as well as BB use and overall response rate (ORR). Univariable and multivariable logistic regression models were used to evaluate associations, and survival analyses were performed using the Kaplan-Meier method. Results: A total of 578 patients were evaluated. The median age of the cohort was 65 years, and 80% of patients were male. The majority of patients (70%) were cirrhotic. The causes of underlying liver disease were as follows: HBV (22%), HCV (36%), alcohol (20.8%), and NASH (13%). Most patients (73.5%) had Child Pugh (CP) class A liver disease, and good performance status with ECOG score either 0 (52%) or 1 (45%). The majority of patients (75%) treated with ICIs received a PD-1 inhibitor alone. There were 360 deaths (62% of patients) with a median follow-up of 30.8 months (Quartiles: 17.2-40.3 months). Two hundred and three (35%) patients had BB use at any point during ICI therapy. Fifty-one percent of these patients were on a nonselective BB whereas 49% were taking a cardio-selective BB. BB use was not significantly correlated with OS (hazard ratio, 1.12; 95% CI, 0.9-1.39; P = 0.298) or ORR (odds ratio, 0.84; 95% CI, 0.54-1.31; P = 0.451) in univariate or multivariate analyses. Conclusions: Patients who used BB while on immunotherapy for unresectable HCC did not have statistically significant differences in OS or ORR compared to patients who did not use BB. More studies are required to elucidate the effect of beta blockade on the microbiome, immune activation, and HCC.