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Optimal use of guideline-directed medical therapy (GDMT) can prevent hospitalization and mortality among patients with heart failure (HF). We aimed to assess the prevalence of GDMT use for HF across geographic regions and country-income levels. We systematically reviewed observational studies (published between January 2010 and October 2020) involving patients with HF with reduced ejection fraction. We conducted random-effects meta-analyses to obtain summary estimates. We included 334 studies comprising 1,507,849 patients (31% female). The majority (82%) of studies were from high-income countries, with Europe (45%) and the Americas (33%) being the most represented regions, and Africa (1%) being the least. Overall prevalence of GDMT use was 80% (95% CI 78%-81%) for ß-blockers, 82% (80%-83%) for renin-angiotensin-system inhibitors, and 41% (39%-43%) for mineralocorticoid receptor antagonists. We observed an exponential increase in GDMT use over time after adjusting for country-income levels (p < 0.0001), but significant gaps persist in low- and middle-income countries. Multi-level interventions are needed to address health-system, provider, and patient-level barriers to GDMT use.

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For decades beta-blockers are a heterogenous group of drugs with diverse pharmacological properties, used in the treatment of high blood pressure. However, their benefit as therapy for hypertension without concomitant compelling indications is controversial. In this article we will discuss the concept of sympathetic overdrive and the theoretical rationale of the use of beta-blockers as antihypertensive drugs. The differences between beta-blockers' generations in terms of anti-hypertensive efficacy and side effects are discussed. Finally, we review the position of the last European guidelines published in 2023 about beta-blockers in the management of arterial hypertension.

Depuis des décennies, les bêtabloquants (BB) sont une gamme hétérogène de médicaments aux propriétés pharmacologiques diverses, utilisés dans le traitement de l'hypertension artérielle (HTA). Cependant, leur bénéfice, en tant que traitement de l'HTA en l'absence d'autre indication absolue à leur emploi, est controversé. Dans cet article, nous abordons le concept d'hyperactivité sympathique et la justification théorique de l'utilisation des BB comme médicaments antihypertenseurs. Les différences entre les générations de BB en termes d'efficacité antihypertensive et d'effets secondaires sont abordées. Enfin, nous revenons sur la position des dernières recommandations européennes publiées en 2023 sur les BB dans la prise en charge de l'hypertension artérielle.

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PURPOSE: The aim of this study was to describe a population of very old people with heart failure (HF), to analyse the use of cardiovascular drugs over time, and to explore factors influencing cardiovascular drug treatment for this group. METHODS: All participants with information regarding HF diagnosis were selected from the Umeå 85+/Gerontological Regional Database (GERDA). The people in GERDA are all ≥85 years old. Trained investigators performed structured interviews and assessments. Information regarding medications and diagnoses was obtained from the participants and from medical records. Medical diagnoses were reviewed and confirmed by an experienced geriatrician. RESULTS: In this very old population, the prevalence of HF was 29.6% among women and 30.7% among men. Between 2000 and 2017, there was an increase in the use of renin-angiotensin (RAS) inhibitors (odds ratio [OR] 1.107, 95% confidence interval [CI] 1.072-1.144) and beta-blockers (BBs) (OR 1.123, 95% CI 1.086-1.161) among persons with HF, whereas the prevalence of loop diuretics (OR 0.899, 95% CI 0.868-0.931) and digitalis (OR 0.864, 95% CI 0.828-0.901) decreased (p < 0.001 for all drug classes). Higher age was associated with lower use of RAS inhibitors and BBs. CONCLUSION: In this HF population, the use of evidence-based medications for HF increased over time. This may be a sign of better awareness among prescribers regarding the under-prescribing of guidelines-recommended treatment to old people. Higher age associated with a lower prevalence of RAS inhibitors and BBs. This might indicate that further improvement is possible but could also represent a more cautious prescribing among frail very old individuals.

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The autonomic nervous system plays a key role in maintaining body hemostasis through both the sympathetic and parasympathetic nervous systems. Sympathetic overstimulation as a reflex to multiple pathologies, such as septic shock, brain injury, cardiogenic shock, and cardiac arrest, could be harmful and lead to autonomic and immunologic dysfunction. The continuous stimulation of the beta receptors on immune cells has an inhibitory effect on these cells and may lead to immunologic dysfunction through enhancing the production of anti-inflammatory cytokines, such as interleukin-10 (IL-10), and inhibiting the production of pro-inflammatory factors, such as interleukin-1B IL-1B and tissue necrotizing factor-alpha (TNF-alpha). Sympathetic overstimulation-induced autonomic dysfunction may also happen due to adrenergic receptor insensitivity or downregulation. Administering anti-adrenergic medication, such as beta-blockers, is a promising treatment to compensate against the undesired effects of adrenergic surge. Despite many misconceptions about beta-blockers, beta-blockers have shown a promising effect in decreasing mortality in patients with critical illness. In this review, we summarize the recently published articles that have discussed using beta-blockers as a promising treatment to decrease mortality in critically ill patients, such as patients with septic shock, traumatic brain injury, cardiogenic shock, acute decompensated heart failure, and electrical storm. We also discuss the potential pathophysiology of beta-blockers in various types of critical illness. More clinical trials are encouraged to evaluate the safety and effectiveness of beta-blockers in improving mortality among critically ill patients.

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OBJECTIVES: This study is aimed to compare the effectiveness of modern therapy including angiotensin receptor-neprilysin inhibitor (ARNI) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) with conventional heart failure treatment in the real world. BACKGROUND: Since ARNI and SGLT2i were introduced to treat heart failure (HF), its therapeutic regimen has modernized from previous treatment with beta-blocker (BB) and angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB) with mineralocorticoid receptor antagonist (MRA) as added-on in HF with reduced ejection fraction (HFrEF). However, a comparison between conventional and modern treatment strategies with drugs in combination has not been performed. METHODS: This observational study (2013-2020), using the Swedish HF Registry, involved 20,849 HF patients. Patients received either conventional (BB, ACEi/ARB, with/without MRA, n = 20,140) or modern (BB, ACEi/ARB, MRA, SGLT2i or BB, ARNI, MRA with/without SGLT2i, n = 709) treatment at the index visit. The endpoints were all-cause and cardiovascular (CV) mortality. RESULTS: Modern HF therapy was associated with a significant 28% reduction in all-cause mortality (adjusted HR [aHR], 0.72 (0.54-0.96); p = 0.024) and a significant 62% reduction in CV mortality (aHR, 0.38 (0.21-0.68); p = 0.0013) compared to conventional HF treatment. Similar results emerged in a sensitivity analysis using propensity score matching. The interaction analyses did not reveal any trends for EF (< 40% and ≥ 40%), sex, age (< 70 and ≥ 70 years), eGFR (< 60 and ≥ 60 ml/min/1.73 m2), and etiology of HF subgroups. CONCLUSION: In this nationwide study, modern HF therapy was associated with significantly reduced all-cause and CV mortality, regardless of EF, sex, age, eGFR, and etiology of HF.

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SOURCE CITATION: Yndigegn T, Lindahl B, Mars K, et al; REDUCE-AMI Investigators. Beta-blockers after myocardial infarction and preserved ejection fraction. N Engl J Med. 2024;390:1372-1381. 38587241.

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BACKGROUND: Premature ventricular contractions (PVCs) are common arrhythmias with diverse clinical implications. This retrospective study aimed to evaluate the efficacy of medical treatments using various clinical, imaging, and electrocardiographic parameters in patients with idiopathic PVCs. METHODS: A total of 1051 patients with idiopathic PVCs were retrospectively analyzed. Patients were categorized into three groups based on treatment response: beta-blocker (BB) responders (479 patients), calcium-channel blocker (CCB) responders (335 patients), and class 1c antiarrhythmic (AA) responders (237 patients). Clinical, imaging, and electrocardiographic data were collected and analyzed to assess the factors influencing treatment response. RESULTS: Age, left ventricular ejection fraction (LVEF), PVC QRS duration, CI variability, and multiple PVC morphologies were identified as significant factors affecting treatment response. Older age and lower LVEF were associated with better response to BB treatment, whereas CCB responders showed narrower QRS complexes. BB responders also exhibited higher CI variability, possibly linked to automaticity mechanisms. Moreover, the BB responder group had a higher frequency of multiple PVC morphologies. CONCLUSION: These findings emphasize the importance of tailored treatment approaches based on individual patient characteristics.

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Background: Depression ranks as a leading contributor to the global disease burden. The potential causal relationship between the use of antihypertensive medications and depression has garnered significant interest. Despite extensive investigation, the nature of this relationship remains a subject of ongoing debate. Therefore, this study aims to evaluate the influence of antihypertensive medications on depression by conducting a Mendelian randomization study focused on drug targets. Method: We focused on the targets of five antihypertensive drug categories: ACE Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), Calcium Channel Blockers (CCBs), Beta-Blockers (BBs), and Thiazide Diuretics (TDs). We collected single-nucleotide polymorphisms (SNPs) associated with these drug targets from genome-wide association study (GWAS) statistics, using them as proxies for the drugs. Subsequently, we conducted a Mendelian randomization (MR) analysis targeting these drugs to explore their potential impact on depression. Results: Our findings revealed that genetic proxies for Beta-Blockers (BBs) were associated with an elevated risk of depression (OR [95%CI] = 1.027 [1.013, 1.040], p < 0.001). Similarly, genetic proxies for Calcium Channel Blockers (CCBs) were linked to an increased risk of depression (OR [95%CI] = 1.030 [1.009, 1.051], p = 0.006). No significant associations were identified between the genetic markers of other antihypertensive medications and depression risk. Conclusion: The study suggests that genetic proxies associated with Beta-Blockers (BBs) and Calcium Channel Blockers (CCBs) could potentially elevate the risk of depression among patients. These findings underscore the importance of considering genetic predispositions when prescribing these medications, offering a strategic approach to preventing depression in susceptible individuals.

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This is an interim analysis of the Beta-blocker (Propranolol) use in traumatic brain injury (TBI) based on the high-sensitive troponin status (BBTBBT) study. The BBTBBT is an ongoing double-blind placebo-controlled randomized clinical trial with a target sample size of 771 patients with TBI. We sought, after attaining 50% of the sample size, to explore the impact of early administration of beta-blockers (BBs) on the adrenergic surge, pro-inflammatory cytokines, and the TBI biomarkers linked to the status of high-sensitivity troponin T (HsTnT). Patients were stratified based on the severity of TBI using the Glasgow coma scale (GCS) and HsTnT status (positive vs negative) before randomization. Patients with positive HsTnT (non-randomized) received propranolol (Group-1; n = 110), and those with negative test were randomized to receive propranolol (Group-2; n = 129) or placebo (Group-3; n = 111). Propranolol was administered within 24 h of injury for 6 days, guided by the heart rate (> 60 bpm), systolic blood pressure (≥ 100 mmHg), or mean arterial pressure (> 70 mmHg). Luminex and ELISA-based immunoassays were used to quantify the serum levels of pro-inflammatory cytokines (Interleukin (IL)-1ß, IL-6, IL-8, and IL-18), TBI biomarkers [S100B, Neuron-Specific Enolase (NSE), and epinephrine]. Three hundred and fifty patients with comparable age (mean 34.8 ± 9.9 years) and gender were enrolled in the interim analysis. Group 1 had significantly higher baseline levels of IL-6, IL-1B, S100B, lactate, and base deficit than the randomized groups (p = 0.001). Group 1 showed a significant temporal reduction in serum IL-6, IL-1ß, epinephrine, and NSE levels from baseline to 48 h post-injury (p = 0.001). Patients with severe head injuries had higher baseline levels of IL-6, IL-1B, S100B, and HsTnT than mild and moderate TBI (p = 0.01). HsTnT levels significantly correlated with the Injury Severity Score (ISS) (r = 0.275, p = 0.001), GCS (r = - 0.125, p = 0.02), and serum S100B (r = 0.205, p = 0.001). Early Propranolol administration showed a significant reduction in cytokine levels and TBI biomarkers from baseline to 48 h post-injury, particularly among patients with positive HsTnT, indicating the potential role in modulating inflammation post-TBI.Trial registration: ClinicalTrials.gov NCT04508244. It was registered first on 11/08/2020. Recruitment started on 29 December 2020 and is ongoing. The study was partly presented at the 23rd European Congress of Trauma and Emergency Surgery (ECTES), April 28-30, 2024, in Estoril, Lisbon, Portugal.

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Background: Thyrotoxic periodic paralysis is a rare and serious complication of hyperthyroidism. Case presentation: A man in his thirties of Asian descent, with non-compliant Graves' disease, presented with extremity paresis. Emergency blood tests revealed severe hypokalaemia, leading to a diagnosis of thyrotoxic periodic paralysis. The combination of uncontrolled hyperthyroidism, Asian ethnicity, paralysis, and severe hypokalaemia without other causes defined the diagnosis. Acute treatment involves non-selective beta-blockers, addressing hyperthyroidism, and potassium supplements. Interpretation: Swift recognition of thyrotoxic periodic paralysis is crucial for timely and life-saving treatment. If triggered by hyperthyroidism, as in Graves' disease, surgery or radioiodine is strongly indicated for definitive treatment. It is noteworthy that euthyroid patients cannot develop thyrotoxic periodic paralysis.

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PURPOSE: This study aimed to investigate the prescription of beta-blockers (ß-blockers) for patients with asthma. METHODS: In this retrospective cross-sectional study using the National Patient Sample (NPS) of the Health Insurance Review and Assessment Service (HIRA) of South Korea, ß-blockers and asthma medications were investigated using generic name codes provided by HIRA. Concomitant administration was identified when a ß-blocker and an asthma medication were co-prescribed in one billing statement or when separate ß-blocker and asthma prescriptions had overlapping dates of use. RESULTS: In the 1027 patients with asthma who were prescribed non-selective ß-blockers (non-SBs), 3087 non-SB prescriptions were identified, of which 62.3% and 37.3% were for carvedilol and propranolol, respectively. Of the 906 patients with asthma prescribed selective ß-blockers (SBs), 2942 SB prescriptions were identified, of which 48.5%, 28.3%, and 20.3% were for bisoprolol, atenolol, and nebivolol, respectively. Overall, 2149 non-SB and 2124 SB prescriptions with overlapping use dates with asthma medications were identified, which were prescribed to 726 and 657 patients, accounting for 70.7% and 72.5% of the patients receiving non-SBs and SBs, respectively. ß2-agonists accounted for 39.9% of the concomitant asthma medications with overlapping dates of use with non-SBs. Co-prescribing of bronchodilators occurred at a rate of 38.7% and 45.1% for the 3087 non-SB prescriptions and 2942 SB prescriptions, respectively. CONCLUSIONS: Carvedilol and propranolol accounted for half of all ß-blockers prescribed to asthma patients. Prescribing ß-blockers to patients with asthma requires caution to prevent exacerbation of asthma and drug interactions between ß-blockers and co-prescribed asthma medications.

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BACKGROUND: Social Anxiety Disorder (SAD) is an anxiety disorder characterized by excessive fear of scrutiny in social situations. Health students are more susceptible to SAD due to academic demands. They may resort to self-medication, particularly beta-blockers (BBs) for managing physical symptoms of SAD. The study aims to investigate the prevalence of beta-blocker use and its relationship with social anxiety disorder among health students at Umm Al-Qura University. METHODS: In this cross-sectional study, 461 undergraduate health students participated in a questionnaire with 30 questions divided into three sections: The Social Phobia Inventory (SPIN), BBs usage behavior questionnaire, and demographic characteristics. RESULTS: The study found 56.2% had SAD. A total of 7.8% of the sample reported using BBs, and no significant correlation was found between the usage of BBs and the SAD score (P = 0.085). CONCLUSION: The study revealed significant relationships between the presence of SAD with gender, history of mental conditions, and correlation between the use of BBs with history of mental conditions. Although BBs usage is low among health students, the prevalence of SAD is alarming. The results could raise awareness about the need for early detection of SAD among health students.

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Heart failure with reduced ejection fraction (HFrEF) is a commonly seen clinical entity in the family physician's practice. This clinical review focuses on the pharmacologic management of chronic HFrEF. Special attention is paid to the classification of heart failure and the newest recommendations from the American Heart Association concerning the use of guideline-directed medical therapy. ß blockers, ACE inhibitors, ARBs, mineralocorticoid receptor antagonists are discussed in detail. The new emphasis on sacubitril-valsartan and SGLT2i's as therapies for HFrEF are reviewed, followed by a brief discussion of more advanced therapies and comorbidity management.

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OBJECTIVES: To determine the prevalence of heart failure (HF) medication prescribing on discharge post-HF-related admission. METHODS: A retrospective audit was conducted for 216 HF admissions over a period of 6 months; medication data from electronic records were collected for analysis. KEY FINDINGS: The prevalence of HF medication prescribing on discharge was: 32.9% (95% confidence interval: 26.6-39.6) renin-angiotensin-aldosterone system inhibitors, 10.6% (6.9-15.6) angiotensin receptor-neprilysin inhibitors, 31.5% (25.4-38.1) HF-specific beta-blockers, 42.6% (35.9-49.5) aldosterone receptor antagonists, and 11.6% (7.6-16.6) sodium-glucose cotransporter-2 inhibitors. CONCLUSION: HF medication prescribing remains relatively low despite the known benefits and recommendations listed in the guidelines.

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Heart failure (HF) is a systemic disease associated with a high risk of morbidity, mortality, increased risk of hospitalizations, and low quality of life. Therefore, effective, systemic treatment strategies are necessary to mitigate these risks. In this manuscript, we emphasize the concept of high-intensity care to optimize guideline-directed medical therapy (GDMT) in HF patients. The document highlights the importance of achieving optimal recommended doses of GDMT medications, including beta-blockers, renin-angiotensin-aldosterone inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter inhibitors to improve patient outcomes, achieve effective, sustainable decongestion, and improve patient quality of life. The document also discusses potential obstacles to GDMT optimization, such as clinical inertia, physiological limitations, comorbidities, non-adherence, and frailty. Lastly, it also attempts to provide possible future scenarios of high-intensive care that could improve patient outcomes.

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This JAMA Clinical Guidelines Synopsis summarizes the 2023 American Heart Association (AHA)/American College of Cardiology (ACC) guideline on management of patients with chronic coronary disease.

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BACKGROUND: We previously demonstrated that higher simple guideline-directed medical therapy (GDMT) scores (comprising renin-angiotensin system inhibitors, ß-blockers, mineralocorticoid antagonists, and sodium-glucose cotransporter 2 inhibitors) at discharge were correlated with improved prognosis in heart failure (HF) patients. HF readmissions are linked to adverse outcomes, emphasizing the need for enhanced optimization of GDMT. METHODS AND RESULTS: Using the simple GDMT score, we evaluated the effect of revising and modifying in-hospital GDMT on the prognosis of patients with HF readmissions. In this retrospective analysis of 2,100 HF patients, we concentrated on 1,222 patients with HF with reduced ejection/moderately reduced ejection fraction, excluding patients with HF with preserved ejection fraction, on dialysis, or who died in hospital. A higher current GDMT score was associated with better HF prognosis. Of the 1,222 patients in the study, we analyzed 372 cases of rehospitalization, calculating the simple GDMT scores at admission and discharge. Patients were divided into groups according to score improvement. Multivariate analysis showed a significant association between improved in-hospital simple GDMT score and the composite outcome (HF readmission+all-cause mortality; hazard ratio 0.459; 95% confidence interval 0.257-0.820; P=0.008). Even after propensity score matching to adjust for background, among rehospitalized patients, those with an improved in-hospital simple GDMT score had a better prognosis. CONCLUSIONS: Our results highlight the potential of robust interventions and score elevation during hospitalization leading to improved outcomes.

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OBJECTIVE: This study evaluates the 3-year clinical outcomes of high Killip grade (III/IV) acute myocardial infarction (AMI) patients treated with either ß-blockers (BB) and angiotensin-converting enzyme inhibitors (ACEI) or BB and angiotensin receptor blockers (ARB). METHODS: A total of 13,105 patients were registered at the Korea Acute Myocardial Infarction Registry at the National Institute of Health (KAMIR-NIH). Among them, 871 patients with high Killip classification AMI were divided into the BB + ACEI group (n = 489) and the BB + ARB group (n = 381). Following propensity score matching, 343 patients were selected in each group. All patients completed a 3-year follow-up period. RESULTS: The results indicate no significant differences between the BB + ACEI group and BB + ARB group in terms of cardiac death, recurrent myocardial infarction, and the rate of repeat percutaneous coronary intervention. However, the BB + ACEI group exhibited significantly lower risks in major adverse cardiac events (HR = 0.574, 95% CI: 0.421-0.783, p < .001), all-cause mortality (HR = 0.561, 95% CI: 0.404-0.778, p = .001), and non-cardiac death (HR = 0.365, 95% CI: 0.208-0.639, p < .001) compared to the BB + ARB group. CONCLUSION: Our results suggest that BB + ACEI treatment is more beneficial than BB + ARB for high Killip grade AMI patients. Additionally, the BB + ACEI group has a superior preventative effect on mortality compared to the BB + ARB group.

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Acute Respiratory Distress Syndrome (ARDS) manifests as an acute inflammatory lung injury characterized by persistent hypoxemia, featuring a swift onset, high mortality, and predominantly supportive care as the current therapeutic approach, while effective treatments remain an area of active investigation. Adrenergic receptors (AR) play a pivotal role as stress hormone receptors, extensively participating in various inflammatory processes by initiating downstream signaling pathways. Advancements in molecular biology and pharmacology continually unveil the physiological significance of distinct AR subtypes. Interventions targeting these subtypes have the potential to induce specific alterations in cellular and organismal functions, presenting a promising avenue as a therapeutic target for managing ARDS. This article elucidates the pathogenesis of ARDS and the basic structure and function of AR. It also explores the relationship between AR and ARDS from the perspective of different AR subtypes, aiming to provide new insights for the improvement of ARDS.

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