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ABSTRACT: Unhealthy lifestyles have placed a significant burden on individuals' cardiovascular health. Anthocyanins are water-soluble flavonoid pigments found in a wide array of common foods and fruits. Anthocyanins have the potential to contribute to the prevention and treatment of cardiovascular disease by improving lipid profiles and vascular function, reducing blood glucose levels and blood pressure, and inhibiting inflammation. These actions have been demonstrated in numerous clinical and preclinical studies. At the cellular and molecular level, anthocyanins and their metabolites could protect endothelial cells from senescence, apoptosis, and inflammation by activating the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthases, silent information regulator 1 (SIRT1), or nuclear factor erythroid2-related factor 2 pathways and inhibiting the nuclear factor kappa B, Bax, or P38 mitogen-activated protein kinase pathways. Furthermore, anthocyanins prevent vascular smooth muscle cell from platelet-derived growth factor -induced or tumor necrosis factor-α-induced proliferation and migration by inhibiting the focal adhesion kinase and extracellular regulated protein kinases signaling pathways. Anthocyanins could also attenuate vascular inflammation by reducing the formation of oxidized lipids, preventing leukocyte adhesion and infiltration of the vessel wall, and macrophage phagocytosis of deposited lipids through reducing the expression of cluster of differentiation 36 and increasing the expression of ATP-binding cassette subfamily A member 1 and ATP-binding cassette subfamily G member 1. At the same time, anthocyanins could lower the risk of thrombosis by inhibiting platelet activation and aggregation through down-regulating P-selectin, transforming growth factor-1, and CD40L. Thus, the development of anthocyanin-based supplements or derivative drugs could provide new therapeutic approaches to the prevention and treatment of vascular diseases.
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Antocianinas , Antiinflamatorios , Enfermedades Cardiovasculares , Transducción de Señal , Humanos , Antocianinas/farmacología , Antocianinas/uso terapéutico , Animales , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Fármacos Cardiovasculares/uso terapéutico , Fármacos Cardiovasculares/farmacologíaRESUMEN
PURPOSE OF REVIEW: Heart failure is a clinical syndrome with signs and symptoms from underlying cardiac abnormality and evidence of pulmonary or systemic congestion on laboratory testing or other objective findings (Bozkurt et al. in Eur J Heart Fail 23:352-380, 2021). Heart failure with reduced ejection fraction (HFrEF), when heart failure is due to underlying reduction in ejection fraction to ≤ 40. The goal of this review is to briefly describe the mechanisms and benefits of the various pharmacological interventions described in the 2022 AHA/ACC/HFSA Guidelines focusing on Stage C: Symptomatic Heart Failure HFrEF, while providing basic guidance on safe use of these medications. RECENT FINDINGS: Use of medications from each class as recommended in the 2022 Guidelines can provide significant morbidity and mortality benefits for our patients. Despite advances in therapeutics for patients with HFrEF, patients are frequently under treated and more research is needed to help optimize management of these complicated patients.
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Insuficiencia Cardíaca , Volumen Sistólico , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Guías de Práctica Clínica como Asunto , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Fármacos Cardiovasculares/uso terapéuticoRESUMEN
Background: Management strategies for stable angina include pharmacotherapy, revascularization, and exercise-based cardiac rehabilitation (CR). The optimal treatment for stable angina patients with severe coronary artery stenosis remains unclear. This study aimed to compare interventional therapy with exercise rehabilitation in this population. Methods: Fifty stable angina patients with severe coronary stenosis who underwent stent implantation were included in the optimal medical therapy (OMT) plus percutaneous coronary intervention (PCI) group, and 50 patients who did not undergo interventional treatment were included in OMT plus CR group receiving exercise rehabilitation guidance for one year. Cardiovascular composite endpoint events, cardiopulmonary fitness, and quality of life scale scores were assessed after one year. Results: No significant difference in incidence of cardiovascular composite endpoint events was observed between OMT plus PCI group with OMT plus CR group (20.0% vs 14.6%) after one year. Cardiopulmonary fitness represented as peak VO2 (19.2±3.5 vs 17.6±3.2 mL/kg/min), peak load (120±19 vs 108±20 W), and AT (13.5±1.5 vs 12.1±1.3 mL/kg/min) were significantly higher in the rehabilitation group than the intervention group after one year. Both groups showed improvement in their quality of life, but the rehabilitation group improved in more scales. Conclusion: Interventional therapy did not reduce cardiovascular events compared to exercise-based rehabilitation in stable angina patients with severe coronary artery stenosis, but the rehabilitation can improve cardiovascular fitness and quality of life more.
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Angina Estable , Rehabilitación Cardiaca , Estenosis Coronaria , Terapia por Ejercicio , Intervención Coronaria Percutánea , Calidad de Vida , Humanos , Masculino , Femenino , Anciano , Terapia por Ejercicio/métodos , Persona de Mediana Edad , Estenosis Coronaria/terapia , Estenosis Coronaria/rehabilitación , Angina Estable/rehabilitación , Angina Estable/terapia , Rehabilitación Cardiaca/métodos , Resultado del Tratamiento , Stents , Capacidad Cardiovascular , Fármacos Cardiovasculares/uso terapéuticoRESUMEN
Hydration status plays a key role in healthy ageing, and it is potentially affected by several factors, including drug consumption. However, research on this issue to date is scarce, especially in highly vulnerable groups, such as the elderly. We aimed to study the relationship linking hydration status, analysed by means of a validated questionnaire, 24 h urine analysis, body composition assessment, and drug consumption in a sample of old adults. A total of 144 elders were included in the study. Cardiovascular drug consumption was significantly associated with a lower water intake in men (ß = -0.282, p = 0.029). Moreover, urinary analysis revealed that total drug intake as well as the consumption of diuretics and cardiovascular drugs were associated with poorer hydration status, whereas genito-urinary drugs were associated with an opposite effect, and these results were confirmed in terms of body composition. Hence, total drug consumption (ß = -0.205), diuretic (ß = -0.408), cardiovascular (ß = -0.297), and genito-urinary drugs (ß = 0.298) were significantly associated (p < 0.05) with total body water. The obtained results confirmed the impact of chronic treatment with certain drugs on hydration status. Nutritional interventions may be of great interest in certain population groups in order to prevent complications due to altered hydration status.
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Composición Corporal , Diuréticos , Ingestión de Líquidos , Estado de Hidratación del Organismo , Humanos , Masculino , Anciano , Femenino , Diuréticos/administración & dosificación , Anciano de 80 o más Años , Agua Corporal , Fármacos Cardiovasculares , Encuestas y Cuestionarios , Deshidratación/epidemiologíaRESUMEN
Phase 3 randomized controlled trials (RCTs), while the gold standard for treatment efficacy and safety, are not always feasible, are expensive, can be prolonged and can be limited in generalizability. Other under-recognized sources of evidence can also help advance drug development. Basic science, proof-of-concept studies and early-phase RCTs can provide evidence regarding the potential for clinical benefit. Real-world evidence generated from registries or observational datasets can provide insights into the treatment of rare diseases that often pose a challenge for trial recruitment. Pragmatic trials embedded in healthcare systems can assess the treatment effects in clinical settings among patient populations sometimes excluded from trials. This Perspective discusses potential sources of evidence that may be used to complement explanatory phase 3 RCTs and to speed the development of new cardiovascular medications. Content is derived from the 19th Global Cardiovascular Clinical Trialists meeting (December 2022), involving clinical trialists, patients, clinicians, regulators, funders and industry representatives.
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Desarrollo de Medicamentos , Humanos , Desarrollo de Medicamentos/métodos , Fármacos Cardiovasculares/uso terapéutico , Fármacos Cardiovasculares/efectos adversos , Ensayos Clínicos Fase III como Asunto , Ensayos Clínicos Pragmáticos como Asunto/métodos , Proyectos de Investigación/normas , Enfermedades Cardiovasculares/tratamiento farmacológico , Medicina Basada en la Evidencia/métodos , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Estudios Observacionales como Asunto/métodosRESUMEN
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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Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/tratamiento farmacológico , Femenino , Masculino , Anciano de 80 o más Años , Prevalencia , Fármacos Cardiovasculares/uso terapéutico , Suecia/epidemiología , Antagonistas Adrenérgicos beta/uso terapéutico , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéuticoRESUMEN
Global health concerns persist due to the multifaceted nature of heart diseases, which include lifestyle choices, genetic predispositions, and emerging post-COVID complications like myocarditis and pericarditis. This broadens the spectrum of cardiovascular ailments to encompass conditions such as coronary artery disease, heart failure, arrhythmias, and valvular disorders. Timely interventions, including lifestyle modifications and regular medications such as antiplatelets, beta-blockers, angiotensin-converting enzyme inhibitors, antiarrhythmics, and vasodilators, are pivotal in managing these conditions. In drug development, topological indices play a critical role, offering cost-effective computational and predictive tools. This study explores modified reverse degree topological indices, highlighting their adjustable parameters that actively shape the degree sequences of molecular drugs. This feature makes the approach suitable for datasets with unique physicochemical properties, distinguishing it from traditional methods that rely on fixed degree approaches. In our investigation, we examine a dataset of 30 drug compounds, including sotagliflozin, dapagliflozin, dobutamine, etc., which are used in the treatment of cardiovascular diseases. Through the structural analysis, we utilize modified reverse degree indices to develop quantitative structure-property relationship (QSPR) models, aiming to unveil essential understandings of their characteristics for drug development. Furthermore, we compare our QSPR models against the degree-based models, clearly demonstrating the superior effectiveness inherent in our proposed method.
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Fármacos Cardiovasculares , Relación Estructura-Actividad Cuantitativa , Fármacos Cardiovasculares/química , Fármacos Cardiovasculares/farmacología , Fenómenos Químicos , HumanosRESUMEN
INTRODUCTION: Clinical trials, essential for medical advancement, vary significantly in methodology and regulatory pathways depending on the type of therapeutic intervention (i.e., drugs or devices). This study aimed to determine whether the drug or device intervention types influence the impact of randomized trials in cardiovascular medicine. METHODS: We analyzed late-breaking randomized controlled trials presented at major cardiology conferences from 2015 to 2021. The primary endpoint was the total number of citations obtained. Secondary endpoints included the number of citations at 1 and 2 years, number of total and 1-year mentions, and several metrics of study conduct and publication. Statistical analysis included tests for comparisons of continuous or categorical variables, based on their distribution, as appropriate. To adjust the results for potential confounders, univariable and multivariable regression models were utilized. Additionally, sensitivity analyses were conducted to explore both the effect of neutral or positive study outcomes on the comparative impact of drug versus device trials and the impact of the coronavirus disease 2019 (COVID-19) pandemic on the primary endpoint. RESULTS: Of 382 eligible randomized trials, 227 (59.4%) were trials of drugs and 155 (40.6%) were trials of devices. Drug trials had a higher median number of total citations compared to device studies (93 [interquartile range {IQR} 48-137] vs. 82 [IQR 39-192]; p = 0.025). This difference was consistent at 1 and 2 years and was also observed in the number of total mentions and mentions at 1 year. All the metrics of study conduct and publication were similar, except for drug studies being more often stopped prematurely (8.8 vs. 1.9%; p = 0.006). After adjusting for multiple potential confounders, the difference in citations and mentions was no longer statistically significant. However, drug trials remained more likely to be stopped prematurely (adjusted odds ratio = 1.15; 95% confidence interval 1.03-1.28; p = 0.009). Positive study outcomes significantly influenced the number of citations and the likelihood of a trial being stopped prematurely. CONCLUSIONS: Drug trials are often stopped early and receive more citations and mentions than device trials. However, these differences are mainly due to factors other than the treatment itself. Studies published simultaneously tend to get more attention, and drug trials with positive results are cited more often than those with neutral results.
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Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , COVID-19 , Enfermedades Cardiovasculares/tratamiento farmacológico , Cardiología , Fármacos Cardiovasculares/uso terapéutico , Equipos y SuministrosRESUMEN
BACKGROUND: Physician underprescribing and patient nonadherence are major barriers to the benefits of guideline-directed medical therapy. An important contributor to both underprescribing and patient nonadherence is concern about medication-related side effects. Yet, there are few to no data on approaches used by physicians to: (1) elicit medication-related side effects, (2) attribute these side effects to specific medications, and (3) take appropriate action. METHODS AND RESULTS: The authors conducted semistructured interviews with physicians to identify facilitators and barriers to each critical step of heart failure medication management: elicitation of side effects, attribution of side effects to a medication, and action in response to attributed side effects. Interviews were transcribed and coded using directed content analysis. For elicitation of potential side effects, limited patient communication and family discordance in reporting were key barriers, whereas guiding questions, measurement, and open channels of communication were key facilitators. For attribution of side effects, confounding from other medications, limited time for clinical encounters, and nonspecific symptoms were key barriers, whereas time-limited medication discontinuation trials and medication rechallenges were key facilitators. For taking action, challenges with weighing risks and benefits and physician fear about causing harm or interfering with other clinicians were barriers, whereas patient-physician communication and the results of a medication discontinuation trials and medication rechallenge were facilitators. CONCLUSIONS: This study generated key facilitators and barriers to 3 key aspects of heart failure medication management related to side effects that should drive future work to improve heart failure medication management.
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Insuficiencia Cardíaca , Cumplimiento de la Medicación , Relaciones Médico-Paciente , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Femenino , Masculino , Pautas de la Práctica en Medicina , Fármacos Cardiovasculares/efectos adversos , Fármacos Cardiovasculares/uso terapéutico , Actitud del Personal de Salud , Persona de Mediana Edad , Entrevistas como Asunto , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Conocimientos, Actitudes y Práctica en Salud , Cardiólogos , ComunicaciónRESUMEN
Partial or complete imaging resolution of left ventricular (LV) systolic dysfunction in patients with heart failure with reduced ejection fraction (HFrEF) has gone by many names in the past few decades, including LV recovery, remission, reverse remodeling, and, most recently, improvement. This phenomenon has been described in a variety of clinical scenarios, including removal of an acute myocardial insult, unloading with durable LV assist devices, and treatment with various devices as well as pharmacotherapies, termed guideline-directed medical therapy (GDMT). Irrespective of definition, systolic improvement is associated with improved clinical outcomes compared to persistent systolic dysfunction. In the past few years, systolic improvement has been distinguished from HFrEF as a new clinical entity referred to as HF with improved EF (HFimpEF). Given the relative novelty of this condition, there is a paucity of data with regard to the clinical trajectory and management of this population. In this review, we describe the history of myocardial improvement terminology and explore notable findings that have led to the delineation of HFimpEF. Additionally, we highlight the importance of understanding LV trajectory and the potential opportunity for new GDMT management for clinicians when treating patients with HFimpEF.
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Insuficiencia Cardíaca , Recuperación de la Función , Volumen Sistólico , Disfunción Ventricular Izquierda , Función Ventricular Izquierda , Remodelación Ventricular , Humanos , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/diagnóstico por imagen , Resultado del Tratamiento , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/terapia , Disfunción Ventricular Izquierda/epidemiología , Prevalencia , Terminología como Asunto , Fármacos Cardiovasculares/uso terapéutico , Estado Funcional , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: Chronic heart failure affects approximately 26 million people globally. World Health Organization data show that only approximately half of chronically ill patients in developed countries adhere to recommended medication, with even lower rates in developing countries. Medication adherence is critical for managing chronic heart failure symptoms, delaying disease progression, and preventing hospitalizations. However, poor adherence increases rehospitalization, morbidity, mortality, and healthcare costs. OBJECTIVE: To assess medication adherence and associated factors among chronic heart failure patients on follow-up at North Shewa Public Hospitals, Oromia Region, Ethiopia, in 2023. METHODS: This institutional-based cross-sectional study was conducted from March 1 to April 30, 2023, G.C. A total of 603 individuals were selected consecutively among those who underwent chronic OPD after being proportionally allocated to five hospitals in the zone. The data were collected using an interviewer-administered questionnaire and a medical chart review. The data were entered into Epi-data version 3.1 and then exported to SPSS version 26 for analysis. The multivariable logistic regression model included variables with a P value < 0.25 in the bivariate analysis. The degree of association was expressed using an adjusted odds ratio (AOR) with a 95% confidence interval (CI) at a P value < 0.05. RESULTS: Among the 603 patients, 56% had optimal medication adherence, with a 95% CI of 52.1 to 60. Being able to read and write (AOR: 2.20; 95% CI: 1.34, 3.61), having a secondary education (AOR: 1.97; 95% CI: 1.06, 3.67), having community-based health insurance (AOR: 1.82; 95% CI: 1.22, 2.71), not having comorbidities (AOR: 1.82; 95% CI: 1.18, 2.52), taking several drugs < 2 (AOR: 2.11; 95% CI: 1.20, 2.45), not adding salt when cooking (AOR: 1.72; 95% CI: 1.20, 2.45), and asking a doctor or nurse without fear (AOR: 1.87; 95% CI: 1.03, 3.40) were factors associated with medication adherence among CHF patients. CONCLUSION: This study revealed that 56% of chronic heart failure patients had optimal medication adherence. Factors associated with higher adherence included higher education, community health insurance, lack of comorbidities, fewer medications, avoiding added salt, and comfortable communication with providers. Health professionals should provide education to strengthen medication adherence.
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Conocimientos, Actitudes y Práctica en Salud , Insuficiencia Cardíaca , Hospitales Públicos , Cumplimiento de la Medicación , Humanos , Etiopía/epidemiología , Masculino , Femenino , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/diagnóstico , Estudios Transversales , Persona de Mediana Edad , Enfermedad Crónica , Factores de Riesgo , Adulto , Anciano , Fármacos Cardiovasculares/uso terapéutico , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIM: Cardiovascular diseases are the leading cause of death globally. Ensuring ongoing use of medicines-medication persistence-is crucial, yet no prior studies have examined this in residential aged care facilities (RACFs). We aimed to identify long-term trajectories of persistence with cardiovascular medicines and determine predictors of persistence trajectories. METHOD: A longitudinal cohort study of 2837 newly admitted permanent residents from 30 RACFs in New South Wales, Australia. We monitored weekly exposure to six cardiovascular medicine classes-lipid modifiers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs), beta-blockers, diuretics, calcium channel blockers (CCB), and cardiac therapy-over 3 years. Group-based trajectory modeling was employed to determine persistence trajectories for each class. RESULTS: At baseline, 76.6% (n = 2172) received at least one cardiovascular medicine with 41.2% receiving lipid modifiers, 31.4% ACEI/ARBs, 30.2% beta-blockers, 24.4% diuretics, 18.7% CCBs, and 14.8% cardiac therapy. The model identified two persistence trajectories for CCBs and three trajectories for all other classes. Sustained high persistence rates ranged from 68.4% (ACEI/ARBs) to 79.8% (beta-blockers) while early decline in persistence and subsequent discontinuation rates ranged from 7.6% (cardiac therapy) to 25.3% (CCBs). Logistic regressions identified 11 predictors of a declining persistence across the six medicine classes. CONCLUSION: Our study revealed varied patterns of cardiovascular medicine use in RACFs, with 2-3 distinctive medicine use trajectories across different classes, each exhibiting a unique clinical profile, and up to a quarter of residents discontinuing a medicine class. Future studies should explore the underlying reasons and appropriateness of nonpersistence to aid in identifying areas for improvement.
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Enfermedades Cardiovasculares , Humanos , Estudios Longitudinales , Masculino , Femenino , Anciano , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Anciano de 80 o más Años , Nueva Gales del Sur , Fármacos Cardiovasculares/uso terapéutico , Estudios de Cohortes , Cumplimiento de la Medicación/estadística & datos numéricos , Hogares para Ancianos/estadística & datos numéricosRESUMEN
BACKGROUND: In patients with in-stent restenosis (ISR) bioresorbable vascular scaffolds (BVS) provide similar results to drug-coated balloons (DCBs) but are inferior to drug-eluting stents (DES) at 1 year. However, the long-term efficacy of BVS in these patients remains unknown. OBJECTIVES: This study sought to assess the long-term safety and efficacy of BVS in patients with ISR. METHODS: RIBS VI (Restenosis Intrastent: Bioresorbable Vascular Scaffolds Treatment; NCT02672878) and RIBS VI Scoring (Restenosis Intrastent: Bioresorbable Vascular Scaffolds Treatment With Scoring Balloon; NTC03069066) are prospective multicenter studies designed to evaluate the results of BVS in patients with ISR (N = 220). The inclusion and exclusion criteria were identical to those used in the RIBS IV (ISR of DES) (Restenosis Intra-stent of Drug-eluting Stents: Drug-eluting Balloon vs Everolimus-eluting Stent; NCT01239940) and RIBS V (ISR of bare-metal stents) (Restenosis Intra-stent of Bare Metal Stents: Paclitaxel-eluting Balloon vs Everolimus-eluting Stent; NCT01239953) randomized trials (including 249 ISR patients treated with DCBs and 249 ISR patients treated with DES). A prespecified comparison of the long-term results obtained with these treatment modalities (ie, DES, DCBs, and BVS) was performed. RESULTS: Clinical follow-up at 3 years was obtained in all (100%) 718 patients. The 3-year target lesion revascularization rate after BVS was 14.1% (vs 12.9% after DCBs [not significant], and 5.2% after DES [HR: 2.80; 95% CI: 1.47-5.36; P = 0.001]). In a landmark analysis (>1 year), the target lesion revascularization rate after BVS was higher than after DES (adjusted HR: 3.41; 95% CI: 1.15-10.08) and DCBs (adjusted HR: 3.33; 95% CI: 1.14-9.70). Very late vessel thrombosis was also more frequent with BVS (BVS: 1.8%, DCBs: 0.4%, DES: 0%; P = 0.03). CONCLUSIONS: In patients with ISR, late clinical results of DES are superior to those obtained with DCBs and BVS. Beyond the first year, DCBs are safer and more effective than BVS.
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Implantes Absorbibles , Reestenosis Coronaria , Diseño de Prótesis , Humanos , Factores de Tiempo , Masculino , Resultado del Tratamiento , Femenino , Estudios Prospectivos , Reestenosis Coronaria/etiología , Reestenosis Coronaria/diagnóstico por imagen , Reestenosis Coronaria/terapia , Persona de Mediana Edad , Anciano , Factores de Riesgo , Angioplastia Coronaria con Balón/instrumentación , Angioplastia Coronaria con Balón/efectos adversos , Fármacos Cardiovasculares/administración & dosificación , Fármacos Cardiovasculares/efectos adversos , Stents , Intervención Coronaria Percutánea/instrumentación , Intervención Coronaria Percutánea/efectos adversos , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Materiales Biocompatibles Revestidos , Stents Liberadores de Fármacos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Recent breakthroughs in human genetics and in information technologies have markedly expanded our understanding at the molecular level of the response to drugs, i.e., pharmacogenetics (PGx), across therapy areas. This review is restricted to PGx for cardiovascular (CV) drugs. First, we examined the PGx information in the labels approved by regulatory agencies in Europe, Japan, and North America and related recommendations from expert panels. Out of 221 marketed CV drugs, 36 had PGx information in their labels approved by one or more agencies. The level of annotations and recommendations varied markedly between agencies and expert panels. Clopidogrel is the only CV drug with consistent PGx recommendation (i.e., "actionable"). This situation prompted us to dissect the steps from discovery of a PGx association to clinical translation. We found 101 genome-wide association studies that investigated the response to CV drugs or drug classes. These studies reported significant associations for 48 PGx traits mapping to 306 genes. Six of these 306 genes are mentioned in the corresponding PGx labels or recommendations for CV drugs. Genomic analyses also highlighted the wide between-population differences in risk allele frequencies and the individual load of actionable PGx variants. Given the high attrition rate and the long road to clinical translation, additional work is warranted to identify and validate PGx variants for more CV drugs across diverse populations and to demonstrate the utility of PGx testing. To that end, pre-emptive PGx combining genomic profiling with electronic medical records opens unprecedented opportunities to improve healthcare, for CV diseases and beyond. SIGNIFICANCE STATEMENT: Despite spectacular breakthroughs in human molecular genetics and information technologies, consistent evidence supporting PGx testing in the cardiovascular area is limited to a few drugs. Additional work is warranted to discover and validate new PGx markers and demonstrate their utility. Pre-emptive PGx combining genomic profiling with electronic medical records opens unprecedented opportunities to improve healthcare, for CV diseases and beyond.
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Fármacos Cardiovasculares , Enfermedades Cardiovasculares , Estudio de Asociación del Genoma Completo , Farmacogenética , Humanos , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/genética , Farmacogenética/métodos , Fármacos Cardiovasculares/uso terapéutico , Fármacos Cardiovasculares/farmacología , Estudio de Asociación del Genoma Completo/métodosAsunto(s)
Angioplastia Coronaria con Balón , Materiales Biocompatibles Revestidos , Humanos , Angioplastia Coronaria con Balón/instrumentación , Angioplastia Coronaria con Balón/efectos adversos , Resultado del Tratamiento , Catéteres Cardíacos , Diseño de Equipo , Stents Liberadores de Fármacos , Fármacos Cardiovasculares/administración & dosificación , Fármacos Cardiovasculares/uso terapéutico , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/diagnóstico por imagenRESUMEN
KRAS gain-of-function mutations are frequently observed in sporadic arteriovenous malformations. The mechanisms underlying the progression of such KRAS-driven malformations are still incompletely understood, and no treatments for the condition are approved. Here, we show the effectiveness of sotorasib, a specific KRAS G12C inhibitor, in reducing the volume of vascular malformations and improving survival in two mouse models carrying a mosaic Kras G12C mutation. We then administered sotorasib to two adult patients with severe KRAS G12C-related arteriovenous malformations. Both patients had rapid reductions in symptoms and arteriovenous malformation size. Targeting KRAS G12C appears to be a promising therapeutic approach for patients with KRAS G12C-related vascular malformations. (Funded by the European Research Council and others.).
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Malformaciones Arteriovenosas , Proteínas Proto-Oncogénicas p21(ras) , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Malformaciones Arteriovenosas/diagnóstico , Malformaciones Arteriovenosas/diagnóstico por imagen , Malformaciones Arteriovenosas/tratamiento farmacológico , Malformaciones Arteriovenosas/genética , Modelos Animales de Enfermedad , Mutación con Ganancia de Función , Mutación , Piperazinas/uso terapéutico , Proteínas Proto-Oncogénicas p21(ras)/genética , Piridinas/uso terapéutico , Pirimidinas , Fármacos Cardiovasculares/uso terapéutico , Adulto JovenRESUMEN
ABSTRACT: Heart rate (HR) stands as a prognostic indicator of cardiovascular disease and a modifiable risk factor in heart failure (HF). Medication intolerance can curtail the application of conventional HR-lowering ß-blockers to the optimum target dose. Ivabradine (IVA), a specific negative-chronotropic agent, selectively inhibits I f current in pacemaker cells of the sinoatrial node without depressing myocardial contractility or comprising hemodynamics. This review summarized ivabradine's clinical labeled and off-label uses and mechanism of action focusing on the clinical outcomes. PubMed was searched up to January 2024 using the main keywords of IVA, coronary artery disease (CAD), HF, postural tachycardia syndrome (POTS), and tachyarrhythmia. To comprehensively review IVA's clinical indications, mechanisms, and therapeutic effects, all studies investigating treatment with IVA in humans were included, comprising different types of studies such as randomized controlled trials and longitudinal prospective observational studies. After screening, 141 studies were included in our review. A large number of reviewed articles were allocated to heart failure with reduced ejection fraction and CAD, suggesting IVA as an alternative to ß-blockers in case of contraindications or intolerance. The beneficial effects of IVA as premedication for coronary computed tomography angiography, HR lowering in POTS, and inappropriate sinus tachycardia constituted most studies among off-label uses. The promising results have been reported on the efficacy of IVA in controlling HR, especially in patients with inappropriate sinus tachycardia or POTS. Owing to the unique mechanism of action, IVA has the potential to be used more frequently in future clinical practice.
Asunto(s)
Fármacos Cardiovasculares , Frecuencia Cardíaca , Ivabradina , Ivabradina/uso terapéutico , Ivabradina/efectos adversos , Humanos , Frecuencia Cardíaca/efectos de los fármacos , Fármacos Cardiovasculares/uso terapéutico , Fármacos Cardiovasculares/efectos adversos , Resultado del Tratamiento , Uso Fuera de lo Indicado , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Animales , Potenciales de Acción/efectos de los fármacosRESUMEN
The aim of this network meta-analysis was to compare the efficacy of various commonly used drugs in treating patients with hypertrophic cardiomyopathy (HCM). Randomized controlled trials on drugs for HCM treatment were retrieved from PubMed, Embase, Cochrane Library, and Web of Science (search cutoff: January 10, 2024). Quality assessment was performed using the risk of bias tool, and data analysis used R software. Seventeen studies (1,133 patients with HCM) were included. The network meta-analysis indicated that mavacamten and perhexiline improved peak oxygen consumption compared with placebo. Mavacamten reduced N-terminal pro-B-type natriuretic peptide, left ventricular mass index, left atrial volume index, and septal E/e' ratio. Losartan decreased systolic blood pressure, whereas candesartan, mavacamten, and valsartan reduced maximum wall thickness. Perhexiline had better efficacy in increasing peak oxygen consumption, and candesartan in reducing maximum wall thickness. No drug significantly improved left ventricular ejection fraction compared with placebo. In conclusion, on the basis of current studies, commonly used drugs may effectively improve some of the outcome measures in patients with HCM, whereas the novel drug mavacamten showed significant therapeutic effects in most of the remaining outcome measures except for left ventricular ejection fraction.
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Compuestos de Bifenilo , Cardiomiopatía Hipertrófica , Metaanálisis en Red , Humanos , Cardiomiopatía Hipertrófica/tratamiento farmacológico , Compuestos de Bifenilo/uso terapéutico , Volumen Sistólico , Consumo de Oxígeno/efectos de los fármacos , Tetrazoles/uso terapéutico , Bencimidazoles/uso terapéutico , Fármacos Cardiovasculares/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Losartán/uso terapéutico , Valsartán/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Evidence suggests that drug-coated balloons may benefit in-stent restenosis (ISR) treatment. However, the efficacy of new-generation sirolimus-coated balloon (SCB) compared with the latest generation drug-eluting stents (DESs) has not been studied in this setting. METHODS: All patients in the EASTBORNE (The All-Comers Sirolimus-Coated Balloon European Registry) and DEB-DRAGON (DEB vs Thin-DES in DES-ISR: Long Term Outcomes) registries undergoing percutaneous coronary intervention for DES-ISR were included in the study. The primary study end point was target lesion revascularization at 24 months. Secondary end points were major adverse cardiovascular events, all-cause death, myocardial infarction, and target vessel revascularization at 24 months. Our goal was to evaluate the efficacy and safety of SCB versus thin-struts DES in ISR at long-term follow-up. RESULTS: A total of 1545 patients with 1679 ISR lesions were included in the pooled analysis, of whom 621 (40.2%) patients with 621 lesions were treated with thin-strut DES and 924 (59.8%) patients with 1045 lesions were treated with SCB. The unmatched cohort showed no differences in the incidence of target lesion revascularization (10.8% versus 11.8%; P=0.568); however, there was a trend toward lower rates of myocardial infarction (7.4% versus 5.0%; P=0.062) and major adverse cardiovascular events (20.8% versus 17.1%; P=0.072) in the SCB group. After propensity score matching (n=335 patients per group), there were no significant differences in the rates of target lesion revascularization (11.6% versus 11.8%; P=0.329), target vessel revascularization (14.0% versus 13.1%; P=0.822), myocardial infarction (7.2% versus 4.5%; P=0.186), all-cause death (5.7% versus 4.2%; P=0.476), and major adverse cardiovascular event (21.5% versus 17.6%; P=0.242) between DES and SCB treatment. CONCLUSIONS: In patients with ISR, angioplasty with SCB compared with thin-struts DES is associated with comparable rates of target lesion revascularization, target vessel revascularization, myocardial infarction, all-cause death, and major adverse cardiovascular events at 2 years.