RESUMEN
BACKGROUND: Stroke prevention with direct-acting oral anticoagulant agents in patients with atrial fibrillation confers a risk of bleeding and limits their use. Asundexian, an activated factor XI (XIa) inhibitor, is an oral anticoagulant that may prevent strokes with less bleeding. METHODS: In a phase 3, international, double-blind trial, we randomly assigned high-risk patients with atrial fibrillation in a 1:1 ratio to receive asundexian at a dose of 50 mg once daily or standard-dose apixaban. The primary efficacy objective was to determine whether asundexian is at least noninferior to apixaban for the prevention of stroke or systemic embolism. The primary safety objective was to determine whether asundexian is superior to apixaban with respect to major bleeding events. RESULTS: A total of 14,810 randomly assigned patients were included in the intention-to-treat population. The mean (±SD) age of the patients was 73.9±7.7 years, 35.2% were women, 18.6% had chronic kidney disease, 18.2% had a previous stroke or transient ischemic attack, 16.8% had received oral anticoagulants for no more than 6 weeks, and the mean CHA2DS2-VASc score (range, 0 to 9, with higher scores indicating a greater risk of stroke) was 4.3±1.3. The trial was stopped prematurely at the recommendation of the independent data monitoring committee. Stroke or systemic embolism occurred in 98 patients (1.3%) assigned to receive asundexian and in 26 (0.4%) assigned to receive apixaban (hazard ratio, 3.79; 95% confidence interval [CI], 2.46 to 5.83). Major bleeding occurred in 17 patients (0.2%) who received asundexian and in 53 (0.7%) who received apixaban (hazard ratio, 0.32; 95% CI, 0.18 to 0.55). The incidence of any adverse event appeared to be similar in the two groups. CONCLUSIONS: Among patients with atrial fibrillation at risk for stroke, treatment with asundexian at a dose of 50 mg once daily was associated with a higher incidence of stroke or systemic embolism than treatment with apixaban in the period before the trial was stopped prematurely. There were fewer major bleeding events with asundexian than with apixaban during this time. (Funded by Bayer; OCEANIC-AF ClinicalTrials.gov number, NCT05643573; EudraCT number, 2022-000758-28.).
RESUMEN
BACKGROUND: While surgery still remains the gold standard treatment for mechanical prosthetic valve thrombosis (MPVT) by many guidelines, the ultraslow low-dose thrombolytic regimen has been reported as a promising alternative. METHODS: In this prospective single-center cohort, patients with acute MPVT were treated with an ultraslow low-dose thrombolytic regimen consisting of 25 mg infusion of recombinant tissue-type plasminogen activator (rtPA) over 25 h. The regimen could be repeated in case of failure until resolution/occurrence of adverse events or a maximum cumulative dose of 150 mg. The primary outcome was the complete MPVT resolution rate; other outcomes included first-dose success rate, major bleeding, thromboembolic events, mortality, and total thrombolytic dose/duration. RESULTS: Between April 2018 to January 2024, 135 episodes of acute MPVT were treated with an ultraslow low-dose thrombolytic regimen in 118 patients. In 118/135 (87.4 %) episodes, right-sided prosthetic valve was involved. Complete success was achieved in 88.1 % of cases, with 39.5 % responding after the first dose. The median total dose was 50 mg over a median of 30 h. Only one fatal intracranial hemorrhage occurred (0.7 %), with no other bleeding or thromboembolic complications. CONCLUSION: The ultraslow low-dose thrombolytic regimen appears to exhibit high efficacy and acceptable safety in treating acute MPVT. Further large clinical trials are essential for validating these preliminary findings.
Asunto(s)
Fibrinolíticos , Prótesis Valvulares Cardíacas , Terapia Trombolítica , Trombosis , Humanos , Femenino , Masculino , Estudios Prospectivos , Terapia Trombolítica/métodos , Prótesis Valvulares Cardíacas/efectos adversos , Persona de Mediana Edad , Trombosis/tratamiento farmacológico , Trombosis/etiología , Fibrinolíticos/administración & dosificación , Fibrinolíticos/uso terapéutico , Anciano , Estudios de Cohortes , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/uso terapéutico , Adulto , Relación Dosis-Respuesta a Droga , Resultado del Tratamiento , Enfermedad AgudaRESUMEN
BACKGROUND: Lower extremity arterial disease (LEAD) and increased aortic stiffness are associated with higher mortality in patients with chronic coronary syndrome, while their prognostic significance after an acute coronary syndrome (ACS) is less known. METHODS: We analyzed prevalence, clinical phenotypes and association of LEAD - assessed by the ankle-brachial index (ABI) - and increased aortic stiffness - assessed by the aortic pulse wave velocity (PWV) - with all-cause mortality and major adverse cardiovascular events (MACE) in patients admitted with an ACS. RESULTS: Among 270 patients admitted for ACS (mean age 67âyears, 80% males), 41 (15%) had an ABI ≤0.9, with 14 of them (34%) presenting with intermittent claudication (symptomatic LEAD). Patients with symptomatic LEAD, compared with those with asymptomatic LEAD or without LEAD, had higher prevalence of cardiovascular risk factors, lower estimated glomerular filtration rate and higher high-sensitivity C-reactive protein. Patients with LEAD, either symptomatic or asymptomatic, more frequently presented with non-ST-elevation myocardial infarction and more frequently had multivessel coronary artery disease. Both symptomatic and asymptomatic LEAD were significantly associated with all-cause mortality after adjustment for confounders, including multivessel disease or carotid artery disease (hazard ratio 4.03, 95% confidence interval 1.61-10.08, P â<â0.01), whereas PWV was not associated with the outcome in the univariable model. LEAD and PWV were not associated with a higher risk of MACE (myocardial infarction or unstable angina, stroke, or transient ischemic attack). CONCLUSIONS: LEAD, either clinical or subclinical, but not increased aortic stiffness, is an independent predictor of all-cause mortality in patients admitted for ACS.
Asunto(s)
Síndrome Coronario Agudo , Índice Tobillo Braquial , Enfermedad Arterial Periférica , Análisis de la Onda del Pulso , Rigidez Vascular , Humanos , Masculino , Síndrome Coronario Agudo/mortalidad , Síndrome Coronario Agudo/fisiopatología , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/complicaciones , Femenino , Anciano , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/mortalidad , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/complicaciones , Pronóstico , Persona de Mediana Edad , Prevalencia , Factores de RiesgoRESUMEN
BACKGROUND: Empagliflozin (EMPA), a selective sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has been shown to reduce major adverse cardiovascular events in patients with heart failure of different etiologies, although the underlying mechanism still remains unclear. Ponatinib (PON) is a multi-tyrosine kinase inhibitor successfully used against myeloid leukemia and other human malignancies, but its cardiotoxicity remains worrisome. Cardiac connexins (Cxs) are both substrates and regulators of autophagy and responsible for proper heart function. Alteration in connexin expression and localization have been described in patients with heart failure. AIMS: To assess whether EMPA can mitigate PON-induced cardiac dysfunction by restoring the connexin 43-autophagy pathway. METHODS AND RESULTS: Male C57BL/6 mice, randomized into four treatment groups (CNTRL, PON, EMPA, PON+EMPA) for 28 days, showed increased autophagy, decreased Cx43 expression as well as Cx43 lateralization, and attenuated systo-diastolic cardiac dysfunction after treatment with EMPA and PON compared with PON alone. Compared with CNTRL (DMSO), cardiomyocyte-differentiated H9c2 (dH9c2) cells treated with PON showed significantly reduced cell viability to approximately 20â¯%, decreased autophagy, increased cell senescence and reduced DNA binding activity of serum response factor (SRF) to serum response elements (SRE), which were paralleled by reduction in cardiac actin expression. Moreover, PON induced a significant increase of Cx43 protein and its S368-phosphorylated form (pS368-Cx43), as well as their displacement from the plasma membrane to the perinuclear and nuclear cellular region. All these effects were reverted by EMPA. CONCLUSION: EMPA attenuates PON-induced cardiotoxicity by reducing senescence, enhancing the SRE-SRF binding and restoring the connexin 43-autophagy pathway. This effect may pave the way to use of SGLT2 inhibitors in attenuating tyrosine-kinase inhibitor cardiotoxicity.
Asunto(s)
Autofagia , Compuestos de Bencidrilo , Cardiotoxicidad , Conexina 43 , Glucósidos , Imidazoles , Miocitos Cardíacos , Piridazinas , Animales , Masculino , Ratones , Ratas , Autofagia/efectos de los fármacos , Compuestos de Bencidrilo/farmacología , Cardiotoxicidad/etiología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Conexina 43/metabolismo , Glucósidos/farmacología , Imidazoles/farmacología , Ratones Endogámicos C57BL , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Piridazinas/farmacología , Transducción de Señal/efectos de los fármacos , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacologíaRESUMEN
Since the 1960s, cardiologists have adopted several binary classification systems for acute myocardial infarction (MI) that facilitated improved patient management. Conversely, for chronic stable manifestations of myocardial ischemia, various classifications have emerged over time, often with conflicting terminology-eg, "stable coronary artery disease" (CAD), "stable ischemic heart disease," and "chronic coronary syndromes" (CCS). While the 2019 European guidelines introduced CCS to impart symmetry with "acute coronary syndromes" (ACS), the 2023 American guidelines endorsed the alternative term "chronic coronary disease." An unintended consequence of these competing classifications is perpetuation of the restrictive terms "coronary" and 'disease', often connoting only a singular obstructive CAD mechanism. It is now important to advance a more broadly inclusive terminology for both obstructive and non-obstructive causes of angina and myocardial ischemia that fosters conceptual clarity and unifies dyssynchronous nomenclatures across guidelines. We, therefore, propose a new binary classification of "acute myocardial ischemic syndromes" and "non-acute myocardial ischemic syndromes," which comprises both obstructive epicardial and non-obstructive pathogenetic mechanisms, including microvascular dysfunction, vasospastic disorders, and non-coronary causes. We herein retain accepted categories of ACS, ST-segment elevation MI, and non-ST segment elevation MI, as important subsets for which revascularization is of proven clinical benefit, as well as new terms like ischemia and MI with non-obstructive coronary arteries. Overall, such a more encompassing nomenclature better aligns, unifies, and harmonizes different pathophysiologic causes of myocardial ischemia and should result in more refined diagnostic and therapeutic approaches targeted to the multiple pathobiological precipitants of angina pectoris, ischemia, and infarction.
RESUMEN
Since the 1960s, cardiologists have adopted several binary classification systems for acute myocardial infarction (MI) that facilitated improved patient management. Conversely, for chronic stable manifestations of myocardial ischaemia, various classifications have emerged over time, often with conflicting terminology-e.g. 'stable coronary artery disease' (CAD), 'stable ischaemic heart disease', and 'chronic coronary syndromes' (CCS). While the 2019 European guidelines introduced CCS to impart symmetry with 'acute coronary syndromes' (ACS), the 2023 American guidelines endorsed the alternative term 'chronic coronary disease'. An unintended consequence of these competing classifications is perpetuation of the restrictive terms 'coronary' and 'disease', often connoting only a singular obstructive CAD mechanism. It is now important to advance a more broadly inclusive terminology for both obstructive and non-obstructive causes of angina and myocardial ischaemia that fosters conceptual clarity and unifies dyssynchronous nomenclatures across guidelines. We, therefore, propose a new binary classification of 'acute myocardial ischaemic syndromes' and 'non-acute myocardial ischaemic syndromes', which comprises both obstructive epicardial and non-obstructive pathogenetic mechanisms, including microvascular dysfunction, vasospastic disorders, and non-coronary causes. We herein retain accepted categories of ACS, ST-segment elevation MI, and non-ST-segment elevation MI, as important subsets for which revascularization is of proven clinical benefit, as well as new terms like ischaemia and MI with non-obstructive coronary arteries. Overall, such a more encompassing nomenclature better aligns, unifies, and harmonizes different pathophysiologic causes of myocardial ischaemia and should result in more refined diagnostic and therapeutic approaches targeted to the multiple pathobiological precipitants of angina pectoris, ischaemia and infarction.
RESUMEN
Multivessel coronary artery disease is present in â¼50% of patients with acute coronary syndrome and, compared with single-vessel disease, entails a higher risk of new ischaemic events and a worse prognosis. Randomized controlled trials have shown the superiority of 'complete revascularization' over culprit lesion-only treatment. Trials, however, only included patients treated with percutaneous coronary intervention (PCI), and evidence regarding complete revascularization with coronary artery bypass graft (CABG) surgery after culprit lesion-only PCI ('hybrid revascularization') is lacking. The CABG after PCI is an open, non-negligible therapeutic option, for patients with non-culprit left main and/or left anterior descending coronary artery disease where evidence in chronic coronary syndrome patients points in several cases to a preference of CABG over PCI. This valuable but poorly studied 'PCI first-CABG later' option presents, however, relevant challenges, mostly in the need of interrupting post-stenting dual antiplatelet therapy (DAPT) for surgery to prevent excess bleeding. Depending on patients' clinical characteristics and coronary anatomical features, either deferring surgery after a safe interruption of DAPT or bridging DAPT interruption with intravenous short-acting antithrombotic agents appears to be a suitable option. Off-pump minimally invasive surgical revascularization, associated with less operative bleeding than open-chest surgery, may be an adjunctive strategy when revascularization cannot be safely deferred and DAPT is not interrupted. Here, the rationale, patient selection, optimal timing, and adjunctive strategies are reviewed for an ideal approach to hybrid revascularization in post-acute coronary syndrome patients to support physicians' choices in a case-by-case patient-tailored approach.
Asunto(s)
Síndrome Coronario Agudo , Puente de Arteria Coronaria , Intervención Coronaria Percutánea , Humanos , Síndrome Coronario Agudo/cirugía , Síndrome Coronario Agudo/terapia , Intervención Coronaria Percutánea/métodos , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/métodos , Enfermedad de la Arteria Coronaria/cirugía , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Selección de PacienteAsunto(s)
Hipertensión Pulmonar , Disfunción Ventricular Derecha , Función Ventricular Derecha , Humanos , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/diagnóstico , Disfunción Ventricular Derecha/fisiopatología , Disfunción Ventricular Derecha/etiología , Enfermedad Crónica , Masculino , Ejercicio Físico , Femenino , Persona de Mediana Edad , Embolia Pulmonar/fisiopatología , Embolia Pulmonar/diagnóstico , Factores de Riesgo , AncianoAsunto(s)
Autofagia , Compuestos de Bencidrilo , Senescencia Celular , Glucósidos , Imidazoles , Miocitos Cardíacos , Piridazinas , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Miocitos Cardíacos/metabolismo , Senescencia Celular/efectos de los fármacos , Autofagia/efectos de los fármacos , Compuestos de Bencidrilo/farmacología , Animales , Imidazoles/farmacología , Piridazinas/farmacología , Glucósidos/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Transducción de Señal/efectos de los fármacos , Células Cultivadas , RatasRESUMEN
The optimal antithrombotic management of atrial fibrillation (AF) patients who require oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) remains unclear. Current guidelines recommend dual antithrombotic therapy (DAT; OAC plus P2Y12 inhibitor - preferably clopidogrel) after a short course of triple antithrombotic therapy (TAT; DAT plus aspirin). Although DAT reduces bleeding risk compared to TAT, this is counterbalanced by an increase in ischaemic events. Aspirin provides early ischaemic benefit, but TAT is associated with an increased haemorrhagic burden; therefore, we propose a 30-day dual antiplatelet therapy (DAPT; aspirin plus P2Y12 inhibitor) strategy post-PCI, temporarily omitting OAC. The study aims to compare bleeding and ischaemic risk between a 30-day DAPT strategy following PCI and a guideline-directed therapy in AF patients requiring OAC. WOEST-3 (ClinicalTrials.gov: NCT04436978) is an investigator-initiated, international, open-label, randomised controlled trial (RCT). AF patients requiring OAC who have undergone successful PCI will be randomised within 72 hours after PCI to guideline-directed therapy (edoxaban plus P2Y12 inhibitor plus limited duration of aspirin) or a 30-day DAPT strategy (P2Y12 inhibitor plus aspirin, immediately discontinuing OAC) followed by DAT (edoxaban plus P2Y12 inhibitor). With a sample size of 2,000 patients, this trial is powered to assess both superiority for major or clinically relevant non-major bleeding and non-inferiority for a composite of all-cause death, myocardial infarction, stroke, systemic embolism or stent thrombosis. In summary, the WOEST-3 trial is the first RCT temporarily omitting OAC in AF patients, comparing a 30-day DAPT strategy with guideline-directed therapy post-PCI to reduce bleeding events without hampering efficacy.
Asunto(s)
Anticoagulantes , Fibrilación Atrial , Hemorragia , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Administración Oral , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Aspirina/efectos adversos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Terapia Antiplaquetaria Doble/métodos , Hemorragia/inducido químicamente , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Resultado del TratamientoAsunto(s)
Anticoagulantes , Fibrilación Atrial , Puente de Arteria Coronaria , Humanos , Anticoagulantes/uso terapéutico , Puente de Arteria Coronaria/efectos adversos , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/etiologíaRESUMEN
Pulmonary arterial hypertension (PAH) is a rare and progressive disorder that affects the pulmonary vasculature. Although recent developments in pharmacotherapy have extended the life expectancy of PAH patients, their 5-year survival remains unacceptably low, underscoring the need for multitarget and more comprehensive approaches to managing the disease. This should incorporate not only medical, but also lifestyle interventions, including dietary changes and the use of nutraceutical support. Among these strategies, n-3 polyunsaturated fatty acids (n-3 PUFAs) are emerging as promising agents able to counteract the inflammatory component of PAH. In this narrative review, we aim at analysing the preclinical evidence for the impact of n-3 PUFAs on the pathogenesis and the course of PAH. Although evidence for the role of n-3 PUFAs deficiencies in the development and progression of PAH in humans is limited, preclinical studies suggest that these dietary components may influence several aspects of the pathobiology of PAH. Further clinical research should test the efficacy of n-3 PUFAs on top of approved clinical management. These studies will provide evidence on whether n-3 PUFAs can genuinely serve as a valuable tool to enhance the efficacy of pharmacotherapy in the treatment of PAH.
RESUMEN
Background: Managing patients with atrial fibrillation (AF) and worsening renal function (WRF) remains a clinical challenge due to the need of dose adjustment of non-vitamin K antagonist oral anticoagulants. Objectives: To determine the incidence of WRF in patients with AF treated with edoxaban, the association of WRF with clinical outcomes, and predictors of WRF and clinical outcomes in these patients. Methods: This is a subanalysis of the Edoxaban Treatment in routiNe clinical prActice for patients with non-valvular Atrial Fibrillation in Europe study (NCT02944019), an observational study of edoxaban-treated patients with AF. WRF was defined as a ≥25% reduction in creatinine clearance between baseline and 2 years. Results: Of the 9,054 patients included (69% of the total 13,133 enrolled), most did not experience WRF (90.3%) during the first 2 years of follow-up. WRF occurred in 9.7% of patients. Patients with WRF had significantly higher rates of all-cause death (3.88%/y vs 1.88%/y; P < 0.0001), cardiovascular death (2.09%/y vs 0.92%/y; P < 0.0001), and major bleeding (1.51%/y vs 0.98%/y; P = 0.0463) compared with those without WRF. Rates of intracranial hemorrhage (0.18%/y vs 0.18%/y) and of any stroke/systemic embolic events were low (0.90%/y vs 0.69%/y; P = 0.3161) in both subgroups. The strongest predictors of WRF were a high CHA2DS2-VASc score, high baseline creatinine clearance, low body weight, and older age. Most predictors of WRF were also predictors of clinical outcomes. Conclusions: WRF occurred in approximately 10% of edoxaban-treated AF patients. Rates of death and major bleeding were significantly higher in patients with WRF than without. Stroke events were low in both subgroups.
Asunto(s)
Clopidogrel , Inhibidores de Agregación Plaquetaria , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Clopidogrel/uso terapéutico , Clopidogrel/efectos adversos , Intervención Coronaria Percutánea/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Cardiovascular trials often use a composite end point and a time-to-first event model. We sought to compare edoxaban versus warfarin using the win ratio, which offers data complementary to time-to-first event analysis, emphasizing the most severe clinical events. METHODS: ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) was a double-blind, randomized trial in which patients with atrial fibrillation were assigned 1:1:1 to a higher dose edoxaban regimen (60/30 mg daily), a lower dose edoxaban regimen (30/15 mg daily), or warfarin. In an exploratory analysis, we analyzed the trial outcomes using an unmatched win ratio approach. The win ratio for each edoxaban regimen was the total number of edoxaban wins divided by the number of warfarin wins for the following ranked clinical outcomes: 1: death; 2: hemorrhagic stroke; 3: ischemic stroke/systemic embolic event/epidural or subdural bleeding; 4: noncerebral International Society on Thrombosis and Haemostasis major bleeding; and 5: cardiovascular hospitalization. RESULTS: 21â 105 patients were randomized to higher dose edoxaban regimen (N=7035), lower dose edoxaban regimen (N=7034), or warfarin (N=7046), yielding >49 million pairs for each treatment comparison. The median age was 72 years, 38% were women, and 59% had prior vitamin K antagonist use. The win ratio was 1.11 (95% CI, 1.05-1.18) for higher dose edoxaban regimen versus warfarin and 1.11 (95% CI, 1.05-1.18) for lower dose edoxaban regimen versus warfarin. The favorable impacts of edoxaban on death (34% of wins) and cardiovascular hospitalization (41% of wins) were the major contributors to the win ratio. Results consistently favored edoxaban in subgroups based on creatine clearance and dose reduction at baseline, with heightened benefit among those without prior vitamin K antagonist use. CONCLUSIONS: In a win ratio analysis of the ENGAGE AF-TIMI 48 trial, both dose regimens of edoxaban were superior to warfarin for the net clinical outcome incorporating ischemic and bleeding events. As the win ratio emphasizes the most severe clinical events, this analysis supports the superiority of edoxaban over warfarin in patients with atrial fibrillation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00781391.
Asunto(s)
Anticoagulantes , Fibrilación Atrial , Inhibidores del Factor Xa , Hemorragia , Piridinas , Tiazoles , Warfarina , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/mortalidad , Fibrilación Atrial/complicaciones , Warfarina/efectos adversos , Warfarina/administración & dosificación , Piridinas/efectos adversos , Piridinas/administración & dosificación , Piridinas/uso terapéutico , Tiazoles/administración & dosificación , Tiazoles/efectos adversos , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/administración & dosificación , Método Doble Ciego , Femenino , Masculino , Resultado del Tratamiento , Anciano , Hemorragia/inducido químicamente , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Factores de Tiempo , Factores de Riesgo , Persona de Mediana Edad , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/mortalidad , Anciano de 80 o más Años , Medición de RiesgoRESUMEN
AIMS: Patients with heart failure (HF) remain often undertreated for multiple reasons, including treatment inertia, contraindications, and intolerance. The OPTIimal PHARMacological therapy for patients with Heart Failure (OPTIPHARM-HF) registry is designed to evaluate the prevalence of evidence-based medical treatment prescription and titration, as well as the causes of its underuse, in a broad real-world population of consecutive patients with HF across the whole ejection fraction spectrum and among different clinical phenotypes. METHODS: The OPTIPHARM-HF registry (NCT06192524) is a prospective, multicenter, observational, national study of adult patients with symptomatic HF, as defined by current international guidelines, regardless of ejection fraction. Both outpatients and inpatients with chronic and acute decompensated HF will be recruited. The study will enroll up to 2500 patients with chronic HF at approximately 35 Italian HF centres. Patients will be followed for a maximum duration of 24 months. The primary objective of the OPTIPHARM-HF registry is to assess prescription and adherence to evidence-based guideline-directed medical therapy (GDMT) in patients with HF. The primary outcome is to describe the prevalence of GDMT use according to target guideline recommendation. Secondary objectives include implementation of comorbidity treatment, evaluation of sequence of treatment introduction and up-titration, description of GDMT implementation in the specific HF population, main causes of GDMT underuse, and assessment of cumulative rate of cardiovascular events. CONCLUSION: The OPTIPHARM-HF registry will provide important implications for improving patient care and adoption of recommended medical therapy into clinical practice among HF patients.
Asunto(s)
Insuficiencia Cardíaca , Sistema de Registros , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Estudios Prospectivos , Volumen Sistólico/fisiología , Adhesión a Directriz , Femenino , Masculino , Italia/epidemiologíaRESUMEN
BACKGROUND: To assess long-term effectiveness and safety of edoxaban in Europe. METHODS AND RESULTS: ETNA-AF-Europe, a prospective, multinational, multi-centre, post-authorisation, observational study was conducted in agreement with the European Medicines Agency. The primary and secondary objectives assessed real-world safety (including bleeding and deaths) and effectiveness (including stroke, systemic embolic events and clinical edoxaban use), respectively. Median (interquartile range) age of the 13,164 patients was 75.0 (68.0-80.0) years; CHA2DS2-VASc and HAS-BLED scores were 3.0 (2.0-4.0) and 2.0 (1.0-2.0), respectively. Follow-up duration was 3.98 (3.21-4.05) years. Patients on edoxaban 30 mg (n = 3042) at baseline were older (80.0 vs 73.0 years), more likely assessed as frail by investigators (27.0% vs 6.6%) and had more comorbidities than those on edoxaban 60 mg (n = 9617; missing dosing information for n = 505). Annualised event rates of all-cause and cardiovascular death in the overall population, edoxaban 60 mg and edoxaban 30 mg groups were 4.1%, 2.8% and 8.4%, and 1.0%, 0.7% and 2.0%, respectively. Annualised rates of stroke were relatively constant throughout the follow-up, transient ischaemic attack and systemic embolism were < 1% in the overall population. Rates of any major and major gastrointestinal bleeding were low, with slightly higher rates for edoxaban 30 vs 60 mg group. Intracranial haemorrhage was uncommon (0.2%). CONCLUSIONS: In European patients with AF, long-term therapy with edoxaban is associated with low and relatively constant annualised rates of stroke and major bleeding. Differences in outcomes between the two approved doses are attributable to differences in clinical characteristics.