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BACKGROUND: Pulmonary embolism may have both physical and psychological consequences for the affected person. Guidelines recommend structured follow-up care, yet this is still not widely practised. Therefore, a national research project was initiated in Denmark in 2021, with the aim of developing, testing, implementing, and evaluating a structured post-pulmonary embolism follow-up care model, 'Attend-PE'. The objective of this feasibility study was to examine the fidelity, acceptability, and appropriateness of the Attend-PE model in a Danish hospital setting. METHODS: This feasibility study was conducted in two Danish hospitals, using a prospective study design with six months' follow-up. The fidelity, acceptability, and appropriateness of the Attend-PE model's components were evaluated using surveys, registrations sheets, and interviews with two physicians, three nurses, and 29 patients. Qualitative data were analysed using a deductive content analysis, while quantitative data were analysed using descriptive statistics. RESULTS: Fidelity with the Attend-PE model was good, with a high participation rate of patients in all components of the model. Acceptability was likewise good, as both patients and health care professionals expressed a high level of satisfaction with the model. The health care professionals considered the model to be relevant and suitable in a Danish hospital setting, confirming appropriateness of the model. CONCLUSION: This study showed that the Attend-PE model for patients with pulmonary embolism is feasible and acceptable in a Danish hospital setting.
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Estudios de Factibilidad , Embolia Pulmonar , Humanos , Embolia Pulmonar/terapia , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Estudios de Seguimiento , Dinamarca , AdultoRESUMEN
BACKGROUND: More than 50% of patients with pulmonary embolism (PE) experience persistent functional limitations. Despite guideline recommendations for a structured integrated care model for patients with PE, consensus on an optimal follow-up strategy is lacking, and evidence is insufficient. OBJECTIVES: To describe the development of a structured model for PE follow-up using coproduction methods. METHODS: Coproduction of A structured integrated postPulmonary Embolism care (Attend-PE) model was conducted from October 2021 to June 2022, featuring participatory design techniques. This was combined with a stepwise approach based on Intervention Mapping to ensure that the developed model was evidence-based and theoretically grounded. RESULTS: Development of the Attend-PE model included 1) a needs assessment mapping follow-up at 18 sites treating PE in Denmark; 2) definition of the overall goal and performance objectives of the Attend-PE model, based on the needs assessment in combination with a literature review; 3) coproduction of the Attend-PE model in workshops with patient representatives, healthcare professionals, and experts in the field; and 4) refinement of the structure and organization of the Attend-PE model and production of the patient education material. The Attend-PE model outlines a structured approach for in-hospital follow-up, involving group-based patient education, individual consultations, and patient-reported outcomes to assess physical and psychological well-being. The model supports a personalized posthospitalization care plan. CONCLUSION: The coproduction process was successful in developing a structured follow-up model aligned with patients' needs, health provider perspectives, and existing guidelines. The Attend-PE model is currently undergoing clinical evaluation to determine its effectiveness and usability.
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BACKGROUND: Patent foramen ovale (PFO) has been associated with ischemic stroke and transient ischemic attack (TIA). Guidelines recommend PFO closure for stroke prevention in selected patients, but the risk of recurrent stroke remains high compared to the background population. We aimed to evaluate the causes of recurrent stroke/TIA and post-interventional complications in patients after PFO closure. METHODS: Patients from the Central Denmark Region who underwent PFO closure at Aarhus University Hospital between November 5, 2018, and May 12, 2023, following an ischemic stroke, TIA, amaurosis fugax or retinal emboli were included. Data on patient demographics, risk factors, procedural details, post-interventional complications and recurrent stroke/TIA were collected from electronic medical records. RESULTS: PFO closure was performed in 310 patients (median age: 49 years). During a median follow-up of 2.6 years (interquartile range: 1.5-3.6, 814 total patient years), recurrent stroke/TIA was observed in 8 patients (2.6%) or 0.98 recurrent strokes per 100 patient years. Recurrent stroke/TIA was more frequent in patients with hypertension (50.0% vs 16.9%, p = 0.039). Recurrent stroke/TIA was related to thrombophilia or haematological conditions entailing hypercoagulability in 62.5% of patients. New-onset atrial fibrillation was observed in 9.4% of patients within 45 days after the procedure. None of these patients subsequently developed an ischemic event. Other adverse outcomes were uncommon. CONCLUSION: Rates of recurrent ischaemic stroke/TIA after PFO closure were comparable to findings in previous trials. Pre-existing vascular risk factors (hypertension), and a hypercoagulable state were associated with recurrent ischaemic stroke/TIA.
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BACKGROUND: The prognostic impact of complete coronary revascularization relative to non-invasive testing methods is unknown. OBJECTIVES: To assess the association between completeness of revascularization defined by CTA-derived fractional flow reserve (FFRCT) and cardiovascular outcomes in patients with stable angina. METHODS: Multicenter 3-year follow-up study of patients with new onset stable angina and ≥ 30% stenosis by CTA. The lesion-specific FFRCT value (two cm-distal-to-stenosis) was registered in all vessels with stenosis and considered abnormal when ≤ 0.80. Patients with FFRCT ≤ 0.80 were categorized as: Completely revascularized (CR-FFRCT), all vessels with FFRCT ≤ 0.80 revascularized; incompletely revascularized (IR-FFRCT), ≥ 1 vessels with FFRCT ≤ 0.80 non-revascularized. Early revascularization (< 90 days from index CTA) categorized vessels as revascularized. The primary endpoint comprised cardiovascular death and non-fatal myocardial infarction; the secondary endpoint vessel-specific late revascularization and non-fatal myocardial infarction. RESULTS: Amongst 900 patients and 1759 vessels, FFRCT was ≤ 0.80 in 377 (42%) patients, 536 (30%) vessels; revascularization was performed in 244 (27%) patients, 340 (19%) vessels. Risk of the primary endpoint was higher for IR-FFRCT (15/210 [7.1%]) compared to CR-FFRCT (4/167 [2.4%]), RR: 2.98; 95% CI: 1.01-8.8, p â= â0.036, and to normal FFRCT (3/523 [0.6%]), RR: 12.45; 95% CI: 3.6-42.6, p â< â0.001. Incidence of the secondary endpoint was higher in non-revascularized vessels with FFRCT ≤ 0.80 (29/250 [12%]) compared to revascularized vessels with FFRCT ≤ 0.80 (5/286 [1.7%]), p â= â0.001, and to vessels with FFRCT > 0.80 (10/1223 [0.8%]), p â< â0.001. CONCLUSION: Incomplete revascularization of patients with lesion-specific FFRCT ≤ 0.80 is associated to unfavorable cardiovascular outcomes compared to those with complete revascularization or FFRCT > 0.80.
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Angina Estable , Angiografía por Tomografía Computarizada , Angiografía Coronaria , Estenosis Coronaria , Reserva del Flujo Fraccional Miocárdico , Valor Predictivo de las Pruebas , Humanos , Masculino , Femenino , Angina Estable/fisiopatología , Angina Estable/mortalidad , Angina Estable/diagnóstico por imagen , Angina Estable/cirugía , Angina Estable/terapia , Persona de Mediana Edad , Anciano , Resultado del Tratamiento , Factores de Riesgo , Factores de Tiempo , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/fisiopatología , Estenosis Coronaria/mortalidad , Estenosis Coronaria/cirugía , Medición de Riesgo , Índice de Severidad de la Enfermedad , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/fisiopatología , Revascularización Miocárdica , Infarto del Miocardio/mortalidad , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/mortalidad , Tomografía Computarizada MultidetectorRESUMEN
BACKGROUND AND AIMS: Chronic kidney disease (CKD) is present in >30% of patients with acute myocardial infarction (MI) and has been associated with lower rates of guideline-directed management and worse prognosis. We investigated the use of guideline-directed management and mortality risk in patients with and without CKD. METHODS: A nationwide cohort study based on health care registers encompassing all patients ≥18 years hospitalized with first-time MI in Denmark from 2010-2022 was conducted. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Probability of guideline-directed management and risk of all-cause mortality in patients with and without CKD were calculated from adjusted multivariable logistic and Cox regression models with probabilities and risks standardized to the distribution of confounders in the population. RESULTS: In total, we identified 21,009 patients who met eligibility criteria. Median age was 72 years, and 61% of patients were males; the median eGFR was 82 ml/min/1.73 m2, and 21% of patients had CKD. The 30-day probabilities of coronary angiography and revascularization were 71% (95% CI 69%-72%) and 78% (95% CI 77-79%), p<0.001; and 52% (95% CI 50%-54%) and 58% (95% CI 58%-59%), p<0.001, in patients with and without CKD, respectively. Probabilities increased during the study period (p for trend 0.05, 0.03, 0.02 and 0.03, respectively). In patients with and without CKD, probability of dual antiplatelet therapy was 67% (95% CI 65%-68%) and 70% (95% CI 69%-71%), p=0.001; while probability of lipid-lowering treatment was 76% (95% CI 75%-78%) and 82% (95% CI 81%-83%), p<0.001. Associated one-year mortality was 21% (95% CI 20%-22%) and 16.4% (95% CI 16%-17%) in patients with and without CKD, respectively. with decreasing mortality rates in both groups during the study period (p for trend 0.03 and 0.01). CONCLUSIONS: Although survival following MI improved for all patients, CKD continued to be associated with lower use of guideline-directed management and higher mortality.
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AIMS: Direct oral anticoagulants (DOACs) are increasingly used off-label to treat patients with left ventricular thrombus (LVT). We analysed available meta-data comparing DOACs and vitamin K antagonists (VKAs) for efficacy and safety. METHODS: We conducted a systematic search and meta-analysis of observational and randomized data comparing DOACs vs. VKAs in patients with LVT. Endpoints of interest were stroke or systemic embolism, thrombus resolution, all-cause death, and a composite bleeding endpoint. Estimates were pooled using a random-effects model meta-analysis, and their robustness was investigated using sensitivity and influential analyses. RESULTS: We identified 22 articles (18 observational studies, 4 small randomized clinical trials) reporting on a total of 3587 patients (2489 VKA vs. 1098 DOAC therapy). The pooled estimates for stroke or systemic embolism [odds ratio (OR): 0.81; 95% confidence interval (CI): 0.57, 1.15] and thrombus resolution (OR: 1.12; 95% CI: 0.86, 1.46) were comparable, and there was low heterogeneity overall across the included studies. The use of DOACs was associated with lower odds of all-cause death (OR: 0.65; 95% CI: 0.46, 0.92) and a composite bleeding endpoint (OR: 0.67; 95% CI: 0.47, 0.97). A risk of bias was evident particularly for observational reports, with some publication bias suggested in funnel plots. CONCLUSION: In this comprehensive analysis of mainly observational data, the use of DOACs was not associated with a significant difference in stroke or systemic embolism, or thrombus resolution, compared with VKA therapy. The use of DOACs was associated with a lower rate of all-cause death and fewer bleeding events. Adequately sized randomized clinical trials are needed to confirm these findings, which could allow a wider adoption of DOACs in patients with LVT.
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Cardiopatías , Hemorragia , Trombosis , Humanos , Administración Oral , Trombosis/mortalidad , Trombosis/tratamiento farmacológico , Trombosis/prevención & control , Trombosis/diagnóstico , Hemorragia/inducido químicamente , Resultado del Tratamiento , Factores de Riesgo , Cardiopatías/mortalidad , Cardiopatías/diagnóstico , Cardiopatías/tratamiento farmacológico , Cardiopatías/complicaciones , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Ventrículos Cardíacos/efectos de los fármacos , Femenino , Medición de Riesgo , Masculino , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/prevención & control , Anciano , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/administración & dosificación , Vitamina K/antagonistas & inhibidores , Persona de Mediana EdadRESUMEN
BACKGROUND: Some autoimmune diseases carry elevated risk for atherosclerotic cardiovascular disease (ASCVD), yet the underlying mechanism and the influence of traditional risk factors remain unclear. OBJECTIVES: This study sought to determine whether autoimmune diseases independently correlate with coronary atherosclerosis and ASCVD risk and whether traditional cardiovascular risk factors modulate the risk. METHODS: The study included 85,512 patients from the Western Denmark Heart Registry undergoing coronary computed tomography angiography. A diagnosis of 1 of 18 autoimmune diseases was assessed. Adjusted OR (aOR) for any plaque, any coronary artery calcification (CAC), CAC of >90th percentile, and obstructive coronary artery disease as well as adjusted HR (aHR) for ASCVD were calculated. RESULTS: During 5.3 years (Q1-Q3: 2.8-8.2 years) of follow-up, 3,832 ASCVD events occurred. A total of 4,064 patients had a diagnosis of autoimmune disease, which was associated with both presence of any plaque (aOR: 1.29; 95% CI: 1.20-1.40), any CAC (aOR: 1.28; 95% CI: 1.19-1.37), and severe CAC of >90th percentile (aOR: 1.53; 95% CI: 1.39-1.68), but not with having obstructive coronary artery disease (aOR: 1.04; 95% CI: 0.91-1.17). Patients with autoimmune diseases had a 46% higher risk (aHR: 1.46; 95% CI: 1.29-1.65) for ASCVD. Traditional cardiovascular risk factors were strongly associated with future ASCVD events, and a favorable cardiovascular risk factor profile in autoimmune patients was associated with â¼54% lower risk compared to patients with presence of risk factors (aHR: 0.46; 95% CI: 0.27-0.81). CONCLUSIONS: Autoimmune diseases were independently associated with higher burden of coronary atherosclerosis and higher risk for future ASCVD events, with risk accentuated by traditional cardiovascular risk factors. These findings suggest that autoimmune diseases increase risk through accelerated atherogenesis and that cardiovascular risk factor control is key for improving prognosis in patients with autoimmune diseases.
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Enfermedades Autoinmunes , Enfermedad de la Arteria Coronaria , Sistema de Registros , Índice de Severidad de la Enfermedad , Humanos , Enfermedad de la Arteria Coronaria/epidemiología , Masculino , Femenino , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/complicaciones , Persona de Mediana Edad , Anciano , Dinamarca/epidemiología , Angiografía por Tomografía Computarizada , Angiografía Coronaria , Factores de Riesgo , Isquemia Miocárdica/epidemiología , Estudios de SeguimientoRESUMEN
BACKGROUND: Reduced effect of antiplatelet therapy has been reported in patients with ST-segment elevation myocardial infarction (STEMI). Multiple factors may concur to explain this, including increased amount of highly reactive immature platelets. OBJECTIVES: To investigate the association between immature platelets and reactivity determined with multicolour flow cytometry using the SYTO-13 dye in STEMI patients. METHODS: We conducted an observational study of 59 patients with acute STEMI. Blood samples were obtained within 24 h after admission and after loading doses of dual antiplatelet therapy. For comparison, samples were obtained from 50 healthy individuals. Immature platelets and platelet reactivity were investigated using multicolour flow cytometry including the SYTO-13 dye that binds to platelet RNA and thus provides a method for subdividing platelets into immature and mature platelets. Additionally, we assessed platelet aggregation, serum-thromboxane B2 levels and standard immature platelet markers. RESULTS: Immature platelets were more reactive than mature platelets in both STEMI patients and healthy individuals (p-values < 0.05). STEMI patients had lower platelet aggregation and thromboxane B2 levels than healthy individuals. We found a positive association between automatically determined immature platelet markers and CD63 expression on activated platelets (Spearman's rho: 0.27 to 0.58, p-values < 0.05). CONCLUSIONS: Our study shows that immature platelets identified with a multicolour flow cytometric method using the SYTO-13 dye are more reactive than mature platelets in patients with acute STEMI and in healthy individuals. The presence of immature platelets may be important for the overall platelet reactivity, which may have implications for the effect of antiplatelet therapy.
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Plaquetas , Citometría de Flujo , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/sangre , Plaquetas/metabolismo , Citometría de Flujo/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Activación Plaquetaria/efectos de los fármacosRESUMEN
Heart failure (HF) patients have a significantly higher risk of new-onset cancer and cancer-associated mortality, compared to subjects free of HF. While both the prevention and treatment of new-onset HF in patients with cancer have been investigated extensively, less is known about the prevention and treatment of new-onset cancer in patients with HF, and whether and how guideline-directed medical therapy (GDMT) for HF should be modified when cancer is diagnosed in HF patients. The purpose of this review is to elaborate and discuss the effects of pillar HF pharmacotherapies, as well as digoxin and diuretics on cancer, and to identify areas for further research and novel therapeutic strategies. To this end, in this review, (i) proposed effects and mechanisms of action of guideline-directed HF drugs on cancer derived from pre-clinical data will be described, (ii) the evidence from both observational studies and randomized controlled trials on the effects of guideline-directed medical therapy on cancer incidence and cancer-related outcomes, as synthetized by meta-analyses will be reviewed, and (iii) considerations for future pre-clinical and clinical investigations will be provided.
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Insuficiencia Cardíaca , Neoplasias , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Neoplasias/epidemiologíaRESUMEN
Although cardiovascular diseases (CVDs) are the leading cause of death worldwide, their pharmacotherapy remains suboptimal. Thus, there is a clear unmet need to develop more effective and safer pharmacological strategies. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2023, including the approval of first-in-class drugs that open new avenues for the treatment of atherosclerotic CVD and heart failure (HF). The new indications of drugs already marketed (repurposing) for the treatment of obstructive hypertrophic cardiomyopathy, hypercholesterolaemia, type 2 diabetes, obesity, and HF; the impact of polypharmacy on guideline-directed drug use is highlighted as well as results from negative clinical trials. Finally, we end with a summary of the most important phase 2 and 3 clinical trials assessing the efficacy and safety of cardiovascular drugs under development for the prevention and treatment of CVDs.
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Fármacos Cardiovasculares , Enfermedades Cardiovasculares , Humanos , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/prevención & control , Fármacos Cardiovasculares/uso terapéutico , Fármacos Cardiovasculares/efectos adversos , Resultado del Tratamiento , Animales , Reposicionamiento de Medicamentos , Desarrollo de MedicamentosRESUMEN
Background The clinical presentation of coronary artery disease can range from asymptomatic, through stable disease in the form of chronic coronary syndrome, to acute coronary syndrome. Chronic coronary syndrome is a frequent condition, and secondary prevention of ischaemic events is essential. Summary Antithrombotic therapy is a key component of secondary prevention strategies, and it may vary in type and intensity depending on patient characteristics, comorbidities, and revascularisation modalities. Dual antiplatelet therapy is the default strategy in patients with chronic coronary syndrome and recent coronary stent implantation, while antiplatelet monotherapy is commonly prescribed for long-term prevention of cardiovascular events. Oral anticoagulation, in combination with antiplatelet therapy or alone, is used in patients with e.g., concomitant atrial fibrillation or venous thromboembolism. Key messages This review provides an overview of antithrombotic treatment strategies in patients with chronic coronary syndrome. Key messages from current guidelines are conveyed, and we provide future perspectives on long-term antithrombotic strategies.
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INTRODUCTION: Up to 50 % of patients surviving a pulmonary embolism (PE) report persisting shortness of breath, reduced physical capacity and psychological distress. As the PE population is heterogeneous compared to other cardiovascular patient groups, outcome measures for assessing physical capacity traditionally used in cardiac populations may not be reliable for the PE population as a whole. This scoping review aims to 1) map performance-based outcome measures (PBOMs) used for assessing physical capacity in PE research, and 2) to report the psychometric properties of the identified PBOMs in a PE population. METHODS: The review was conducted according to the Joanna Briggs Institute framework for scoping reviews and reported according to the PRISMA-Extension for Scoping Reviews guideline. RESULTS: The systematic search of five databases identified 4585 studies, of which 243 studies met the inclusion criteria. Of these, 185 studies focused on a subgroup of patients with chronic thromboembolic pulmonary hypertension. Ten different PBOMs were identified in the included studies. The 6-minute walk test (6MWT) and cardiopulmonary exercise test (CPET) were the most commonly used, followed by the (Modified) Bruce protocol and Incremental Shuttle Walk test. No studies reported psychometric properties of any of the identified PBOMs in a PE population. CONCLUSIONS: Publication of studies measuring physical capacity within PE populations has increased significantly over the past 5-10 years. Still, not one study was identified, reporting the validity, reliability, or responsiveness for any of the identified PBOMs in a PE population. This should be a priority for future research in the field.
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Prueba de Esfuerzo , Embolia Pulmonar , Humanos , Reproducibilidad de los Resultados , Embolia Pulmonar/diagnóstico , Psicometría , Evaluación de Resultado en la Atención de SaludRESUMEN
BACKGROUND: The association between coronary computed tomography angiography (CTA) derived fractional flow reserve (FFRCT) and risk of recurrent angina in patients with new onset stable angina pectoris (SAP) and stenosis by CTA is uncertain. METHODS: Multicenter 3-year follow-up study of patients presenting with symptoms suggestive of new onset SAP who underwent first-line CTA evaluation and subsequent standard-of-care treatment. All patients had at least one ≥30 â% coronary stenosis. A per-patient lowest FFRCT-value ≤0.80 represented an abnormal test result. Patients with FFRCT ≤0.80 who underwent revascularization were categorized according to completeness of revascularization: 1) Completely revascularized (CR-FFRCT), all vessels with FFRCT ≤0.80 revascularized; or 2) incompletely revascularized (IR-FFRCT) ≥1 vessels with FFRCT ≤0.80 non-revascularized. Recurrent angina was evaluated using the Seattle Angina Questionnaire. RESULTS: Amongst 769 patients (619 [80 â%] stenosis ≥50 â%, 510 [66 â%] FFRCT ≤0.80), 174 (23 â%) reported recurrent angina at follow-up. An FFRCT ≤0.80 vs â> â0.80 associated to increased risk of recurrent angina, relative risk (RR): 1.82; 95 â% CI: 1.31-2.52, p â< â0.001. Risk of recurrent angina in CR-FFRCT (n â= â135) was similar to patients with FFRCT >0.80, 13 â% vs 15 â%, RR: 0.93; 95 â% CI: 0.62-1.40, p â= â0.72, while IR-FFRCT (n â= â90) and non-revascularized patients with FFRCT ≤0.80 (n â= â285) had increased risk, 37 â% vs 15 â% RR: 2.50; 95 â% CI: 1.68-3.73, p â< â0.001 and 30 â% vs 15 â%, RR: 2.03; 95 â% CI: 1.44-2.87, p â< â0.001, respectively. Use of antianginal medication was similar across study groups. CONCLUSION: In patients with SAP and coronary stenosis by CTA undergoing standard-of-care guided treatment, FFRCT provides information regarding risk of recurrent angina.
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Angiografía por Tomografía Computarizada , Angiografía Coronaria , Estenosis Coronaria , Reserva del Flujo Fraccional Miocárdico , Valor Predictivo de las Pruebas , Recurrencia , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Factores de Riesgo , Estudios de Seguimiento , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/fisiopatología , Estenosis Coronaria/terapia , Factores de Tiempo , Medición de Riesgo , Angina Estable/fisiopatología , Angina Estable/diagnóstico por imagen , Angina Estable/terapia , Índice de Severidad de la Enfermedad , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/fisiopatología , PronósticoRESUMEN
BACKGROUND: Reduced effect of antiplatelet therapy has been reported in patients with ST-segment elevation myocardial infarction (STEMI). MicroRNAs (miRs) may influence platelet function and maturity, and subsequently the effect of antiplatelet therapy. OBJECTIVES: We aimed to explore the association between miR expression and platelet function and maturity in patients with acute STEMI and healthy individuals. METHODS: We performed an observational study of STEMI patients admitted directly to primary percutaneous coronary intervention. Patients were treated with antiplatelet therapy according to guidelines. Within 24 hours after admission, blood samples were obtained to measure: the expression of 10 candidate miRs, platelet function markers using advanced flow cytometry, platelet aggregation, serum thromboxane B2, and platelet maturity markers. Furthermore, blood samples from healthy individuals were obtained to determine the normal variation. RESULTS: In total, 61 STEMI patients and 50 healthy individuals were included. STEMI patients had higher expression of miR-21-5p, miR-26b-5p, and miR-223-3p and lower expression of miR-150-5p, miR423-5p, and miR-1180-3p than healthy individuals. In STEMI patients, the expression of miR-26b-5p showed the most consistent association with platelet function (all p-values <0.05, Spearman's rho ranging from 0.27 to 0.41), while the expression of miR-150-5p and miR-223-3p showed negative associations with platelet function. No association between miR expression and platelet maturity markers was observed. CONCLUSION: In patients with STEMI, the expression of six miRs was significantly different from healthy individuals. The expression of miR-26b-5p may affect platelet function in acute STEMI patients and potentially influence the effect of antiplatelet therapy.
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MicroARNs , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/genética , Infarto del Miocardio con Elevación del ST/terapia , Inhibidores de Agregación Plaquetaria/uso terapéutico , MicroARNs/genética , Agregación PlaquetariaRESUMEN
Venous thromboembolism (VTE) is a frequent complication of cancer, and management of cancer-associated thrombosis (CAT) is challenging due to increased risks of bleeding and recurrent VTE. Recent trials have shown an acceptable efficacy and safety of direct oral anticoagulants (DOACs) in the treatment of CAT compared to low-molecular weight heparin. Although DOACs provide an effective and convenient treatment option in CAT, the need to assess the risk of drug-drug interactions (DDI) with antineoplastic therapies poses a barrier to their use in clinical practice. With the aim of supporting the assessment of CAT patients for treatment with DOAC, this review provides a comprehensive overview of the compatibility of antineoplastic therapies with the individual DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban). Using several data sources, we characterized 100 widely used antineoplastic agents with regard to their effect on p-glycoprotein and cytochrome P450, both important in the transport and elimination of DOACs. This enabled us to evaluate 400 "DOAC-antineoplastic agent"-pairs regarding their likelihood to interact (unlikely, potential, or likely), ultimately leading to clinical recommendations on the appropriateness of concomitant use for each pair. A potential or likely DDI was identified for 12% of the evaluated pairs. For nearly all antineoplastic agents, at least one DOAC was considered compatible.
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Antineoplásicos , Neoplasias , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiología , Tromboembolia Venosa/complicaciones , Anticoagulantes/uso terapéutico , Dabigatrán/uso terapéutico , Rivaroxabán/uso terapéutico , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Antineoplásicos/efectos adversos , Interacciones Farmacológicas , Administración OralRESUMEN
Importance: Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke. Objective: To evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke. Design, Setting, and Participants: This was a randomized clinical trial conducted at 4 stroke centers in Denmark that included 1500 patients with prehospital stroke symptoms for less than 4 hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023). Intervention: The intervention was delivered using an inflatable cuff on 1 upper extremity (RIC cuff pressure, ≤200 mm Hg [n = 749] and sham cuff pressure, 20 mm Hg [n = 751]). Each treatment application consisted of 5 cycles of 5 minutes of cuff inflation followed by 5 minutes of cuff deflation. Treatment was started in the ambulance and repeated at least once in the hospital and then twice daily for 7 days among a subset of participants. Main Outcomes and Measures: The primary end point was improvement in functional outcome measured as a shift across the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) at 90 days in the target population with a final diagnosis of ischemic or hemorrhagic stroke. Results: Among 1500 patients who were randomized (median age, 71 years; 591 women [41%]), 1433 (96%) completed the trial. Of these, 149 patients (10%) were diagnosed with transient ischemic attack and 382 (27%) with a stroke mimic. In the remaining 902 patients with a target diagnosis of stroke (737 [82%] with ischemic stroke and 165 [18%] with intracerebral hemorrhage), 436 underwent RIC and 466 sham treatment. The median mRS score at 90 days was 2 (IQR, 1-3) in the RIC group and 1 (IQR, 1-3) in the sham group. RIC treatment was not significantly associated with improved functional outcome at 90 days (odds ratio [OR], 0.95; 95% CI, 0.75 to 1.20, P = .67; absolute difference in median mRS score, -1; -1.7 to -0.25). In all randomized patients, there were no significant differences in the number of serious adverse events: 169 patients (23.7%) in the RIC group with 1 or more serious adverse events vs 175 patients (24.3%) in the sham group (OR, 0.97; 95% CI, 0.85 to 1.11; P = .68). Upper extremity pain during treatment and/or skin petechia occurred in 54 (7.2%) in the RIC group and 11 (1.5%) in the sham group. Conclusions and Relevance: RIC initiated in the prehospital setting and continued in the hospital did not significantly improve functional outcome at 90 days in patients with acute stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT03481777.
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Isquemia , Poscondicionamiento Isquémico , Accidente Cerebrovascular , Anciano , Femenino , Humanos , Hemorragia Cerebral/etiología , Hemorragia Cerebral/terapia , Ataque Isquémico Transitorio/terapia , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular/terapia , Poscondicionamiento Isquémico/métodos , Extremidades/irrigación sanguínea , Recuperación de la Función , Dinamarca , Accidente Cerebrovascular Hemorrágico/terapiaRESUMEN
BACKGROUND AND AIMS: Obstructive sleep apnea (OSA) may accelerate arterial calcification, but the relation remains unexplored in diabetic kidney disease (DKD). We examined the associations between OSA, coronary calcification and large artery stiffness in patients with DKD and reduced renal function. METHODS: Patients with type 2 diabetes, estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 and urine albumin-creatinine ratio (UACR) > 30 mg/g were tested for OSA quantified by the apnea-hypopnea index (AHI, events/hour). Patients without OSA (AHI< 5) were compared to patients with moderate (AHI 15-29) or severe (AHI ≥30) OSA and underwent computed tomography angiography with coronary Agatston scoring (CAS) to quantify coronary calcification. Arterial stiffness was determined as carotid-femoral pulse wave velocity (PWV). RESULTS: Among 114 patients with acceptable AHI recordings had 43 no OSA, 33 mild OSA and 38 moderate-severe OSA. Mean age of the 74 patients completing the study was 71.5 ± 9.4 years (73% males), eGFR 32.2 ± 12.3 ml/min/1.73 m2 and UACR 533 (192-1707) mg/g. CAS (ln-transformed) was significantly higher in patients with OSA compared to patients without (6.6 ± 1.7 vs. 5.6 ± 2.4, p = 0.04), and the same was observed for PWV (11.9 ± 2.7 vs. 10.5 ± 2.2 m/s, p = 0.02). In multivariable linear regression analyses adjusted for sex, age, body mass index, UACR, and mean arterial pressure, moderate-severe OSA remained significantly associated with PWV but not with CAS. Dominance analysis revealed OSA as the third and second most important factor relative to CAS and PWV respectively. CONCLUSIONS: In DKD patients, moderate-severe OSA is a significant predictor of arterial stiffness but is not independently associated with coronary calcification.
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AIM: To identify the absolute risk, causes and factors associated with rehospitalization within 1 year of discharge with a pulmonary embolism (PE). METHODS AND RESULTS: Using the Danish nationwide registries, all patients admitted with a first-time PE between 2000 and 2020 and discharged alive were included. Subsequent hospitalizations were categorized and crude cumulative incidences, were used to estimate the absolute risk (AR) of any rehospitalization and specific causes of rehospitalizations. Risk factors for rehospitalization were investigated using cause specific Cox regression models.A total of 55 201 patients were identified. The median age of the study population was 70 years (inter quartile range: 59;79), and the most prevalent comorbidities were cancer (29.3%) and ischemic heart disease (12.7%). The 1-year AR of any rehospitalization after discharge with a PE was 48.6% (95% confidence interval (CI); 48.2%-48.8%). The most common cause for being rehospitalized was due to respiratory disease (1-year AR: 9.5% (95% CI: 9.3%-9.8%)), followed by cardiovascular disease (1-year AR: 6.3% (95% CI: 5.9%-6.5%)), cancer (1-year AR: 6.0% (95% CI: 5.8%-6.4%)), venous thromboembolism (1-year AR: 5.2% (95% CI: 5.0%-5.2%)), and symptom diagnoses (1-year AR: 5.2% (95%CI: 5.0%-5.4%)). Factors that were associated with an increased risk of rehospitalization were cancer, liver disease, chronic obstructive pulmonary disease, chronic kidney disease, and immobilization. CONCLUSION: Patients with PE have a high risk of rehospitalization, with almost half of patients being rehospitalized within 1 year. Identification of high-risk patients may help target interventions aiming at reducing the risk of rehospitalization.
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AIMS: To characterize and follow patients with ST-segment elevation myocardial infarction (STEMI) at high bleeding risk (HBR) according to the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score, and to examine the use of P2Y12 inhibitors and the subsequent risk of major adverse cardiovascular events (MACE) and bleeding. METHODS AND RESULTS: This single-centre cohort study included 6179 consecutive STEMI patients who underwent percutaneous coronary intervention (PCI) at Copenhagen University Hospital, Rigshospitalet, between 2009 and 2016. Individual linkage to nationwide registries was conducted to obtain information on diagnoses, claimed drugs, and vital status. Of the 5532 (89.5%) patients with available PRECISE-DAPT scores, 33.0% were at HBR and more often elderly and female with more comorbidities than non-HBR patients. One-year cumulative incidence rates per 100 person-years were 8.7 and 2.1 for major bleeding and 36.8 and 8.3 for MACE in HBR and non-HBR patients, respectively. Among the 4749 (85.8%) patients who survived and collected a P2Y12 inhibitor ≤7 days from discharge, 68.2% of HBR patients were treated with ticagrelor or prasugrel and 31.8% with clopidogrel, while 18.2% non-HBR patients were treated with clopidogrel. Adherence was high for all (>75% days coverage). The risk of MACE was lower in ticagrelor- and prasugrel-treated patients than in clopidogrel-treated patients without differences in major bleeding. CONCLUSION: One-third of PCI-treated all-comer patients with STEMI were at HBR according to the PRECISE-DAPT score and were more often treated with potent P2Y12 inhibitors instead of clopidogrel. Thus, ischaemic risk may be weighted over bleeding risk in STEMI patients at HBR.