Cardiovascular toxicity of checkpoint inhibitors: review of associated toxicity and design of the Spanish Immunotherapy Registry of Cardiovascular Toxicity

Immune checkpoint inhibitors (ICI) have changed the prognosis of many tumors. However, concerning associated cardiotoxicity has been reported. Little is known about the real-life incidence-specific surveillance protocols or the translational correlation between the underlying mechanisms and the clinical presentation of ICI-induced cardiotoxicity. The lack of data from prospective studies led us to review the current knowledge and to present the creation of the Spanish Immunotherapy Registry of Cardiovascular Toxicity (SIR-CVT), a prospective registry of patients receiving ICI that aims to examine the role of hsa-miR-Chr8:96, (a specific serum biomarker of myocarditis) in the early diagnosis of ICI-induced myocarditis. An exhaustive prospective cardiac imaging study will be performed before and during the first 12 months of treatment. The correlation between clinical, imaging, and immunologic parameters may improve our understanding of ICI-induced cardiotoxicity and enable simpler surveillance protocols. We assess ICI-induced cardiovascular toxicity and describe the rationale of the SIR-CVT (AU)

Impact of the Spanish consensus for improving lipid control on patients admitted for an acute coronary syndrome.

INTRODUCTION: In 2020, the Spanish Society of Cardiology published a consensus to improve lipid control in secondary prevention patients. This study was aimed to assess the impact of the implementation of this consensus in clinical practice. METHODS: Non-interventional, national and multicenter study, with a prospective and retrospective design in two cohorts. Implementation of the consensus was performed on the prospective cohort. Prospective cohort included patients with acute coronary syndrome (ACS) from December 2020 to March 2022 and were followed-up for 3 months. Retrospective cohort included patients with ACS in the same hospital, matched for main baseline clinical characteristics, between August 2019 to February 2020, with a follow-up of 3 months. Additionally, patients were included if they had previously received lipid-lowering therapy and LDL cholesterol (LDL-C) was >55 mg/dL. RESULTS: A total of 516 patients were included (245 in the prospective cohort and 271 in the retrospective cohort). Overall, mean age was 67.9 ± 11.4 years, 73.8 % were men, and 35.8 % had diabetes. At discharge, 98.4 % and 98.9 %, respectively (P = 0.71) were taking statins (90.6% vs 88.9 %; P = 0.564 high intensity statins), 58.4% vs 33.2 %; P<0.001 ezetimibe, 1.2% vs 0.4 %; P = 0.35 PCSK9 inhibitors. During the follow-up, the dose of statins was increased in 11.4% vs 3.3 % (P<0.001), and ezetimibe was added in 25.7% vs 25.8 % (P = 0.976). At study end, significantly more patients achieved LDL-C <55 mg/dL in the prospective cohort (45.6% vs 33.5 %; P = 0.013). CONCLUSIONS: The implementation of the Spanish lipid consensus was associated with a significant improvement of LDL-C control after only 3 months.

Control de la hipercolesterolemia en España: una misma situación con diferentes realidades autonómicas / Hypercholesterolaemia control in Spain: The same situation with different regional realities

Introducción y objetivos: La estrategia de prevención cardiovascular en las comunidades autónomas (CCAA) puede ser variable, al estar transferidas las competencias en sanidad. El objetivo del estudio fue conocer el control de la dislipemia y la terapia hipolipemiante utilizada en pacientes de alto/muy alto riesgo cardiovascular (RCV) por CCAA. Métodos: Estudio descriptivo, transversal, multicéntrico no aleatorizado basado en una metodología de consenso. Se recogió información de práctica clínica en 145 áreas sanitarias de 17CCAA españolas mediante reuniones presenciales y cuestionarios realizados a los 435 médicos participantes. Se recopilaron datos agregados no identificables de 10 pacientes dislipémicos consecutivos que cada participante hubiera visitado recientemente. Resultados: De los 4.010 pacientes compilados, 649 (16%) eran de alto y 2.458 (61%) de muy alto RCV. La distribución de los 3.107 pacientes de alto/muy alto RCV fue equilibrada entre regiones, pero hubo diferencias interterritoriales (p<0,0001) en la consecución del objetivo de cLDL<70 e <55mg/dl, respectivamente. Las estatinas de alta intensidad en monoterapia o combinadas con ezetimiba y/o inhibidores PCSK9 se utilizaron en el 44, el 21 y el 4% de los pacientes de alto RCV, mientras que en los de muy alto RCV era del 38, del 45 y del 6%, respectivamente. El uso de estas terapias hipolipemiantes a nivel nacional fue significativamente diferente entre regiones (p=0,0079). Conclusiones: A pesar de que la distribución de los pacientes de alto/muy alto RCV fue similar entre CCAA, se identificaron diferencias interterritoriales en el grado de consecución del objetivo terapéutico en cLDL y de utilización de la terapia hipolipemiante. (AU)

Introduction and objective: The cardiovascular prevention strategy by autonomous communities can be variable since the competences in health are transferred. The objective of the study was to determine the degree of dyslipidaemia control and the lipid-lowering pharmacological therapy used in patients at high/very high cardiovascular risk (CVR) by autonomous communities. Methods: Observational, cross-sectional, descriptive study based on a consensus methodology. Information on the clinical practice of 145 health areas belonging to 17 Spanish autonomous communities was collected through face-to-face meetings and questionnaires administered to the 435 participating physicians. Furthermore, aggregate non-identifiable data were compiled from 10 consecutive dyslipidaemic patients that each participant had recently visited. Results: Of the 4010 patients collected, 649 (16%) had high and 2458 (61%) very high CVR. The distribution of the 3107 high/very high CVR patients was balanced across regions, but there were inter-regional differences (P<.0001) in the achievement of target LDL-C <70 and <55mg/dL, respectively. High-intensity statins in monotherapy or in combination with ezetimibe and/or PCSK9 inhibitors were used in 44, 21 and 4% of high CVR patients, while in those at very high CVR it rose to 38, 45 and 6%, respectively. The use of these lipid-lowering therapies at national level was significantly different between regions (P=.0079). Conclusions: Even though the distribution of patients at high/very high CVR was similar between autonomous communities, inter-territorial differences were identified in the degree of achievement of LDL cholesterol therapeutic goal and use of lipid-lowering therapy. (AU)

Adverse Clinical Outcomes and Associated Predictors in Rivaroxaban-Treated Atrial Fibrillation Patients With Renal Impairment.

Renal impairment confers worse prognosis in patients with atrial fibrillation (AF) but there is scarce evidence about the influence of direct-acting oral anticoagulants in routine clinical practice. Herein, we compared clinical outcomes between patients with AF with and without renal impairment on rivaroxaban and investigated predictors for clinical outcomes in patients with AF with renal impairment. This was a multicenter study including patients with AF on rivaroxaban for at least 6 months. During 2.5 years follow-up, ischemic strokes (IS)/transient ischemic attacks (TIA)/systemic embolisms (SE)/myocardial infarctions (MI), major bleeding, and major adverse cardiovascular events (MACE) were recorded. Creatinine clearance (CrCl) was estimated using the Cockroft-Gault equation, renal impairment was defined as a CrCl <60 ml/min, and 1,433 patients (34.8% with CrCl <60 ml/min) were included. Patients with CrCl <60 ml/min showed higher event rates for major bleeding (1.87%/year vs 0.62%/year; p = 0.003) and MACE (1.97%/year vs 0.62%/year; p = 0.002) but similar event rates for IS/TIA/SE/MI (0.66%/year vs 0.67%/year; p = 0.955). In patients with renal impairment, CHA2DS2-VASc was associated with higher risk of IS/TIA/SE/MI; HAS-BLED and any dependency level were associated with higher risk of major bleeding; and male gender and heart failure were associated with higher risk of MACE. Antiplatelets were independently associated with increased risk of IS/TIA/SE/MI and MACE. In conclusion, in patients with AF on rivaroxaban, the incidence of IS/TIA/SE/MI did not increase in those with renal impairment, suggesting that rivaroxaban may be an effective option in this subgroup. In patients with AF, male gender, heart failure, dependency, antiplatelets, CHA2DS2-VASc, and HAS-BLED were associated with increased risk of adverse outcomes.

Environmental gaseous pollutants are related to increase of acute coronary syndrome in Valencia region, Spain / Los contaminantes gaseosos ambientales están relacionados con el aumento del síndrome coronario agudo

Introduction and aims Environmental pollution are one of the most relevant risk factors to atherosclerosis. To know awareness about the importance of urban air pollution as a trigger for hospital admission due to acute coronary syndrome (ACS), this study analyzed levels of different gaseous air pollutants in the air and its correlation with number of ACS. Methods Epidemiological data of patients admitted for ACS in five towns during the years 2006–2008 were recovered. Clinical data regarding admissions for ACS were obtained from the hospital admission services. Measures of seven air contaminants were recovered from the environmental stations. Mixed model including sex, age, location, and the average levels of air pollutants contaminants as fixed effects and its interaction were performed. Results The incidence rate of ACS is higher in man than woman, and higher in older people than young. The maximum ACS were in the last trimester of the year, was the most elevated levels of gaseous pollutants have been found. Levels of NO2, NO, and CO are positively correlated between them, and negatively correlated with O3 levels. All air pollutants analyzed increase the number of ACS hospital admission in the five locations evaluated. Conclusions Levels of gaseous pollutants are related between them, being the levels of NO2, NO, and CO, positively correlated, and negatively correlated with levels of O3. Number of ACS hospital admission increases with levels of five air gaseous pollutants studied (AU)

Introducción y objetivos La contaminación ambiental es uno de los factores de riesgo más relevantes para la aterosclerosis. Para conocer la importancia de la contaminación del aire urbano como desencadenante del ingreso hospitalario por síndrome coronario agudo (SCA), este estudio analizó los niveles de diferentes contaminantes atmosféricos gaseosos en el aire y su correlación con el número de SCA. Métodos Se recuperaron datos epidemiológicos de pacientes ingresados por SCA en 5 municipios durante los años 2006 a 2008. Los datos clínicos relativos a los ingresos por SCA se obtuvieron de los servicios de ingreso hospitalario. Se recuperaron medidas de 7 contaminantes del aire de las estaciones ambientales. Se realizó un modelo mixto que incluye sexo, edad, ubicación y los niveles promedio de contaminantes atmosféricos como efectos fijos y su interacción. Resultados La tasa de incidencia de SCA es mayor en hombres que en mujeres, y mayor en personas mayores que en jóvenes. La mayoría de los SCA se dieron en el último trimestre del año, cuando se encontraron niveles más elevados de gases contaminantes. Los niveles de NO2, NO y CO se correlacionan positivamente entre ellos y negativamente con los niveles de O3. Todos los contaminantes atmosféricos analizados aumentan el número de ingresos hospitalarios por SCA en las 5 localidades evaluadas. Conclusiones Los niveles de contaminantes gaseosos se relacionan entre sí, estando los niveles de NO2, NO y CO correlacionados positivamente entre sí y negativamente con los niveles de O3. El número de ingresos hospitalarios por SCA aumenta con los niveles de 5 contaminantes gaseosos del aire estudiados (AU)

Cardiovascular toxicity of checkpoint inhibitors: review of associated toxicity and design of the Spanish Immunotherapy Registry of Cardiovascular Toxicity.

Immune checkpoint inhibitors (ICI) have changed the prognosis of many tumors. However, concerning associated cardiotoxicity has been reported. Little is known about the real-life incidence-specific surveillance protocols or the translational correlation between the underlying mechanisms and the clinical presentation of ICI-induced cardiotoxicity. The lack of data from prospective studies led us to review the current knowledge and to present the creation of the Spanish Immunotherapy Registry of Cardiovascular Toxicity (SIR-CVT), a prospective registry of patients receiving ICI that aims to examine the role of hsa-miR-Chr8:96, (a specific serum biomarker of myocarditis) in the early diagnosis of ICI-induced myocarditis. An exhaustive prospective cardiac imaging study will be performed before and during the first 12 months of treatment. The correlation between clinical, imaging, and immunologic parameters may improve our understanding of ICI-induced cardiotoxicity and enable simpler surveillance protocols. We assess ICI-induced cardiovascular toxicity and describe the rationale of the SIR-CVT.

Impact of physician's perception about LDL cholesterol control in clinical practice when treating patients in Spain.

BACKGROUND AND AIMS: We aimed to understand the impact of physicians' perception about LDL-cholesterol (LDLc) control on the management of patients with dyslipidemia in Spain. METHODS: We performed a cross-sectional and multicenter study, in which 435 healthcare professionals participated in face-to-face meetings, collecting qualitative and quantitative information related to hypercholesterolemia management. Additionally, aggregated anonymized data of the last 10 patients with hypercholesterolemia attended by each physician were collected. RESULTS: A total of 4,010 patients (8%, 13%, 16% and 61% with low, moderate, high, and very high cardiovascular [CV] risk) were included. Physicians' perception was that 62% of their patients attained LDLc goals (66%, 63%, 61% and 56%, for low, moderate, high and very high CV risk, respectively). However, when looking into the data only 31% (vs 62% p<0.01) of patients attained the LDLc goals (47%, 36%, 22% and 25%, respectively). Overall, 33% of patients were taking high intensity statins, 32% statin/ezetimibe, 21% low/moderate intensity statins and 4% PCSK9 inhibitors. These numbers were 38%, 45%, 8% and 6% for very high risk patients and 44%, 21%, 21% and 4% for high CV risk patients. In 32% of patients, a change in lipid lowering therapy was performed after the visit, mainly combining statins/ezetimibe (55%). CONCLUSIONS: In Spain, most patients with dyslipidemia do not achieve the recommended LDLc goals because of an insufficient intensification of lipid lowering therapy. On the one hand, this is in part due to physicians misperception on preventive LDLc control and the need for repeated advice to patient, and, on the other, to the lack of patient adherence.

Hypercholesterolaemia control in Spain: The same situation with different regional realities. / Control de la hipercolesterolemia en España: una misma situación con diferentes realidades autonómicas.

INTRODUCTION AND OBJECTIVE: The cardiovascular prevention strategy by autonomous communities can be variable since the competences in health are transferred. The objective of the study was to determine the degree of dyslipidaemia control and the lipid-lowering pharmacological therapy used in patients at high/very high cardiovascular risk (CVR) by autonomous communities. METHODS: Observational, cross-sectional, descriptive study based on a consensus methodology. Information on the clinical practice of 145 health areas belonging to 17 Spanish autonomous communities was collected through face-to-face meetings and questionnaires administered to the 435 participating physicians. Furthermore, aggregate non-identifiable data were compiled from 10 consecutive dyslipidaemic patients that each participant had recently visited. RESULTS: Of the 4010 patients collected, 649 (16%) had high and 2458 (61%) very high CVR. The distribution of the 3107 high/very high CVR patients was balanced across regions, but there were inter-regional differences (P<.0001) in the achievement of target LDL-C <70 and <55mg/dL, respectively. High-intensity statins in monotherapy or in combination with ezetimibe and/or PCSK9 inhibitors were used in 44, 21 and 4% of high CVR patients, while in those at very high CVR it rose to 38, 45 and 6%, respectively. The use of these lipid-lowering therapies at national level was significantly different between regions (P=.0079). CONCLUSIONS: Even though the distribution of patients at high/very high CVR was similar between autonomous communities, inter-territorial differences were identified in the degree of achievement of LDL cholesterol therapeutic goal and use of lipid-lowering therapy.

Environmental gaseous pollutants are related to increase of acute coronary syndrome in Valencia region, Spain.

INTRODUCTION AND AIMS: Environmental pollution are one of the most relevant risk factors to atherosclerosis. To know awareness about the importance of urban air pollution as a trigger for hospital admission due to acute coronary syndrome (ACS), this study analyzed levels of different gaseous air pollutants in the air and its correlation with number of ACS. METHODS: Epidemiological data of patients admitted for ACS in five towns during the years 2006-2008 were recovered. Clinical data regarding admissions for ACS were obtained from the hospital admission services. Measures of seven air contaminants were recovered from the environmental stations. Mixed model including sex, age, location, and the average levels of air pollutants contaminants as fixed effects and its interaction were performed. RESULTS: The incidence rate of ACS is higher in man than woman, and higher in older people than young. The maximum ACS were in the last trimester of the year, was the most elevated levels of gaseous pollutants have been found. Levels of NO2, NO, and CO are positively correlated between them, and negatively correlated with O3 levels. All air pollutants analyzed increase the number of ACS hospital admission in the five locations evaluated. CONCLUSIONS: Levels of gaseous pollutants are related between them, being the levels of NO2, NO, and CO, positively correlated, and negatively correlated with levels of O3. Number of ACS hospital admission increases with levels of five air gaseous pollutants studied.

Use of Direct Acting Oral Anticoagulants in Elderly Patients with Atrial Fibrillation: A Multicenter, Cross-Sectional Study in Spain.

Non-vitamin K antagonist oral anticoagulants (NOACs) have substantially improved anticoagulation. However, data on NOAC use among elderly patients are scarce. We sought to describe NOAC use among elderly AF patients in Spain. We performed a non-interventional, multicenter, multispecialty, cross-sectional study in elderly (≥75 years) AF patients treated with NOACs for stroke prevention. Patients' characteristics by NOAC treatment were compared using standardized differences (SDD). NOAC dosing was classified according to the Spanish summary of products characteristics (SmPC) into appropriate (recommended dose) and inappropriate (under and overdosed). Multivariate logistic regression analyses were used to explore factors associated with inappropriate dosing. 500 patients were included. Mean (SD) age was 81.5 (4.7) years, and 50% were women. Mean (SD) creatinine clearance was 57.4 mL/min (18.8), and 23.6% were frail. Dabigatran treatment totaled 38.4%, rivaroxaban 15.2%, apixaban 33.2%, and edoxaban 13.2%. Almost one-fourth of elderly patients treated with NOACs in Spain were inappropriately dosed (underdosing 14.4% and overdosing 9.6%). Underdosing was significantly associated with weight (OR = 1.03, 95%CI = 1.0-1.1), while higher a EHRA score decreased the risk of underdosing (OR = 0.47, 95%CI = 0.2-1.0). Overdosing was significantly associated with a history of ischemic stroke (OR = 2.95, 95%CI = 1.1-7.7). Addressing incorrect dosing among elderly AF patients is relevant to improve patient outcomes.

Identification of Secondary Prevention Patients Eligible for PCSK9 Inhibitors Therapy According to the Routine Clinical Practice in Spain.

INTRODUCTION: Many patients at very high risk of cardiovascular (CV) events would benefit from lipid-lowering therapies (LLT) intensification to decrease their risk. This study aimed to identify the real-world secondary prevention patients potentially eligible for proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i) in Spain. METHODS: This retrospective cohort study included adult patients registered in the IQVIA Spanish Electronic Medical Records outpatient database (2014-2020), diagnosed with myocardial infarction (MI), unstable angina (UA), ischaemic stroke (IS), transient ischaemic attack (TIA) or peripheral artery disease (PAD) and with ≥ 1 low-density lipoprotein cholesterol (LDL-C) or total cholesterol measurements. Longitudinal data were collected from the initial diagnosis to the end of the study period or follow-up loss. RESULTS: The study included 9516 patients, 63.9% male, mean (SD) age 67.7 (12.5) years and mean LDL-C 117.3 (38.8) mg/dL. MI, IS and PAD were the most severe events reported during the study period (28.5%, 18.7% and 29.3% of patients, respectively). At the time of last available LDL-C assessment (≥ 3 months post-event), 64.4% patients were on LLT. Of those, 45.4%, 46.9% and 7.7% were on high-, moderate- and low-intensity LLT. Overall, 9.6% patients achieved LDL-C < 55 mg/dL (24.2% LDL-C < 70 mg/dL). Furthermore, 17.9% patients receiving optimized oral LLT showed LDL-C > 100 mg/dL (LDL-C reimbursement threshold for PCSK9i in Spain). CONCLUSION: Up to 82% of patients with atherosclerotic CV disease do not achieve LDL-C levels recommended by the 2019 ESC/EAS guidelines despite being on optimized oral LLT therapy. In 17.9% of these patients LDL-C levels exceed 100 mg/dL, being eligible for PCSK9i in Spain.

Safety and efficacy of a cardiovascular polypill in people at high and very high risk without a previous cardiovascular event: the international VULCANO randomised clinical trial.

BACKGROUND: Cardiovascular (CV) polypills are a useful baseline treatment to prevent CV diseases by combining different drug classes in a single pill to simultaneously target more than one risk factor. The aim of the present trial was to determine whether the treatment with the CNIC-polypill was at least non-inferior to usual care in terms of low-density lipoprotein cholesterol (LDL-c) and systolic BP (SBP) values in subjects at high or very high risk without a previous CV event. METHODS: The VULCANO was an international, multicentre open-label trial involving 492 participants recruited from hospital clinics or primary care centres. Patients were randomised to the CNIC-polypill -containing aspirin, atorvastatin, and ramipril- or usual care. The primary outcome was the comparison of the mean change in LDL-c and SBP values after 16 weeks of treatment between treatment groups. RESULTS: The upper confidence limit of the mean change in LDL-c between treatments was below the prespecified margin (10 mg/dL) and above zero, and non-inferiority and superiority of the CNIC-polypill (p = 0.0001) was reached. There were no significant differences in SBP between groups. However, the upper confidence limit crossed the prespecified non-inferiority margin of 3 mm Hg. Significant differences favoured the CNIC-polypill in reducing total cholesterol (p = 0.0004) and non-high-density lipoprotein cholesterol levels (p = 0.0017). There were no reports of major bleeding episodes. The frequency of non-serious gastrointestinal disorders was more frequent in the CNIC-polypill arm. CONCLUSION: The switch from conventional treatment to the CNIC-polypill approach was safe and appears a reasonable strategy to control risk factors and prevent CVD. Trial registration This trial was registered in the EU Clinical Trials Register (EudraCT) the 20th February 2017 (register number 2016-004015-13; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2016-004015-13 ).

Predicting performance of the HAS-BLED and ORBIT bleeding risk scores in patients with atrial fibrillation treated with Rivaroxaban: Observations from the prospective EMIR Registry.

BACKGROUND: Assessing bleeding risk during the decision-making process of starting oral anticoagulation (OAC) therapy in atrial fibrillation (AF) patients is essential. Several bleeding risk scores have been proposed for vitamin K antagonist users but, few studies have focused on validation of these bleeding risk scores in patients taking direct oral anticoagulants (DOACs). The aim was to compare the predictive ability of HAS-BLED and ORBIT bleeding risk scores in AF patients taking rivaroxaban in the EMIR ('Estudio observacional para la identificación de los factores de riesgo asociados a eventos cardiovasculares mayores en pacientes con fibrilación auricular no valvular tratados con un anticoagulante oral directo [Rivaroxaban]) Study. METHODS AND RESULTS: EMIR Study was an observational, multicenter, post-authorization, and prospective study that involved AF patients under OAC with rivaroxaban at least 6 months before enrolment. We analysed baseline clinical characteristics and adverse events after 2.5 years of follow-up and validated the predictive ability of HAS-BLED and ORBIT scores for major bleeding (MB) events.We analysed 1433 patients with mean age of 74.2 ± 9.7 (44.5% female). Mean HAS-BLED score was 1.6 ± 1.0 and ORBIT score was 1.1 ± 1.2. The ORBIT score categorised a higher proportion of patients as 'low-risk' (87.1%) compared with 53.5% using the HAS-BLED score. There were 33 MB events (1.04%/year) and 87 patients died (2.73%/year). Both HAS-BLED and ORBIT had a good predictive ability for MB{Area under the curve (AUC) 0.770, [95% confidence interval (CI) 0.693-0.847; P <0.001] and AUC 0.765 (95% CI 0.672-0.858; P <0.001), respectively}. There was a non-significant difference for discriminative ability of the two tested scores (P = 0.930) and risk reclassification in terms of net reclassification improvement (NRI) -5.7 (95% CI -42.4-31.1; P = 0.762). HAS-BLED score showed the best calibration and ORBIT score showed the largest mismatch in calibration, particularly in higher predicted risk patients. CONCLUSION: In a prospective real-world AF population under rivaroxaban from EMIR registry, the HAS-BLED score had good predictive performance and calibration compared with ORBIT score for MB events. ORBIT score presented worse calibration than HAS-BLED in this DOAC treated population.

Impact of heart failure on the clinical profile and outcomes in patients with atrial fibrillation treated with rivaroxaban. Data from the EMIR study.

BACKGROUND: The aim of this study was to analyze the impact of the presence of heart failure (HF) on the clinical profile and outcomes in patients with atrial fibrillation (AF) anticoagulated with rivaroxaban. METHODS: Observational and non-interventional study that included AF adults recruited from 79 Spanish centers, anticoagulated with rivaroxaban ≥ 6 months before inclusion. Data were analyzed according to baseline HF status. RESULTS: Out of 1,433 patients, 326 (22.7%) had HF at baseline. Compared to patients without HF, HF patients were older (75.3 ± 9.9 vs. 73.8 ± 9.6 years; p = 0.01), had more diabetes (36.5% vs. 24.3%; p < 0.01), coronary artery disease (28.2% vs. 12.9%; p < 0.01), renal insufficiency (31.7% vs. 22.6%; p = 0.01), higher CHA2DS2-VASc (4.5 ± 1.6 vs. 3.2 ± 1.4; p < 0.01) and HAS-BLED (1.8 ± 1.1 vs. 1.5 ± 1.0; p < 0.01). After a median follow-up of 2.5 years, among HF patients, annual rates of stroke/systemic embolism/transient ischemic attack, major adverse cardiovascular events (MACE) (non-fatal myocardial infarction, revascularization and cardiovascular death), cardiovascular death, and major bleeding were 1.2%, 3.0%, 2.0%, and 1.4%, respectively. Compared to those patients without HF, HF patients had greater annual rates of MACE (3.0% vs. 0.5%; p < 0.01) and cardiovascular death (2.0% vs. 0.2%; p < 0.01), without significant differences regarding other outcomes, including thromboembolic or bleeding events. Previous HF was an independent predictor of MACE (odds ratio 3.4; 95% confidence interval 1.6-7.3; p = 0.002) but not for thromboembolic events or major bleeding. CONCLUSIONS: Among AF patients anticoagulated with rivaroxaban, HF patients had a worse clinical profile and a higher MACE risk and cardiovascular mortality. HF was independently associated with the development of MACE, but not with thromboembolic events or major bleeding.

Rivaroxaban for the prevention of outcomes in patients with atrial fibrillation in clinical practice: an indirect comparison of national and international registries.

Objective: To analyze the effectiveness and safety of rivaroxaban in patients with atrial fibrillation (AF). Methods: The clinical profile and outcomes of the EMIR study were indirectly compared with those of ROCKET-AF, eight other Spanish observational studies and XANTUS. Results: In EMIR, mean age was 74.2 years and CHA2DS2-VASc was 3.5. In the rivaroxaban arm of the ROCKET-AF trial, mean age was 73 years and CHADS2 was 3.5, whereas in the Spanish studies mean age ranged from 74.9 years to 78.4 years and CHA2DS2-VASc from 3.5 to 4.3. In EMIR, rates of stroke/systemic embolism, major adverse cardiovascular events, cardiovascular death and major bleeding were 0.57, 1.07, 0.63 and 1.04 events/100 patient-years, respectively. In ROCKET-AF, these numbers were 1.7, 3.91, 1.53 and 3.6 events/100 patient-years, respectively. In the Spanish studies, rates of stroke and major bleeding were 0-1.8 and 0.22-4.2 events/100 patient-years, respectively. In XANTUS, rates of stroke, major adverse cardiovascular events and major bleeding were 0.7, 1.8 and 2.1 events/100 patient-years, respectively. Conclusion: Despite the fact that rivaroxaban is prescribed for elderly patients with a high thromboembolic risk, rates of outcomes remain low.

Projected impact of treatment intensification with statin, ezetimibe, and statin plus ezetimibe fixed-dose combination on MACE across six countries.

AIMS: The 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) dyslipidaemia guidelines recommend achievement of low-density lipoprotein cholestrol (LDL-C) goals based on an individual's risk. We aimed to evaluate the impact of guideline adoption with statin, ezetimibe, and statin plus ezetimibe fixed-dose combination (FDC) on LDL-C goal achievement and incidence of major adverse cardiovascular events (MACE) across six countries. METHODS AND RESULTS: A simulation model with a five-year horizon (2020-2024) was developed based on Institute for Health Metrics and Evaluation Global Burden of Disease Study database with a business-as-usual (BAU) scenario representing status quo, intervention scenario-1 representing treatment with statin and ezetimibe as separate agents, and intervention scenario-2 representing treatment with statin or statin plus ezetimibe FDC. MACE was defined as the composite of myocardial infarction, ischaemic stroke, and cardiovascular death. The mean population LDL-C was reduced from 4.25 mmol/L in the BAU scenario, to 3.65 mmol/L and 3.59 mmol/L in intervention scenarios-1 and -2, respectively. Compared with BAU, intervention scenarios-1 and-2 resulted in relative reduction of MACE by 5.4% and 6.4% representing ∼3.7 and 4.4 million MACE averted, respectively, across six countries over 5 years. The absolute benefit in terms of MACE averted was highest for China, whereas France had highest relative reduction in MACE with both intervention scenarios compared with BAU. CONCLUSION: The 2019 ESC/EAS guideline-based treatment intensification with strategies based on statin, ezetimibe, and statin plus ezetimibe FDC is estimated to result in a substantial population-level benefit in terms of MACE averted compared with BAU.

Protocolo del observatorio de las dislipemias: Tratamiento de la hipercolesterolemia en España, contexto e identificación de medidas de mejora en práctica clínica habitual / Dyslipidemia observatory: Treatment of hypercholesterolemia in Spain, context and levers for improvement in clinical practice

Introducción y objetivos: El tratamiento de las dislipemias presenta gran variabilidad en la práctica clínica e importantes limitaciones que dificultan la consecución de los objetivos terapéuticos. Por ello, se ha diseñado un proyecto para evaluar el control de la dislipemia en España, identificar los puntos de mejora y tratar de optimizarlo. El objetivo de este artículo es describir la metodología del observatorio del tratamiento del paciente dislipémico en España. Métodos: Observatorio de recogida de información basada en la práctica clínica habitual y experiencia de los profesionales de la salud que atienden a pacientes dislipémicos en España. El observatorio recoge información por área sanitaria, a través de: (i) reunión presencial con tres especialidades médicas diferentes y (ii) información cuantitativa de manejo de pacientes con hipercolesterolemia (cuestionario ad hoc). La información incluye perfiles de paciente atendidos, carga asistencial, guías y protocolos utilizados, grado de control alcanzado, limitaciones y oportunidades de mejora en práctica clínica. Resultados: Se busca incluir 145 áreas sanitarias, contando con la participación de hasta 435 profesionales médicos de las 17 Comunidades Autónomas de España. La información recogida de los participantes permitirá disponer de datos agregados de más de 4.000 pacientes. Conclusiones: Este observatorio pretende conocer cómo se está tratando la hipercolesterolemia en la práctica clínica en España. Aunque los resultados preliminares muestran una importante área de mejora en el tratamiento de las dislipemias, se identifican también mecanismos para impulsar un cambio hacia la optimización de resultados en salud.(AU)

Introduction and objectives: The treatment of dyslipidemia exhibits wide variability in clinical practice and important limitations that make lipid-lowering goals more difficult to attain. Getting to know the management of these patients in clinical practice is key to understand the existing barriers and to define actions that contribute to achieving the therapeutic goals from the most recent Clinical Practice Guidelines. Methods: Observatory where the information gathered is based on routine clinical practice and the experience from the healthcare professionals involved in the treatment of dyslipidemia in Spain. The information is collected by health area through: (i) face-to-face meeting with three different medical specialties and (ii) quantitative information related to hypercholesterolemia patients’ management (ad-hoc questionnaire). Information includes patients’ profiles, assistance burden, guidelines and protocols used, goal attainment, limitations and opportunities in clinical practice. Results: 145 health areas are planned to be included, with the participation of up to 435 healthcare professionals from the 17 Autonomous Regions of Spain. Information collection will result in aggregated data from over four thousand patients. Conclusions: This observatory aims to understand how hypercholesterolemia is being treated in routine clinical practice in Spain. Even though the preliminary results show important improvement areas in the treatment of dyslipidemias, mechanisms to drive a change towards health outcomes optimization are also identified.(AU)

Cardiac telerehabilitation with long-term follow-up reduces GlycA and improves lipoprotein particle profile: A randomised controlled trial.

BACKGROUND: A 10-month strategy of cardiac telerehabilitation (CTR) improved outcomes over a standard centre-based cardiac rehabilitation (CBCR), as recently published. We hypothesised that prolonged telerehabilitation could also improve proinflammatory status and lipoprotein particle composition. METHODS: A randomised controlled trial compared a prolonged CTR program with CBCR in post-ACS patients. Patient's age was 18-72 years with low-risk criteria. Blood samples were drawn at baseline, at 4- and 10-months follow-up. Advanced lipoprotein characterization was performed using the NMR-based Liposcale test. Signals from glycoproteins (GlycA and GlycB) were also assessed. RESULTS: The final analysis included 31 patients in the CTR group and 25 patients in the CBCR group. GlycA decreased in the CTR group (p = 0,007). LDL particle number (LDL-P) increase in both groups, but it was at the expense of small-sized LDL in the CBCR group (p = 0.012). Triglycerides in intermediate-density lipoprotein (IDL-TG) increased only in the CBCR group (p = 0.043). The triglyceride-to-HDL (TG/HDL) ratio decreased only in the CTR group (p = 0.006). The TG/HDL ratio was correlated with GlycA (Spearman's correlation coefficient: 0.558, p < 0.001) but not with CRP (p = 0.101). CONCLUSIONS: Our results showed that a 10-month CTR program reduced GlycA levels, the TG/HDL ratio and avoided unfavourable long-term changes in lipoprotein particle composition. Registration at http://ClinicalTrials.gov. NCT number: 04942977.

Gender differences in antithrombotic treatment in patients with atrial fibrillation from Spain versus the rest of Western Europe. GLORIA-AF Program

Background and objective:Thromboembolic risk is higher in women than men with non-valvular atrial fibrillation (NVAF). Published data indicate variability in antithrombotic use by gender and region. We analyzed gender-specific antithrombotic treatment patterns in Spain and rest of Western Europe (rWE) in patients with NVAF.Methods:GLORIA-AF (Phase III) is a global, prospective, observational study which enrolled newly diagnosed NVAF patients with CHA2DS2-VAScs≥1 (2014–2016). Analyses were performed comparing antithrombotic treatments by gender in Spain and rWE.Results:This analysis included 1163 and 7972 patients from Spain and rWE, respectively. Stroke risk was higher in women than men in both Spain and rWE. While in rWE, bleeding risk and antithrombotic treatment pattern were similar between genders, in Spain bleeding risk in women was lower and more females compared to men received OACs (95.0% versus 92.4%, d=−0.1078, respectively). Fewer Spanish patients received direct oral anticoagulants (DOACs) (women 32.1%, men 25.3%) than vitamin-K-antagonists (VKAs) (women 63.0%, men 67.1%) vs. rWE patients. In Spain women received more DOACs compared to men (56.0% versus 44.0%).Conclusions:OAC rates were higher in Spain as compared to rWE. More women received OACs in Spain, while in rWE no difference by gender was observed. DOACs in rWE are the most prescribed OAC while in Spain, due to prescription barriers, its use remains low for both genders and VKAs are preferred. Spanish women received more DOACs compared to men. (NCT01468701). (AU)

Antecedentes y objetivo:El riesgo tromboembólico es mayor en mujeres que en varones con fibrilación auricular no valvular (FANV). Existen diferencias en el uso de anticoagulantes (ACO) según sexo y zona geográfica. Se estudiaron los patrones de anticoagulación por sexo en España y el resto de Europa Occidental (rEO) en pacientes con FANV.Métodos:GLORIA-AF es un estudio observacional prospectivo (fase III) que incluyó a pacientes con diagnóstico reciente de FANV y CHA2DS2-VASc>1 (2014-2016). Se analizó la prescripción de anticoagulantes por sexo en España y el rEO.Resultados:Se incluyó a 1.163 pacientes de España y 7.972 del rEO. El riesgo de ictus fue superior en mujeres tanto en España como en el rEO. El riesgo de hemorragia y el tratamiento antitrombótico fueron similares en ambos sexos en el rEO; en España, el riesgo de hemorragia fue menor en mujeres y estas recibieron más ACO que los varones (95,0% vs. 92,4%, d=–0,1078). En España, menos pacientes recibieron ACO directos (ACOD) (mujeres 32,1%, varones 25,3%) vs. antagonistas de la vitamina K (AVK) (mujeres 63,0%, varones 67,1%), y las mujeres recibieron más ACOD que los varones (56,0% vs. 44,0%).Conclusiones:En España se emplearon más ACO que en el rEO y más mujeres fueron tratadas con ACO, mientras que en el rEO no hubo diferencias por sexo. En el rEO, los ACOD se emplearon más. En España, los ACOD se emplean menos por restricciones de prescripción y se emplean más los AVK. Las mujeres españolas reciben más ACOD que los varones. (NCT01468701). (AU)