Withdrawal of drug therapy in responders to cardiac resynchronization therapy: rationale and design of the REMOVE trial.

INTRODUCTION AND OBJECTIVES: Cardiac resynchronization therapy (CRT) is an effective treatment for patients with nonischemic dilated cardiomyopathy associated with left bundle branch block (LBBB). In these patients, the device can normalize left ventricular ejection fraction (LVEF). Nevertheless, it remains unclear whether CRT responders still require neurohormonal blockers. The aim of this study is to determine the long-term safety of withdrawing drug therapy in these patients. METHODS: The REMOVE trial is a prospective, multicenter, open-label and randomized 1:1 study designed to assess the effect of withdrawing neurohormonal blockers in patients with nonischemic dilated cardiomyopathy associated with left bundle branch block who recovered LVEF after CRT. The study will include a 12-month follow-up with the option to continue into the follow-up extension phase for up to 24 months. The primary endpoint is the recurrence of cardiomyopathy defined as any of the following criteria: a) a reduction in LVEF >10% (provided the LVEF is <50%); b) a reduction in LVEF >10% accompanied by an increase >15% in the indexed end-systolic volume relative to the previous value and in a range higher than the normal values, or c) decompensated heart failure requiring intravenous diuretic administration. In patients meeting the primary endpoint, drug therapy will be restarted. CONCLUSIONS: The results of this study will help to enhance our understanding of CRT superresponders, a specific group of patients. Registred at ClinicalTrials.gov (Identifier: NCT05151861).

Antithrombotic Strategy in Secondary Prevention for High-Risk Patients with Previous Acute Coronary Syndrome: Overlap between the PEGASUS Eligibility and the COMPASS Eligibility in a Large Multicenter Registry.

BACKGROUND: Patients with previous acute coronary syndrome (ACS) are at high risk of recurrent adverse cardiovascular events. Recently, prolonged dual antiplatelet therapy (DAPT) and oral anticoagulation therapy (OAT) have been shown to reduce recurrent ischemic events to the expense of an increase in bleeding events. The number of patients potentially eligible for these therapies in real life remains to be determined. METHODS: Among ACS patients from five registries and one randomized controlled trial, we assessed the proportion of patients eligible for the PEGASUS strategy only and the proportion of patients eligible for the COMPASS strategy only, and set out the proportion of patients with an overlap between the strategies. FINDINGS: Among the 10,048 evaluable patients, we found that 5373 (53.4%) were eligible for the PEGASUS strategy and 3841 (38.2%) were eligible for the COMPASS strategy, with a group of 3444 (34.4%) overlapping between the two strategies. The number of patients eligible for the PEGASUS strategy only was 1929 (19.2%) and the number eligible for the COMPASS strategy only was 397 (4.0%); 4278 (42.6%) were eligible for neither a PEGASUS strategy nor a COMPASS strategy. INTERPRETATION: In a large cohort of ACS patients, one in three patients was eligible for either a prolonged DAPT with ticagrelor 60 mg and low-dose aspirin or a dual pathway inhibition approach with rivaroxaban 2.5 mg and low-dose aspirin.

Safety and efficacy of different P2Y12 inhibitors in patients with acute coronary syndromes stratified by the PRAISE risk score: a multicentre study.

AIMS: To establish the safety and efficacy of different dual antiplatelet therapy (DAPT) combinations in patients with acute coronary syndrome (ACS) according to their baseline ischaemic and bleeding risk estimated with a machine learning derived model [machine learning-based prediction of adverse events following an acute coronary syndrome (PRAISE) score]. METHODS AND RESULTS: Incidences of death, re-acute myocardial infarction (re-AMI), and Bleeding Academic Research Consortium 3-5 bleeding with aspirin plus different P2Y12 inhibitors (clopidogrel or potent P2Y12 inhibitors: ticagrelor or prasugrel) were appraised among patients of the PRAISE data set grouped in four subcohorts: low-to-moderate ischaemic and bleeding risk; low-to-moderate ischaemic risk and high bleeding risk; high ischaemic risk and low-to-moderate bleeding risk; and high ischaemic and bleeding risk. Hazard ratios (HRs) for the outcome measures were derived with inverse probability of treatment weighting adjustment. Among patients with low-to-moderate bleeding risk, clopidogrel was associated with higher rates of re-AMI in those at low-to-moderate ischaemic risk [HR 1.69, 95% confidence interval (CI) 1.16-2.51; P = 0.006] and increased risk of death (HR 3.2, 1.45-4.21; P = 0.003) and re-AMI (HR 2.23, 1.45-3.41; P < 0.001) in those at high ischaemic risk compared with prasugrel or ticagrelor, without a difference in the risk of major bleeding. Among patients with high bleeding risk, clopidogrel showed comparable risk of death, re-AMI, and major bleeding vs. potent P2Y12 inhibitors, regardless of the baseline ischaemic risk. CONCLUSION: Among ACS patients with non-high risk of bleeding, the use of potent P2Y12 inhibitors is associated with a lower risk of death and recurrent ischaemic events, without bleeding excess. Patients deemed at high bleeding risk may instead be safely addressed to a less intensive DAPT strategy with clopidogrel.

Ticagrelor or Clopidogrel After an Acute Coronary Syndrome in the Elderly: A Propensity Score Matching Analysis from 16,653 Patients Treated with PCI Included in Two Large Multinational Registries.

PURPOSE: Higher risk of bleeding with ticagrelor over clopidogrel in elderly patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) has been suggested. We assessed the incidence of major bleedings (MB), reinfarction (re-MI), and all-cause death to evaluate safety and efficacy of ticagrelor versus clopidogrel in such population. METHODS: Real-world registries RENAMI and BleeMACS were merged. The pooled cohort was divided into two groups, clopidogrel versus ticagrelor. Statistical analysis considered patients <75 versus ≥75 years old. Endpoints were BARC 3-5 MB, re-MI, and all-cause death at 1-year follow-up. The study included 16,653 patients (13,153 < 75 and 3500 ≥ 75 years). Ticagrelor was underused in elderly patients (16.3% versus 20.8%, P < 0.001). Using propensity score matching (PSM), two treatment groups of 1566 patients were included in the final analysis. RESULTS: Ticagrelor was able to prevent re-MI (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.2-0.6; P < 0.001) and all-cause death (HR, 0.60; 95% CI, 0.4-0.9; P = 0.026) irrespective of age. In patients ≥75 years, ticagrelor reduced all-cause death (HR, 0.32; 95% CI, 0.1-0.8; P = 0.012) and re-MI (HR, 0.25; 95% CI, 0.1-1.1, P = 0.072). Moreover, even with the limit of the low number of events, ticagrelor did not significantly increase the incidence of MB (HR, 1.49; 95% CI, 0.70-3.0; P = 0.257). At multiple Cox regression, age (HR, 1.03; 95% CI, 1.02-1.05; P < 0.001) resulted an independent risk factor for bleeding. CONCLUSION: In our study, reflecting the results from two large retrospective, real-world registries, Ticagrelor did not significantly increase MB compared with clopidogrel in elderly patients with ACS treated with PCI, while significantly improving 1-year survival. Further studies on elderly patients are suggested.

Ticagrelor versus prasugrel in acute coronary syndrome: sex-specific analysis from the RENAMI Registry.

BACKGROUND: The use of potent P2Y12 inhibitors (ticagrelor & prasugrel) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary interventions (PCI) is a class I recommendation. We performed a sex-specific analysis comparing the difference in efficacy and safety outcomes between ticagrelor and prasugrel in a real-world ACS population. METHODS: Data from the multicenter REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) for 4424 ACS patients who underwent PCI and were treated with ticagrelor or prasugrel between 2012 to 2016 were analyzed. Mean follow-up was 17±9 months. RESULTS: After propensity score matching, there was no significant difference in the occurrence of primary endpoint of net adverse cardiac events between ticagrelor and prasugrel in men (HR: 0.94; 95% CI: 0.69-1.29; P=0.71), or women (HR: 1.17; 95% CI: 0.63-2.20; P=0.62; P interaction [sex] = 0.40). Similarly, no differences were found in the occurrence of any of the secondary endpoints (MACE, all cause death, re-infarction, stent thrombosis, BARC major bleeding and BARC any bleeding) between the two P2Y12 groups between men and women. CONCLUSIONS: In this real-world ACS population, no relative difference in efficacy or safety outcomes were found between ticagrelor and prasugrel between sexes.

Machine learning-based prediction of adverse events following an acute coronary syndrome (PRAISE): a modelling study of pooled datasets.

BACKGROUND: The accuracy of current prediction tools for ischaemic and bleeding events after an acute coronary syndrome (ACS) remains insufficient for individualised patient management strategies. We developed a machine learning-based risk stratification model to predict all-cause death, recurrent acute myocardial infarction, and major bleeding after ACS. METHODS: Different machine learning models for the prediction of 1-year post-discharge all-cause death, myocardial infarction, and major bleeding (defined as Bleeding Academic Research Consortium type 3 or 5) were trained on a cohort of 19 826 adult patients with ACS (split into a training cohort [80%] and internal validation cohort [20%]) from the BleeMACS and RENAMI registries, which included patients across several continents. 25 clinical features routinely assessed at discharge were used to inform the models. The best-performing model for each study outcome (the PRAISE score) was tested in an external validation cohort of 3444 patients with ACS pooled from a randomised controlled trial and three prospective registries. Model performance was assessed according to a range of learning metrics including area under the receiver operating characteristic curve (AUC). FINDINGS: The PRAISE score showed an AUC of 0·82 (95% CI 0·78-0·85) in the internal validation cohort and 0·92 (0·90-0·93) in the external validation cohort for 1-year all-cause death; an AUC of 0·74 (0·70-0·78) in the internal validation cohort and 0·81 (0·76-0·85) in the external validation cohort for 1-year myocardial infarction; and an AUC of 0·70 (0·66-0·75) in the internal validation cohort and 0·86 (0·82-0·89) in the external validation cohort for 1-year major bleeding. INTERPRETATION: A machine learning-based approach for the identification of predictors of events after an ACS is feasible and effective. The PRAISE score showed accurate discriminative capabilities for the prediction of all-cause death, myocardial infarction, and major bleeding, and might be useful to guide clinical decision making. FUNDING: None.

Aortic valve stenosis provides complementary information to bleeding risk scores in non-valvular atrial fibrillation patients initiating anticoagulation.

BACKGROUND: The identification of modifiable bleeding risk factors may be of relevance. The aim is to evaluate if aortic stenosis (AS) provides additional information to bleeding risk scores for predicting major bleeding (MB) in non-valvular atrial fibrillation (AF). METHODS: We designed a retrospective multi-center study including 2880 consecutive non-valvular AF patients initiating oral anticoagulation between January 2013 and December 2016. AS was defined as moderate or severe according to European echocardiography guidelines criteria. HASBLED, ATRIA and ORBIT scores were used to evaluate the bleeding risk. MB was defined according to the International Society on Thrombosis and Haemostasia criteria and registered at 18 months of follow-up. RESULTS: 168 (5.8%) patients had AS. Patients with AS had higher risk for MB compared to those without AS (HR = 2.13, 95% CI: 1.40-3.23, P < 0.001). Patients without AS and low-intermediate bleeding risk (0 points) showed the lowest MB rate, whereas the MB rate observed among patients with AS and high bleeding risk (2 points) was the highest one. Discrimination and reclassification analyses showed that AS provided additional information to bleeding risk scores for predicting MB at 18 months of follow-up. CONCLUSIONS: In this population, AS was associated with an increased risk for MB at midterm follow-up. The three scoring systems showed a moderate discriminatory ability for MB. Moreover, the addition of AS was associated with a significant improvement in their predictive accuracy. We suggest that the presence of this valvulopathy should be taken into account for bleeding risk assessment.

Long versus short dual antiplatelet therapy in acute coronary syndrome patients treated with prasugrel or ticagrelor and coronary revascularization: Insights from the RENAMI registry.

INTRODUCTION: The benefits of short versus long-term dual antiplatelet therapy (DAPT) based on the third generation P2Y12 antagonists prasugrel or ticagrelor, in patients with acute coronary syndromes treated with percutaneous coronary intervention remain to be clearly defined due to current evidences limited to patients treated with clopidogrel. METHODS: All acute coronary syndrome patients from the REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) undergoing percutaneous coronary intervention and treated with aspirin, prasugrel or ticagrelor were stratified according to DAPT duration, that is, shorter than 12 months (D1 group), 12 months (D2 group) and longer than 12 months (D3 group). The three groups were compared before and after propensity score matching. Net adverse clinical events (NACEs), defined as a combination of major adverse cardiac events (MACEs) and major bleedings (including therefore all cause death, myocardial infarction and Bleeding Academic Research Consortium (BARC) 3-5 bleeding), were the primary end points, MACEs (a composite of all cause death and myocardial infarction) the secondary one. Single components of NACEs were co-secondary end points, along with BARC 2-5 bleeding, cardiovascular death and stent thrombosis. RESULTS: A total of 4424 patients from the RENAMI registry with available data on DAPT duration were included in the model. After propensity score matching, 628 patients from each group were selected. After 20 months of follow up, DAPT for 12 months and DAPT for longer than 12 months significantly reduced the risk of NACE (D1 11.6% vs. D2 6.7% vs. D3 7.2%, p = 0.003) and MACE (10% vs. 6.2% vs. 2.4%, p < 0.001) compared with DAPT for less than 12 months. These differences were driven by a reduced risk of all cause death (7.8% vs. 1.3% vs. 1.6%, p < 0.001), cardiovascular death (5.1% vs. 1.0% vs. 1.2%, p < 0.0001) and recurrent myocardial infarction (8.3% vs. 5.2% vs. 3.5%, p = 0.002). NACEs were lower with longer DAPT despite a higher risk of BARC 2-5 bleedings (4.6% vs. 5.7% vs. 6.2%, p = 0.04) and a trend towards a higher risk of BARC 3-5 bleedings (2.4% vs. 3.3% vs. 3.9%, p = 0.06). These results were not consistent for female patients and those older than 75 years old, due to an increased risk of bleedings which exceeded the reduction in myocardial infarction. CONCLUSION: In unselected real world acute coronary syndrome patients treated with percutaneous coronary intervention, DAPT with prasugrel or ticagrelor prolonged beyond 12 months markedly reduces fatal and non-fatal ischaemic events, offsetting the increased risk deriving from the higher bleeding risk. On the contrary, patients >75 years old and female ones showed a less favourable risk-benefit ratio for longer DAPT due to excess of bleedings.

P2Y12 inhibitors in acute coronary syndrome patients with renal dysfunction: an analysis from the RENAMI and BleeMACS projects.

AIMS: The aim of the present study was to establish the safety and efficacy profile of prasugrel and ticagrelor in real-life acute coronary syndrome (ACS) patients with renal dysfunction. METHODS AND RESULTS: All consecutive patients from RENAMI (REgistry of New Antiplatelets in patients with Myocardial Infarction) and BLEEMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registries were stratified according to estimated glomerular filtration rate (eGFR) lower or greater than 60 mL/min/1.73 m2. Death and myocardial infarction (MI) were the primary efficacy endpoints. Major bleedings (MBs), defined as Bleeding Academic Research Consortium bleeding types 3 to 5, constituted the safety endpoint. A total of 19 255 patients were enrolled. Mean age was 63 ± 12; 14 892 (77.3%) were males. A total of 2490 (12.9%) patients had chronic kidney disease (CKD), defined as eGFR <60 mL/min/1.73 m2. Mean follow-up was 13 ± 5 months. Mortality was significantly higher in CKD patients (9.4% vs. 2.6%, P < 0.0001), as well as the incidence of reinfarction (5.8% vs. 2.9%, P < 0.0001) and MB (5.7% vs. 3%, P < 0.0001). At Cox multivariable analysis, potent P2Y12 inhibitors significantly reduced the mortality rate [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.54-0.96; P = 0.006] and the risk of reinfarction (HR 0.53, 95% CI 0.30-0.95; P = 0.033) in CKD patients as compared to clopidogrel. The reduction of risk of reinfarction was confirmed in patients with preserved renal function. Potent P2Y12 inhibitors did not increase the risk of MB in CKD patients (HR 1.00, 95% CI 0.59-1.68; P = 0.985). CONCLUSION: In ACS patients with CKD, prasugrel and ticagrelor are associated with lower risk of death and recurrent MI without increasing the risk of MB.

Average daily ischemic versus bleeding risk in patients with ACS undergoing PCI: Insights from the BleeMACS and RENAMI registries.

BACKGROUND: The risk of recurrent ischemia and bleeding after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) may vary during the first year of follow-up according to clinical presentation, and medical and interventional strategies. METHODS: BleeMACS and RENAMI are 2 multicenter registries enrolling patients with ACS treated with PCI and clopidogrel, prasugrel, or ticagrelor. The average daily ischemic and bleeding risks (ADIR and ADBR) in the first year after PCI were the primary end points. The difference between ADBR and ADIR was calculated to estimate the potential excess of bleeding/ischemic events in a given period or specific subgroup. RESULTS: A total of 19,826 patients were included. Overall, in the first year after PCI, the ADBR was 0.008085%, whereas ADIR was 0.008017% (P = .886). In the first 2 weeks ADIR was higher than ADBR (P = .013), especially in patients with ST-segment elevation myocardial infarction or incomplete revascularization. ADIR continued to be, albeit non-significantly, greater than ADBR up to the third month, whereas ADBR became higher, although not significantly, afterward. Patients with incomplete revascularization had an excess in ischemic risk (P = .003), whereas non-ST-segment elevation ACS patients and those on ticagrelor had an excess of bleeding (P = .012 and P = .022, respectively). CONCLUSIONS: In unselected ACS patients, ADIR and ADBR occurred at similar rates within 1 year after PCI. ADIR was greater than ADBR in the first 2 weeks, especially in ST-segment elevation myocardial infarction patients and those with incomplete revascularization. In the first year, ADIR was higher than ADBR in patients with incomplete revascularization, whereas ADBR was higher in non-ST-segment elevation ACS patients and in those discharged on ticagrelor.

Efficacy and Safety of Clopidogrel, Prasugrel and Ticagrelor in ACS Patients Treated with PCI: A Propensity Score Analysis of the RENAMI and BleeMACS Registries.

INTRODUCTION: Real-life data comparing clopidogrel, prasugrel, and ticagrelor for unselected patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) are lacking, as are data for the temporal distribution of ischemic and bleeding risks. METHODS: A total of 19,825 patients were enrolled from the RENAMI and BleeMACS registries. Both were multicenter, retrospective, observational registries including the data and outcomes of consecutive patients with ACS who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT). We evaluated the long-term outcome stratified by the different antiplatelet agents. RESULTS: A total of 14,105 patients (71.2%) were treated with clopidogrel, 2364 patients (11.9%) with prasugrel and 3356 patients (16.9%) with ticagrelor. After propensity score matching, at 1 year, prasugrel reduced the incidence of net adverse clinical events (NACE; a composite endpoint of all-cause death, myocardial infarction [MI] and Bleeding Academic Research Consortium [BARC] 3-5 bleeding) (4.2% vs.7.6%, p = 0.002) and of major adverse cardiovascular events (MACE; a composite endpoint of death and MI) compared with clopidogrel (2.6% vs. 5.2%, p = 0.007). Ticagrelor decreased rates of MACE compared with clopidogrel (2.7% vs. 6.2%, p < 0.001), but not of NACE (6.6% vs. 8.7%, p = 0.07). Ticagrelor presented similar performance in terms of MACE compared with prasugrel (2.8% vs. 2.4%, p = 0.56), with a trend towards a reduction in MI (0.2% vs. 0.4%, p = 0.56), but with higher risk of BARC 3-5 bleedings (3.8% vs. 1.7%, p = 0.04). In the daily risk analysis, clopidogrel presented a binomial distribution with a peak of ischemic risk at 3 months, which decreased towards bleedings; prasugrel had a constant equivalence between opposite risks; and ticagrelor constantly reduced recurrent MIs despite higher risk of BARC 3-5 events. CONCLUSION: In real life, ticagrelor is more effective in reducing ischemic events during the first year after ACS, despite an increased risk of major bleedings, while prasugrel assures a better balance between ischemic and bleeding recurrent events.

Comparative external validation of the PRECISE-DAPT and PARIS risk scores in 4424 acute coronary syndrome patients treated with prasugrel or ticagrelor.

BACKGROUND: The PRECISE-DAPT and PARIS risk scores (RSs) were recently developed to help clinicians at individualizing the optimal dual antiplatelet therapy duration (DAPT) after percutaneous coronary intervention (PCI). Nevertheless, external validation of these RSs it has not yet been performed in ACS (acute coronary syndrome) patients treated with prasugrel or ticagrelor in a real- world scenario. METHODS: 4424 ACS patients who underwent PCI and survived to hospital discharge, from January 2012 to December 2016 at 12 European centers, were included. PRECISE-DAPT and PARIS bleeding RS, as well as PARIS ischemic RS, were computed, and their performance at predicting major bleeding (MB; BARC type 3 or 5) and ischemic events (MI and stent thrombosis) during follow up was compared. RESULTS: After a median follow-up of 14 (interquartile range 12-20.9) months, 83 (1.88%) patients developed MB and 133 (3.0%) suffered an ischemic episode. PRECISE-DAPT performed better than PARIS bleeding RS (c-statistic = 0.653 vs. 0.593; p = .01 for comparison) in predicting MB. The RSs performance for MB prediction remained consistent in STEMI patients (c-statistic = 0.632 vs 0.575) or in those treated with prasugrel (c-statistic = 0.623 vs 0.586). PARIS ischemic RS exhibited superior discrimination in predicting ischemic complications compared to PRECISE-DAPT (c-statistic = 0.604 vs 0.568 p = .05 for comparison). CONCLUSION: Our data provide support to the use of PRECISE-DAPT in MB risk stratification for patients receiving DAPT in form of aspirin and prasugrel or ticagrelor whereas the PARIS ischemic RS has potential to complement the risk prediction with respect to ischemic events.

Prevalencia e implicación pronóstica de la enfermedad valvular en pacientes con fibrilación auricular que inician anticoagulantes orales / Prevalence and prognostic implications of valve disease in patients with atrial fibrillation initiating direct oral anticoagulants

Introducción y objetivos: La enfermedad valvular en los pacientes con fibrilación auricular incluidos en los ensayos clínicos con anticoagulantes orales directos (ACOD) es frecuente y se asocia con peor pronóstico. El objetivo es evaluar la prevalencia de valvulopatía y su influencia en los eventos clínicos en la práctica clínica real. Métodos: Registro multicéntrico retrospectivo que incluyó a 2.297 pacientes consecutivos con fibrilación auricular no valvular que iniciaron tratamiento con ACOD entre enero de 2013 y diciembre de 2016. La enfermedad valvular se definió como afección moderada o grave. El evento principal fue la combinación de muerte, ictus o accidente isquémico transitorio/embolia sistémica o hemorragia mayor. Se realizó un análisis de riesgos competitivos mediante un modelo de regresión de Fine y Gray, con la muerte como evento competitivo. Resultados: Tenían valvulopatía 499 pacientes (21,7%), y la insuficiencia mitral fue la más frecuente (13,7%). Los pacientes con valvulopatía eran de más edad y con mayor comorbilidad. Tras el análisis multivariable, la enfermedad valvular fue predictora del evento combinado (HR=1,54; IC95%, 1,22-1,94; p<0,001), muerte (HR=1,44; IC95%, 1,09-1,91, p=0,010) y hemorragia mayor (HR=1,85; IC95%, 1,23-2,79, p=0,003), pero no de eventos tromboembólicos (p >0,05). Conclusiones: En pacientes con fibrilación auricular no valvular que inician tratamiento con ACOD, la enfermedad valvular es frecuente y se asocia con mayor riesgo de muerte, ictus o accidente isquémico transitorio/embolia sistémica o complicaciones hemorrágicas. Estos hallazgos confirman los resultados de los ensayos clínicos y los expande al ámbito de la práctica clínica real

Introduction and objectives: Valvular heart disease in patients with atrial fibrillation included in clinical trials with direct oral anticoagulants (DOAC) is common and is associated with worse prognosis. The aim of this study was to evaluate the prevalence of valvular heart disease and its influence on clinical events in real-world clinical practice. Methods: We conducted a retrospective multicenter registry including 2297 consecutive patients with nonvalvular atrial fibrillation initiating DOAC between January 2013 and December 2016. Valvular heart disease was defined as moderate or severe involvement. The primary study endopoint was the composite of death, stroke or transient ischemic attack/systemic embolism or major bleeding. A competing risks analysis was carried out using a Fine and Gray regression model, with death being the competing event. Results: A total of 499 (21.7%) patients had significant valvular heart disease. The most common form was mitral regurgitation (13.7%). Patients with valvular heart disease were older and had more comorbidities. After multivariable analysis, valvular heart disease was associated with a higher risk for the primary endpoint (HR, 1.54; 95%CI, 1.22-1.94; P<.001), death (HR, 1.44; 95%CI, 1.09-1.91, P=.010), and major bleeding (HR, 1.85; 95%CI, 1.23-2.79, P=.003), but there was no association with thromboembolic events (P >.05). Conclusions: In patients with nonvalvular atrial fibrillation initiating DOACs, valvular heart disease is common and increases the risk of mortality, stroke, transient ischemic attack/systemic embolism, and major bleeding complications. These findings confirm the results of clinical trials and expand them to a real-life clinical setting

Effect of concomitant antiplatelet therapy in patients with nonvalvular atrial fibrillation initiating non-vitamin K antagonists.

BACKGROUND: Antiplatelet therapy (APT) use in combination with oral anticoagulation is common among patients with atrial fibrillation, but there is scarce information regarding its effect on outcomes in patients on non-vitamin K antagonist oral anticoagulants (NOAC). We aimed to evaluate the safety and efficacy of APT use in a 'real-world' cohort of nonvalvular atrial fibrillation (NVAF) patients initiating NOAC. DESIGN: We conducted a retrospective multicentre study including 2361 consecutive NVAF patients initiating NOAC between January 2013 and December 2016. Patients with an acute ischaemic event within the last 12 months (acute coronary syndrome, stroke or revascularization) were excluded. Patients were followed up, and all clinical events were recorded at 3 months. The primary outcome of the study was major bleeding, and the secondary outcomes were stroke, nonfatal myocardial infarction, intracranial bleeding and death. RESULTS: One hundred forty-five (6.1%) patients received concomitant APT, and aspirin was the more common (79%). At 3 months, 25 (1.1%) patients had major bleeding, 8 (0.3%) had nonfatal myocardial infarction, 7 (0.3%) had ischaemic stroke, and 40 (1.7%) died. After multivariate adjustment, concomitant APT was associated with higher risk for major bleeding (HR = 3.62, 95% CI 1.32-9.89; P = .012), but was not associated with a higher risk of other clinical outcomes. CONCLUSIONS: Concomitant APT use is uncommon among these patients and does not seem to be associated with lower rates of ischaemic events or death. However, there are signals for an increased risk of bleeding, which reinforces current guideline recommendations.

Real-life behaviour of direct oral anticoagulants in a Spanish cohort with non-valvular atrial fibrillation: Refase Registry.

Aim: To analyse the effectiveness and safety of DOAC (direct oral anticoagulants) in non-valvular atrial fibrillation (NVAF) patients attending clinical practice.Methods: Retrospective study of AF patients who started treatment with DOAC from January 1, 2013 to December 31, 2016 in three Spanish hospitals. Mean follow-up was 1.6 years. The primary outcomes were rates of all-cause death, ischaemic stroke, and bleeding. These outcomes were also studied depending on correct dosage adjustment and standard/adjusted dose.Results: The study included 2494 patients (age = 76.0 ± 9.5 years, CHA2DS2-VASc = 4.0 ± 1.6). The most prescribed DOAC was rivaroxaban (41.1%). Patients taking dabigatran were the youngest (mean age = 73.1 ± 10.3 years), with better kidney function (mean CrCl = 80.6 ± 35.8 ml/min) and lower CHA2DS2-VASc (3.7 ± 1.4) and HAS-BLED (2.1 ± 0.9) scores. Patients taking apixaban were the oldest, and had the highest CHA2DS2-VASc and HAS-BLED scores (4.3 ± 1.6 and 2.6 ± 0.9, respectively). Rates of stroke/major bleeding/intracranial bleeding were 1.8/3.0/0.3 events per 100 patient-years, respectively, with no differences among DOAC. Based on dose adjustment according to technical data, it was observed that 517 patients (23.5%) received DOAC doses inconsistent with labelling (p < .001) and, within this group, under-dosed patients had a higher death rate although it did not reach a significant result after multivariate adjustment.Conclusions: The results of safety and efficacy are very similar to those of other previously published national registries. There were no differences among the different types of DOAC regarding outcomes. However, it was found that people taking the adjusted dose of the drug seemed to have a higher risk of death. A non-negligible proportion of patients received DOAC doses inconsistent with labelling (mostly underdose).

Correction to: Real-World Data of Prasugrel vs. Ticagrelor in Acute Myocardial Infarction: Results from the RENAMI Registry.

The first author's name which previously read.

Real-World Data of Prasugrel vs. Ticagrelor in Acute Myocardial Infarction: Results from the RENAMI Registry.

BACKGROUND: Limited data are available concerning differences in clinical outcomes for real-life patients treated with ticagrelor versus prasugrel after percutaneous coronary intervention (PCI). OBJECTIVE: Our objective was to determine and compare the efficacy and safety of ticagrelor and prasugrel in a real-world population. METHODS: RENAMI was a retrospective, observational registry including the data and outcomes of consecutive patients with acute coronary syndrome (ACS) who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT) between January 2012 and January 2016. The mean follow-up period was 17 ± 9 months. In total, 11 university hospitals from six European countries participated. After propensity-score matching, there were no substantial differences in the baseline clinical and interventional features. All patients were treated with acetylsalicylic acid plus prasugrel 10 mg once daily or acetylsalicylic acid plus ticagrelor 90 mg twice daily. Mean duration of DAPT was 12.04 ± 3.4 months with prasugrel and 11.90 ± 4.1 months with ticagrelor (p = 0.47). The primary and secondary endpoints were long-term net adverse clinical events (NACE) and major adverse cardiovascular events (MACE), respectively, along with their single components. Subgroup analysis for freedom from NACE and MACE was performed according to length of DAPT and clinical presentation [ST-elevation myocardial infarction (STEMI)-ACS versus non-ST-elevation myocardial infarction (NSTEMI)-ACS]. RESULTS: In total, 4424 patients (2725 ticagrelor, 1699 prasugrel) were enrolled. After propensity-score matching, 1290 patients in each cohort were included in the analysis. At 12 months, the incidence of both NACE and MACE was lower with prasugrel (NACE: 5.3% vs. 8.5% [p = 0.001]; MACE: 5% vs. 8.1% [p =  0.001]) mainly driven by a reduction in recurrent myocardial infarction (MI) (2.4 vs. 4.0%; p = 0.029) and a lower rate of Bleeding Academic Research Consortium (BARC) 3-5 bleeding (1.5 vs. 2.9%; p = 0.011). The benefit of prasugrel was confirmed for patients with NSTEMI and for those discharged with a DAPT regimen of ≤ 12 months. Only a trend in the reduction of NACE and MACE was noted for STEMI or for those treated with longer DAPT. CONCLUSIONS: Comparison of these drugs suggested that prasugrel is safer and more efficacious than ticagrelor in combination with aspirin after NSTEMI but not STEMI. No differences were found for events occurring after 12 months. The nonrandomized design of the present research means further studies are required to support these findings.