Variables affecting the quality of anticoagulation in atrial fibrillation patients newly initiating vitamin K antagonists: insights from the national and multicentre SULTAN registry.

AIMS: Vitamin K antagonists (VKAs) are effective drugs reducing the risk for stroke in atrial fibrillation (AF), but the benefits derived from such therapy depend on the international normalized ratio (INR) maintenance in a narrow therapeutic range. Here, we aimed to determine independent variables driving poor anticoagulation control [defined as a time in therapeutic range (TTR) <65%] in a 'real world' national cohort of AF patients. METHODS AND RESULTS: The SULTAN registry is a multicentre, prospective study, involving patients with non-valvular AF from 72 cardiology units expert in AF in Spain. At inclusion, all patients naïve for oral anticoagulation were started with VKAs for the first time. For the analysis, the first month of anticoagulation and those patients with <3 INR determinations were disregarded. Patients were followed up during 1 year. A total of 870 patients (53.9% male, the mean age of 73.6 ± 9.2 years, mean CHA2DS2-VASc and HAS-BLED of 3.3 ± 1.5 and 1.4 ± 0.9, respectively) were included in the full analysis set. In overall, 7889 INR determinations were available. At 1-year, the mean TTR was 63.1 ± 22.1% and 49.2% patients had a TTR < 65%. Multivariate Cox regression analysis showed that coronary artery disease [odds ratio (OR) 1.81, 95% confidence interval (CI) 1.14-2.87; P = 0.012] and amiodarone use (OR 1.54, 95% CI 1.01-2.34; P = 0.046) were independently associated with poor quality of anticoagulation (TTR <65%). CONCLUSION: This study demonstrated that the quality of anticoagulation in AF patients newly starting VKAs is sub-optimal. Previous coronary artery disease and concomitant use of amiodarone were identified as independent variables affecting the poor quality of VKA therapy during the first year.

Supervised exercise for acute coronary patients in primary care: a randomized clinical trial.

BACKGROUND: Functional capacity is a prognostic factor for coronary patients; accordingly, they are recommended to walk. OBJECTIVE: To assess whether an exercise program supervised in primary care increases their functional capacity more than unsupervised walking. METHODS: A randomized clinical trial was carried out at eight primary care centres of the Spanish Health Service and involving 97 incident cases of low-risk acute coronary patients, <80 years old, randomly assigned to either an unsupervised walking program (UW group; n = 51) or a 6-month cycle ergometer exercise program with gradually increasing frequency and workload intensity supervised by primary care nurses (SE group; n = 46). The two groups received the same common components of secondary prevention care. Changes in functional capacity were assessed in terms of peak oxygen consumption (VO2peak) during exercise testing measured at baseline and at 7 months by cardiologists blinded to group assignment. RESULTS: Overall, 76% of participants completed the study, 30 in the SE and 44 in the UW. Both groups increased baseline-adjusted VO2peak: 5.56ml/kg per minute in the SE (95% confidence interval [CI] 3.38-7.74) and 1.64ml/kg per minute in the UW (95% CI -0.15 to 3.45). The multivariate-adjusted difference between groups was 4.30ml/kg per minute (95% CI 1.82-6.79; P = 0.001) when analyzing completers and 2.83ml/kg per minute (95% CI 0.61-5.05; P = 0.01) in the intention-to-treat analysis, including all participants with baseline values carried forward for those lost to follow-up. CONCLUSIONS: A cycle ergometer exercise program supervised by primary care nurses increased the functional capacity of coronary patients more than unsupervised walking with a clinically relevant difference.

Clinical profile and outcomes in very elderly patients with atrial fibrillation anticoagulated with rivaroxaban: data from the EMIR study.

Objectives: To analyze the clinical profile, adequacy of treatment with rivaroxaban and outcomes in octogenarians with atrial fibrillation (AF), taking rivaroxaban in clinical practice. Methods: Observational and non-interventional study that included AF adults recruited from 79 Spanish centers, anticoagulated with rivaroxaban ≥ 6 months before being included. Data were analyzed according to age (≥ 80 vs. < 80 years) at baseline. Results: Out of 1433 patients, 453 (31.6%) were octogenarians at baseline. Compared to younger patients, octogenarians had more comorbidities, higher CHA2DS2-VASc (4.5 ± 1.3 vs. 3.0 ± 1.4; P < 0.001) and HAS-BLED scores (2.0 ± 1.0 vs. 1.4 ± 1.0; P < 0.001). Overall, the dose of rivaroxaban was adequately prescribed in 83.4% of patients, but more frequently in the younger population (71.1% vs. 89.1%; P = 0.039). After a mean follow-up of 2.2 ± 0.6 years, annual rates of stroke + systemic embolism + transient ischemic attack, MACE, cardiovascular death and major bleeding were 1.03%, 1.24%, 1.03% and 1.75%, respectively, in octogenarian patients. Except for progressive heart failure death and major bleeding, rates of outcomes in octogenarians were similar compared to younger patients. In octogenarians, the concomitant use of antiplatelet agents and non-severe dementia were independently associated with the development of ischemic stroke, whereas previous coronary revascularization and heart failure with MACE, and higher HAS-BLED score with major bleeding. Conclusions: In clinical practice, around one third of patients taking rivaroxaban are octogenarians. These patients have many comorbidities and a high thromboembolic risk. Despite that, rates of adverse events remain low. Rivaroxaban is adequately prescribed in the majority of octogenarians.

Trends in clinical profile and medical treatments of atrial fibrillation patients over the last 10 years.

AIM: We sought to define trends in AF prevalence and its medical management using recent data based on data from two cross-sectional studies performed in a European country in 1999 and 2009. METHODS: CARDIOTENS 1999 and CARDIOTENS 2009 were two observational, cross-sectional, multicenter studies. Patients were recruited in from primary care and cardiology outpatient clinics. A total of 32 051 and 25 137 subjects were analyzed in the two studies, 1540 and 1524 of them, respectively, diagnosed with AF. RESULTS: Over the course of the study period there was an increase in the prevalence of AF (from 4.8% to 6.1%), mainly due to the higher prevalence of AF in patients aged over 70 years (24.7% vs. 37.1%). Furthermore, patients with AF had a higher prevalence of hypertension (64.9% vs. 87.0%), diabetes (19.0% vs. 37.4%), heart failure (30.8% vs. 34.8%), coronary artery disease (23.0% vs. 25.8%) and previous stroke (1.5% vs. 8.9%). An overall increase in prescription of antithrombotic/antiplatelet therapy was observed (33.0% vs. 62.7% and 31.0% vs. 38.2% respectively); the difference observed in 1999 between prescription of oral anticoagulation by general practitioners and cardiologists was not seen in the later study. Differences in prescription of angiotensin-converting enzyme inhibitors (28.0% vs. 40.7%), angiotensin receptor blockers (10.0% vs. 40.0%), beta-blockers (14.0% vs. 41.5%) and calcium channel blockers (21.0% vs. 34.9%) were also identified. CONCLUSIONS: The number of patients with AF and a higher risk for thromboembolic events increased over the last 10 years. More aggressive antithrombotic treatment has been observed, especially in older patients.

Outcomes and factors associated with mortality in patients with atrial fibrillation and heart failure: FARAONIC study.

BACKGROUND: Heart failure (HF) and atrial fibrillation (AF) are common and coexistent conditions. HYPOTHESIS: To investigate the adverse events and mortality risk factors in patients with AF and HF treated with rivaroxaban in Spain. METHODS: Multicenter, prospective and observational study with a follow-up of 2 years, that included adults, with a diagnosis of nonvalvular AF and chronic HF, anticoagulated with rivaroxaban at least 4 months before being enrolled. RESULTS: A total of 672 patients from 71 Spanish centers were recruited, of whom 658 (97.9%) were included in the safety analysis and 552 (82.1%) in the per protocol analysis. At baseline, the mean age was 73.7 ± 10.9 years, 65.9% were male, 51.3% had HF with preserved ejection fraction and 58.7% were on New York Heart Association functional class II. CHA2 DS2 -VASc was 4.1 ± 1.5. During the follow-up, 11.6% of patients died and around one-quarter of patients were hospitalized or visited the emergency department, being HF worsening/progression the main cause (51.1%), with a 2.9% of thromboembolic events and 2.0% of acute coronary syndromes. Major bleeding occurred in 3.1% of patients, with 0.5% experiencing intracranial bleeding but no fatalities. Compliance with HF treatment was associated with a lower risk of death (hazard ratio: 0.092; 95% confidence interval: 0.03-0.31). CONCLUSIONS: Among patients with HF and AF anticoagulated with rivaroxaban, incidences of thromboembolic or hemorrhagic complications were low. The most important factor for improving survival was compliance with HF drugs, what strengths the need for early treatment with HF disease-modifying therapy and anticoagulation.

Non-embolic outcomes in patients with cardiovascular disease and atrial fibrillation treated with rivaroxaban.

Aim: It is not well known how comorbidities may change the prognosis of atrial fibrillation (AF) patients. This study was aimed to analyze the impact of cardiovascular disease on this population. Materials & methods: EMIR was a multicenter, prospective study, including 1433 AF patients taking rivaroxaban for ≥6 months. Data were analyzed according to the presence of vascular disease. Results: Coronary artery disease was detected in 16.4%, peripheral artery disease/aortic plaque in 6.7%, vascular disease in 28.3%. Patients with coronary artery disease had higher rates (per 100 patient-years) of major adverse cardiovascular events (2.98 vs 0.71; p < 0.001) and cardiovascular death (1.79 vs 0.41; p = 0.004). Those with vascular disease had higher rates of thromboembolic events (1.47 vs 0.44; p = 0.007), major adverse cardiovascular events (2.03 vs 0.70; p = 0.004), and cardiovascular death (1.24 vs 0.39; p = 0.025). Patients with peripheral artery disease/aortic plaque had similar rates. Conclusion: AF patients with vascular disease have a higher risk of non-embolic outcomes.

Gender differences in drug titration among heart failure patients with reduced ejection fraction in the ETIFIC trial.

INTRODUCTION AND OBJECTIVES: Optimal medical therapy decreases mortality and heart failure (HF) hospitalizations in HF patients with reduced left ventricular ejection fraction. Women have been underrepresented in clinical trials and not specifically evaluated. This study aimed to compare the safety and effectiveness of drug titration in women vs men. METHODS: This post hoc gender study of the ETIFIC multicenter randomized trial included hospitalized patients with new-onset HF with reduced ejection fraction and New York Heart Association II-III and no contraindications to beta-blockers. A structured 4-month titration process was implemented in HF clinics. The primary endpoint was the mean relative dose (% of target dose) of beta-blockers achieved by women vs men. Secondary endpoints included the mean relative doses of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists, adverse events, and other clinical outcomes at 6 months. RESULTS: A total of 320 patients were included, 83 (25.93%) women and 237 (74.06%) men (76 vs 213 analyzed). The mean±standard deviation of the relative doses achieved by women vs men were as follows: beta-blockers 62.08%±30.72% vs 64.4%±32.77%, with a difference of-2.32% (95%CI,-10.58-5.94), P = .580; and mineralocorticoid receptor antagonists 79.85%±27.72% vs 67.29%±31.43%, P =.003. No other differences in drug dosage were found. Multivariate analysis showed nonsignificant differences. CV mortality was 1 (1.20%) vs 3 (1.26%), P=1, and HF hospitalizations 0 (0.00%) vs 10 (4.22%), P=.125. CONCLUSIONS: In a post hoc analysis from the HF-titration ETIFIC trial, we found nonsignificant gender differences in drug dosage, cardiovascular mortality, and HF hospitalizations. Trial registry number: NCT02546856.

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.

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.

Outcomes and predictive value of the 2MACE score in patients with atrial fibrillation treated with rivaroxaban in a prospective, multicenter observational study: The EMIR study.

BACKGROUND: The aim of the study was to evaluate the performance of the 2MACE in patients with atrial fibrillation (AF) treated with rivaroxaban and to improve the accuracy of 2MACE. METHODS: This was a post-authorization and observational study of AF adults treated with rivaroxaban for ≥ 6 months. The primary endpoint was any of the major adverse cardiac events (MACE), namely, cardiovascular death, non-fatal myocardial infarction, and myocardial revascularization. The area under the curve (AUC) was calculated to evaluate the performance of 2MACE, and a new score, 2MACER to predict MACE. RESULTS: A total of 1433 patients were included (74.2 ± 9.7 years, CHA2DS2-VASc 3.5 ± 1.5, 26.9% 2MACE ≥ 3). The annual event rates (follow-up 2.5 years) were 1.07% for MACE, 0.66% for thromboembolic events and 1.04% for major bleeding. Patients with 2MACE ≥ 3 (vs. < 3) had higher risk of stroke/systemic embolism/transient ischemic attack (odds ratio [OR] 5.270; 95% CI 2.216-12.532), major bleeding (OR 4.624; 95% CI 2.163-9.882), MACE (OR 3.202; 95% CI 1.548-6.626) and cardiovascular death (OR 3.395; 95% CI 1.396-8.259). 2MACE was recalculated giving 1 more point to patients with baseline a glomerular filtration rate < 50 mL/min/1.73 m² (2MACER); 2MACER vs. 2MACE: IDI 0.1%, p = 0.126; NRI 23.9%, p = 0.125; AUC: 0.651 (95% CI 0.547-0.755) vs. 0.638 (95% CI 0.534-0.742), respectively; p = 0.361. CONCLUSIONS: In clinical practice, AF patients anticoagulated with rivaroxaban exhibit a low risk of events. 2MACE score acts as a modest predictor of a higher risk of adverse outcomes in this population. 2MACER did not significantly increase the ability of 2MACE to predict MACE.

Clinical development of bempedoic acid: phase 2 and phase 3 clinical trials. / Desarrollo clínico de ácido bempedoico: estudios fase 2 y fase 3.

We review all the phase II and III studies carried out with bempedoic acid at the dose of 180mg, alone or in combination with different lipid-lowering drugs and in different subgroups of patients that unequivocally show the efficacy and safety of the drug. We point out some of the potential advantages of its use in clinical practice in patients with statin intolerance and the efficacy in reducing LDL-c when combined with statins, and with statins and ezetimibe, as well as in reducing inflammation markers pending the results of the CV Clear Outcomes trial that will end in 2022.

Noninferiority of heart failure nurse titration versus heart failure cardiologist titration. ETIFIC multicenter randomized trial.

INTRODUCTION AND OBJECTIVES: Beta-blockers, angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin-II-receptor-blockers (ARB), and mineralocorticoid-receptor antagonists decrease mortality and heart failure (HF) hospitalizations in HF patients with reduced left ventricular ejection fraction. The effect is dose-dependent. Careful titration is recommended. However, suboptimal doses are common in clinical practice. This study aimed to compare the safety and efficacy of dose titration of the aforementioned drugs by HF nurses vs HF cardiologists. METHODS: ETIFIC was a multicenter (n=20) noninferiority randomized controlled open label trial. A total of 320 hospitalized patients with new-onset HF, reduced ejection fraction and New York Heart Association II-III, without beta-blocker contraindications were randomized 1:1 in blocks of 4 patients each stratified by hospital: 164 to HF nurse titration vs 156 to HF cardiologist titration (144 vs 145 analyzed). The primary endpoint was the beta-blocker mean relative dose (% of target dose) achieved at 4 months. Secondary endpoints included ACE inhibitors, ARB, and mineralocorticoid-receptor antagonists mean relative doses, associated variables, adverse events, and clinical outcomes at 6 months. RESULTS: The mean±standard deviation relative doses achieved by HF nurses vs HF cardiologists were as follows: beta-blockers 71.09%±31.49% vs 56.29%±31.32%, with a difference of 14.8% (95%CI, 7.5-22.1), P <.001; ACE inhibitors 72.61%±29.80% vs 56.13%±30.37%, P <.001; ARB 44.48%±33.47% vs 43.51%±33.69%, P=.93; and mineralocorticoid-receptor antagonists 71%±32.12% vs 70.47%±29.78%, P=.86; mean±standard deviation visits were 6.41±2.82 vs 2.81±1.58, P <.001, while the number (%) of adverse events were 34 (23.6) vs 30 (20.7), P=.55; and at 6 months HF hospitalizations were 1 (0.69) vs 9 (5.51), P=.01. CONCLUSIONS: ETIFIC is the first multicenter randomized trial to demonstrate the noninferiority of HF specialist-nurse titration vs HF cardiologist titration. Moreover, HF nurses achieved higher beta-blocker/ACE inhibitors doses, with more outpatient visits and fewer HF hospitalizations. Trial registry number: NCT02546856.

Rationale and design of a randomised controlled trial evaluating the effectiveness of an exercise program to improve the quality of life of patients with heart failure in primary care: The EFICAR study protocol.

BACKGROUND: Quality of life (QoL) decreases as heart failure worsens, which is one of the greatest worries of these patients. Physical exercise has been shown to be safe for people with heart failure. Previous studies have tested heterogeneous exercise programs using different QoL instruments and reported inconsistent effects on QoL. The aim of this study is to evaluate the effectiveness of a new exercise program for people with heart failure (EFICAR), additional to the recommended optimal treatment in primary care, to improve QoL, functional capacity and control of cardiovascular risk factors. METHODS/DESIGN: Multicenter clinical trial in which 600 patients with heart failure in NYHA class II-IV will be randomized to two parallel groups: EFICAR and control. After being recruited, through the reference cardiology services, in six health centres from the Spanish Primary Care Prevention and Health Promotion Research Network (redIAPP), patients are followed for 1 year after the beginning of the intervention. Both groups receive the optimized treatment according to the European Society of Cardiology guidelines. In addition, the EFICAR group performs a 3 month supervised progressive exercise program with an aerobic (high-intensity intervals) and a strength component; and the programme continues linked with community resources for 9 months. The main outcome measure is the change in health-related QoL measured by the SF-36 and the Minnesota Living with Heart Failure Questionnaires at baseline, 3, 6 and 12 months. Secondary outcomes considered are changes in functional capacity measured by the 6-Minute Walking Test, cardiac structure (B-type natriuretic peptides), muscle strength and body composition. Both groups will be compared on an intention to treat basis, using multi-level longitudinal mixed models. Sex, age, social class, co-morbidity and cardiovascular risk factors will be considered as potential confounding and predictor variables. DISCUSSION: A key challenges of this study is to guarantee the safety of the patients; however, the current scientific evidence supports the notion of there being no increase in the risk of decompensation, cardiac events, hospitalizations and deaths associated with exercise, but rather the opposite. Safety assurance will be based on an optimized standardised pharmacological therapy and health education for all the participants. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT01033591.

Benefit of primary percutaneous coronary interventions in the elderly with ST segment elevation myocardial infarction.

OBJECTIVE: Primary percutaneous coronary intervention (P-PCI) has demonstrated its efficacy in patients with ST segment elevation myocardial infarction (STEMI). However, patients with STEMI ≥75 years receive less P-PCI than younger patients despite their higher in-hospital morbimortality. The objective of this analysis was to determine the effectiveness of P-PCI in patients with STEMI ≥75 years. METHODS: We included 979 patients with STEMI ≥75 years, from the ATención HOspitalaria del Síndrome coronario study, a registry of 8142 consecutive patients with acute coronary syndrome admitted at 31 Spanish hospitals in 2014-2016. We calculated a propensity score (PS) for the indication of P-PCI. Patients that received or not P-PCI were matched by PS. Using logistic regression, we compared the effectiveness of performing P-PCI versus non-performance for the composite primary event, which included death, reinfarction, acute pulmonary oedema or cardiogenic shock during hospitalisation. RESULTS: Of the included patients, 81.5 % received P-PCI. The matching provided two groups of 169 patients with and without P-PCI. Compared with its non-performance, P-PCI presented a composite event OR adjusted by PS of 0.55 (95% CI 0.34 to 0.89). CONCLUSIONS: Receiving a P-PCI was significantly associated with a reduced risk of major intrahospital complications in patients with STEMI aged 75 years or older.

Would the Use of Edoxaban Be Cost-effective for the Prevention of Stroke and Systemic Embolism in Patients With Nonvalvular Atrial Fibrillation in Spain?

INTRODUCTION AND OBJECTIVES: To assess the cost-effectiveness of edoxaban vs acenocoumarol in the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF) in Spain. METHODS: Markov model, adapted to the Spanish setting from the perspective of the National Health System, stimulating the progression of a hypothetical cohort of patients with NVAF throughout their lifetime, with different health states: stroke, haemorrhage, and other cardiovascular complications. Efficacy and safety data were obtained from the available clinical evidence (mainly from the phase III ENGAGE AF-TIMI 48 study). The costs of managing NVAF and its complications were obtained from Spanish sources. RESULTS: Edoxaban use led to 0.34 additional quality-adjusted life years (QALY) compared with acenocoumarol. The incremental cost with edoxaban was 3916€, mainly because of higher pharmacological costs, which were partially offset by lower costs of treatment monitoring and managing NVAF events and complications. The cost per QALY was 11 518€, within the thresholds commonly considered cost-effective in Spain (25 000-30 000 €/QALY). The robustness of the results was confirmed by various sensitivity analyses. CONCLUSIONS: Edoxaban is a cost-effective alternative to acenocoumarol in the prevention of stroke and systemic embolism in patients with NVAF in Spain.

Effect of acetate-free biofiltration with a potassium-profiled dialysate on the control of cardiac arrhythmias in patients at risk: a pilot study.

Cardiac arrhythmias are a frequent event in chronic hemodialysis patients. The aim of this study was to evaluate the efficacy and safety of acetate-free hemofiltration with potassium-profiled dialysate (AFB-K) dialysis compared with constant potassium acetate-free biofiltration (AFB). Twelve patients (mean age 79 years) affected by cardiac arrhythmias or at a high risk for arrhythmia (advanced age, hypertension, left ventricular hypertrophy, heart valve disease, coronary artery disease, diabetes, paroxysmal atrial fibrillation) participated in a single-center, sequential cohort study. All were treated with hemodialysis 3 times per week, using constant potassium AFB for the first 3 weeks, followed by an AFB-K dialysate for the subsequent 3 weeks. The hemofilter, duration of dialysis, and electrolyte concentration were the same in both treatments. Both AFB-K and constant potassium AFB dialytic techniques were safe and well tolerated. The results of biochemical tests were similar, except for serum potassium levels after 2 hr of dialysis, which were significantly higher in the AFB-K group (4.0 mmol/L) than in the constant potassium AFB group (3.6 mmol/L) (p<0.001). All cardiac variables improved during AFB-K dialysis. There was a significant reduction of postdialysis QT intervals corrected for heart rate in the AFB-K group (448.8 ms) compared with the constant potassium AFB group (456.8 ms) (p=0.039). The severity and mean number of ventricular extasystoles also decreased (163.5 vs. 444.5/24 hr). Potassium profiling during hemodialysis treatment may be beneficial for patients with arrhythmias or at those risk of arrhythmias, particularly those with predialysis hyperkalemia.

Use of the cardiovascular polypill 40mg in secondary cardiovascular prevention. / Uso de la polipíldora cardiovascular 40mg en prevención cardiovascular secundaria.

Controlling cardiovascular risk factors (CV) is essential for patients with cardiovascular disease. The CV polypill contains aspirin 100mg, atorvastatin 20mg or 40mg, and ramipril 2.5mg, 5mg or 10mg in a fixed combination pill. The objective was to review the evidence on the secondary prevention of cardiovascular disease, to establish the eventual patient profiles suitables to consider the use of CV polypill with atorvastatin 40mg in secondary CV prevention (P40PS), and to define the priority situations most adequate for the use of P40PS. A bibliographic review was carried out, which was complemented with the clinical opinion of 19 specialists. During hospitalization and discharge, P40PS is an option for patients admitted because of an atherothrombotic event, peripheral arterial disease, or other causes, and with the indication of the monocomponents. Its priority use is proposed in: prior intolerance to the highest dose of atorvastatin (80mg), age>75 years, low weight, stage 3 of chronic renal failure, hypothyroidism, drug interactions and Asian origin. Outside the hospital setting, the P40PS is a therapeutic alternative in patients with a need for secondary CV prevention and with indication to receive the monocomponents. The priority situations to receive the P40PS are: to be taking the three components separately, to require polypharmacy, lack of adherence or understanding of the treatment, and lack of control of CV risk factors. This work is the first with proposals for the use of P40PS and can facilitate the treatment of patients with cardiovascular disease in secondary prevention.

Homogenization of the lipid profile values. / Homogeneización de los valores del perfil lipídico.

Analytical reports from the clinical laboratory are essential to guide clinicians about what lipid profile values should be considered altered and, therefore, require intervention. Unfortunately, there is a great heterogeneity in the lipid values reported as "normal, desirable, recommended or referenced" by clinical laboratories. This can difficult clinical decisions and be a barrier to achieve the therapeutic goals for cardiovascular prevention. A recent international recommendation has added a new heterogeneity factor for the interpretation of lipid profile, such as the possibility of measuring it without previous fasting. All this justifies the need to develop a document that adapts the existing knowledge to the clinical practice of our health system. In this regard, professionals from different scientific societies involved in the measurement and use of lipid profile data have developed this document to establish recommendations that facilitate their homogenization.

[Gender differences in early reperfusion treatment after myocardial infarction]. / Diferencias de género en el tratamiento de revascularización precoz del infarto agudo de miocardio.

BACKGROUND AND OBJECTIVE: Clinical variability in myocardial infarction (MI) regarding age, comorbidities and atypical symptoms could determine gender differences in inhospital care. This study analyzes the magnitude and determinants of differences between men and women in early reperfusion therapy in people hospitalized after MI. PATIENTS AND METHOD: 2,836 patients who arrived to hospital with MI were studied (IBERICA-Basque Country study). The relative risk (RR) of receiving early reperfusion for men versus women, adjusted by age, clinical characteristics, risk factors, and pre-hospital delay was estimated. The effect decomposition methodology and the log binomial regression were applied. RESULTS: 29% of patients were women with a median age of 77 years. The RR of revascularization in men compared to women was different according to age. When factors such as hypertension diabetes, Killip III-IV at admission and atypical symptoms were taken into account, statistically significant differences between sexes were not detected at 45 years old (RR=0.91; 95% CI=0.77-1.07). However, for 64 years old and over, the RR of reperfusion was 1.24 (95% CI=1.05-1.47). Both the differences by sex and the sex-age interaction were no longer statistically significant after adjusting by pre-hospital delay. CONCLUSIONS: The delay to receive medical care in elderly women is responsible of gender differences in early reperfusion. It is necessary to analyze the reasons for treatment-seeking delay.

Design of a multicentre randomized controlled trial to assess the safety and efficacy of dose titration by specialized nurses in patients with heart failure. ETIFIC study protocol.

AIMS: Heart failure (HF) is associated with many hospital admissions and relatively high mortality, rates decreasing with administration of beta-blockers (BBs), angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists. The effect is dose dependent, suboptimal doses being common in clinical practice. The 2012 European guidelines recommend close monitoring and dose titration by HF nurses. Our main aim is to compare BB doses achieved by patients after 4 months in intervention (HF nurse-managed) and control (cardiologist-managed) groups. Secondary aims include comparing doses of the other aforementioned drugs achieved after 4 months, adverse events, and outcomes at 6 months in the two groups. METHODS: We have designed a multicentre (20 hospitals) non-inferiority randomized controlled trial, including patients with new-onset HF, left ventricular ejection fraction ≤40%, and New York Heart Association class II-III, with no contraindications to BBs. We will also conduct qualitative analysis to explore potential barriers to and facilitators of dose titration by HF nurses. In the intervention group, HF nurses will implement titration as prescribed by cardiologists, following a protocol. In controls, cardiologists will both prescribe and titrate doses. The study variables are doses of each of the drugs after 4 months relative to the target dose (%), New York Heart Association class, left ventricular ejection fraction, N-terminal pro B-type natriuretic peptide levels, 6 min walk distance, comorbidities, renal function, readmissions, mortality, quality of life, and psychosocial characteristics. CONCLUSIONS: The trial seeks to assess whether titration by HF nurses of drugs recommended in practice guidelines is safe and not inferior to direct management by cardiologists. The results could have an impact on clinical practice.