Patterns of comorbidities in patients with atrial fibrillation and impact on management and long-term prognosis: an analysis from the Prospective Global GLORIA-AF Registry.

BACKGROUND: Clinical complexity, as the interaction between ageing, frailty, multimorbidity and polypharmacy, is an increasing concern in patients with AF. There remains uncertainty regarding how combinations of comorbidities influence management and prognosis of patients with atrial fibrillation (AF). We aimed to identify phenotypes of AF patients according to comorbidities and to assess associations between comorbidity patterns, drug use and risk of major outcomes. METHODS: From the prospective GLORIA-AF Registry, we performed a latent class analysis based on 18 diseases, encompassing cardiovascular, metabolic, respiratory and other conditions; we then analysed the association between phenotypes of patients and (i) treatments received and (ii) the risk of major outcomes. Primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). Secondary exploratory outcomes were also analysed. RESULTS: 32,560 AF patients (mean age 70.0 ± 10.5 years, 45.4% females) were included. We identified 6 phenotypes: (i) low complexity (39.2% of patients); (ii) cardiovascular (CV) risk factors (28.2%); (iii) atherosclerotic (10.2%); (iv) thromboembolic (8.1%); (v) cardiometabolic (7.6%) and (vi) high complexity (6.6%). Higher use of oral anticoagulants was found in more complex groups, with highest magnitude observed for the cardiometabolic and high complexity phenotypes (odds ratio and 95% confidence interval CI): 1.76 [1.49-2.09] and 1.57 [1.35-1.81], respectively); similar results were observed for beta-blockers and verapamil or diltiazem. We found higher risk of the primary outcome in all phenotypes, except the CV risk factor one, with highest risk observed for the cardiometabolic and high complexity groups (hazard ratio and 95%CI: 1.37 [1.13-1.67] and 1.47 [1.24-1.75], respectively). CONCLUSIONS: Comorbidities influence management and long-term prognosis of patients with AF. Patients with complex phenotypes may require comprehensive and holistic approaches to improve their prognosis.

Educational status affects prognosis of patients with heart failure with reduced ejection fraction: A post-hoc analysis from the WARCEF trial.

AIMS: The influence of social determinants of health (SDOH) on the prognosis of Heart Failure and reduced Ejection Fraction (HFrEF) is increasingly reported. We aim to evaluate the contribution of educational status on outcomes in patients with HFrEF. METHODS: We used data from the WARCEF trial, which randomized HFrEF patients with sinus rhythm to receive Warfarin or Aspirin; educational status of patients enrolled was collected at baseline. We defined three levels of education: low, medium and high level, according to the highest qualification achieved or highest school grade attended. We analysed the impact of the educational status on the risk of the primary composite outcome of all-cause death, ischemic stroke (IS) and intracerebral haemorrhage (ICH); components of the primary outcome were also analysed as secondary outcomes. RESULTS: 2295 patients were included in this analysis; of these, 992 (43.2%) had a low educational level, 947 (41.3%) had a medium education level and the remaining 356 (15.5%) showed a high educational level. Compared to patients with high educational level, those with low educational status showed a high risk of the primary composite outcome (adjusted hazard ratio [aHR]: 1.31, 95% confidence intervals [CI] 1.02-1.69); a non-statistically significant association was observed in those with medium educational level (aHR: 1.20, 95%CI: .93-1.55). Similar results were observed for all-cause death, while no statistically significant differences were observed for IS or ICH. CONCLUSION: Compared to patients with high educational levels, those with low educational status had worse prognosis. SDOH should be considered in patients with HFrEF. CLINICAL TRIAL REGISTRATION: NCT00041938.

Prediction of new-onset atrial fibrillation with the C2HEST score in patients admitted with community-acquired pneumonia.

PURPOSE: Patients hospitalized for community-acquired pneumonia (CAP) may have a higher risk of new-onset atrial fibrillation (NOAF). The C2HEST score was developed to evaluate the NOAF risk in the general population. Data on the value of the C2HEST score in acute patients admitted with CAP are lacking. We want to establish the predictive value of C2HEST score for NOAF in patients with CAP. METHODS: Patients with CAP enrolled in the SIXTUS cohort were enrolled. C2HEST score was calculated at baseline. In-hospital NOAF was recorded. Receiver-operating Characteristic (ROC) curve and multivariable Cox proportional hazard regression analysis were performed. RESULTS: We enrolled 473 patients (36% women, mean age 70.6 ± 16.5 years), and 54 NOAF occurred. Patients with NOAF were elderly, more frequently affected by hypertension, heart failure, previous stroke/transient ischemic attack, peripheral artery disease and hyperthyroidism. NOAF patients had also higher CURB-65, PSI class and CHA2DS2-VASc score. The C-index of C2HEST score for NOAF was 0.747 (95% confidence interval [95%CI] 0.705-0.786), higher compared to CURB-65 (0.611, 95%CI 0.566-0.655, p = 0.0016), PSI (0.665, 95%CI 0.621-0.708, p = 0.0199) and CHA2DS2-VASc score (0.696, 95%CI 0.652-0.737, p = 0.0762). The best combination of sensitivity (67%) and specificity (70%) was observed with a C2HEST score ≥ 4. This result was confirmed by the multivariable Cox analysis (Hazard Ratio [HR] for C2HEST score ≥ 4 was 10.7, 95%CI 2.0-57.9; p = 0.006), independently from the severity of pneumonia. CONCLUSION: The C2HEST score was a useful predictive tool to identify patients at higher risk for NOAF during hospitalization for CAP. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov (NCT01773863).

Validating the predictive ability of the 2MACE score for major adverse cardiovascular events in patients with atrial fibrillation: results from phase II/III of the GLORIA-AF registry.

The 2MACE score was specifically developed as a risk-stratification tool in atrial fibrillation (AF) to predict cardiovascular outcomes. We evaluated the predictive ability of the 2MACE score in the GLORIA-AF registry. All eligible patients from phase II/III of the prospective global GLORIA-AF registry were included. Major adverse cardiac events (MACEs) were defined as the composite outcome of stroke, myocardial infarction and cardiovascular death. Cox proportional hazards were used to examine the relationship between the 2MACE score and study outcomes. Predictive capability of the 2MACE score was investigated using receiver-operating characteristic curves. A total of 25,696 patients were included (mean age 71 years, female 44.9%). Over 3 years, 1583 MACEs were recorded. Patients who had MACE were older, with more cardiovascular risk factors and were less likely to be managed using a rhythm-control strategy. The median 2MACE score in the MACE and non-MACE groups were 2 (IQR 1-3) and 1 (IQR 0-2), respectively (p < 0.001). The 2MACE score was positively associated with an increase in the risk of MACE, with a score of ≥ 2 providing the best combination of sensitivity (69.6%) and specificity (51.6%), HR 2.47 (95% CI, 2.21-2.77). The 2MACE score had modest predictive performance for MACE in patients with AF (AUC 0.655 (95% CI, 0.641-0.669)). Our analysis in this prospective global registry demonstrates that the 2MACE score can adequately predict the risk of MACE (defined as myocardial infarction, CV death and stroke) in patients with AF. Clinical trial registration: http://www.clinicaltrials.gov . Unique identifiers: NCT01468701, NCT01671007 and NCT01937377.

Prediction of early death after atrial fibrillation diagnosis using a machine learning approach: A French nationwide cohort study.

AIMS: Atrial fibrillation is associated with important mortality but the usual clinical risk factor based scores only modestly predict mortality. This study aimed to develop machine learning models for the prediction of death occurrence within the year following atrial fibrillation diagnosis and compare predictive ability against usual clinical risk scores. METHODS AND RESULTS: We used a nationwide cohort of 2,435,541 newly diagnosed atrial fibrillation patients seen in French hospitals from 2011 to 2019. Three machine learning models were trained to predict mortality within the first year using a training set (70% of the cohort). The best model was selected to be evaluated and compared with previously published scores on the validation set (30% of the cohort). Discrimination of the best model was evaluated using the C index. Within the first year following atrial fibrillation diagnosis, 342,005 patients (14.4%) died after a period of 83 (SD 98) days (median 37 [10-129]). The best machine learning model selected was a deep neural network with a C index of 0.785 (95% CI, 0.781-0.789) on the validation set. Compared to clinical risk scores, the selected model was superior to the CHA2DS2-VASc and HAS-BLED risk scores and superior to dedicated scores such as Charlson Comorbidity Index and Hospital Frailty Risk Score to predict death within the year following atrial fibrillation diagnosis (C indexes: 0.597; 0.562; 0.643; 0.626 respectively. P < .0001). CONCLUSION: Machine learning algorithms predict early death after atrial fibrillation diagnosis and may help clinicians to better risk stratify atrial fibrillation patients at high risk of mortality.

Mobile health technology integrated care in atrial fibrillation patients with diabetes mellitus in China: A subgroup analysis of the mAFA-II cluster randomized clinical trial.

BACKGROUND: The Mobile Health Technology for Improved Screening and Optimized Integrated Care in AF (mAFA-II) prospective randomized trial showed the efficacy of a mobile health (mHealth) implemented 'Atrial fibrillation Better Care' (ABC) pathway for the integrated care management of patients with atrial fibrillation (AF). In this ancillary analysis, we evaluated the effect of mAFA intervention according to the history of diabetes mellitus (DM). METHODS: The mAFA-II trial enrolled 3324 AF patients across 40 centres in China, between June 2018 and August 2019. In this analysis, we assessed the interaction between history of DM and the effect of mAFA intervention on the risk of the primary composite outcome of stroke, thromboembolism, all-cause death and rehospitalizations. Results were expressed as adjusted hazard ratio (aHR) and 95% confidence intervals (95%CI). The effect of mAFA intervention on exploratory secondary outcomes was also assessed. RESULTS: Overall, 747 (22.5%) patients had DM (mean age: 72.7 ± 12.3, 39.6% females; 381 allocated to mAFA intervention). mAFA intervention was associated with a significant risk reduction for the primary composite outcome both in patients with and without DM (aHR [95%CI]: .36 [.18-.73] and .37 [.23-.61], respectively, p for interaction = .941). A significant interaction was found only for the composite of recurrent AF, heart failure and acute coronary syndromes (pint =.025), with lower effect of mAFA intervention in patients with DM. CONCLUSIONS: A mHealth-technology implemented ABC pathway showed a consistent effect in reducing the risk of the primary composite outcome in AF patients with and without DM. TRIAL REGISTRATION: WHO International Clinical Trials Registry Platform (ICTRP) Registration number: ChiCTR-OOC-17014138.

A systematic review and meta-analysis on oncological radiotherapy in patients with a cardiac implantable electronic device: Prevalence and predictors of device malfunction in 3121 patients.

BACKGROUND: The number of patients with cardiac implantable electronic devices (CIEDs) undergoing radiotherapy (RT) for cancer treatment is growing. At present, prevalence and predictors of RT-induced CIEDs malfunctions are not defined. METHODS: Systematic review and meta-analysis conducted following the PRISMA recommendations. PubMed, Scopus and Google Scholar were searched from inception to 31/01/2022 for studies reporting RT-induced malfunctions in CIEDs patients. Aim was to assess the prevalence of RT-induced CIEDs malfunctions and identify potential predictors. RESULTS: Thirty-two out of 3962 records matched the inclusion criteria and were included in the meta-analysis. A total of 135 CIEDs malfunctions were detected among 3121 patients (6.6%, 95% confidence interval [CI]: 5.1%-8.4%). The pooled prevalence increased moving from pacemaker (PM) to implantable cardioverter defibrillator (ICD), and cardiac resynchronization therapy and defibrillator (CRT-D) groups (4.1%, 95% CI: 2.9-5.8; 8.2% 95% CI: 5.9-11.3; and 19.8%, 95% CI: 11.4-32.2 respectively). A higher risk ratio (RR) of malfunctions was found when neutron-producing energies were used as compared to non-neutron-producing energies (RR 9.98, 95% CI: 5.09-19.60) and in patients with ICD/CRT-D as compared to patients with PM/CRT-P (RR 2.07, 95% CI: 1.40-3.06). On the contrary, no association was found between maximal radiation dose at CIED >2 Gy and CIEDs malfunctions (RR 0.93; 95% CI: 0.31-2.76). CONCLUSIONS: Radiotherapy related CIEDs malfunction had a prevalence ranging from 4% to 20%. The use of neutron-producing energies and more complex devices (ICD/CRT-D) were associated with higher risk of device malfunction, while the radiation dose at CIED did not significantly impact on the risk unless higher doses (>10 Gy) were used.

Impact of chronic obstructive pulmonary disease in patients with atrial fibrillation: an analysis from the GLORIA-AF registry.

AIMS: Chronic obstructive pulmonary disease (COPD) may influence management and prognosis of atrial fibrillation (AF), but this relationship has been scarcely explored in contemporary global cohorts. We aimed to investigate the association between AF and COPD, in relation to treatment patterns and major outcomes. METHODS AND RESULTS: From the prospective, global GLORIA-AF registry, we analysed factors associated with COPD diagnosis, as well as treatment patterns and risk of major outcomes in relation to COPD. The primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). A total of 36 263 patients (mean age 70.1 ± 10.5 years, 45.2% females) were included; 2,261 (6.2%) had COPD. The prevalence of COPD was lower in Asia and higher in North America. Age, female sex, smoking, body mass index, and cardiovascular comorbidities were associated with the presence of COPD. Chronic obstructive pulmonary disease was associated with higher use of oral anticoagulant (OAC) [adjusted odds ratio (aOR) and 95% confidence interval (CI): 1.29 (1.13-1.47)] and higher OAC discontinuation [adjusted hazard ratio (aHR) and 95% CI: 1.12 (1.01-1.25)]. Chronic obstructive pulmonary disease was associated with less use of beta-blocker [aOR (95% CI): 0.79 (0.72-0.87)], amiodarone and propafenone, and higher use of digoxin and verapamil/diltiazem. Patients with COPD had a higher hazard of primary composite outcome [aHR (95% CI): 1.78 (1.58-2.00)]; no interaction was observed regarding beta-blocker use. Chronic obstructive pulmonary disease was also associated with all-cause death [aHR (95% CI): 2.01 (1.77-2.28)], MACEs [aHR (95% CI): 1.41 (1.18-1.68)], and major bleeding [aHR (95% CI): 1.48 (1.16-1.88)]. CONCLUSION: In AF patients, COPD was associated with differences in OAC treatment and use of other drugs; Patients with AF and COPD had worse outcomes, including higher mortality, MACE, and major bleeding.

Mid-Regional Pro-Adrenomedullin Can Predict Organ Failure and Prognosis in Sepsis?

Sepsis causes immune dysregulation and endotheliitis, with an increase in mid-regional pro-adrenomedullin (MR-proADM). The aim of the study is to determine an MR-proADM value that, in addition to clinical diagnosis, can identify patients with localized infection or those with sepsis/septic shock, with specific organ damage or with the need for intensive care unit (ICU) transfer and prognosis. The secondary aim is to correlate the MR-proADM value with the length of stay (LOS). In total, 301 subjects with sepsis (124/301 with septic shock) and 126 with localized infection were retrospectively included. In sepsis, MR-proADM ≥ 3.39 ng/mL identified acute kidney injury (AKI); ≥2.99 ng/mL acute respiratory distress syndrome (ARDS); ≥2.28 ng/mL acute heart failure (AHF); ≥2.55 ng/mL Glascow Coma Scale (GCS) < 15; ≥3.38 multi-organ involvement; ≥3.33 need for ICU transfer; ≥2.0 Sequential Organ Failure Assessment (SOFA) score ≥ 2; and ≥3.15 ng/mL non-survivors. The multivariate analysis showed that MR-proADM ≥ 2 ng/mL correlates with AKI, anemia and SOFA score ≥ 2, and MR-proADM ≥ 3 ng/mL correlates with AKI, GCS < 15 and SOFA score ≥ 2. A correlation between mortality and AKI, GCS < 15, ICU transfer and cathecolamine administration was found. In localized infection, MR-proADM at admission ≥ 1.44 ng/mL identified patients with AKI; ≥1.0 ng/mL with AHF; and ≥1.44 ng/mL with anemia and SOFA score ≥ 2. In the multivariate analysis, MR-proADM ≥ 1.44 ng/mL correlated with AKI, anemia, SOFA score ≥ 2 and AHF. MR-proADM is a marker of oxidative stress due to an infection, reflecting severity proportionally to organ damage.

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry.

BACKGROUND: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The 'Atrial fibrillation Better Care' (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. METHODS: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. RESULTS: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58-0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52-0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58-0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56-0.98) and composite outcome (aHR: 0.76, 95%CI 0.60-0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. CONCLUSIONS: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients.

Epidemiology of cerebral microbleeds and risk of adverse outcomes in atrial fibrillation: a systematic review and meta-analysis.

AIMS: The aim of this study is to perform a systematic review and meta-analysis on the epidemiology of cerebral microbleeds (CMBs) and the risk of intracranial haemorrhage (ICH) and ischaemic stroke (IS) in patients with atrial fibrillation (AF). METHODS AND RESULTS: PubMed and EMBASE databases were systematically searched from inception to 6 March 2021. All studies reporting the prevalence of CMBs and incidence of ICH and IS in AF patients with and without CMBs were included. Meta-analysis was conducted using random-effect models; odds ratios (ORs), 95% confidence intervals (CIs), and prediction intervals (PIs) were calculated for each outcome. Subgroup analyses were performed according to the number and localization of CMBs. A total of 562 studies were retrieved, with 17 studies finally included in the meta-analysis. Prevalence of CMBs in AF population was estimated at 28.3% (95% CI: 23.8-33.4%). Individuals with CMBs showed a higher risk of ICH (OR: 3.04, 95% CI: 1.83-5.06, 95% PI 1.23-7.49) and IS (OR: 1.78, 95% CI: 1.26-2.49, 95% PI 1.10-2.87). Patients with ≥5 CMBs showed a higher risk of ICH. Metaregression showed how higher of prevalence of diabetes mellitus in AF cohort is associated with higher prevalence of CMBs. CONCLUSIONS: Cerebral microbleeds are common in patients with AF, found in almost one out of four subjects. Cerebral microbleeds were associated with both haemorrhagic and thromboembolic events in AF patients. Moreover, the risk of ICH increased consistently with the burden of CMBs. Cerebral microbleeds may represent an important overlooked risk factor for both ICH and IS in adults with AF.

Mobile health technology integrated care in older atrial fibrillation patients: a subgroup analysis of the mAFA-II randomised clinical trial.

BACKGROUND: The Mobile Health Technology for Improved Screening and Optimized Integrated Care in AF (mAFA-II) randomised trial demonstrated the efficacy of a mobile health (mHealth) technology-implemented 'Atrial fibrillation Better Care' (ABC) pathway-approach (mAFA intervention) in reducing the risk of adverse events in patients with atrial fibrillation (AF). Whether these benefits also apply to older patients is unclear. In this ancillary analysis, we evaluated the effect of mAFA intervention among older AF patients. METHODS: The mAFA-II trial enrolled adult AF patients across 40 centres in China. For this analysis, we defined older patients as those aged ≥75 years. Primary outcome was the composite of ischemic stroke or thromboembolism, all-cause death and rehospitalisation. The effect of mAFA intervention was assessed through multivariable Cox-regression models. We also evaluated the interaction between age and effect of the mAFA intervention in the main trial population. RESULTS: In this analysis, we included 1,163 AF patients ≥75 years (mean age: 82.6 ± 5.3 years, 43.1% females); 520 were allocated to mAFA intervention, 643 to usual care. mAFA intervention was associated with a significant reduction of the primary composite outcome (adjusted hazard ratio [aHR]: 0.58, 95% confidence interval [CI]: 0.35-0.97) and rehospitalisations alone (aHR: 0.47, 95%CI: 0.24-0.91). Significant interaction between age and mAFA intervention effect was observed for both the composite outcome (P = 0.002) and rehospitalisation alone (P = 0.015), with the effect decreasing as age increased, particularly among patients ≥80 years old. CONCLUSIONS: A mHealth technology-implemented ABC pathway is effective in reducing adverse clinical outcomes in older AF patients. The benefits obtained with mAFA intervention were attenuated at extreme ages.

Epidemiology and impact of frailty in patients with atrial fibrillation in Europe.

BACKGROUND: Frailty is a medical syndrome characterised by reduced physiological reserve and increased vulnerability to stressors. Data regarding the relationship between frailty and atrial fibrillation (AF) are still inconsistent. OBJECTIVES: We aim to perform a comprehensive evaluation of frailty in a large European cohort of AF patients. METHODS: A 40-item frailty index (FI) was built according to the accumulation of deficits model in the AF patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. Association of baseline characteristics, clinical management, quality of life, healthcare resources use and risk of outcomes with frailty was examined. RESULTS: Among 10,177 patients [mean age (standard deviation) 69.0 (11.4) years, 4,103 (40.3%) females], 6,066 (59.6%) were pre-frail and 2,172 (21.3%) were frail, whereas only 1,939 (19.1%) were considered robust. Baseline thromboembolic and bleeding risks were independently associated with increasing FI. Frail patients with AF were less likely to be treated with oral anticoagulants (OACs) (odds ratio 0.70, 95% confidence interval 0.55-0.89), especially with non-vitamin K antagonist OACs and managed with a rhythm control strategy, compared with robust patients. Increasing frailty was associated with a higher risk for all outcomes examined, with a non-linear exponential relationship. The use of OAC was associated with a lower risk of outcomes, except in patients with very/extremely high frailty. CONCLUSIONS: In this large cohort of AF patients, there was a high burden of frailty, influencing clinical management and risk of adverse outcomes. The clinical benefit of OAC is maintained in patients with high frailty, but not in very high/extremely frail ones.

Prevalence, management and impact of chronic obstructive pulmonary disease in atrial fibrillation: a systematic review and meta-analysis of 4,200,000 patients.

AIM: Prevalence of chronic obstructive pulmonary disease (COPD) in atrial fibrillation (AF) patients is unclear, and its association with adverse outcomes is often overlooked. Our aim was to estimate the prevalence of COPD, its impact on clinical management and outcomes in patients with AF, and the impact of beta-blockers (BBs) on outcomes in patients with COPD. METHODS AND RESULTS: A systematic review and meta-analysis was conducted according to international guidelines. All studies reporting the prevalence of COPD in AF patients were included. Data on comorbidities, BBs and oral anticoagulant prescription, and outcomes (all-cause death, cardiovascular (CV) death, ischaemic stroke, major bleeding) were compared according to COPD and BB status. Among 46 studies, pooled prevalence of COPD was 13% [95% confidence intervals (CI) 10-16%, 95% prediction interval 2-47%]. COPD was associated with higher prevalence of comorbidities, higher CHA2DS2-VASc score and lower BB prescription [odds ratio (OR) 0.77, 95% CI 0.61-0.98]. COPD was associated with higher risk of all-cause death (OR 2.22, 95% CI 1.93-2.55), CV death (OR 1.84, 95% CI 1.39-2.43), and major bleeding (OR 1.45, 95% CI 1.17-1.80); no significant differences in outcomes were observed according to BB use in AF patients with COPD. CONCLUSION: COPD is common in AF, being found in 13% of patients, and is associated with increased burden of comorbidities, differential management, and worse outcomes, with more than a two-fold higher risk of all-cause death and increased risk of CV death and major bleeding. Therapy with BBs does not increase the risk of adverse outcomes in patients with AF and COPD.

Sex and Gender-Related Issues in Heart Failure.

Understanding the role of sex- and gender-related factors, when dealing with a global growing epidemic such as heart failure, is a much needed and unmet goal for health care providers and scientists in order to design targeted strategies, aimed at improving both clinical and patient reported outcomes measures in women and men with heart failure. The present review provides an overview of the current available evidence on sex- and gender-related differences in heart failure.

Real-World Use of Apixaban for Stroke Prevention in Atrial Fibrillation: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: The use of oral anticoagulant therapy for stroke prevention in atrial fibrillation has been transformed by the availability of the nonvitamin K antagonist oral anticoagulants. Real-world studies on the use of nonvitamin K antagonist oral anticoagulants would help elucidate their effectiveness and safety in daily clinical practice. Apixaban was the third nonvitamin K antagonist oral anticoagulants introduced to clinical practice, and increasing real-world studies have been published. Our aim was to summarize current evidence about real-world studies on apixaban for stroke prevention in atrial fibrillation. METHODS: We performed a systematic review and meta-analysis of all observational real-world studies comparing apixaban with other available oral anticoagulant drugs. RESULTS: From the original 9680 results retrieved, 16 studies have been included in the final meta-analysis. Compared with warfarin, apixaban regular dose was more effective in reducing any thromboembolic event (odds ratio: 0.77; 95% confidence interval: 0.64-0.93), but no significant difference was found for stroke risk. Apixaban was as effective as dabigatran and rivaroxaban in reducing thromboembolic events and stroke. The risk of major bleeding was significantly lower for apixaban compared with warfarin, dabigatran, and rivaroxaban (relative risk reduction, 38%, 35%, and 46%, respectively). Similarly, the risk for intracranial hemorrhage was significantly lower for apixaban than warfarin and rivaroxaban (46% and 54%, respectively) but not dabigatran. The risk of gastrointestinal bleeding was lower with apixaban when compared with all oral anticoagulant agents (P<0.00001 for all comparisons). CONCLUSIONS: Use of apixaban in real-life is associated with an overall similar effectiveness in reducing stroke and any thromboembolic events when compared with warfarin. A better safety profile was found with apixaban compared with warfarin, dabigatran, and rivaroxaban.

Gender related differences in treatment and response to statins in primary and secondary cardiovascular prevention: The never-ending debate.

Statins are a main curbstone in the prevention of cardiovascular disease (CVD), pandemic in 21st century. CVD displays evident sex and gender differences, not only in clinical manifestation and outcomes but also in pharmacological treatment. Whether statin therapy should be differentially prescribed according to sex is a matter of debate. Aside a different pharmacological action, statins are not proven to be less effective in one gender comparing to the other, nor to be less safe. Nevertheless, up to date evidence shows that statins have not been adequately tested in women, especially in primary prevention trials. Since data-lacking, making a treatment decision on women is potentially harmful, although female individuals represent the majority of the population and they have a greater lifetime CVD risk. Therefore, adequately powered randomized control trials with longer follow-up are warranted to establish if a benefit on CV events and mortality prevention exists in both sexes. The aim of the present review is to summarize the sex and gender differences in statin use: it raises concerns and updates perspectives towards an evidence-based and sex-tailored prevention of CVD management.