Incidence, type and prediction of death in anticoagulated patients with atrial fibrillation: a post-hoc analysis from the SPORTIF trials

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Proietti ◽  
J.M River-Caravaca ◽  
D Pastori ◽  
G.Y.H Lip

Abstract Introduction Patients with atrial fibrillation (AF) are at substantially increased risk of death. Uncertainty still remains about the best risk tool to to stratify and predict mortality risk. Aim To report the incidence of death according to cause in anticoagulated AF patients. Second, to evaluate the predictive ability of several risk scores. Methods Patients from the warfarin arms of the SPORTIF trials were considered for analysis. All-cause death, cardiovascular (CV) death and non-CV death were study outcomes. The 2MACE score, crude number of diseases (CND), charlson comorbidity index (CCI) and GARFIELD-AF Death score were predictive tools. Results 3665 patients (mean [SD] age 70.9 [8.9] years. 69.5% males; median [IQR] CHA2DS2-VASc 3 [2–4]) were analysed. Median [IQR] scores were: 2MACE 2 [1–3]; CND 5 [3–7]; CCI 2 [1–3]. Throughout a median [IQR] of 567 [491–652] days there were 204 (5.6%) all-cause deaths, 134 (3.7%) CV deaths and 70 (1.9%) non-CV deaths. The incidence of all-cause death was 3.59 per 100 patient-years, and for CV death and non-CV death, 2.39 per 100 patient-years and 1.23 per 100 patient-years, respectively. Cumulative incidence of all cause, CV and non-CV deaths is are shown in the Figure. After multivariable adjustment, all the tools were found associated with an increased risk of all-cause death (2MACE HR: 1.28, 95% CI: 1.17–1.40; CND HR: 1.07, 95% CI: 1.04–1.11; CCI HR: 1.33, 95% CI: 1.22–1.44; GARFIELD-AF Death HR: 1.85, 95% CI: 1.52–2.26 per each 0.100 increase). Similar results were found for CV death and non-CV death. All risk tools were only modestly predictive of the three outcomes (c-indexes <0.7; Table). In predicting all-cause death, CCI and GARFIELD-AF Death were similarly predictive with small differences compared to other tools; conversely 2MACE and GARFIELD-AF Death showed similar predictive capacity for CV death, while CND and CCI had a slightly better predictivity for non-CV death. Conclusions AF patients have a high mortality, particularly for CV death. All risk scores are associated with occurrence of all-cause mortality, having a similar (but modest) predictive capacity. GARFIELD-AF Death and the simpler 2MACE had the highest predictive value for CV death, while multimorbidity tools (CND and CCI) were more predictive for Non-CV death. Cumulative Incidence of Death Events Funding Acknowledgement Type of funding source: None

2018 ◽  
Vol 27 (6) ◽  
pp. 633-644 ◽  
Author(s):  
Marco Proietti ◽  
Alessio Farcomeni ◽  
Giulio Francesco Romiti ◽  
Arianna Di Rocco ◽  
Filippo Placentino ◽  
...  

Aims Many clinical scores for risk stratification in patients with atrial fibrillation have been proposed, and some have been useful in predicting all-cause mortality. We aim to analyse the relationship between clinical risk score and all-cause death occurrence in atrial fibrillation patients. Methods We performed a systematic search in PubMed and Scopus from inception to 22 July 2017. We considered the following scores: ATRIA-Stroke, ATRIA-Bleeding, CHADS2, CHA2DS2-VASc, HAS-BLED, HATCH and ORBIT. Papers reporting data about scores and all-cause death rates were considered. Results Fifty studies and 71 scores groups were included in the analysis, with 669,217 patients. Data on ATRIA-Bleeding, CHADS2, CHA2DS2-VASc and HAS-BLED were available. All the scores were significantly associated with an increased risk for all-cause death. All the scores showed modest predictive ability at five years (c-indexes (95% confidence interval) CHADS2: 0.64 (0.63–0.65), CHA2DS2-VASc: 0.62 (0.61–0.64), HAS-BLED: 0.62 (0.58–0.66)). Network meta-regression found no significant differences in predictive ability. CHA2DS2-VASc score had consistently high negative predictive value (≥94%) at one, three and five years of follow-up; conversely it showed the highest probability of being the best performing score (63% at one year, 60% at three years, 68% at five years). Conclusion In atrial fibrillation patients, contemporary clinical risk scores are associated with an increased risk of all-cause death. Use of these scores for death prediction in atrial fibrillation patients could be considered as part of holistic clinical assessment. The CHA2DS2-VASc score had consistently high negative predictive value during follow-up and the highest probability of being the best performing clinical score.


Author(s):  
Marco Proietti ◽  
José Miguel Rivera-Caravaca ◽  
María Asunción Esteve-Pastor ◽  
Francisco Marín ◽  
Gregory YH Lip

Background: Evaluation of thromboembolic risk is essential in anticoagulated atrial fibrillation (AF) patients. The CHA2DS2-VASc score is largely validated and recommended by most guidelines. The GARFIELD-AF Stroke score has been proposed as an alternative score. Methods: We analyzed warfarin-treated patients from SPORTIF III and V studies. Any thromboembolic event [TE] was an adjudicated study outcome. We compared the two scores capacity in predicting any TE occurrence. Results 3665 patients (median [IQR] age 72 [66-77] years; 30.5% female) were included in this analysis. After a mean (SD) follow-up of 566.3 (142.5) days, 148 (4.03%) TEs were recorded. Both continuous CHA2DS2-VASc and GARFIELD-AF were associated with TE (HR:1.37, 95% CI:1.22-1.53 and HR:2.43, 95% CI:1.72-3.42), with modest predictive ability (c-indexes:0.63, 95% CI:0.59-0.68 and 0.61, 95% CI:0.56-0.66, respectively), with no differences. CHA2DS2-VASc quartiles showed an increasing cumulative risk, while in GARFIELD-AF only the highest quartile (Q4) demonstrated an increased TE risk. On multivariate Cox regression analysis, CHA2DS2-VASc quartiles were associated with increasing risk of TE whereas for GARFIELD-AF only Q4 showed an association with TE. Discrimination analysis showed that GARFIELD-AF quartiles were associated with a 48.7% reduction in discriminatory ability. Using Decision Curve Analysis (DCA), CHA2DS2-VASc was associated with improved clinical usefulness and net clinical benefit, compared with GARFIELD-AF. Conclusions: In a warfarin-treated trial cohort of AF patients, both CHA2DS2-VASc and GARFIELD-AF Stroke scores were associated with adjudicated TE events, with modest predictive capacity. Simpler CHA2DS2-VASc score improved discriminatory capacity compared to more complex GARFIELD-AF score, demonstrating improved clinical usefulness and net clinical benefit.


Author(s):  
Jack W. O'Sullivan ◽  
Anna Shcherbina ◽  
Johanne M. Justesen ◽  
Mintu Turakhia ◽  
Marco Perez ◽  
...  

Background - Atrial fibrillation (AF) is associated with a five-fold increased risk of ischemic stroke. A portion of this risk is heritable, however current risk stratification tools (CHA 2 DS 2 -VASc) don't include family history or genetic risk. We hypothesized that we could improve ischemic stroke prediction in patients with AF by incorporating polygenic risk scores (PRS). Methods - Using data from the largest available GWAS in Europeans, we combined over half a million genetic variants to construct a PRS to predict ischemic stroke in patients with AF. We externally validated this PRS in independent data from the UK Biobank, both independently and integrated with clinical risk factors. The integrated PRS and clinical risk factors risk tool had the greatest predictive ability. Results - Compared with the currently recommended risk tool (CHA 2 DS 2 -VASc), the integrated tool significantly improved net reclassification (NRI: 2.3% (95%CI: 1.3% to 3.0%)), and fit (χ2 P =0.002). Using this improved tool, >115,000 people with AF would have improved risk classification in the US. Independently, PRS was a significant predictor of ischemic stroke in patients with AF prospectively (Hazard Ratio: 1.13 per 1 SD (95%CI: 1.06 to 1.23)). Lastly, polygenic risk scores were uncorrelated with clinical risk factors (Pearson's correlation coefficient: -0.018). Conclusions - In patients with AF, there appears to be a significant association between PRS and risk of ischemic stroke. The greatest predictive ability was found with the integration of PRS and clinical risk factors, however the prediction of stroke remains challenging.


2021 ◽  
Vol 17 ◽  
Author(s):  
Bryce Alexander ◽  
Gary Tse ◽  
Manuel Martinez-Selles ◽  
Adrian Baranchuk

: Atrial conduction disorders result from impaired propagation of cardiac impulses from the sinoatrial node through the atrial conduction pathways. Disorders affecting interatrial conduction alter P-wave characteristics on the surface electrocardiogram. A variety of P-wave indices reflecting derangements in atrial conduction have been described and have been associated with an increased risk of atrial fibrillation (AF) and stroke. Interatrial block (IAB) is the most well-known and described of the different P-wave indices and is important clinically due to its ability to predict patients who are at risk of the development of AF and other supraventricular tachycardias. P-Wave Axis is a measure of the net direction of atrial depolarization and is determined by calculating the net vector of the P-wave electrical activation in the six limb-leads using the hexaxial reference system. It has been associated with stroke and it has proposed that this variable be added to the existing CHA2DS2-VASc score to create a P2-CHA2DS2-VASc score to improve stroke prediction. PTerminal Force in V1 is thought to be an epiphenomenon of advanced atrial fibrotic disease and has been shown to be associated with a higher risk of death, cardiac death, and congestive heart failure as well as an increased risk of AF. Pwave Dispersion is defined as the difference between the shortest and longest P-wave duration recorded on multiple concurrent surface ECG leads on a standard 12-lead ECG and has also been associated with development of AF and AF recurrence. P-wave voltage in lead I (PVL1) is thought to be an electrocardiographic representation of cardiac conductive properties and therefore, the extent of atrial fibrosis relative to myocardial mass. Reduced PVL1 has been demonstrated to be associated with new-onset AF in patients with coronary artery disease and may be useful for predicting AF. Recently a risk score (the MVP risk score) has been developed using IAB and PVL1 to predict atrial fibrillation and has shown good predictive ability to determine patients at high risk of developing atrial fibrillation. The MVP risk score is currently undergoing validation in other populations. This section reviews the different P-wave indices in depth reflecting atrial conduction abnormalities in depth.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jack W Osullivan ◽  
Anna Shcherbina ◽  
Johanne M Justesen ◽  
Mintu Turakhia ◽  
Marco V Perez ◽  
...  

Introduction: Atrial fibrillation (AF) is associated with a five-fold increased risk of ischemic stroke. A portion of this risk is heritable, however current risk stratification tools (CHA 2 DS 2 -VASc) don’t include family history or genetic risk. Hypothesis: A polygenic risk scores (PRS) is both independently, and in integrated with clinical risk factors, predictive of ischemic stroke in patients with Atrial Fibrillation. Methods: Using data from the largest available GWAS in Europeans, we combined over half a million genetic variants to construct a PRS to predict ischemic stroke in patients with AF. We externally validated this PRS in independent data from the UK Biobank (UK Biobank), both independently and integrated with clinical risk factors. Results: The integrated PRS and clinical risk factors risk tool had the greatest predictive ability. Compared with the currently recommended risk tool (CHA 2 DS 2 -VASc), the integrated tool significantly improved net reclassification (NRI: 2.3% (95%CI: 1.3% to 3.0%)), and fit (χ2 P =0.002). Independently, PRS was a significant predictor of ischemic stroke in patients with AF prospectively (Hazard Ratio: 1.13 per 1 SD (95%CI: 1.04 to 1.21)). Lastly, polygenic risk scores were uncorrelated with clinical risk factors (Pearson’s correlation coefficient: -0.018). Conclusions: In patients with AF, there appears to be a significant association between PRS and risk of ischemic stroke. The greatest predictive ability was found with the integration of PRS and clinical risk factors, however the prediction of stroke remains challenging.


2019 ◽  
Vol 13 ◽  
pp. 175394471986067 ◽  
Author(s):  
Alejandra Gutierrez ◽  
Rushad Patell ◽  
Lisa Rybicki ◽  
Alok A. Khorana

Background: The role of cancer-specific factors for ischemic stroke and mortality in patients with cancer and atrial fibrillation (AF) is unknown. We evaluated the utility of a previously validated risk tool for venous thromboembolism (VTE) in cancer outpatients [Khorana score (KS)] in predicting stroke and mortality in cancer patients with AF. Methods: We conducted a retrospective cohort study of patients with cancer and AF at the Cleveland Clinic from 2008 to 2014. Outcomes, CHADS2, CHA2DS2-VASc, and KS scores were calculated from date of cancer diagnosis. Prognostic factors were identified with Fine and Gray regression (for stroke) or Cox proportional hazards analysis (for mortality). Results: The study population comprised 1181 patients. Genitourinary (19%), lung (18%), and gastrointestinal (13%) were the most frequent cancers. Overall, 67% had CHADS2 ⩾ 2, 57% had an intermediate KS (1–2), and 7% high KS (⩾3). Median follow up was 26.5 months (range 0.03–76). At a median of 8.2 months (range 0–61), 45 patients (3.8%) developed a stroke and 418 (35%) died. In multivariable analysis a high KS (HR 4.5, 95% CI 3.2–6.3, p < 0.001) was associated with a quadruple risk of death and every point increase in CHADS2 score had a 20% increased risk of death (HR 1.19, 95% CI 1.1–1.2, p < 0.001). The addition of KS did not improve risk stratification for ischemic stroke to CHADS2. Conclusion: In patients with cancer and AF, CHADS2 and CHA2DS2-VASc but not KS were predictive of ischemic stroke. A high KS represented a unique predictor of mortality beyond traditional risk scores.


2020 ◽  
Author(s):  
Jack W. O’Sullivan ◽  
Anna Shcherbina ◽  
Johanne M Justesen ◽  
Mintu Turakhia ◽  
Marco Perez ◽  
...  

AbstractBackgroundAtrial fibrillation (AF) is associated with a five-fold increased risk of ischemic stroke. A portion of this risk is heritable, however current risk stratification tools (CHA2DS2-VASc) don’t include family history or genetic risk. We hypothesized that we could improve ischemic stroke prediction in patients with AF by incorporating polygenic risk scores (PRS).ObjectivesTo construct and test a PRS to predict ischemic stroke in patients with AF, both independently and integrated with clinical risk factors.MethodsUsing data from the largest available GWAS in Europeans, we combined over half a million genetic variants to construct a PRS to predict ischemic stroke in patients with AF. We externally validated this PRS in independent data from the UK Biobank (UK Biobank), both independently and integrated with clinical risk factors.ResultsThe integrated PRS and clinical risk factors risk tool had the greatest predictive ability. Compared with the currently recommended risk tool (CHA2DS2-VASc), the integrated tool significantly improved net reclassification (NRI: 2.3% (95%CI: 1.3% to 3.0%)), and fit (χ2 P =0.002). Using this improved tool, >115,000 people with AF would have improved risk classification in the US. Independently, PRS was a significant predictor of ischemic stroke in patients with AF prospectively (Hazard Ratio: 1.13 per 1 SD (95%CI: 1.06 to 1.23))). Lastly, polygenic risk scores were uncorrelated with clinical risk factors (Pearson’s correlation coefficient: −0.018).ConclusionsIn patients with AF, there appears to be a significant association between PRS and risk of ischemic stroke. The greatest predictive ability was found with the integration of PRS and clinical risk factors, however the prediction of stroke remains challenging.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Andreea Cristina Ivănescu ◽  
Gheorghe-Andrei Dan

AbstractIntroduction: Atrial fibrillation (AF) is the most frequent hospitalized arrhythmia. It associates increased risk of death, stroke and heart failure (HF). Stroke risk scores, especially CHA2DS2-VASc, have been applied also for populations with different diseases. There is, however, limited data focusing on the ability of these scores to predict HF decompensation.Methods: We conducted a retrospective observational study on a cohort of 204 patients admitted for cardiovascular pathology to the Cardiology Ward of our tertiary University Hospital. We aimed to determine whether the stroke risk scores could predict hospitalisations for acute decompensated HF in AF patients.Results: C-statistics for CHADS2 and R2CHADS2 showed a modest predictive ability for hospitalisation with decompensated HF (CHADS2: AUC 0.631 p=0.003; 95%CI 0.560-0.697. R2CHADS2: AUC 0.619; 95%CI 0.548-0.686; p=0.004), a marginal correlation for CHA2DS2-VASc (AUC 0.572 95%CI 0.501-0.641 with a p value of only 0.09, while the other scores failed to show a correlation. A CHADS2≥2 showed a RR=2.96, p<0.0001 for decompensated HF compared to a score <2. For R2CHADS2 ≥2, RR= 2.41, p=0.001 compared to a score <2. For CHA2DS2-VASc≥2 RR=2.18 p=0.1, compared to CHA2DS2-VASc <2. The correlation coefficients showed a weak correlation for CHADS2 (r=0.216; p=0.001) and even weaker for R2CHADS2 (r=0.197; p=0.0047 and CHA2DS2-VASc (r=0.14; p=0.035).Conclusions: Among AF patients, CHADS2, CHA2DS2-VASc and R2CHADS2 were associated with the risk of hospitalisation for decompensated HF while ABC and ATRIA failed to show an association. However, predictive accuracy was modest and the clinical utility for this outcome remains to be determined.


Neurology ◽  
2021 ◽  
Vol 96 (12) ◽  
pp. 557-559
Author(s):  
Luciano A. Sposato ◽  
David J. Seiffge

2021 ◽  
Vol 1 (11) ◽  
pp. 12-19
Author(s):  
O. D. Ostroumova ◽  
V. N. Butorov ◽  
N. A. Arablinsky ◽  
R. R. Romanovsky ◽  
S. V. Batyukina

Clinical practice and ongoing scientific research in recent years show the importance of the problem of multimorbidity in atrial fibrillation (AF). The prevalence of AF in the general population is 1–2%, while the frequency of its occurrence increases with age – from less than 0.5% at the age of 40–50 to 5–15% at the age of 80. Only 19.6% of patients with AF have no comorbidities, 69.3% of patients have 1 to 3 comorbidities, and 11.1% of patients with AF had 4 and more comorbidities. In patients with AF and with 4 and more comorbidities, the risk of death from all causes is almost seven times higher than in patients without comorbidities. As shown by the post hoc analysis of the ARISTOTLE study, apixaban was equally effective and safe in both patients without concomitant pathology and in muliborbid patients. The efficacy and safety of apixaban has been shown in AF and concomitant arterial hypertension, heart failure, coronary heart disease, including in patients with acute coronary syndrome, diabetes mellitus, chronic kidney disease and chronic obstructive pulmonary disease. The data of scientific research in recent years are reflected in the recommendations of the Ministry of Health of the Russian Federation on AF (2020), which presents a separate section on the management of patients with concomitant diseases. It is emphasized that apixaban has shown its superiority over warfarin and other direct oral anticoagulants in terms of efficacy and safety, both in isolated AF and in patients with concomitant diseases, which makes its choice preferable in the treatment of multimirbidity AF patients.


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