scholarly journals Stroke risk based on classification of atrial fibrillation: real-world vs clinical trial

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
W.Y Ding ◽  
J.M Rivera-Caravaca ◽  
F Marin ◽  
V Roldan ◽  
G.Y.H Lip
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trial ◽  
Incidence Rate ◽  
Real World ◽  
Stroke Risk ◽  
Clinical Classification ◽  
Temporal Rhythm ◽  
Anticoagulated Patients ◽  
Trial Participants

Abstract Background The most widely accepted clinical classification of atrial fibrillation (AF) is according to temporal rhythm-based patterns, reflecting the notion that most patients initially suffer from transient episodes that prolong over time due to atrial substrate remodelling as the disease progresses. Therefore, it may be speculated that patients with extended episodes of “continuous” AF (persistent, long-standing persistent and permanent AF) may be at higher risk of stroke complications compared to paroxysmal AF (pAF). However, the risk of stroke according to clinical classification of AF remains poorly defined. In this study, we assessed the impact of AF type on stroke risk in patients with AF from “real-world” and “clinical trial” cohorts. Methods Post-hoc analysis of patient-level data from the Murcia AF Project and AMADEUS trial. All patients were anticoagulated. Patients were grouped into those with pAF and non-pAF. pAF was defined as AF that terminates spontaneously or with intervention within seven days of onset. Non-pAF was defined as AF that lasted longer than seven days, including persistent, long-standing persistent and permanent AF subtypes. Study endpoint was the incidence rate of ischaemic stroke. A modified CHA2DS2-VAS“c” score that applied one additional point for a “c” criterion of continuous AF (i.e. non-pAF) was calculated. Results 5,917 patients were included; 1,361 (23.0%) real-world and 4,556 (77.0%) clinical trial. Real-world patients had a median age of 76 (interquartile range [IQR] 71–81) years with 51.3% females compared to a median age of 71 (IQR 64–77) years with 33.5% females among clinical trial participants. Baseline demographics were comparable in both groups in the real-world cohort but clinical trial participants with non-pAF were older, predominantly male and had more comorbidities compared to those with pAF. Crude stroke rates were comparable between the groups in real-world patients (incidence rate ratio [IRR] 0.72 [95% CI, 0.37–1.28], p=0.259) though clinical trial participants with non-pAF (vs. pAF) had a significantly higher crude rate of stroke events (IRR 4.66 [95% CI, 2.41–9.48], p<0.001). Using multivariable cox regression analysis, AF type was not independently associated with stroke risk in the real-world (adjusted hazard ratio [HR] 1.41 [95% CI, 0.80–2.50], p=0.239) and clinical trial (adjusted HR 1.17 [95% CI, 0.62–2.20], p=0.621) cohorts, after accounting for known risk factors using the CHA2DS2-VASc score. Using receiver operating characteristic curves analysis, we found no significant improvement in the CHA2DS2-VAS“c” compared to CHA2DS2-VASc score in either cohort (p>0.05). Conclusion Overall, there was no association between the temporal rhythm-based patterns of AF and stroke risk among anticoagulated patients, suggesting that this should not be a consideration when assessing the need for anticoagulation in AF. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals Prediction of Residual Stroke Risk in Anticoagulated Patients with Atrial Fibrillation: mCARS

2021 ◽  
Vol 10 (15) ◽  
pp. 3357
Author(s):  
Wern Yew Ding ◽  
José Miguel Rivera-Caravaca ◽  
Francisco Marin ◽  
Christian Torp-Pedersen ◽  
Vanessa Roldán ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trial ◽  
Real World ◽  
Stroke Risk ◽  
Risk Estimation ◽  
Absolute Risk ◽  
Oral Anticoagulants ◽  
Absolute Risk Reduction ◽  
The Real ◽  
Anticoagulated Patients

Our ability to evaluate residual stroke risk despite anticoagulation in atrial fibrillation (AF) is currently lacking. The Calculator of Absolute Stroke Risk (CARS) has been proposed to predict 1-year absolute stroke risk in non-anticoagulated patients. We aimed to determine whether a modified CARS (mCARS) may be used to assess the residual stroke risk in anticoagulated AF patients from ‘real-world’ and ‘clinical trial’ cohorts. We studied patient-level data of anticoagulated AF patients from the real-world Murcia AF Project and AMADEUS clinical trial. Individual mCARS were estimated for each patient. None of the patients were treated with non-vitamin K antagonist oral anticoagulants. The predicted residual stroke risk was compared to actual stroke risk. 3503 patients were included (2205 [62.9%] clinical trial and 1298 [37.1%] real-world). There was wide variation of CARS for each category of CHA2DS2-VASc score in both cohorts. Average predicted residual stroke risk by mCARS (1.8 ± 1.8%) was identical to actual stroke risk (1.8% [95% CI, 1.3–2.4]) in the clinical trial, and broadly similar in the real-world (2.1 ± 1.9% vs. 2.4% [95% CI, 1.6–3.4]). AUCs of mCARS for prediction of stroke events in the clinical trial and real-world were 0.678 (95% CI, 0.598–0.758) and 0.712 [95% CI, 0.618–0.805], respectively. mCARS was able to refine stroke risk estimation for each point of the CHA2DS2-VASc score in both cohorts. Personalised residual 1-year absolute stroke risk in anticoagulated AF patients may be estimated using mCARS, thereby allowing an assessment of the absolute risk reduction of treatment and facilitating a patient-centred approach in the management of AF. Such identification of patients with high residual stroke risk could help target more aggressive interventions and follow-up.

scholarly journals Novel tool for predicting residual stroke risk in atrial fibrillation: mCARS

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
WY Ding ◽  
JM Rivera-Caravaca ◽  
F Marin ◽  
C Torp-Pedersen ◽  
V Roldan ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trial ◽  
Real World ◽  
Stroke Risk ◽  
Risk Estimation ◽  
The Real ◽  
Funding Sources ◽  
Level Data ◽  
Aggressive Interventions

Abstract Funding Acknowledgements Type of funding sources: None. Background Recently, CARS was proposed to predict 1-year absolute stroke risk in non-anticoagulated patients with atrial fibrillation (AF). We aimed to determine whether a modified CARS (mCARS) may be used to assess the residual stroke risk in anticoagulated AF patients. Methods We studied patient-level data of anticoagulated AF patients from the real-world Murcia AF Project and AMADEUS clinical trial. Individual mCARS was estimated for each patient using an estimated 64% risk reduction with anticoagulation. Results 3,503 patients were included (2,205 [62.9%] clinical trial and 1,298 [37.1%] real-world). In the clinical trial cohort, the median age was 71 (IQR 65-77) and CHA2DS2-VASc score 3 (IQR 2-4). In the real-world cohort, the median age was 76 (IQR 70-81) and CHA2DS2-VASc score 4 (IQR 3-5). At 1-year, there were 40 and 31 stroke events in the clinical trial and real-world cohorts, respectively. Average predicted residual stroke risk by mCARS was identical to actual stroke risk (1.8 [±1.8%] vs. 1.8% [95% CI, 1.3-2.4]) in the clinical trial, and broadly similar in the real-world (2.1 [±1.9%] vs. 2.4% [95% CI, 1.6-3.4]). Additionally, these values were comparable across the subgroups stratified by CHA2DS2-VASc score in both cohorts. AUCs of mCARS for prediction of stroke events in the clinical trial and real-world were 0.678 (95% CI, 0.598-0.758) and 0.712 (95% CI, 0.618-0.805), respectively. In an exploratory analysis, we found that mCARS was able to refine stroke risk estimation for each point of the CHA2DS2-VASc score in both cohorts. Conclusion Personalised residual 1-year absolute stroke risk in anticoagulated AF patients may be estimated using mCARS. Such patients with high residual stroke risk may benefit from more aggressive interventions and follow-up. Absolute 1-year stroke risk Clinical Trial Real-World Median (IQR) Range Median (IQR) Range CHA2DS2-VASc score 0 NA 0.9 (0.6 - 1.3) 0.2 - 1.4 CHA2DS2-VASc score 1 1.1 (0.7 - 1.4) 0.2 - 2.0 1.4 (0.9 - 1.7) 0.2 - 13.0 CHA2DS2-VASc score 2 2.0 (1.5 - 2.4) 0.3 - 10.8 2.1 (1.5 - 2.6) 0.3 - 10.8 CHA2DS2-VASc score 3 2.6 (2.1 - 3.4) 0.4 - 13.3 2.8 (2.5 - 3.4) 0.9 - 13.3 CHA2DS2-VASc score 4 3.6 (2.8 - 5.6) 0.3 - 18.1 3.9 (3.3 - 5.0) 1.1 - 21.0 CHA2DS2-VASc score 5 6.7 (3.6 - 14.0) 1.9 - 20.9 4.8 (3.9 - 12.2) 1.2 - 21.0 CHA2DS2-VASc score 6 13.6 (5.5 - 15.8) 2.4 - 21.8 12.8 (4.8 - 16.7) 2.2 - 21.8 CHA2DS2-VASc score 7 15.7 (14.5 - 17.4) 4.5 - 21.9 15.6 (5.9 - 17.5) 4.1 - 23.5 CHA2DS2-VASc score 8 16.5 (14.0 - 18.5) 13.1 - 20.3 16.9 (15.7 - 19.5) 13.6 - 21.0 IQR, interquartile range; NA, not applicable.

scholarly journals Number needed to treat for net effect of anticoagulation in atrial fibrillation

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
WY Ding ◽  
JM Rivera-Caravaca ◽  
F Marin ◽  
G Li ◽  
V Roldan ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trial ◽  
Major Bleeding ◽  
Real World ◽  
Stroke Risk ◽  
Absolute Risk ◽  
Baseline Risk ◽  
Number Needed To Treat ◽  
Bleeding Events ◽  
Risk Increase

Abstract Funding Acknowledgements Type of funding sources: None. Background The benefit of oral anticoagulation (OAC) in atrial fibrillation (AF) must be balanced against any potential risk of harm. We aimed to evaluate the "NNT for net effect" (NNTnet) using CARS in anticoagulated patients with AF. Methods We used patient-level data from the real-world Murcia AF Project and AMADEUS clinical trial. Baseline risk of stroke was calculated using CARS while major bleeding was estimated from prior studies. Stroke and major bleeding events at 1-year were determined. NNTnet was calculated as a reciprocal of the net effect of ARR with OAC (NNTnet= 1 / (ARRstroke - ARIbleeding)). Results 3,511 patients were included (1,306 [37.2%] real-world patients and 2,205 [62.8%] clinical trial). The absolute 1-year stroke risk was similar across both cohorts and the main results are presented in the Table. In both cohorts, the NNTnet was significantly lower in patients with an excess stroke risk of ≥2% by CARS. Among real-world patients with a very high (>10%) baseline stroke risk, the use of OAC was associated with an ARRstroke of 10.9% and ARIbleeding of 1.2%, generating an overall NNTnet of 11. In the clinical trial, the use of OAC was associated with an ARRstroke of 11.0% and ARIbleeding of 0.6%, generating an overall NNTnet of 10. Conclusion Overall, the NNTnet approach in AF incorporates information regarding baseline risk of stroke and major bleeding, and relative effects of OAC with the potential to include multiple additional outcomes and weighting of events based on their perceived effects by individual patients. This simple and intuitive metric may be useful to improve communication and optimise the patient-centred management of AF. NNT in Real-World and Clinical Trial Real-World Clinical Trial Ischaemic stroke risk at 1-year Baseline risk without anticoagulation (%) 5.7% (95% CI 5.5 - 6.0) 5.1% (95% CI 4.9 - 5.3) Anticoagulation-mediated risk (%) 1.7% (95% CI 1.1 - 2.6) 1.3% (95% CI 0.8 - 1.8) Absolute risk reduction (%) 4.0% 3.8% NNTbenefit 25 27 Major bleeding risk at 1-year Baseline risk without anticoagulation (%) 2.3% 2.3% Anticoagulation-mediated risk (%) 3.3% (95% CI 2.4 - 4.4) 3.9% (95% CI 3.1 - 4.8) Absolute risk increase (%) 1.0% 1.6% NNTharm 100 63 NNTnet 34 46

Abstract 171: Warfarin Use And Stroke Risk Among Patients With Nonvalvular Atrial Fibrillation In A Large Managed Care Population

2012 ◽  
Vol 5 (suppl_1) ◽  
Author(s):  
Steven B Deitelzweig ◽  
Erin Buysman ◽  
Brett Pinsky ◽  
Michael Lacey ◽  
Yonghua Jing ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Managed Care ◽  
Treatment Period ◽  
Real World ◽  
Warfarin Therapy ◽  
Stroke Risk ◽  
Nonvalvular Atrial Fibrillation ◽  
Chads2 Score ◽  
Warfarin Treatment

Introduction Warfarin discontinuation among real world nonvalvular atrial fibrillation (NVAF) patients is common. Hypothesis We hypothesized that in a managed care population, warfarin discontinuation is associated with increased stroke risk. Methods Patients who initiated warfarin therapy between Jan 2005 and Jun 2009 and had a healthcare claim related to AF within 30 days prior to the first warfarin claim, but no evidence of valvular disease, were included. Warfarin discontinuation was defined as a supply gap of >60 days without evidence of International Normalized Ratio (INR) measurements. Follow-up was divided into periods of warfarin treatment and discontinuation. Stroke events were identified based on claims for inpatient stays with a primary diagnosis for stroke or transient ischemic attack (TIA). Cox proportional hazards models were constructed to assess the relationship between warfarin discontinuation and incident stroke while adjusting for baseline demographics, stroke and bleeding risk, and comorbidities, as well as time-dependent antiplatelet use, stroke, and bleeding events in the prior warfarin treatment period. Results The mean (SD) age of the study sample (N=16,253) was 67±12 years; 64.8% was male. Mean CHADS2 score was 1.84±1.30; mean HAS-BLED score was 2.00±1.18. Half (51.4%) of patients discontinued warfarin therapy at least once and the overall sample had a mean of 1.87 warfarin treatment periods during a mean of 668 days follow-up. Approximately 1186 patients (7%) had a stroke or TIA at any site of service during follow-up. Risk of stroke significantly increased during warfarin discontinuation periods compared with therapy periods (HR 1.60; 95%CI 1.35-1.90; P<.0001). Stroke risk was significantly increased for patients with baseline CHADS2 score ≥2 (HR 2.69; 95%CI 1.44-5.03; P=.002), HAS-BLED score ≥3 (HR 1.46; 95%CI 1.05-2.05; P=.027), or who had a bleeding (HR 1.29; 95%CI 1.06-1.57; P=.013) or stroke event (HR 3.04; 95%CI 2.47-3.75; P<.0001) in the prior treatment period. Conclusions In the real world, over half of patients on anticoagulation therapy had treatment gaps or permanently discontinued therapy. These usage patterns, as well as prior bleeding, were associated with increased stroke risk.

Atrial Fibrillation and Mitral Regurgitation: Clinical Performance of Direct Oral Anticoagulants in a Real-World Setting

2020 ◽  
Vol 25 (6) ◽  
pp. 564-569
Author(s):  
Enrico Melillo ◽  
Anna Rago ◽  
Riccardo Proietti ◽  
Emilio Attena ◽  
Maddalena Carrella ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Mitral Regurgitation ◽  
Incidence Rate ◽  
Real World ◽  
Clinical Performance ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Annual Incidence ◽  
Research Database ◽  
Annual Incidence Rate

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is frequently present in patients with mitral regurgitation (MR). Currently, there is a lack of real-world evidence specifically addressing the clinical performance of direct oral anticoagulants (DOACs) in patients with AF and concomitant MR. Therefore, the aim of the present study was to assess the efficacy and safety profile of DOACs therapy in patients with AF and MR. Methods: Data for this study were sourced from the Atrial Fibrillation Research Database in the Department of Cardiology at Monaldi Hospital. The database was queried for AF patients with MR who were prescribed DOACs therapy. The primary safety outcome was defined as the annual incidence rate of major bleeding events and the primary effectiveness outcome as the annual incidence rate of all events classified as ischemic stroke, transient ischemic attacks, and systemic embolisms. Results: Consecutive AF patients with concomitant mild to severe MR who received DOACs therapy (n = 259) were included. Patients were dichotomized in 2 groups according to MR severity: a mild-to-moderate group (MR 1-2+; n = 151) and a moderate-to-severe group (MR 3-4+; n = 108). The incidence rate of major bleedings was significantly higher in MR 3-4+ group (3.92%) compared with the MR 1-2+ group (1.18%; hazard ratio [HR]: 3.2; 95% CI: 1.4-7.3; P = .0059). The incidence rate of thromboembolic events between MR 3-4+ group (0.66%) and MR 1-2+ group (0.62%) was not significantly different (HR: 0.75; P = .823). Conclusions: In the present study, there was no difference in the efficacy profile of DOACs between AF patients with mild-to-moderate and moderate-to-severe MR. Considering the increased bleeding risk, a close and careful follow-up should be warranted for patients with moderate-to-severe MR.

scholarly journals Effectiveness of structured, hospital-based, nurse-led atrial fibrillation clinics: a comparison between a real-world population and a clinical trial population

Open Heart ◽  
2016 ◽  
Vol 3 (1) ◽  
pp. e000335 ◽  
Author(s):  
Ina Qvist ◽  
Jeroen M L Hendriks ◽  
Dorthe S Møller ◽  
Andi E Albertsen ◽  
Helle M Mogensen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trial ◽  
Real World ◽  
World Population

Edoxaban versus placebo, aspirin, or aspirin plus clopidogrel for stroke prevention in atrial fibrillation

2015 ◽  
Vol 114 (08) ◽  
pp. 403-409 ◽  
Author(s):  
Lars Rasmussen ◽  
Torben Larsen ◽  
Andrew Blann ◽  
Flemming Skjøth ◽  
Gregory Lip
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trial ◽  
Real World ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Published Data ◽  
Real World Data ◽  
Once Daily ◽  
Increased Risk ◽  
Reduced Risk

SummaryAs non-valvular atrial fibrillation (AF) brings a risk of stroke, oral anticoagulants (OAC) are recommended. In ‘real world’ clinical practice, many patients (who may be, or perceived to be, intolerant of OACs) are either untreated or are treated with anti-platelet agents. We hypothesised that edoxaban has a better net clinical benefit (NCB, balancing the reduction in stroke risk vs increased risk of haemorrhage) than no treatment or anti-platelet agents. We performed a network meta-analysis of published data from 24 studies of 203,394 AF patients to indirectly compare edoxaban with aspirin alone, aspirin plus clopidogrel, and placebo. Edoxaban 30 mg once daily significantly reduced the risk of all stroke, ischaemic stroke and mortality compared to placebo and aspirin. Compared to aspirin plus clopidogrel, there was a lower risk of intra-cranial haemorrhage (ICH). Edoxaban 60 mg once-daily had a reduced risk of any stroke and systemic embolism compared to placebo, aspirin, and aspirin plus clopidogrel. Mortality rates for both edoxaban doses were estimated to be lower compared to any anti-platelet, and significantly lower compared to placebo. With overall reduced risk of ischemic stroke and ICH, both edoxaban doses bring a NCB of mean (SD) 1.68 (0.15) saved events per 100 patients per year compared to anti-platelet drugs in a clinical trial population. The NCB was demonstrated to be lower, at 0.77 (0.12) events saved (p< 0.01) when modeled to data from a ‘real world’ cohort of AF patients. In conclusion, edoxaban is likely to provide even better protection from stroke and ICH than placebo, aspirin alone, or aspirin plus clopidogrel in both clinical trial populations and unselected community populations. Both edoxaban doses would also bring a positive NCB compared to anti-platelet drugs or placebo/non-treatment based on ‘real world’ data.Note: The review process for this paper was fully handled by Christian Weber, Editor in Chief.

Outcomes in anticoagulated patients with atrial fibrillation and with mitral or aortic valve disease

Heart ◽  
2018 ◽  
Vol 104 (15) ◽  
pp. 1292-1299 ◽  
Author(s):  
Dragos Vinereanu ◽  
Alice Wang ◽  
Hillary Mulder ◽  
Renato D Lopes ◽  
Petr Jansky ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trial ◽  
Major Bleeding ◽  
Treatment Effect ◽  
P Value ◽  
Efficacy And Safety ◽  
Systemic Embolism ◽  
Clinical Trial Registration ◽  
Safety Outcomes ◽  
Anticoagulated Patients

ObjectiveTo assess stroke/systemic embolism, major bleeding and other outcomes, and treatment effect of apixaban versus warfarin, in patients with atrial fibrillation (AF) and different types of valvular heart disease (VHD), using data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial.MethodsThere were 14 793 patients with known VHD status, categorised as having moderate or severe mitral regurgitation (MR) (n=3382), aortic regurgitation (AR) (n=842) or aortic stenosis (AS) (n=324); patients with moderate or severe mitral stenosis were excluded from the trial. Baseline characteristics, efficacy and safety outcomes were compared between each type and no significant VHD. Treatment effect was assessed using an adjusted model.ResultsPatients with MR or AR had similar rates of stroke/systemic embolism and bleeding compared with patients without MR or AR, respectively. Patients with AS had significantly higher event rates (presented as rate per 100 patient-years of follow-up) of stroke/systemic embolism (3.47 vs 1.36; adjusted HR (adjHR) 2.21, 95% CI 1.35 to 3.63), death (8.30 vs 3.53; adjHR 1.92, 95% CI 1.41 to 2.61), major bleeding (5.31 vs 2.53; adjHR 1.80, 95% CI 1.19 to 2.75) and intracranial bleeding (1.29 vs 0.51; adjHR 2.54, 95% CI 1.08 to 5.96) than patients without AS. The superiority of apixaban over warfarin on stroke/systemic embolism was similar in patients with versus without MR (HR 0.69, 95% CI 0.46 to 1.04 vs HR 0.79, 95% CI 0.63 to 1.00; interaction P value 0.52), with versus without AR (HR 0.57, 95% CI 0.27 to 1.20 vs HR 0.78, 95% CI 0.63 to 0.96; interaction P value 0.52), and with versus without AS (HR 0.44, 95% CI 0.17 to 1.13 vs HR 0.79, 95% CI 0.64 to 0.97; interaction P value 0.19). For each of the primary and secondary efficacy and safety outcomes, there was no evidence of a different effect of apixaban over warfarin in patients with any VHD subcategory.ConclusionsIn anticoagulated patients with AF, AS is associated with a higher risk of stroke/systemic embolism, bleeding and death. The efficacy and safety benefits of apixaban compared with warfarin were consistent, regardless of presence of MR, AR or AS.Clinical trial registrationARISTOTLE clinical trial number NCT00412984.

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