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

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.

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A Distribution-based Method for Assessing The Differences between Clinical Trial Target Populations and Patient Populations in Electronic Health Records

Applied Clinical Informatics ◽

10.4338/aci-2013-12-ra-0105 ◽

2014 ◽

Vol 05 (02) ◽

pp. 463-479 ◽

Cited By ~ 30

Author(s):

P. Ryan ◽

Y. Zhang ◽

F. Liu ◽

J. Gao ◽

J.T. Bigger ◽

...

Keyword(s):

Type 2 Diabetes ◽

Clinical Trial ◽

Clinical Trials ◽

Electronic Health Records ◽

Real World ◽

World Population ◽

Health Records ◽

Target Populations ◽

Electronic Health

SummaryObjective: To improve the transparency of clinical trial generalizability and to illustrate the method using Type 2 diabetes as an example.Methods: Our data included 1,761 diabetes clinical trials and the electronic health records (EHR) of 26,120 patients with Type 2 diabetes who visited Columbia University Medical Center of New-York Presbyterian Hospital. The two populations were compared using the Generalizability Index for Study Traits (GIST) on the earliest diagnosis age and the mean hemoglobin A1c (HbA1c) values.Results: Greater than 70% of Type 2 diabetes studies allow patients with HbA1c measures between 7 and 10.5, but less than 40% of studies allow HbA1c<7 and fewer than 45% of studies allow HbA1c>10.5. In the real-world population, only 38% of patients had HbA1c between 7 and 10.5, with 12% having values above the range and 52% having HbA1c<7. The GIST for HbA1c was 0.51. Most studies adopted broad age value ranges, with the most common restrictions excluding patients >80 or <18 years. Most of the real-world population fell within this range, but 2% of patients were <18 at time of first diagnosis and 8% were >80. The GIST for age was 0.75. Conclusions: We contribute a scalable method to profile and compare aggregated clinical trial target populations with EHR patient populations. We demonstrate that Type 2 diabetes studies are more generalizable with regard to age than they are with regard to HbA1c. We found that the generalizability of age increased from Phase 1 to Phase 3 while the generalizability of HbA1c decreased during those same phases. This method can generalize to other medical conditions and other continuous or binary variables. We envision the potential use of EHR data for examining the generaliz-ability of clinical trials and for defining population-representative clinical trial eligibility criteria.Citation: Weng C, Li Y, Ryan P, Zhang Y, Liu F, Gao J, Bigger JT, Hripcsak G. A distribution-based method for assessing the differences between clinical trial target populations and patient populations in electronic health records. Appl Clin Inf 2014; 5: 463–479 http://dx.doi.org/10.4338/ACI-2013-12-RA-0105

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Response to checkpoint inhibitors (CPI) in sarcomatoid renal cell carcinoma (sRCC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e17095 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e17095-e17095

Author(s):

Iris Yeong- Fung Sheng ◽

Wei Wei ◽

Kunal Desai ◽

Kimberly D. Allman ◽

Allison Martin ◽

...

Keyword(s):

Clinical Trial ◽

Real World ◽

Systemic Therapy ◽

Checkpoint Inhibitors ◽

Cleveland Clinic ◽

Clinical Trial Data ◽

Trial Data ◽

Rank Test ◽

World Population ◽

Related Factors

e17095 Background: sRCC have a generally poor prognosis though recent clinical trial data suggest improved outcomes with CPI. We present a real-world experience of metastatic sRCC patients (pts) treated with a variety of CPI. Methods: Pts with sRCC treated with CPI Cleveland Clinic from 1/1/2015 to 12/31/2019 were identified. Overall survival (OS) was estimated using Kaplan-Meier and compared by log rank test. Results: Of 28 eligible pts identified with sRCC, median age 58, 82% Caucasian, all KPS score > 80%, 86% had IMDC intermediate/poor risk disease, 75% were clear cell, and 71% had prior nephrectomy. 46.4% had prior non-CPI systemic therapy. CPI therapy in this cohort included: 46% nivolumab monotherapy, 18% axitinib/pembrolizumab, 21% ipilimumab/nivolumab, 4% atezolizumab/bevacizumab, 7% atezolizumab, 4% carboplatin/pemetrexed/pembrolizumab. At a median follow up of 13.6 months (range 6.5-31.4), ORR was 36% (4% CR, 32% PR) and median OS was 13.8 months (95% CI: 9.23-NA). Median time to response was 3.2 months (range 2.4-13.1) and median duration of response was 8.1 months (range 0-25.5). Ten of the 13 patients started subsequent therapy due to progression. At the time of analysis, 39% were still alive and 25% of patients were still on initial I/O therapy (7+ -30+ months). There were no clear correlations between specific disease-related factors (including IMDC risk, time-to treatment of > or < 1 year, or prior systemic therapy) and response (all were p > 0.05). Conclusions: ORR and CR rates were lower in this real-world population of metastatic sRCC pts compared to clinical trial data, which should be a result of various CPI treatments and lines of treatment. However, these data highlight the heterogeneity of sRCC in general and need for additional investigations into impact of percentage of sarcomatoid features, genomic analyses, line of therapy, and CPI choice to optimize outcomes in sRCC pts.

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A decisional model to individualize warfarin recommendations: Expected impact on treatment and outcome rates in a real-world population with atrial fibrillation

International Journal of Cardiology ◽

10.1016/j.ijcard.2015.11.035 ◽

2016 ◽

Vol 203 ◽

pp. 785-790 ◽

Cited By ~ 1

Author(s):

Maura Marcucci ◽

Flemming Skjøth ◽

Gregory Y.H. Lip ◽

Alfonso Iorio ◽

Torben Bjerregaard Larsen

Keyword(s):

Atrial Fibrillation ◽

Real World ◽

World Population ◽

Impact On Treatment

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Three year incidence and duration of atrial fibrillation episodes among a large, real-world population of cryptogenic stroke patients with insertable cardiac monitors

European Heart Journal ◽

10.1093/ehjci/ehaa946.0394 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

P.D Ziegler ◽

J.D Rogers ◽

M Richards ◽

A.J Nichols ◽

S.W Ferreira ◽

...

Keyword(s):

Atrial Fibrillation ◽

Real World ◽

Stroke Prevention ◽

Detection Rate ◽

Large Population ◽

Cryptogenic Stroke ◽

World Population ◽

Median Frequency ◽

Secondary Stroke Prevention

Abstract Background/Introduction The primary goal of monitoring for atrial fibrillation (AF) after cryptogenic stroke (CS) is secondary stroke prevention. Therefore, long-term monitoring of CS patients with insertable cardiac monitors (ICMs) is likely important to ensure appropriate secondary stroke prevention therapy, regardless of when AF is detected after the index event. However, long-term data on the incidence and duration of AF from real-world populations are sparse. Purpose To investigate the long-term incidence and duration of AF episodes in real-world clinical practice among a large population of patients with ICMs placed for AF detection following CS. Methods We included patients from a large device manufacturer's database who received an ICM for the purpose of AF detection following CS and were monitored for up to 3 years. All detected AF episodes (≥2 minutes) were adjudicated. We quantified the AF detection rate for various episode duration thresholds using Kaplan-Meier survival estimates, analyzed the maximum duration of AF episodes, and measured the time to initial AF detection. Results A total of 1247 patients (65.3±13.0 years, 53% male) were included and followed for 763±362 days. AF episodes (n=5456) were detected in 257 patients, resulting in a median frequency of 5 episodes [IQR 2–19] per patient. At 3 years, the AF detection rate for episodes ≥2 minutes was 24.2%. The AF detection rates at 3 years for episodes ≥6 minutes, ≥30 minutes, and ≥1 hour were 22.4%, 20.6%, and 19.1%, respectively. The median duration of the longest detected AF episode was 4.4 [IQR 1.2–13.9] hours and the median time to AF detection was 129 [IQR 45–354] days. Conclusion AF episodes were detected via ICMs in approximately one-quarter of CS patients within 3 years of follow-up. More than 75% of patients with AF detected had episodes lasting ≥1 hour and half had episodes lasting ≥4 hours. Detection of the first AF episode typically occurred beyond the range of conventional ambulatory monitors. Long-term surveillance of CS patients is likely important given the appreciable incidence, frequency, and duration of these AF episodes. Funding Acknowledgement Type of funding source: None

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Abstract TMP40: Impact of Age on Atrial Fibrillation Detection among a Large, Real-World Population of Cryptogenic Stroke Patients with Insertable Cardiac Monitors

Stroke ◽

10.1161/str.47.suppl_1.tmp40 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Mark Richards ◽

John D Rogers ◽

Scott W Ferreira ◽

Allan J Nichols ◽

Jodi L Koehler ◽

...

Keyword(s):

Atrial Fibrillation ◽

Median Time ◽

Real World ◽

Detection Rate ◽

Recurrent Stroke ◽

Anticoagulation Therapy ◽

Cryptogenic Stroke ◽

World Population ◽

Time To Detection ◽

The Impact

Introduction: Detection of atrial fibrillation (AF) in patients with a cryptogenic stroke (CS) is critical for reducing the risk of recurrent stroke by enabling oral anticoagulation therapy. However, the impact of age on AF detection and the optimum duration of AF monitoring in patients following a CS is not well characterized. We investigated the impact of age on AF detection among a large, real-world cohort of unselected patients with an implantable cardiac monitor (ICM) placed following CS. Methods: Patients in the de-identified Medtronic Discovery™ Link database who received an ICM (Reveal LINQ™) for AF detection following CS were included and monitored for up to 182 days. All AF episodes were adjudicated. We compared the mean age between patients with vs. without AF detected and compared the median time to detection of the first AF episode between younger (age ≤65) and older (age >65) patients. Results: Among 1247 patients (mean age 65.3±13.0, 53% male) followed for 182 [IQR 182-182] days, 1521 AF episodes were detected in 147 patients and resulted in an AF detection rate of 12.2%. Patients with AF detected were significantly older than patients without AF detected (71.3±10.9 vs. 64.5±13.1 years, respectively; p<0.001). The median time to detection of the first AF episode was shorter for older vs. younger patients (43 [10-91] vs. 89 [29-127] days, respectively; p=0.016; Figure). Conclusion: Continuous monitoring of CS patients with an ICM resulted in an AF detection rate of 12.2% within the initial 6 months. Patients with AF detected were older and patients >65 years of age had shorter times to initial AF detection. However even among older patients, the majority of AF occurred outside the range of external monitoring devices and thus highlights the importance of long-term monitoring with ICMs in the management of CS patients.

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Predictive Value of the HAS-BLED and ATRIA Bleeding Scores for the Risk of Serious Bleeding in a “Real-World” Population With Atrial Fibrillation Receiving Anticoagulant Therapy

CHEST Journal ◽

10.1378/chest.12-0608 ◽

2013 ◽

Vol 143 (1) ◽

pp. 179-184 ◽

Cited By ~ 128

Author(s):

Vanessa Roldán ◽

Francisco Marín ◽

Hermógenes Fernández ◽

Sergio Manzano-Fernandez ◽

Pilar Gallego ◽

...

Keyword(s):

Atrial Fibrillation ◽

Anticoagulant Therapy ◽

Real World ◽

Predictive Value ◽

World Population

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Number needed to treat for net effect of anticoagulation in atrial fibrillation: Real‐World vs . Clinical Trial Evidence

British Journal of Clinical Pharmacology ◽

10.1111/bcp.14961 ◽

2021 ◽

Author(s):

Wern Yew Ding ◽

José Miguel Rivera‐Caravaca ◽

Francisco Marín ◽

Guowei Li ◽

Vanessa Roldán ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Trial ◽

Real World ◽

Number Needed To Treat ◽

Clinical Trial Evidence ◽

Trial Evidence

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

EP Europace ◽

10.1093/europace/euab116.158 ◽

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.

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