Comparative adherence between DOAC and VKA in patients with atrial fibrillation: a 23-year retrospective observational study in Canada

Abstract Background A recent systematic review highlighted significant gaps in the evidence on atrial fibrillation (AF) patients' adherence to oral anticoagulants (OAC). Current evidence suffers from short follow-up times, focuses on the first OAC and does not take switching into account. There is also lack of observational data on adherence to warfarin due to its varying dose that complicates the calculations. As such there is lack of evidence on comparative adherence between VKAs and DOACs and whether the convenience of DOACs translates into better adherence in AF patients. Purpose Our objective was to measure AF patients' long-term OAC adherence and compare the impact of taking direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) on adherence, while accounting for switching. Methods Using linked, population-based administrative data containing physician billings, hospitalization and prescription records of 4.8 million British Columbians (1996–2019), incident adult cases of AF were identified. The primary measure of adherence was proportion of days covered (PDC). Consecutive rolling 90-day windows were created for each patient starting from their first OAC prescription fill date until the end of their follow-up. The PDC for each 90-day rolling window was calculated and averaged to yield mean adherence over the follow-up period for each patient. Permanent medication discontinuation resulted in a PDC of 0 for all subsequent rolling windows after their supply ran out. As such, both poor execution and non-persistence were measured simultaneously. The association between drug class and adherence was assessed using generalized mixed effect linear regression models with drug class treated as time-varying covariate to account for switching. Results The study cohort was 30,264 AF patients [mean age 72.2 years (SD11.0), 44.6% female, mean CHA2DS2-VASc 2.94 (SD1.4)] with mean follow-up of 7.7 (SD 4.8) years. The mean PDC was 0.71 (SD 0.27) with 51% of the cohort having mean PDC values below the conventional threshold of adherence (PDC<0.8). Adherence dropped over time with the greatest decline in the first two years after therapy initiation. After controlling for all other confounders and accounting for switching, taking VKA compared to DOAC was, on average, associated with a 1-day decrease in number of days of medication-taking per year. Conclusion AF patients' OAC adherence was below the conventional threshold of 0.8, and dropped over time, particularly in the first two years. Drug class had no clinically meaningful impact on medication adherence. Our study highlights the need for effective adherence interventions particularly early in OAC therapy. Our findings also emphasizes that prescribers should not assume inherently better adherence for DOACs and should instead choose OAC in conversation with the patient and in accordance with their values and preferences. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Canadian Institutes of Health Research grant

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Time at home among nonvalvular atrial fibrillation patients treated with non-vitamin K antagonist oral anticoagulants versus warfarin

European Heart Journal ◽

10.1093/eurheartj/ehab724.0573 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

S Deitelzweig ◽

A Keshishian ◽

A Kang ◽

A Jenkins ◽

N Atreja ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Index Date ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Nursing Facility ◽

Home Setting ◽

The Impact ◽

At Home

Abstract Background Clinical trials and real-world database studies have shown the benefits of non-vitamin K antagonist oral anticoagulants (NOACs) compared to warfarin; however, measures of functional outcomes are critical in evaluating a patient's quality of life. Previous measures of time spent out of hospital in a home setting and time spent receiving disease-related care among non-valvular atrial fibrillation (NVAF) patients are lacking in the current literature. Purpose This analysis was based on the previously published ARISTOPHANES study, and used multiple data sources to evaluate the amount of time spent at a patient's home among NVAF patients who were prescribed NOACs versus warfarin. Methods This retrospective observational study used US data from CMS Medicare and four commercial databases to select adult NVAF patients who initiated apixaban, dabigatran, rivaroxaban, or warfarin (01JAN2013–30SEP2015). Time at home and time at home without external AF-related care were measured during the 180 days after the index date (OAC prescription). Time at home was defined as days from index date without any of the following: an inpatient, skilled nursing facility or nursing facility, hospice, or inpatient rehabilitation facility admission. Time at home and without external AF-related care was defined as days away from home and days with a claim for bleeding, stroke/systemic embolism, AF, or an INR test. Each day a claim was observed was counted as one day. In each database, three 1:1 NOAC-warfarin propensity-score-matched (PSM) cohorts were created before pooling the results. After PSM, a subgroup of patients who were alive and had ≥180 days of follow-up was created. Poisson regression was conducted in each NOAC-warfarin matched cohort to compare time at home and time at home without external AF-related care. Results After matching, a total of 100,977 apixaban-warfarin, 36,990 dabigatran-warfarin, and 125,068 rivaroxaban-warfarin patient pairs were selected. Of those patients, 38–46% had 180 days of follow-up available. Across treatment cohorts, approximately 75% of patients were at home for the 180-day follow-up. Apixaban, dabigatran, and rivaroxaban patients had 1.3, 0.9, and 0.8 more days at home, respectively, compared to warfarin patients. Patients treated with apixaban had 13.4 more days at home without AF-related care compared to warfarin, while dabigatran and rivaroxaban had 11.6 and 11.7 more days at home without AF-related care compared to warfarin. A greater proportion of warfarin patients than NOAC patients had an INR test (81–82% vs 14–21%), and days with INR testing were the main driver for external AF-related care for warfarin patients. Conclusion Among NVAF patients treated with OACs, NOACs were associated with a longer time at home and time at home without external AF-related care compared to warfarin. These results can help inform healthcare providers and patients regarding the impact of NOAC treatment in NVAF patients. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bristol-Myers Squibb Company and Pfizer Inc.

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Decline in renal function and oral anticoagulation dose reduction among patients with atrial fibrillation

Heart ◽

10.1136/heartjnl-2019-315792 ◽

2020 ◽

Vol 106 (5) ◽

pp. 358-364 ◽

Cited By ~ 6

Author(s):

Taku Inohara ◽

DaJuanicia N Holmes ◽

Karen Pieper ◽

Rosalia G Blanco ◽

Larry A Allen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Renal Function ◽

Dose Reduction ◽

Oral Anticoagulation ◽

Oral Anticoagulants ◽

Bleeding Complications ◽

The Us ◽

Informed Treatment ◽

Over Time

ObjectiveNon-vitamin K oral anticoagulants (NOACs) require dose adjustment for renal function. We sought to investigate change in renal function over time in patients with atrial fibrillation (AF) and whether those on NOACs have appropriate dose adjustments according to its decline.MethodsWe included patients with AF enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II registry treated with oral anticoagulation. Worsening renal function (WRF) was defined as a decrease of >20% in creatinine clearance (CrCl) from baseline. The US Food and Drug Administration (FDA)-approved package inserts were used to define the reduction criteria of NOACs dosing.ResultsAmong 6682 patients with AF from 220 sites (median age (25th, 75th): 72.0 years (65.0, 79.0); 57.1% male; median CrCl at baseline: 80.1 mL/min (57.4, 108.5)), 1543 patients (23.1%) experienced WRF with mean decline in CrCl during 2 year follow-up of −6.63 mL/min for NOACs and −6.16 mL/min for warfarin. Among 4120 patients on NOACs, 154 (3.7%) patients had a CrCl decline sufficient to warrant FDA-recommended dose reductions. Of these, NOACs dosing was appropriately reduced in only 31 (20.1%) patients. Compared with patients with appropriately reduced NOACs, those without were more likely to experience bleeding complications (major bleeding: 1.7% vs 0%; bleeding hospitalisation: 2.6% vs 0%) at 1 year.ConclusionsIn the US practice, about one-fourth of patients with AF had >20% decline in CrCl over time during 2 year follow-up. As a result, about 3.7% of those treated with NOACs met guideline criteria for dose reduction, but of these, only 20.1% actually had a reduction.

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Association of left ventricular end-diastolic diameter with incidence of thromboembolism in patients with non-valvular atrial fibrillation: the Fushimi AF Registry

European Heart Journal ◽

10.1093/eurheartj/ehab724.0466 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

Y Tezuka ◽

K Doi ◽

Y Hamatani ◽

Y An ◽

M Ishii ◽

...

Keyword(s):

Atrial Fibrillation ◽

Thrombus Formation ◽

Oral Anticoagulants ◽

Japanese Patients ◽

Left Ventricular ◽

Rank Test ◽

National Budget ◽

Public Grant ◽

The Impact

Abstract Background Atrial fibrillation (AF) is a common arrhythmia and a risk factor for thromboembolism including ischemic stroke (IS) and systemic embolism (SE). Thrombus formation mainly occurs in the left atrium (LA), but we reported that relative wall thickness (RWT) of left ventricle (LV) was independently associated with IS/SE among patients with non-valvular AF. Little is known about the impact of LV size on thromboembolism in patients with AF. We investigated the relationship between left ventricular end-diastolic diameter (LVDd) and incidence of IS /SE, using data from the Fushimi AF Registry. Methods The Fushimi AF Registry, a community-based prospective survey, was designed to enroll all of the AF patients in the community. Follow-up data were available for 4,472 patients as of November 2020, and the median follow-up period was 1,820 days. Of them, we excluded 226 patients with mitral stenosis or prior cardiac valve surgery. Among 4,246 non-valvular AF patients, follow-up data including LVDd at the baseline from echocardiography were available for 3,311 patients. We divided these patients into three groups according to LVDd tertile (T1:<44.0 mm; n=1,091, T2: 44.0–48.5; n=1,112, T3: 48.5 or above; n=1,108), and compared the clinical characteristics and outcomes. Results Percentage of female (T1 vs. T2 vs T3; 56.5 vs. 37.5 vs. 34.1%; p<0.01), age (76.2±9.9 vs. 72.8±10.7 vs. 71.9±11.1 years; p<0.01), height (156.3±9.9 vs. 160.4±9.4 vs. 163.7±9.5 cm; p<0.01), BMI (21.8±3.9 vs. 23.3±3.6 vs. 24.2±4.4 kg/m2; p<0.01), prevalence of hypertension (58.8 vs. 64.1 vs. 67.7%; p<0.01), vascular disease (7.4 vs. 8.8 vs. 15.2%; p<0.01), CHA2DS2-VASc score (3.59±1.68 vs. 3.27±1.70 vs. 3.31±1.73; p<0.01) and the prescription of oral anticoagulants (OACs) were different among groups. LV ejection fraction (65.9±8.7 vs. 65.0±9.1 vs. 57.7±14.4%; p<0.01), LA diameter (40.7±7.9 vs. 42.8±7.3 vs. 45.8±7.6 mm; p<0.01), LVRWT (0.471±0.090 vs. 0.411±0.064 vs. 0.366±0.063; p<0.01) and LV mass index (79.6±21.4 vs. 93.5±20.4 vs. 117.6±30.3 g/m2; p<0.01) were different. Prevalence of prior stroke/SE and prior major bleeding were comparable among groups. In Kaplan-Meier analysis, the incidence of IS/SE was different among the groups during the median follow-up period of 1,826 days (T1 vs. T2 vs T3; 2.1 vs. 1.9 vs. 1.1 per 100 person-years; p<0.01, by log-rank test) (Figure). LVDd (All age, hazard ratio [95% confidential interval]: T1/T3 1.57 [1.09–2.29]; p=0.02, T2/T3 1.55 [1.11–2.17]; p<0.01: less than 75 years, T1/T3 2.27 [1.24–4.22]; p<0.01, T2/T3 1.54 [0.89–2.70]; p=0.12: 75 years or above, T1/T3 1.33 [0.83–2.14]; p=0.08, T2/T3 1.57 [1.04–2.40]; p=0.03) was an independent predictor of the incidence of IS/SE after adjustment by the components of CHA2DS2-VASc score, LA diameter, LVRWT, type of AF and the prescription of OACs (Table). Conclusion LVDd was independently associated with IS/SE among Japanese patients with non-valvular AF. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): the Practical Research Project for Life-Style-related Diseases including Cardiovascular Diseases and Diabetes Mellitus from Japan Agency for Medical Research and Development

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Continuation or discontinuation of oral anticoagulants after an increase in HAS-BLED scores and the risks of clinical outcomes in patients with atrial fibrillation. a nationwide cohort study

European Heart Journal ◽

10.1093/ehjci/ehaa946.0638 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

T.F Chao ◽

J.N Liao ◽

G.Y.H Lip ◽

S.A Chen

Keyword(s):

Atrial Fibrillation ◽

Clinical Outcomes ◽

Oral Anticoagulants ◽

Antiplatelet Agents ◽

Bleeding Risk ◽

Risk Profile ◽

Bleeding Events ◽

Concurrent Use ◽

The Impact

Abstract Background The bleeding risk profile of patients with atrial fibrillation (AF) may change over time and the increment of HAS-BLED score (a validated bleeding risk score) is perceived to result in discontinuations of oral anticoagulants (OACs). The goal of the present study was to investigate the changes of HAS-BLED scores of AF patients initially with a low bleeding risk (HAS-BLED 0–2). Second, the impact of continuation or discontinuation of OACs on clinical outcomes after patients' bleeding risk profile worsened (ie HAS-BLED increased) were also studied. Methods The present study used the Taiwan nationwide health insurance research (NHIRD) database. From year 2000 to 2015, a total of 24,990 AF patients aged >20 years with a CHA2DS2-VASc score >1 (males) or >2 (females) having a HAS-BLED score of 0–2 who were treated with OACs (warfarin or NOACs) were identified and followed up for changes of the HAS-BLED scores. The risks of clinical outcomes were compared between patients who continued or stopped OAC's once their HAS-BLED score increased to ≥3. Results Mean HAS-BLED score of study population continuously increased from 1.54 (SD 1.63) at baseline, to 3.33 (SD 1.36) at the end of follow up with increasing age and incident comorbidities (Figure A). At end of 1 year, 5,229 (20.9%) patients had an increment of their HAS-BLED score to ≥3, mainly due to newly diagnosed impaired renal function, occurrences of bleeding events and concurrent use of antiplatelet agents or NSAIDs. Among 4,777 patients who consistently had a HAS-BLED score > =3, 1,062 (22.2%) stopped their use of OACs. Patients who kept on OACs (n=3,715; 77.8%) even after their HAS-BLED score increased to ≥3 were associated with a lower risk of ischemic stroke (aHR 0.601), major bleeding (aHR 0.780), all-cause mortality (aHR 0.876) and any adverse events (aHR 0.748) (Figure B). Conclusions For patients whose HAS-BLED scores increased to ≥3, the continuation of OACs (which occurred in the majority of patients) was associated with better clinical outcomes. An increased HAS-BLED score in AF patients is not a reason to withhold OACs, but reminds physicians to correct modifiable bleeding risk factors and follow up patients more closely. The low risk of bleeding despite continuing OAC in high HAS-BLED score patients may reflect the early reviews and careful follow-up of these “high risk” patients (as recommended in guidelines). Funding Acknowledgement Type of funding source: None

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Time at home among nonvalvular atrial fibrillation patients treated with non-vitamin K antagonist oral anticoagulants: an ARISTOPHANES analysis

European Heart Journal ◽

10.1093/eurheartj/ehab724.0574 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

S Deitelzweig ◽

A Keshishian ◽

A Kang ◽

A Jenkins ◽

N Atreja ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Index Date ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Patient Centered ◽

Nursing Facility ◽

The Impact ◽

At Home

Abstract Background Patient-centered outcomes, such as home time, are becoming increasingly important quality-of-life measures. There are limited data on the impact of oral anticoagulants (OACs) on home time among patients with non-valvular atrial fibrillation. Purpose This analysis, based on the previously published ARISTOPHANES study, used five US insurance claims databases (CMS Medicare and four commercial databases) to compare home time among NVAF patients who were prescribed non-vitamin K antagonist OACs (NOACs). Methods Adult NVAF patients who were newly prescribed apixaban, dabigatran, or rivaroxaban (01JAN2013–30SEP2015) were selected. Time at home was calculated as the number of days from the index date (NOAC prescription) without any of the following: an inpatient, skilled nursing facility (SNF) or nursing facility, hospice, or inpatient rehabilitation facility admission. Time at home and without external AF-related care was defined as days from index date without any events from the home time endpoint or any days with a claim for bleeding, stroke/systemic embolism (S/SE), AF, or an INR test. Time at home and without external AF-related care were measured during the 180 days of follow-up; patients were required to have been alive and have 180 days of follow-up post index. In each database, three 1:1 NOAC-NOAC propensity-score-matched (PSM) cohorts were created before combining the databases. For each NOAC-NOAC matched cohort, Poisson regression was conducted to compare time at home and time at home without external AF-related care. Results After PSM, 37,314 apixaban-dabigatran, 107,236 apixaban-rivaroxaban, and 37,693 rivaroxaban-dabigatran patient pairs were created of which 37–44% had 180 days of follow-up available. Across the NOAC cohorts, approximately 21–25% of patients had an admission to a hospital, SNF, nursing facility, rehabilitation center, or hospice during the 180-day follow-up. The time at home was generally consistent between the NOAC cohorts (177 days); however, apixaban patients had 0.5 more days at home compared to rivaroxaban patients. Across all NOAC cohorts, 7–8% had a claim for a S/SE, 11–15% had a claim for bleeding, and 15–22% had an INR test, while 87–89% of all patients had an AF-claim during the 180-day follow-up. Patients prescribed apixaban had 1 more day at home without external AF-related care compared to dabigatran, and 1.5 more days at home without external AF-related care compared to rivaroxaban. Dabigatran had <1 more day at home without external AF-related care compared to rivaroxaban. Conclusion Among NVAF patients treated with NOACs, there were small differences in the time at home and time at home without external AF-related care during the first 6 months of NOAC treatment. As NVAF is a chronic condition, it is important to understand the impact of NOAC treatment on these patient-centered outcomes. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bristol-Myers Squibb Company and Pfizer Inc.

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Plasma natriuretic peptide level is an independent determinant of major clinical outcomes in atrial fibrillation patients without heart failure: the Fushimi AF Registry

European Heart Journal ◽

10.1093/ehjci/ehaa946.0673 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

Y Hamatani ◽

M Iguchi ◽

Y Aono ◽

K Ishigami ◽

S Ikeda ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Clinical Outcomes ◽

Prognostic Marker ◽

Oral Anticoagulants ◽

Systemic Embolism ◽

The Mean

Abstract Background Atrial fibrillation (AF) increases the risk of death, stroke/systemic embolism and heart failure (HF). Plasma natriuretic peptide (NP) level is an important prognostic marker in HF patients. However, little is known regarding the prognostic significance of plasma NP level in AF patients without HF. Purpose The aim of this study is to investigate the relationship between plasma NP level and clinical outcomes such as all-cause death, stroke/systemic embolism and HF hospitalization during follow-up period in AF patients without HF. Methods The Fushimi AF Registry is a community-based prospective survey of AF patients in our city. The inclusion criterion of the registry is the documentation of AF at 12-lead electrocardiogram or Holter monitoring at any time, and there are no exclusion criteria. We started to enroll patients from March 2011, and follow-up data were available for 4,466 patients by the end of November 2019. From the registry, we excluded 1,220 patients without a pre-existing HF (defined as having one of the following; prior hospitalization for HF, New York Heart Association class ≥2, or left ventricular ejection fraction <40%). Among 3,246 AF patients without HF, we investigated 1,189 patients with the data of plasma BNP (n=401) or N-terminal pro-BNP (n=788) level at the enrollment. We divided the patients according to the quartile of each plasma BNP or NT-pro BNP level and compared the backgrounds and outcomes between these 4 groups stratified by plasma NP level. Results Of 1,189 patients, the mean age was 72.1±10.2 years, 454 (38%) were female and 684 (58%) were paroxysmal AF. The mean CHADS2 and CHA2DS2-VASc score were 1.6±1.1 and 2.9±1.5, respectively. Oral anticoagulants were prescribed in 671 (56%) at baseline. The median (interquartile range) BNP and N-terminal pro-BNP level were 84 (38, 176) and 500 (155, 984) pg/ml, respectively. Patients with high plasma NP level were older, and demonstrated lower prevalence of paroxysmal AF, higher CHADS2 and CHA2DS2-VASc scores and higher prevalence of chronic kidney disease and oral anticoagulants prescription (all P<0.01). A total of 165 all-cause death, 114 stroke/systemic embolism and 103 HF hospitalization occurred during the median follow-up period of 5.0 years. Kaplan-Meier curves demonstrated that higher plasma NP level was significantly associated with the incidences of all-cause death, stroke/systemic embolism and HF hospitalization in AF patients without HF (Figure 1A). Multivariable Cox regression analysis revealed that plasma NP level could stratify the risk of clinical outcomes even after adjustment by type of AF, CHA2DS2-VASc score, chronic kidney disease and oral anticoagulant prescription (Figure 1B). Conclusion Plasma NP level is a significant prognostic marker for all-cause death, stroke/systemic embolism and HF hospitalization in AF patients without HF, suggesting the importance of measuring plasma NP level in AF patients even without HF. Figure 1 Funding Acknowledgement Type of funding source: None

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T3 Are Burns a Chronic Condition: Examining Physical and Mental Functioning up to 20 Years After Injury

Journal of Burn Care & Research ◽

10.1093/jbcr/irab032.002 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

pp. S2-S3

Author(s):

Callie Abouzeid ◽

Audrey E Wolfe ◽

Gretchen J Carrougher ◽

Nicole S Gibran ◽

Radha K Holavanahalli ◽

...

Keyword(s):

Mental Health ◽

Hospital Stay ◽

National Database ◽

Time Points ◽

Patient Reported ◽

Burn Survivors ◽

Population Demographic ◽

The Impact ◽

Over Time

Abstract Introduction Burn survivors often face many long-term physical and psychological symptoms associated with their injury. To date, however, few studies have examined the impact of burn injuries on quality of life beyond 2 years post-injury. The purpose of this study is to examine the physical and mental well-being of burn survivors up to 20 years after injury. Methods Data from the Burn Model System National Database (1997–2020) were analyzed. Patient-reported outcome measures were collected at discharge with a recall of preinjury status, and then at 5, 10, 15, and 20 years after injury. Outcomes examined were the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the Short Form-12. Trajectories were developed using linear mixed methods model with repeated measures of PCS and MCS scores over time and controlling for demographic and clinical variables. The model fitted score trajectory was generated with 95% confidence intervals to demonstrate score changes over time and associations with covariates. Results The study population included 420 adult burn survivors with a mean age of 42.4 years. The population was mainly male (66%) and white (76.4%) with a mean burn size of 21.5% and length of hospital stay of 31.3 days. Higher PCS scores were associated with follow-up time points closer to injury, shorter hospital stay, and younger age. Similarly, higher MCS scores were associated with earlier follow-up time points, shorter hospital stay, female gender, and non-perineal burns. MCS trajectories are demonstrated in the Figure. Conclusions Burn survivors’ physical and mental health worsened over time. Such a trend is different from previous reported results for mental health in the general population. Demographic and clinical predictors of recovery over time are identified.

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The Number of Concomitant Drugs and the Safety of Direct Oral Anticoagulants in Routine Care Patients with Atrial Fibrillation

TH Open ◽

10.1055/s-0040-1721499 ◽

2020 ◽

Vol 04 (04) ◽

pp. e417-e426

Author(s):

Carline J. van den Dries ◽

Sander van Doorn ◽

Patrick Souverein ◽

Romin Pajouheshnia ◽

Karel G.M. Moons ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Routine Care ◽

P Value ◽

Risk Of Mortality ◽

Mortality Effect

Abstract Background The benefit of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) on major bleeding was less prominent among atrial fibrillation (AF) patients with polypharmacy in post-hoc randomized controlled trials analyses. Whether this phenomenon also exists in routine care is unknown. The aim of the study is to investigate whether the number of concomitant drugs prescribed modifies safety and effectiveness of DOACs compared with VKAs in AF patients treated in general practice. Study Design Adult, nonvalvular AF patients with a first DOAC or VKA prescription between January 2010 and July 2018 were included, using data from the United Kingdom Clinical Practice Research Datalink. Primary outcome was major bleeding, secondary outcomes included types of major bleeding, nonmajor bleeding, ischemic stroke, and all-cause mortality. Effect modification was assessed using Cox proportional hazard regression, stratified for the number of concomitant drugs into three strata (0–5, 6–8, ≥9 drugs), and by including the continuous variable in an interaction term with the exposure (DOAC vs. VKA). Results A total of 63,600 patients with 146,059 person-years of follow-up were analyzed (39,840 person-years of DOAC follow-up). The median age was 76 years in both groups, the median number of concomitant drugs prescribed was 7. Overall, the hazard of major bleeding was similar between VKA-users and DOAC-users (hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.87–1.11), though for apixaban a reduction in major bleeding was observed (HR 0.81; 95% CI 0.68–0.98). Risk of stroke was comparable, while risk of nonmajor bleeding was lower in DOAC users compared with VKA users (HR 0.92; 95% CI 0.88–0.97). We did not observe any evidence for an impact of polypharmacy on the relative risk of major bleeding between VKA and DOAC across our predefined three strata of concomitant drug use (p-value for interaction = 0.65). For mortality, however, risk of mortality was highest among DOAC users, increasing with polypharmacy and independent of the type of DOAC prescribed (p-value for interaction <0.01). Conclusion In this large observational, population-wide study of AF patients, risk of bleeding, and ischemic stroke were comparable between DOACs and VKAs, irrespective of the number of concomitant drugs prescribed. In AF patients with increasing polypharmacy, our data appeared to suggest an unexplained yet increased risk of mortality in DOAC-treated patients, compared with VKA recipients.

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Kidney function decline is associated with an accelerated increase in plasma homocysteine in older adults: a longitudinal study

British Journal Of Nutrition ◽

10.1017/s0007114521001690 ◽

2021 ◽

pp. 1-21

Author(s):

Hui Zhang ◽

Yi Li ◽

Meng Hao ◽

Xiaoyan Jiang ◽

Jiucun Wang ◽

...

Keyword(s):

Kidney Function ◽

Repeated Measurements ◽

Baseline Survey ◽

Mixed Effect ◽

Pronounced Increase ◽

Crude Model ◽

The Mean ◽

Kidney Function Decline ◽

Over Time

Abstract Background: Few studies have been conducted to investigate the association of kidney function decline with the trajectories of homocysteine (Hcy) over time, using repeated measurements. We aimed to investigate the association of kidney function with changes in plasma Hcy levels over time. Methods: Data were collected from the Rugao Longevity and Ageing Study. In detail, plasma Hcy and creatinine levels were measured in both waves (waves 2, 3 and 4) during the 3.5-year follow-up (N = 1135). Wave 2 was regarded as the baseline survey. The estimated glomerular filtration rate (eGFR) was calculated based on creatinine. Subjects were categorized into four groups according to quartiles of eGFR at baseline. Linear mixed-effect models were used to investigate the association of eGFR with subsequent plasma Hcy levels. Results: The mean eGFR at baseline was 90.84 (11.42) mL/min/1.73 m2. The mean plasma Hcy level was 14.09 (6.82) at baseline and increased to 16.28 (8.27) and 17.36 (10.39) μmol/L during follow-ups. In the crude model, the interaction between time and eGFR at baseline was significant (β = −0.02, 95% CI: −0.02 to −0.01, p = 0.002). After adjusting for confounding factors, a significant relationship remained (β = −0.02, 95% CI: −0.02 to −0.01, p = 0.003), suggesting that kidney function decline at baseline was associated with a faster increase in Hcy levels. Conclusion: Kidney function decline is associated with a more pronounced increase in plasma Hcy levels. Further studies with longer follow-up periods and larger sample sizes are needed to validate our findings.

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Clinical outcomes of Japanese atrial fibrillation patients with combined valvular heart disease: the Fushimi AF Registry

European Heart Journal ◽

10.1093/ehjci/ehaa946.0528 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

K Doi ◽

K Ishigami ◽

Y Aono ◽

S Ikeda ◽

Y Hamatani ◽

...

Keyword(s):

Atrial Fibrillation ◽

Heart Disease ◽

Incidence Rate ◽

Clinical Outcomes ◽

Valvular Heart Disease ◽

Cardiac Death ◽

Clinical Characteristics ◽

Valve Disease ◽

The Impact

Abstract Background We previously reported that valvular heart disease (VHD) was not at the significant risk of stroke/systemic embolism (SE), but was associated with an increased risk of hospitalization for heart failure (HF) in Japanese atrial fibrillation patients. However, the impact of combined VHD on clinical outcomes has been little known. Purpose The aim of this study is to investigate the prevalence of combined VHD and its clinical characteristics and impact on outcomes such as stroke/SE, all-cause death, cardiac death and hospitalization for HF. Method The Fushimi AF Registry is a community-based prospective survey of AF patients in one of the wards of our city which is a typical urban district of Japan. We started to enroll patients from March 2011, and follow-up data were available for 4,466 patients by the end of November 2019. In the entire cohort, echocardiography data were available for 3,574 patients. 68 AF patients with prosthetic heart valves were excluded and we compared clinical characteristics and outcomes between 488 single VHD (103 Aortic valve disease (AVD), 315 mitral valve disease (MVD), 70 tricuspid valve disease (TVD)) and 158 combined VHD (46 AVD and MVD, 11 AVD and TVD, 66 MVD and TVD, 35 AVD and MVD and TVD). Result Compared with single VHD, patients with combined VHD were older (combined vs. single VHD: 78.5 vs. 76.0 years, respectively; p<0.01), more likely to have persistent/permanent type AF (73.4% vs. 63.9%, p=0.02) and prescription of warfarin (63.1% vs. 53.8%, p=0.04). Combined VHD was less likely to have diabetes mellitus (13.9% vs. 23.6%, p=0.01) and dyslipidemia (26.6% vs. 40.4%, p<0.01). Sex, body weight, hypertension, pre-existing HF were comparable between the two groups. During the median follow-up of 1,474 days, the incidence rate of stroke/SE was not significantly different between the two groups (1.58 vs. 1.89 per 100 person-years, respectively, log rank p=0.10). The incidence rate of all-cause death (7.35 vs. 5.33, p=0.65), cardiac death (1.20 vs. 0.99, p=0.91) and hospitalization for HF (5.55 vs. 4.43, p=0.53) were also not significantly different. We previously reported AVD had significant impacts on cardiac adverse outcomes in AF patients, and we further analyzed event rates between combined VHD including AVD (AVD and MVD/TVD) and without AVD (MVD and TVD). Combined VHD with AVD group had higher incidence rate of all-cause death (10.7 vs. 5.79, p=0.03) than that without AVD group. However, the incidence rate of stroke/SE (1.98 vs. 1.56, p=0.59), cardiac death (0.98 vs. 1.14, p=0.68), hospitalization for HF (8.03 vs. 5.38, p=0.17) were not significantly different between the two groups. Conclusion As compared with single VHD, the risk of stroke/SE, all-cause death, cardiac death and hospitalization for HF in combined VHD was not significantly different. Among patients with combined VHD, those having AVD had higher incidence rate of all-cause death than those without AVD. Figure 1 Funding Acknowledgement Type of funding source: None

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