P4779High facility preference for rivaroxaban in atrial fibrillation increases risk of major bleeding compared to facility preference for apixaban

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A N Bonde ◽  
T Martinussen ◽  
C Y Lee ◽  
J Bhattacharya ◽  
G Y H Lip ◽  
...  

Abstract Background No randomized trial has compared efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF). Previous real-world comparisons could be biased by patient characteristics of importance for treatment selection, but instrumental variables could potentially account for measured and unmeasured confounders. Purpose To compare efficacy and safety of rivaroxaban and apixaban using facility preference for type of NOAC as instrumental variable. Methods AF patients started on apixaban or rivaroxaban were identified using nationwide registries. We categorized patients according to facility preference for type of NOAC, measured as percentage of the prior 20 AF patients started on rivaroxaban in the same facility. Occurrence of stroke/thromboembolism (TE), major bleeding, myocardial infarction and all-cause mortality during two years of follow-up were investigated using adjusted Cox regressions. To further examine general frailty according to facility preferences we also investigated occurrence of cancer, urogenital tract infection, dehydration and fracture. Results We analyzed 6264 AF patients initiated on rivaroxaban or apixaban. Compared with patients treated in facilities that used rivaroxaban in 0–20% of cases, the adjusted hazard ratio for bleeding was 1.05 when treated in a facility with 25–40% use; 1.40 with 45–60% use; 1.50 with 65–80% use; and 1.81 for 85–100% use (Ptrend=0.002). Higher facility level use of rivaroxaban was not associated with increased risk of stroke/TE (Ptrend=0.06), myocardial infarction (Ptrend=0.87) or all-cause mortality (Ptrend=0.91), and there was no association between facility preference for rivaroxaban and risk of cancer (Ptrend=0.83), urogenital tract infection (Ptrend=0.49), dehydration (Ptrend=0.91) or fracture (Ptrend=0.47). Characteristics by facility preference Percent of previous AF patients from facility started on rivaroxaban P for trend 0–20% 25–40% 45–60% 65–80% 85–100% No. of patients 1406 1421 1551 930 956 Received rivaroxaban, (%) 279, (19.8) 499, (35.1) 711, (45.8) 632, (68.0) 774, (81.0) <0.001 Standard dose, (%) 1216, (86.5) 1232, (86.7%) 1366, (88.1%) 793, (85.3%) 824, (86.2%) 0.62 Median age, (interquartile range) 70, (63.3–74) 69, (63–74) 70, (64–74) 70, (64–75) 70, (63–75) 0.11 Below median income, (%) 740, (52.6) 699, (49.2) 764, (49.3) 458, (49.3) 471, (49.3) 0.31 Prior stroke, (%) 99, (7.0) 115, (8.1) 134, (8.6) 69, (7.4) 74, (7.7) 0.56 Prior bleeding, (%) 136, (9.7) 141, (9.9) 163, (10.5) 91, (9.8) 97, (10.1) 0.51 Antiplatelet therapy, (%) 445, (31.7) 465, (32.7) 491, (31.7) 303, (32.6) 317, (33.2) 0.49 Rate of events according to instrument Conclusion High facility preference for rivaroxaban increases risk of major bleeding compared to facility preference for apixaban. Acknowledgement/Funding This study was funded by an unrestricted grant from the Capital Region of Denmark, Foundation for Health Research.

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
I Cavallari ◽  
G Verolino ◽  
G Patti

Abstract Background Anticoagulation in patients with cancer and atrial fibrillation (AF) is particularly challenging given the higher risk of both thrombotic and bleeding complications in this setting. Data regarding the efficacy and safety of non-vitamin K oral anticoagulants (NOACs) in AF patients with malignancy remain unclear. Purpose In the present meta-analysis we further investigate the efficacy and safety of NOACs compared to warfarin in patients with AF and cancer assuming that available studies may be individually underpowered for endpoints at low incidence, i.e. stroke, major and intracranial bleeding. Methods We performed a systematic review and meta-analysis of studies comparing the use of NOACs vs. warfarin in AF patients with cancer. Efficacy outcome measures included stroke or systemic embolism, venous thromboembolism and mortality. Safety outcome measures were major bleeding and intracranial hemorrhage. Results We pooled data from 6 identified studies enrolling a total of 31,756 AF patients with cancer. Mean follow-up was 1.7 years. Patients with cancer had significantly increased annualized rates of venous thromboembolism (1.38% vs. 0.74%), major bleeding (9.01% vs. 5.13%), in particular major gastrointestinal bleeding (2.38% vs. 1.60%), and all-cause mortality (17.73% vs. 8.50%) vs. those without (all P values <0.001), whereas the incidence of stroke or systemic embolism and intracranial hemorrhage did not differ. Compared with warfarin, treatment with NOACs nominally decreased the risk of stroke or systemic embolism (5.41% vs. 2.70%; odds ratio, OR; 95% confidence intervals, CI 0.51, 0.26–1.01; P=0.05; Figure), mainly of ischemic stroke (OR 0.56; 95% CI 0.35–0.89; P=0.01), and the risk of venous thromboembolism (OR 0.51; 95% CI 0.42–0.61; P<0.001). In cancer patients receiving NOACs there was a significant reduction of major bleeding (3.95% vs. 4.66%; OR 0.66, 95% CI 0.46–0.94; P=0.02; Figure) and intracranial hemorrhage (0.26% vs. 0.66%; OR 0.25, 95% CI 0.08–0.82; P=0.02) vs. warfarin, with no difference in gastrointestinal major bleeding rates. Conclusion AF patients on oral anticoagulation and concomitant cancer are at higher risk of venous thromboembolism, major bleeding and all-cause mortality. NOACs may represent a safer and more effective alternative to warfarin also in this setting of patients.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Weijia Li ◽  
Damianos Kokkinidis ◽  
Yu Chiang Wang

Background: Most of the randomized clinical trials that led to the wide use of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in patients with atrial fibrillation (AF) originated from western countries. We aimed to systematically review and quantitatively synthesize the real-world data regarding the efficacy and safety of dabigatran, rivaroxaban, and apixaban compared to warfarin for stroke prevention in Asian patients with non-valvular AF. Methods: Medline and Cochrane databases were reviewed. A random-effect model meta-analysis was used and I-square was utilized to assess the heterogeneity. The primary outcome was ischemic stroke. The secondary outcomes were all-cause mortality, major bleeding, intracranial hemorrhage, and gastrointestinal bleeding. Results: Twelve studies from East Asia or Southeast Asia and 429496 patients in total were included. Dabigatran, rivaroxaban, and apixaban were associated with a significant reduction in the incidence of ischemic stroke (HR=0.78, 95% CI, 0.65-0.94; HR=0.79, 95% CI, 0.74-0.85, HR=0.70, 95% CI, 0.62-0.78; respectively), all-cause mortality (HR=0.68, 95% CI, 0.56-0.83; HR=0.66, 95% CI, 0.52-0.84; HR=0.66, 95% CI, 0.49-0.90; respectively), and major bleeding (HR=0.61, 95%CI, 0.54-0.69; HR=0.70, 95% CI, 0.54-0.90; HR=0.58, 95% CI, 0.43-0.78; respectively) compared to warfarin. Conclusion: Dabigatran, rivaroxaban, and apixaban appear to be superior to warfarin in both efficacy and safety in Asian patients with non-valvular AF.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Yamashita ◽  
C.C Wang ◽  
Y.-H Kim ◽  
R De Caterina ◽  
P Kirchhof ◽  
...  

Abstract Background The prevalence of atrial fibrillation (AF) and the need for appropriate anticoagulation increase with age. The benefit/risk profile of direct oral anticoagulants such as edoxaban in elderly population with AF in regular clinical practice is therefore of particular interest. Purpose Analyses of Global ETNA-AF data were performed to report patient characteristics, edoxaban treatment, and 1-year clinical events by age subgroups. Methods Global ETNA-AF is a multicentre, prospective, noninterventional program conducted in Europe, Japan, Korea, Taiwan, and other Asian countries. Demographics, baseline characteristics, and 1-year clinical event data were analysed in four age subgroups. Results Of 26,823 patients included in this analysis, 50.4% were ≥75 years old and 11.6% were ≥85 years. Increase in age was generally associated with lower body weight, lower creatinine clearance, higher CHA2DS2-VASc and HAS-BLED scores, and a higher percentage of patients receiving the reduced dose of 30 mg daily edoxaban. At 1-year, rates of ISTH major bleeding and ischaemic stroke were generally low across all age subgroups. The proportion of intracranial haemorrhage within major bleeding events was similar across age groups. All-cause mortality increased with age more than cardiovascular mortality. Conclusion Data from Global ETNA-AF support the safety and effectiveness of edoxaban in elderly AF patients (including ≥85 years) in routine clinical care with only a small increase in intracranial haemorrhage. The higher all-cause mortality with increasing age is not driven by cardiovascular causes. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Daiichi Sankyo


2021 ◽  
Vol 10 (13) ◽  
pp. 2924
Author(s):  
Domenico Acanfora ◽  
Marco Matteo Ciccone ◽  
Valentina Carlomagno ◽  
Pietro Scicchitano ◽  
Chiara Acanfora ◽  
...  

Diabetes mellitus (DM) represents an independent risk factor for chronic AF and is associated with unfavorable outcomes. We aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF), with and without diabetes mellitus (DM), using a new risk index (RI) defined as: RI =Rate of EventsRate of Patients at Risk. In particular, an RI lower than 1 suggests a favorable treatment effect. We searched MEDLINE, MEDLINE In-Process, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. The risk index (RI) was calculated in terms of efficacy (rate of stroke/systemic embolism (stroke SEE)/rate of patients with and without DM; rate of cardiovascular death/rate of patients with and without DM) and safety (rate of major bleeding/rate of patients with and without DM) outcomes. AF patients with DM (n = 22,057) and 49,596 without DM were considered from pivotal trials. DM doubles the risk index for stroke/SEE, major bleeding (MB), and cardiovascular (CV) death. The RI for stroke/SEE, MB, and CV death was comparable in patients treated with warfarin or DOACs. The lowest RI was in DM patients treated with Rivaroxaban (stroke/SEE, RI = 0.08; CV death, RI = 0.13). The RIs for bleeding were higher in DM patients treated with Dabigatran (RI110 = 0.32; RI150 = 0.40). Our study is the first to use RI to homogenize the efficacy and safety data reported in the DOACs pivotal studies against warfarin in patients with and without DM. Anticoagulation therapy is effective and safe in DM patients. DOACs appear to have a better efficacy and safety profile than warfarin. The use of DOACs is a reasonable alternative to vitamin-K antagonists in AF patients with DM. The RI can be a reasonable tool to help clinicians choose between DOACs or warfarin in the peculiar set of AF patients with DM.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Chiarito ◽  
D Cao ◽  
J Nicolas ◽  
A Roumeliotis ◽  
D Power ◽  
...  

Abstract Background The presence of any benefits associated with radial or femoral access among patients undergoing coronary angiography and percutaneous coronary interventions (PCI) is still debated. Purpose Our aim is to provide a comprehensive quantitative appraisal of the effects of access site on the risks of stroke, myocardial infarction, and major bleeding in patients undergoing coronary angiography with or without PCI. Methods In January 2020, we searched PubMed, Embase, and meeting abstracts for randomized trials comparing radial versus femoral access for coronary angiography with or without subsequent PCI. Odds ratios (OR) were used as metric of choice for treatment effects with random-effects models. Co-primary efficacy endpoints were stroke and myocardial infarction. Primary safety endpoint was major bleeding. Secondary endpoints were all cause mortality and vascular complications. Heterogeneity was assessed with the I-squared index. This study is registered with PROSPERO. Results We identified 31 trials, including 30,414 patients. Risks of stroke (OR 1.11, 95% CI 0.76–1.64, I2=0%) and myocardial infarction (OR 0.90, 95% CI 0.79–1.03, I2=0%) were comparable between radial and femoral access. Radial access was associated with a reduction for the risk of major bleeding as compared to femoral access (OR 0.53, 95% CI 0.42–0.67, I2=3.3%) with a number needed to treat of 92. Findings were consistent regardless clinical features and procedure performed, with the only exception of an increased benefit of the radial access in patients with chronic coronary syndrome (p forinteraction=0.005). The risk for all-cause mortality (OR 0.73, 95% CI 0.61–0.89, I2=0%) and vascular complication (OR 0.32, 95% CI 0.23–0.44, I2=16.7%) was significantly lower in the radial compared to femoral access group. Conclusions In patients undergoing coronary angiography with or without PCI, radial compared to femoral access did not reduce the risk of stroke and myocardial infarction, with no impact on the effect estimates of clinical presentation, age, gender, or subsequent PCI. Whereas, radial access is associated with a significant risk reduction of major bleeding as compared to femoral access. The benefit favoring radial access is of important clinical relevance in view of the relatively low number needed to treat to prevent a major bleeding and the significant impact on mortality. Funding Acknowledgement Type of funding source: None


2014 ◽  
Vol 112 (08) ◽  
pp. 276-286 ◽  
Author(s):  
Carlos Martinez ◽  
Anja Katholing ◽  
Saul Freedman

SummaryIt was the aim of this study to determine prognosis of incidentally detected ambulatory atrial fibrillation (IA-AF) and its response to antithrombotic therapy. We performed a cohort study of 5,555 patients with IA-AF (mean age 70.9 ± 10.1, 38.4% female) and 24,705 age- and gender-matched controls without AF followed three years using UK Clinical Practice Research Datalink. We measured incidence rates of stroke, all-cause mortality, myocardial infarction, major bleeding, and effect of antithrombotic therapy. Patients with IA-AF had mean CHA2DS2VASc score 2.5 ± 1.5, 73% with score ≥2. The stroke incidence rate (IR) was 19.4 (95% confidence interval 17.1 – 21.9)/1,000 person-years vs 8.4 (7.7 – 9.1) in controls (p<0.001), mortality 40.1 (36.8 – 43.6)/1,000 person-years vs 20.9 (19.8 – 22.0) in controls (p<0.001), and myocardial infarction 9.0 (7.5 – 10.8)/1,000 person-years vs 6.5 (5.9 – 7.2) in controls (p<0.001). IRs of all endpoints increased with age. Oral anticoagulant ± antiplatelet therapy received by 51.0% in year following IA-AF was associated with adjusted hazard ratio (HR) of 0.35 (0.17 – 0.71) for stroke, and 0.56 (0.36 – 0.85) for death compared to no therapy, while antiplatelet treatment was associated with a non-significant reduction of HR: 0.81 (0.51 – 1.29) for stroke, and 0.80 (0.55 – 1.15) for death, though both carried a similar small non-significant adjusted excess IR of major bleeding. In conclusion, asymptomatic AF detected incidentally is associated with a significant adverse effect on stroke and death, with reduction in both associated with oral anticoagulant but not antiplatelet treatment. This provides justification to assess cost-effectiveness of community screening to detect unknown AF.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Anda Bularga ◽  
Mohammed Meah ◽  
Dimitrios Doudesis ◽  
Anoop S Shah ◽  
Nicholas L Mills ◽  
...  

Introduction: Dual antiplatelet therapy (DAPT) is the cornerstone of pharmacological treatment for patients with acute coronary syndrome (ACS) and in those undergoing percutaneous coronary intervention for stable coronary disease. Despite widespread use, the optimal duration of DAPT remains uncertain. We present an updated meta-analysis comparing outcomes in short-term DAPT (≤ 6 months) versus long-term DAPT (≥ 12 months). Methods: Four major databases were searched for randomised controlled trials of interest. The primary outcome was all-cause mortality. Secondary safety outcomes included any bleeding and major bleeding. Efficacy outcomes included cardiovascular death, myocardial infarction, stent thrombosis, coronary revascularization and thrombotic stroke. Further subgroup analysis stratified by index presentation and a sensitivity analysis to evaluate shorter duration DAPT (≤3 months) was performed. Results: Nineteen randomised controlled trials were included (n=60,879) of which 8 compared shorter duration DAPT (≤3 months) with standard duration (12 months) (n=38,036). Short-term DAPT was associated with an apparent modest increase in myocardial infarction (risk ratio [RR] 1.09; 95% confidence interval [CI], 0.98-1.22) with a major reduction in bleeding (RR 0.68; 95% CI, 0.55-0.83) for major bleeding and (RR 0.66; 95% CI, 0.56-0.77 for any bleeding) and an overall apparent reduction in all-cause mortality (RR 0.90; 95% CI 0.81-1.01). These associations persisted when comparing shorter duration DAPT to standard duration. Subgroup analysis of patients with stable disease or ACS identified no significant heterogenicity in efficacy, safety or mortality outcomes. Conclusion: In the largest meta-analysis to date comparing duration of DAPT, we show that short (≤ 6 months) and shorter (≤ 3 months) DAPT is associated with continuing trends for small reductions in all-cause mortality irrespective of index presentation.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Mahmoud El Iskandarani ◽  
Islam Shatla ◽  
Muhammad Khalid ◽  
Bara El Kurdi ◽  
Timir Paul ◽  
...  

Background: Current guidelines recommend against the use of direct oral anticoagulation (DOAC) therapy in patients with atrial fibrillation (AF) in the setting of significant liver disease (LD) due to lack of evidence in safety and efficacy studies. However, recently studies have investigated the role of DOAC in comparison to Vitamin K antagonist (VKA) in this category of patients. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of this approach. Hypothesis: DOAC is safe and effective compared to VKA in AF with LD patients. Method: Unrestricted search of the PubMed, EMBASE, and Cochrane databases performed from inception until June 1, 2020 for studies comparing DOAC with VKA including more than 100 AF patients with LD. Relevant data were extracted and analyzed using Revman 5.3 software. Hazard ratio (HR) and 95% Confidence interval (CI) were calculated using the random-effects model. Result: A total of 5 studies (3 retrospective and 2 post hoc analysis) were included examining 39,064 patients with AF and LD (25,398 DOAC vs 13,669 VKA). DOAC is associated with lower risk of major bleeding compared to VKA with a HR of 0.68 (95% CI 0.47-0.98; I 2 =53%), all-cause mortality (HR 0.74;95% CI 0.59-0.94; I 2 =61%), and intracranial bleeding (HR 0.48; 95% CI 0.40-0.58; I 2 =0). There was no significant difference in ischemic stroke risk (HR 0.73; 95% CI 0.47-1.14; I 2 =72%) and gastrointestinal bleeding risk (0.96; 95% CI 0.61-1.51; I 2 =41%) between DOAC and VKA. Conclusion: DOAC is non-inferior to VKA regarding ischemic stroke prevention in AF patients with LD. Moreover, DOAC is associated with a lower risk of major bleeding, intracranial bleeding and all-cause mortality. Further randomized trials are needed to validate our findings.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Emma Kirstine Laugesen ◽  
Laila Staerk ◽  
Nicholas Carlson ◽  
Anne-Lise Kamper ◽  
Jonas Bjerring Olesen ◽  
...  

Abstract Background We aimed to compare effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin-K antagonists (VKA) in atrial fibrillation (AF) patients with chronic kidney disease (CKD) not receiving dialysis. Methods By using personal identification numbers, we cross-linked individual-level data from Danish administrative registries. We identified every citizen with a prior diagnosis of AF and CKD who initiated NOAC or VKA (2011–2017). An external analysis of 727 AF patients with CKD (no dialysis) was performed to demonstrate level of kidney function in a comparable population. Study outcomes included incidents of stroke/thromboembolisms (TEs), major bleedings, myocardial infarctions (MIs), and all-cause mortality. We used Cox proportional hazards models to determine associations between oral anticoagulant treatment and outcomes. Results Of 1560 patients included, 1008 (64.6%) initiated VKA and 552 (35.4%) initiated NOAC. In a comparable population we found that 95.3% of the patients had an estimated glomerular filtration rate (eGFR) < 59 mL/min. Patients treated with NOAC had a significantly decreased risk of major bleeding (hazard ratio (HR): 0.47, 95% confidence interval (CI): 0.26–0.84) compared to VKA. There was not found a significant association between type of anticoagulant and risk of stroke/TE (HR: 0.83, 95% CI: 0.39–1.78), MI (HR: 0.45, 95% CI: 0.18–1.11), or all-cause mortality (HR: 0.99, 95% CI: 0.77–1.26). Conclusion NOAC was associated with a lower risk of major bleeding in patients with AF and CKD compared to VKA. No difference was found in risk of stroke/TE, MI, and all-cause mortality.


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