Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials

Ruff, Christian T.; Giugliano, Robert P.; Braunwald, Eugene; Hoffman, Elaine; Deenadayalu, Naveen; Ezekowitz, Michael D.; Camm, A. John; Weitz, Jeffrey I.; Lewis, Basil S.; Parkhomenko, Alexander; Yamashita, Takeshi; Antman, Elliott M.

doi:10.1016/s0140-6736(13)62343-0

Cited by 4,197 publications

(3,247 citation statements)

References 40 publications

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“…Furthermore, some clinicians have supported utilizing certain OACs, or reduced doses of OACs in various clinical scenarios often associated with a frail state (eg, >75 years old, renal impairment) 7. The fact that our evaluations of DOACs in frail NVAF patients are generally consistent with the overall study population findings from phase III randomized trials of DOACs versus warfarin,22 may provide clinicians with added confidence in anticoagulating frail patients with NVAF.…”

Section: Discussionmentioning

confidence: 66%

Effectiveness and Safety of Apixaban, Dabigatran, and Rivaroxaban Versus Warfarin in Frail Patients With Nonvalvular Atrial Fibrillation

Martinez

Sood

Bunz³

et al. 2018

JAHA

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BackgroundFrailty predicts poorer outcomes and decreased anticoagulation use in patients with nonvalvular atrial fibrillation. We sought to assess the effectiveness and safety of apixaban, dabigatran and rivaroxaban versus warfarin in frail nonvalvular atrial fibrillation patients.Methods and ResultsUsing US MarketScan claims data from November 2011 to December 2016, we identified frail oral anticoagulant‐naïve nonvalvular atrial fibrillation patients with ≥12 months of continuous insurance coverage before oral anticoagulant initiation. Frailty status was determined using the Johns Hopkins Claims‐based Frailty Indicator score (≥0.20 indicating frailty). Users of apixaban, dabigatran, or rivaroxaban were separately 1:1 matched to warfarin users via propensity‐scores, with residual absolute standardized differences <0.1 being achieved for all covariates after matching. Patients were followed for up to 2 years or until an event, insurance disenrollment or end of follow‐up. Rates of stroke or systemic embolism and major bleeding were compared using Cox regression and reported as hazard ratios (HRs) and 95% confidence intervals (CIs). In total, 2700, 2784, and 5270 patients were included in the apixaban, dabigatran, and rivaroxaban 1:1 matched analyses to warfarin. At 2 years, neither apixaban nor dabigatran were associated with differences in the hazard of stroke or systemic embolism (HR=0.78; 95% CI=0.46–1.35 and HR=0.94; 0.60–1.45) or major bleeding (HR=0.72; 95% CI=0.49–1.06 and HR=0.87; 95% CI=0.63–1.19) versus warfarin. Rivaroxaban was associated with reduced stroke or systemic embolism at 2 years (HR=0.68; 95% CI=0.49–0.95) without significantly altering major bleeding risk (HR=1.07; 95% CI=0.81–1.32).ConclusionsOur study found rivaroxaban but not apixaban or dabigatran to be associated with reduced SSE versus warfarin in frail nonvalvular atrial fibrillation patients. No direct‐acting oral anticoagulants demonstrated a significant difference in major bleeding versus warfarin.

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Section: Discussionmentioning

confidence: 66%

Effectiveness and Safety of Apixaban, Dabigatran, and Rivaroxaban Versus Warfarin in Frail Patients With Nonvalvular Atrial Fibrillation

Martinez

Sood

Bunz³

et al. 2018

JAHA

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“…However, such miscoding and misclassification are highly unlikely to be different between patients with normal liver function and those with ILF. The favorable efficacy and safety profiles of NOACs versus warfarin in patients with normal liver function were comparable to the results of meta‐analyses and real‐world data 32, 33, 34. Second, we did not analyze the quality of anticoagulation control as reflected by time in therapeutic range in the warfarin group, given the close relationship between the time in therapeutic range and thromboembolism or bleeding.…”

Section: Discussionmentioning

confidence: 78%

“…Elderly patients often have more comorbidities and polypharmacy, which are associated with higher bleeding risk than those without 28, 29, 30, 31. Our study agreed with a meta‐analysis of 4 major clinical trials of NOAC with improved efficacy in S/SE (relative risk: 0.81; 95% CI, 0.73–0.91; P <0.0001) and all‐cause mortality (relative risk: 0.90; 95% CI, 0.85–0.95; P <0.0001) and increased gastrointestinal bleeding (relative risk: 1.25; 95% CI, 1.01–1.55; P =0.04) when NOAC prescription was compared with warfarin 32. Our studies showed similar findings in patients with AF and normal liver function with significantly reduced S/SE (aHR: 0.75; 95% CI, 0.65–0.88; P <0.001) and death (aHR: 0.69; 95% CI, 0.60–0.80; P <0.001), with no difference in major bleeding (aHR: 0.83; 95% CI, 0.62–1.11; P =0.201) or gastrointestinal bleeding (aHR: 1.36; 95% CI, 0.99–1.88; P =0.059).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Non–Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients With Impaired Liver Function: A Retrospective Cohort Study

Wang

Kuo

et al. 2018

JAHA

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BackgroundPatients with impaired liver function (ILF) were excluded from clinical trials that investigated non–vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in patients with atrial fibrillation. The aim of this study was to evaluate the efficacy and safety of NOACs in atrial fibrillation patients with ILF.Methods and ResultsA cohort study based on electronic medical records was conducted from 2009 to 2016 at a multicenter healthcare provider in Taiwan and included 6451 anticoagulated atrial fibrillation patients (aged 76.7±7.0 years, 52.5% male). Patients were classified into 2 subgroups: patients with normal liver function (n=5818) and patients with ILF (n=633, 9.8%). Cox regression analysis was performed to investigate the risks of thromboembolism, bleeding, and death associated with use of NOACs and warfarin in patients with normal liver function and ILF, respectively. In patients with normal liver function, compared with warfarin therapy (n=2928), NOAC therapy (n=4048) was associated with significantly lower risks of stroke or systemic embolism (adjusted hazard ratio: 0.75; 95% confidence interval, 0.65–0.88; P<0.001) and death (adjusted hazard ratio: 0.69; 95% confidence interval, 0.60–0.80; P<0.001) with no difference in major bleeding or gastrointestinal bleeding. In patients with ILF, compared with warfarin therapy (n=394), NOAC therapy (n=342) was associated with significantly lower risk of death (adjusted hazard ratio: 0.64; 95% confidence interval, 0.49–0.83; P<0.001), but no difference in stroke or systemic embolism, major bleeding, or gastrointestinal bleeding.ConclusionsIn atrial fibrillation patients with ILF, NOAC therapy and warfarin therapy were associated with similar risks of stroke or systemic embolism, major bleeding, and gastrointestinal bleeding.

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“…Although the mainstay of anticoagulation has been warfarin (Coumadin; Bristol‐Myers Squibb) for >20 years, the direct oral anticoagulants (DOACs) have been shown to have similar, or in some cases even superior, efficacy:safety ratios in AF patients without valvular heart disease,3 and this has led to their approval by regulatory agencies; wide adoption in Canadian, American, and European guidelines; and increasing use in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Use of Direct Oral Anticoagulants in Canadian Primary Care Practice 2010–2015: A Cohort Study From the Canadian Primary Care Sentinel Surveillance Network

McAlister

Garrison

Kosowan

et al. 2018

JAHA

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BackgroundAs questions have been raised about the appropriateness of direct oral anticoagulant (DOAC) dosing among outpatients with atrial fibrillation, we examined this issue in patients being managed by primary care providers.Methods and ResultsThis was a retrospective cohort new‐user study using electronic medical records from 744 Canadian primary care clinicians. Potentially inappropriate DOAC prescribing was defined as prescribing lower or higher doses than those recommended by guidelines for patients with nonvalvular atrial fibrillation. Of the 6658 patients with nonvalvular atrial fibrillation who were prescribed a DOAC (mean age: 74.8; 55% male), 626 (9.4%) had a CHADS 2 score of 0, and 168 (2.5%) had a CHADS‐VASc score of 0. Of the DOAC prescriptions, 527 (7.7%) were deemed potentially inappropriate: 496 (7.2%) were potentially underdosed, and 31 (0.5%) were prescribed a dose that was higher than recommended. Patients were more likely to be prescribed lower‐than‐recommended doses if they were female (adjusted odds ratio [aOR]: 1.3 [95% confidence interval (CI), 1.0–1.5]), had multiple comorbidities (aOR: 1.4 [95% CI, 1.1–1.8])—particularly heart failure (aOR: 1.6 [95% CI, 1.2–2.0]) or dementia (aOR: 1.4 [95% CI, 1.1–1.8])—or if they were also taking aspirin (aOR: 1.7 [95% CI, 1.3–2.1]) or nonsteroidal anti‐inflammatory drugs (aOR: 1.2 [95% CI, 1.02–1.5]). Potentially inappropriate DOAC dosing was more common in rural practices (aOR: 2.1 [95% CI, 1.7–2.6]) or smaller practices (aOR: 1.9 [95% CI, 1.6–2.4] for practices smaller than median).ConclusionsThe vast majority of DOAC prescriptions in our cohort of primary care–managed patients appeared to be for appropriate doses, particularly since prescribing a reduced dose of DOAC may be appropriate in frail patients or those taking other medications that predispose to bleeding.

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Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials

Cited by 4,197 publications

References 40 publications

Effectiveness and Safety of Apixaban, Dabigatran, and Rivaroxaban Versus Warfarin in Frail Patients With Nonvalvular Atrial Fibrillation

Effectiveness and Safety of Apixaban, Dabigatran, and Rivaroxaban Versus Warfarin in Frail Patients With Nonvalvular Atrial Fibrillation

Efficacy and Safety of Non–Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients With Impaired Liver Function: A Retrospective Cohort Study

Use of Direct Oral Anticoagulants in Canadian Primary Care Practice 2010–2015: A Cohort Study From the Canadian Primary Care Sentinel Surveillance Network

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