Twice- or Once-Daily Dosing of Novel Oral Anticoagulants for Stroke Prevention: A Fixed-Effects Meta-Analysis with Predefined Heterogeneity Quality Criteria

Background: In non-valvular atrial fibrillation (NVAF) patients, those receiving once-daily (QD) versus twice-daily (BID) non vitamin-K antagonist oral anticoagulants (NOACs) may have better medication adherence. The impact on stroke and bleed risk is not known. Objective: To estimate the impact of adherence differences between QD vs BID therapies on bleed and stroke risks in NVAF patients. Methods: The relation between adherence (proportion of days covered [PDC]) for QD vs BID NOACs and one year bleed risk was modeled using claims data from Truven Health Analytics MarketScan databases (7/2012-10/2015). Next, the relation between adherence and bleeding was calibrated to match that seen in the placebo and NOAC arms of previous randomized controlled trials (RCTs). Finally, we used adherence rates for QD (PDC=0.849) and BID (PDC=0.738) cardiovascular medications from a meta-analysis (Coleman et al.). These rates were used in the calibrated model to estimate bleeds. An analogous method was applied to evaluate the impact of QD vs BID adherence on stroke risk. Results: The relation between PDC and risks of bleed and stroke was modeled using claims data (N=65,022) and calibrated using RCTs. In the calibrated model, compared with BID dosing, QD dosing was associated with 81 fewer strokes (34% reduction) and 14 more bleeds (6% more) per 10,000 patients/year (Figure). Conclusion: Among NVAF patients, better adherence to QD dosing was associated with a significantly lower stroke risk of QD but similar risk of bleed.

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Abstract 12901: Novel Oral Anticoagulants Are Associated With Decreased Recurrence of Venous Thromboembolism in Patients With Cancer: An Updated Meta-Analysis

Circulation ◽

10.1161/circ.142.suppl_3.12901 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Sunil Upadhaya ◽

Seetharamprasad Madala ◽

Sunil Badami

Keyword(s):

Venous Thromboembolism ◽

Major Bleeding ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Novel Oral Anticoagulants ◽

P Value ◽

Patients With Cancer ◽

Randomized Controlled ◽

All Cause Mortality ◽

Recurrent Vte

Introduction: Patients with cancer are at high risk for recurrent thromboembolic phenomenon. Use of novel oral anticoagulants (NOAC) for treatment of venous thromboembolism (VTE) in such patients is controversial. We conducted this updated meta-analysis to evaluate the pooled efficacy and safety of NOAC in patients with cancer. Methods: We did systematic search of PubMed and Cochrane library databases for randomized controlled trials comparing NOAC with low molecular weight heparin (LMWH) for VTE treatment in cancer patients till April 2020. The efficacy outcomes were recurrent VTE and all-cause mortality rates, and the primary safety outcome was incidence of major bleeding rate. Results: Four randomized controlled studies comparing NOAC with LMWH (1446 patients in NOAC group and 1448 patients in LMWH group) were included in our study. Use of NOAC lead to significant reduction in recurrent VTE rate (odds ratio (OR): 0.55 [0.36-0.84], I 2 = 45 %, p value = 0.006) (Figure 1). However, we did not find any significant difference in rate of major bleeding (OR: 1.30 [0.76-2.23], I 2 = 35%, p value = 0.34) (Figure 2) and all-cause mortality (OR: 1 [0.80 - 1.26], I 2 = 33%, p value = 0.98). Conclusions: This updated meta-analysis showed comparatively lower pooled recurrent VTE rate in patient being treated with NOAC, whereas similar rates of major bleeding and all-cause death. NOAC are more efficacious and has similar safety profile compared with LMWH.

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Novel oral anticoagulants for stroke prevention in atrial fibrillation: a focus on the older patient

International Journal of General Medicine ◽

10.2147/ijgm.s39379 ◽

2013 ◽

pp. 167 ◽

Cited By ~ 12

Author(s):

S.w. Yates

Keyword(s):

Atrial Fibrillation ◽

Stroke Prevention ◽

Oral Anticoagulants ◽

Novel Oral Anticoagulants ◽

Older Patient

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Cost-Effectiveness Of Novel Oral Anticoagulants For Stroke Prevention In Patients With Non-Valvular Atrial Fibrillation In China

Value in Health ◽

10.1016/j.jval.2018.07.233 ◽

2018 ◽

Vol 21 ◽

pp. S30

Author(s):

W Guo ◽

X Tian ◽

W Li ◽

S Han

Keyword(s):

Atrial Fibrillation ◽

Cost Effectiveness ◽

Stroke Prevention ◽

Oral Anticoagulants ◽

Novel Oral Anticoagulants

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Novel oral anticoagulants for stroke prevention in atrial fibrillation: results of the European Heart Rhythm Association survey

EP Europace ◽

10.1093/europace/eut292 ◽

2013 ◽

Vol 15 (10) ◽

pp. 1526-1532 ◽

Cited By ~ 16

Author(s):

G. Y. H. Lip ◽

M. G. Bongiorni ◽

D. Dobreanu ◽

T. Lewalter ◽

J. Hastrup Svendsen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Stroke Prevention ◽

Oral Anticoagulants ◽

Heart Rhythm ◽

Novel Oral Anticoagulants

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

Thrombosis and Haemostasis ◽

10.1160/th15-05-0383 ◽

2015 ◽

Vol 114 (08) ◽

pp. 403-409 ◽

Cited By ~ 8

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.

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