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. 2024 Jan 24;1(1):CD014678.
doi: 10.1002/14651858.CD014678.pub2.

Non-vitamin-K-antagonist oral anticoagulants (NOACs) after acute myocardial infarction: a network meta-analysis

Samer Al Said  1 , Klaus Kaier  2 , Wael Sumaya  3 , Dima Alsaid  4 , Daniel Duerschmied  5   6 , Robert F Storey  7 , C Michael Gibson  8 , Dirk Westermann  1 , Samer Alabed  7
Affiliations

Non-vitamin-K-antagonist oral anticoagulants (NOACs) after acute myocardial infarction: a network meta-analysis

Samer Al Said et al. Cochrane Database Syst Rev. .

Abstract

Background: Balancing the risk of bleeding and thrombosis after acute myocardial infarction (AMI) is challenging, and the optimal antithrombotic therapy remains uncertain. The potential of non-vitamin K antagonist oral anticoagulants (NOACs) to prevent ischaemic cardiovascular events is promising, but the evidence remains limited.

Objectives: To evaluate the efficacy and safety of non-vitamin-K-antagonist oral anticoagulants (NOACs) in addition to background antiplatelet therapy, compared with placebo, antiplatelet therapy, or both, after acute myocardial infarction (AMI) in people without an indication for anticoagulation (i.e. atrial fibrillation or venous thromboembolism).

Search methods: We searched CENTRAL, MEDLINE, Embase, the Conference Proceedings Citation Index - Science, and two clinical trial registers in September 2022 with no language restrictions. We checked the reference lists of included studies for any additional trials.

Selection criteria: We searched for randomised controlled trials (RCTs) that evaluated NOACs plus antiplatelet therapy versus placebo, antiplatelet therapy, or both, in people without an indication for anticoagulation after an AMI.

Data collection and analysis: Two review authors independently checked the results of searches to identify relevant studies, assessed each included study, and extracted study data. We conducted random-effects pairwise analyses using Review Manager Web, and network meta-analysis using the R package 'netmeta'. We ranked competing treatments by P scores, which are derived from the P values of all pairwise comparisons and allow ranking of treatments on a continuous 0-to-1 scale.

Main results: We identified seven eligible RCTs, including an ongoing trial that we could not include in the analysis. Of the six RCTs involving 33,039 participants, three RCTs compared rivaroxaban with placebo, two RCTs compared apixaban with placebo, and one RCT compared dabigatran with placebo. All participants in the six RCTs received concomitant antiplatelet therapy. The available evidence suggests that rivaroxaban compared with placebo reduces the rate of all-cause mortality (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.69 to 0.98; number needed to treat for an additional beneficial outcome (NNTB) 250; 3 studies, 21,870 participants; high certainty) and probably reduces cardiovascular mortality (RR 0.83, 95% CI 0.69 to 1.01; NNTB 250; 3 studies, 21,870 participants; moderate certainty). There is probably little or no difference between apixaban and placebo in all-cause mortality (RR 1.09, 95% CI 0.88 to 1.35; number needed to treat for an additional harmful outcome (NNTH) 334; 2 studies, 8638 participants; moderate certainty) and cardiovascular mortality (RR 0.99, 95% CI 0.77 to 1.27; number needed to treat not applicable; 2 studies, 8638 participants; moderate certainty). Dabigatran may reduce the rate of all-cause mortality compared with placebo (RR 0.57, 95% CI 0.31 to 1.06; NNTB 63; 1 study, 1861 participants; low certainty). Dabigatran compared with placebo may have little or no effect on cardiovascular mortality, although the point estimate suggests benefit (RR 0.72, 95% CI 0.34 to 1.52; NNTB 143; 1 study, 1861 participants; low certainty). Two of the investigated NOACs were associated with an increased risk of major bleeding compared to placebo: apixaban (RR 2.41, 95% CI 1.44 to 4.06; NNTH 143; 2 studies, 8544 participants; high certainty) and rivaroxaban (RR 3.31, 95% CI 1.12 to 9.77; NNTH 125; 3 studies, 21,870 participants; high certainty). There may be little or no difference between dabigatran and placebo in the risk of major bleeding (RR 1.74, 95% CI 0.22 to 14.12; NNTH 500; 1 study, 1861 participants; low certainty). The results of the network meta-analysis were inconclusive between the different NOACs at all individual doses for all primary outcomes. However, low-certainty evidence suggests that apixaban (combined dose) may be less effective than rivaroxaban and dabigatran for preventing all-cause mortality after AMI in people without an indication for anticoagulation.

Authors' conclusions: Compared with placebo, rivaroxaban reduces all-cause mortality and probably reduces cardiovascular mortality after AMI in people without an indication for anticoagulation. Dabigatran may reduce the rate of all-cause mortality and may have little or no effect on cardiovascular mortality. There is probably no meaningful difference in the rate of all-cause mortality and cardiovascular mortality between apixaban and placebo. Moreover, we found no meaningful benefit in efficacy outcomes for specific therapy doses of any investigated NOACs following AMI in people without an indication for anticoagulation. Evidence from the included studies suggests that rivaroxaban and apixaban increase the risk of major bleeding compared with placebo. There may be little or no difference between dabigatran and placebo in the risk of major bleeding. Network meta-analysis did not show any superiority of one NOAC over another for our prespecified primary outcomes. Although the evidence suggests that NOACs reduce mortality, the effect size or impact is small; moreover, NOACs may increase major bleeding. Head-to-head trials, comparing NOACs against each other, are required to provide more solid evidence.

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Conflict of interest statement

SAS: no conflicts of interest. KK: no conflicts of interest. WS: no conflicts of interest; works as an interventional cardiologist in Halifax. DA: no conflicts of interest. DD: speaker honoraria from Bayer Healthcare, Pfizer Canada Inc., Daiichi Sankyo; published opinions for Deutsche Medizinische Wochenschrift; works as a health professional at University Medical Center Mannheim, Germany. RFS: consultant for Alnylam Pharmaceuticals, AstraZeneca, Bayer, Bristol Myers Squibb, Chiesi Farmaceutici, CSL Behring, Cytosorbents, GlyCardial Diagnostics, Hengrui, Idorsia, Intas Pharmaceuticals, Pfizer UK, Novartis, PhaseBio, Sanofi Aventis, Thromboserin; works as a health professional at Sheffield Teaching Hospitals NHS Foundation Trust. CMG: consultant for AstraZeneca, Bayer HealthCare Pharmaceuticals Inc., CSL Behring, Janssen Global Services, LLC, Johnson & Johnson Health Care Systems Inc.; Physician at Beth Israel Deaconess Medical Center. DW: consultant for Bayer, AstraZeneca, ABIOMED, Novartis. SA: no conflicts of interest; Cardiac Radiologist at Sheffield Teaching Hospitals.

Figures

1
1
Network diagram for primary outcomes ‐ primary analyses (non‐vitamin‐K‐antagonist oral anticoagulants, all doses combined): all‐cause death and cardiovascular death (Primary outcomes). Circles represent the drug as a node in the network; lines represent direct comparisons. Nodes are weighted according to the number of studies that included the respective intervention. Edges are weighted according to the number of participants included in the respective comparison. Numbers on the lines represent the number of trials and participants for each comparison. We combined these two primary outcomes in a single plot since they have the same number of interventions, studies, and participants.
2
2
Network diagram for primary outcomes ‐ primary analyses (non‐vitamin‐K‐antagonist oral anticoagulants, all doses combined): major bleeding (Primary outcomes). Circles represent the drug as a node in the network. Lines represent direct comparisons. Nodes are weighted according to the number of studies that included the respective intervention. Edges are weighted according to the number of participants included in the respective comparison. Numbers on the lines represent the number of trials and participants for each comparison.
3
3
Network plot for primary outcomes ‐ secondary analyses (differences doses of non‐vitamin‐K‐antagonist oral anticoagulants): all‐cause death, cardiovascular death, and major bleeding (Primary outcomes). Circles represent the drug as a node in the network. Lines represent direct comparisons. Nodes are weighted according to the number of studies that included the respective intervention. Edges are weighted according to the number of participants included in the respective comparison. We combined these secondary outcomes in a single plot since they have the same number of interventions, studies, and participants.
4
4
PRISMA study flow diagram.
5
5
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
6
6
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1: NOACs (all doses combined) versus placebo: all‐cause mortality, Outcome 1: All‐cause mortality (apixaban versus placebo)
1.2
1.2. Analysis
Comparison 1: NOACs (all doses combined) versus placebo: all‐cause mortality, Outcome 2: All‐cause mortality (rivaroxaban versus placebo)
1.3
1.3. Analysis
Comparison 1: NOACs (all doses combined) versus placebo: all‐cause mortality, Outcome 3: All‐cause mortality (dabigatran versus placebo)
2.1
2.1. Analysis
Comparison 2: NOACs (all doses combined) versus placebo: cardiovascular mortality, Outcome 1: Cardiovascular mortality (apixaban versus placebo)
2.2
2.2. Analysis
Comparison 2: NOACs (all doses combined) versus placebo: cardiovascular mortality, Outcome 2: Cardiovascular mortality (rivaroxaban versus placebo)
2.3
2.3. Analysis
Comparison 2: NOACs (all doses combined) versus placebo: cardiovascular mortality, Outcome 3: Cardiovascular mortality (dabigatran versus placebo)
3.1
3.1. Analysis
Comparison 3: NOACs (all doses combined) versus placebo: major bleeding, Outcome 1: Major bleeding (apixaban versus placebo)
3.2
3.2. Analysis
Comparison 3: NOACs (all doses combined) versus placebo: major bleeding, Outcome 2: Major bleeding (rivaroxaban versus placebo)
3.3
3.3. Analysis
Comparison 3: NOACs (all doses combined) versus placebo: major bleeding, Outcome 3: Major bleeding (dabigatran versus placebo)
4.1
4.1. Analysis
Comparison 4: Apixaban (different doses) versus placebo, Outcome 1: All‐cause mortality
4.2
4.2. Analysis
Comparison 4: Apixaban (different doses) versus placebo, Outcome 2: Cardiovascular mortality
4.3
4.3. Analysis
Comparison 4: Apixaban (different doses) versus placebo, Outcome 3: Major bleeding
4.4
4.4. Analysis
Comparison 4: Apixaban (different doses) versus placebo, Outcome 4: Myocardial infarction
4.5
4.5. Analysis
Comparison 4: Apixaban (different doses) versus placebo, Outcome 5: Stroke
4.6
4.6. Analysis
Comparison 4: Apixaban (different doses) versus placebo, Outcome 6: Stent thrombosis
4.7
4.7. Analysis
Comparison 4: Apixaban (different doses) versus placebo, Outcome 7: Non‐major bleeding
5.1
5.1. Analysis
Comparison 5: Rivaroxaban (different doses) versus placebo, Outcome 1: All‐cause mortality
5.2
5.2. Analysis
Comparison 5: Rivaroxaban (different doses) versus placebo, Outcome 2: Cardiovascular mortality
5.3
5.3. Analysis
Comparison 5: Rivaroxaban (different doses) versus placebo, Outcome 3: Major bleeding
5.4
5.4. Analysis
Comparison 5: Rivaroxaban (different doses) versus placebo, Outcome 4: Myocardial infarction
5.5
5.5. Analysis
Comparison 5: Rivaroxaban (different doses) versus placebo, Outcome 5: Stroke
5.6
5.6. Analysis
Comparison 5: Rivaroxaban (different doses) versus placebo, Outcome 6: Stent thrombosis
5.7
5.7. Analysis
Comparison 5: Rivaroxaban (different doses) versus placebo, Outcome 7: Non‐major bleeding
5.8
5.8. Analysis
Comparison 5: Rivaroxaban (different doses) versus placebo, Outcome 8: Systemic embolism
6.1
6.1. Analysis
Comparison 6: Dabigatran (different doses) versus placebo, Outcome 1: All‐cause mortality
6.2
6.2. Analysis
Comparison 6: Dabigatran (different doses) versus placebo, Outcome 2: Cardiovascular mortality
6.3
6.3. Analysis
Comparison 6: Dabigatran (different doses) versus placebo, Outcome 3: Major bleeding
6.4
6.4. Analysis
Comparison 6: Dabigatran (different doses) versus placebo, Outcome 4: Myocardial infarction
6.5
6.5. Analysis
Comparison 6: Dabigatran (different doses) versus placebo, Outcome 5: Stroke
7.1
7.1. Analysis
Comparison 7: Apixaban 5 mg versus apixaban 10 mg, Outcome 1: All‐cause mortality
7.2
7.2. Analysis
Comparison 7: Apixaban 5 mg versus apixaban 10 mg, Outcome 2: Cardiovascular mortality
7.3
7.3. Analysis
Comparison 7: Apixaban 5 mg versus apixaban 10 mg, Outcome 3: Major bleeding
7.4
7.4. Analysis
Comparison 7: Apixaban 5 mg versus apixaban 10 mg, Outcome 4: Myocardial infarction
7.5
7.5. Analysis
Comparison 7: Apixaban 5 mg versus apixaban 10 mg, Outcome 5: Stroke
7.6
7.6. Analysis
Comparison 7: Apixaban 5 mg versus apixaban 10 mg, Outcome 6: Non‐major bleeding
8.1
8.1. Analysis
Comparison 8: Rivaroxaban 5 mg versus rivaroxaban 10 mg, Outcome 1: All‐cause mortality
8.2
8.2. Analysis
Comparison 8: Rivaroxaban 5 mg versus rivaroxaban 10 mg, Outcome 2: Cardiovascular mortality
8.3
8.3. Analysis
Comparison 8: Rivaroxaban 5 mg versus rivaroxaban 10 mg, Outcome 3: Major bleeding
8.4
8.4. Analysis
Comparison 8: Rivaroxaban 5 mg versus rivaroxaban 10 mg, Outcome 4: Myocardial infarction
8.5
8.5. Analysis
Comparison 8: Rivaroxaban 5 mg versus rivaroxaban 10 mg, Outcome 5: Stroke
8.6
8.6. Analysis
Comparison 8: Rivaroxaban 5 mg versus rivaroxaban 10 mg, Outcome 6: Stent thrombosis
8.7
8.7. Analysis
Comparison 8: Rivaroxaban 5 mg versus rivaroxaban 10 mg, Outcome 7: Non‐major bleeding
9.1
9.1. Analysis
Comparison 9: Rivaroxaban 5 mg versus rivaroxaban 15 mg, Outcome 1: All‐cause mortality
9.2
9.2. Analysis
Comparison 9: Rivaroxaban 5 mg versus rivaroxaban 15 mg, Outcome 2: Cardiovascular mortality
9.3
9.3. Analysis
Comparison 9: Rivaroxaban 5 mg versus rivaroxaban 15 mg, Outcome 3: Major bleeding
9.4
9.4. Analysis
Comparison 9: Rivaroxaban 5 mg versus rivaroxaban 15 mg, Outcome 4: Myocardial infarction
9.5
9.5. Analysis
Comparison 9: Rivaroxaban 5 mg versus rivaroxaban 15 mg, Outcome 5: Stroke
9.6
9.6. Analysis
Comparison 9: Rivaroxaban 5 mg versus rivaroxaban 15 mg, Outcome 6: Non‐major bleeding
10.1
10.1. Analysis
Comparison 10: Rivaroxaban 5 mg versus rivaroxaban 20 mg, Outcome 1: All‐cause mortality
10.2
10.2. Analysis
Comparison 10: Rivaroxaban 5 mg versus rivaroxaban 20 mg, Outcome 2: Cardiovascular mortality
10.3
10.3. Analysis
Comparison 10: Rivaroxaban 5 mg versus rivaroxaban 20 mg, Outcome 3: Major bleeding
10.4
10.4. Analysis
Comparison 10: Rivaroxaban 5 mg versus rivaroxaban 20 mg, Outcome 4: Myocardial infarction
10.5
10.5. Analysis
Comparison 10: Rivaroxaban 5 mg versus rivaroxaban 20 mg, Outcome 5: Stroke
10.6
10.6. Analysis
Comparison 10: Rivaroxaban 5 mg versus rivaroxaban 20 mg, Outcome 6: Non‐major bleeding
11.1
11.1. Analysis
Comparison 11: Rivaroxaban 10 mg versus rivaroxaban 15 mg, Outcome 1: All‐cause mortality
11.2
11.2. Analysis
Comparison 11: Rivaroxaban 10 mg versus rivaroxaban 15 mg, Outcome 2: Cardiovascular mortality
11.3
11.3. Analysis
Comparison 11: Rivaroxaban 10 mg versus rivaroxaban 15 mg, Outcome 3: Major bleeding
11.4
11.4. Analysis
Comparison 11: Rivaroxaban 10 mg versus rivaroxaban 15 mg, Outcome 4: Myocardial infarction
11.5
11.5. Analysis
Comparison 11: Rivaroxaban 10 mg versus rivaroxaban 15 mg, Outcome 5: Stroke
11.6
11.6. Analysis
Comparison 11: Rivaroxaban 10 mg versus rivaroxaban 15 mg, Outcome 6: Non‐major bleeding
12.1
12.1. Analysis
Comparison 12: Rivaroxaban 10 mg versus rivaroxaban 20 mg, Outcome 1: All‐cause mortality
12.2
12.2. Analysis
Comparison 12: Rivaroxaban 10 mg versus rivaroxaban 20 mg, Outcome 2: Cardiovascular mortality
12.3
12.3. Analysis
Comparison 12: Rivaroxaban 10 mg versus rivaroxaban 20 mg, Outcome 3: Major bleeding
12.4
12.4. Analysis
Comparison 12: Rivaroxaban 10 mg versus rivaroxaban 20 mg, Outcome 4: Myocardial infarction
12.5
12.5. Analysis
Comparison 12: Rivaroxaban 10 mg versus rivaroxaban 20 mg, Outcome 5: Stroke
12.6
12.6. Analysis
Comparison 12: Rivaroxaban 10 mg versus rivaroxaban 20 mg, Outcome 6: Non‐major bleeding
13.1
13.1. Analysis
Comparison 13: Rivaroxaban 15 mg versus rivaroxaban 20 mg, Outcome 1: All‐cause mortality
13.2
13.2. Analysis
Comparison 13: Rivaroxaban 15 mg versus rivaroxaban 20 mg, Outcome 2: Cardiovascular mortality
13.3
13.3. Analysis
Comparison 13: Rivaroxaban 15 mg versus rivaroxaban 20 mg, Outcome 3: Major bleeding
13.4
13.4. Analysis
Comparison 13: Rivaroxaban 15 mg versus rivaroxaban 20 mg, Outcome 4: Myocardial infarction
13.5
13.5. Analysis
Comparison 13: Rivaroxaban 15 mg versus rivaroxaban 20 mg, Outcome 5: Stroke
13.6
13.6. Analysis
Comparison 13: Rivaroxaban 15 mg versus rivaroxaban 20 mg, Outcome 6: Non‐major bleeding
14.1
14.1. Analysis
Comparison 14: Dabigatran 50 mg BD versus dabigatran 75 mg BD, Outcome 1: All‐cause mortality
14.2
14.2. Analysis
Comparison 14: Dabigatran 50 mg BD versus dabigatran 75 mg BD, Outcome 2: Cardiovascular mortality
14.3
14.3. Analysis
Comparison 14: Dabigatran 50 mg BD versus dabigatran 75 mg BD, Outcome 3: Major bleeding
14.4
14.4. Analysis
Comparison 14: Dabigatran 50 mg BD versus dabigatran 75 mg BD, Outcome 4: Myocardial infarction
14.5
14.5. Analysis
Comparison 14: Dabigatran 50 mg BD versus dabigatran 75 mg BD, Outcome 5: Stroke
15.1
15.1. Analysis
Comparison 15: Dabigatran 50 mg BD versus dabigatran 110 mg BD, Outcome 1: All‐cause mortality
15.2
15.2. Analysis
Comparison 15: Dabigatran 50 mg BD versus dabigatran 110 mg BD, Outcome 2: Cardiovascular mortality
15.3
15.3. Analysis
Comparison 15: Dabigatran 50 mg BD versus dabigatran 110 mg BD, Outcome 3: Major bleeding
15.4
15.4. Analysis
Comparison 15: Dabigatran 50 mg BD versus dabigatran 110 mg BD, Outcome 4: Myocardial infarction
15.5
15.5. Analysis
Comparison 15: Dabigatran 50 mg BD versus dabigatran 110 mg BD, Outcome 5: Stroke
16.1
16.1. Analysis
Comparison 16: Dabigatran 50 mg BD versus dabigatran 150 mg BD, Outcome 1: All‐cause mortality
16.2
16.2. Analysis
Comparison 16: Dabigatran 50 mg BD versus dabigatran 150 mg BD, Outcome 2: Cardiovascular mortality
16.3
16.3. Analysis
Comparison 16: Dabigatran 50 mg BD versus dabigatran 150 mg BD, Outcome 3: Major bleeding
16.4
16.4. Analysis
Comparison 16: Dabigatran 50 mg BD versus dabigatran 150 mg BD, Outcome 4: Myocardial infarction
16.5
16.5. Analysis
Comparison 16: Dabigatran 50 mg BD versus dabigatran 150 mg BD, Outcome 5: Stroke
17.1
17.1. Analysis
Comparison 17: Dabigatran 75 mg BD versus dabigatran 110 mg BD, Outcome 1: All‐cause mortality
17.2
17.2. Analysis
Comparison 17: Dabigatran 75 mg BD versus dabigatran 110 mg BD, Outcome 2: Cardiovascular mortality
17.3
17.3. Analysis
Comparison 17: Dabigatran 75 mg BD versus dabigatran 110 mg BD, Outcome 3: Major bleeding
17.4
17.4. Analysis
Comparison 17: Dabigatran 75 mg BD versus dabigatran 110 mg BD, Outcome 4: Myocardial infarction
17.5
17.5. Analysis
Comparison 17: Dabigatran 75 mg BD versus dabigatran 110 mg BD, Outcome 5: Stroke
18.1
18.1. Analysis
Comparison 18: Dabigatran 75 mg BD versus dabigatran 150 mg BD, Outcome 1: All‐cause mortality
18.2
18.2. Analysis
Comparison 18: Dabigatran 75 mg BD versus dabigatran 150 mg BD, Outcome 2: Cardiovascular mortality
18.3
18.3. Analysis
Comparison 18: Dabigatran 75 mg BD versus dabigatran 150 mg BD, Outcome 3: Major bleeding
18.4
18.4. Analysis
Comparison 18: Dabigatran 75 mg BD versus dabigatran 150 mg BD, Outcome 4: Myocardial infarction
18.5
18.5. Analysis
Comparison 18: Dabigatran 75 mg BD versus dabigatran 150 mg BD, Outcome 5: Stroke
19.1
19.1. Analysis
Comparison 19: Dabigatran 110 mg BD versus dabigatran 150 mg BD, Outcome 1: All‐cause mortality
19.2
19.2. Analysis
Comparison 19: Dabigatran 110 mg BD versus dabigatran 150 mg BD, Outcome 2: Cardiovascular mortality
19.3
19.3. Analysis
Comparison 19: Dabigatran 110 mg BD versus dabigatran 150 mg BD, Outcome 3: Major bleeding
19.4
19.4. Analysis
Comparison 19: Dabigatran 110 mg BD versus dabigatran 150 mg BD, Outcome 4: Myocardial infarction
19.5
19.5. Analysis
Comparison 19: Dabigatran 110 mg BD versus dabigatran 150 mg BD, Outcome 5: Stroke
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References

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REDEEM {published data only}
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    1. Oldgren J, Budaj A, Granger CB, Khder Y, Roberts J, Siegbahn A, et al. Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial. European Heart Journal 2011;32(22):2781-9. - PubMed
    1. Oldgren J, Wallentin L, Budaj A, Granger CB, Harper R, Khder Y, et al. Randomised dabigatran etexilate dose finding study in patients with acute coronary syndromes post index event with additional risk factors for cardiovascular complications also receiving aspirin and clopidogrel (RE-DEEM). Circulation 2010;120(21):2160-1.

References to studies excluded from this review

Alizadeh 2019 {published data only}
    1. Alizadeh M, Antoniou S, Fhadil S, Rathod R, Guttmann O, Knight C, et al. The use of direct oral anti-coagulations (DOACs) compared to vitamin K antagonist in patients with left ventricular thrombus after acute myocardial infarction. European Heart Journal 2019;40(Suppl 1):4026.
Borst 2018 {published data only}
    1. Borst O, Munzer P, Alnaggar N, Geue S, Tegtmeyer R, Rath D, et al. Inhibitory mechanisms of very low-dose rivaroxaban in non-ST-elevation myocardial infarction. Blood Advances 2018;2(6):715-30. - PMC - PubMed
Devereaux 2018 {published data only}
    1. Devereaux PJ, Duceppe E, Guyatt G, Tandon V, Rodseth R, Biccard BM, et al. Dabigatran in patients with myocardial injury after non-cardiac surgery (MANAGE): an international, randomised, placebo-controlled trial. Lancet 2018;391(10137):2325-34. - PubMed
Duceppe 2018 {published data only}
    1. Duceppe E, Yusuf S, Tandon V, Rodseth R, Biccard BM, Xavier D, et al. Design of a randomized placebo-controlled trial to assess dabigatran and omeprazole in patients with myocardial injury after noncardiac surgery (MANAGE). Canadian Journal of Cardiology 2018;34(3):295-302. - PubMed
Euctr 2013a {published data only}
    1. EUCTR2012-004180-43-CZ. Rivaroxaban for the prevention of major cardiovascular events in coronary or peripheral artery disease. www.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2012-004180-43-CZ 2013.
Euctr 2013b {published data only}
    1. EUCTR2013-000046-19-BG. A study to assess the effectiveness and safety of rivaroxaban in reducing the risk of death, myocardial infarction or stroke in participants with heart failure and coronary artery disease following an episode of decompensated heart failure. www.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2013-000046-19-BG 2013.
Gao 2015 {published data only}
    1. Gao F, Shen H, Wang Z, Yang S, Liu X, Zhou Y. Risk of hemorrhagic and ischemic stroke for dual antiplatelet therapy and new generation oral anticoagulants in patients with acute coronary syndrome. Journal of the American College of Cardiology 2015;66(16 Suppl 1):C158.
Greenberg 2018a {published data only}
    1. Greenberg BH, Anker SD, Byra WM, Nessel CC, Cleland JG, Fu M, et al. Effects of rivaroxaban on thrombotic events in heart failure patients with coronary disease and sinus rhythm. Circulation 2018;138(25):e761-2.
Greenberg 2018b {published data only}
    1. Greenberg B, Anker S, Byra WM, Fu M, Nessel CC, Cleland JG, et al. A randomized study comparing rivaroxaban with placebo in subjects with heart failure and significant coronary artery disease following an episode of decompensated heart failure: the COMMANDER HF study. Journal of Cardiac Failure 2018;24(11):811.
Kopin 2016 {published data only}
    1. Kopin D, Sherwood MW, Jones WS, Granger CB, Lopes RD, Alexander JH, et al. Percutaneous coronary intervention and antiplatelet therapy on apixaban or warfarin: insights from the ARISTOTLE trial. Circulation 2016;134:Suppl 1.
Lee 2018 {published data only}
    1. Lee J, Nakanishi R, Li D, Shaikh K, Shekar C, Osawa K, et al. Randomized trial of rivaroxaban versus warfarin in the evaluation of progression of coronary atherosclerosis. American Heart Journal 2018;206:127-30. - PubMed
NCT04333407 {published data only}
    1. NCT04333407. Preventing cardiac complication of COVID-19 disease with early acute coronary syndrome therapy: a randomised controlled trial. clinicaltrials.gov/show/NCT04333407 (first received 3 April 2020).
NCT04688723 {published data only}
    1. NCT04688723. Dual therapy with dabigatran/ticagrelor versus dual therapy with dabigatran/clopidogrel in ACS patients with indication for NOAC undergoing PCI. clinicaltrials.gov/show/NCT04688723 (first received 30 December 2020).
NCT04805710 {published data only}
    1. NCT04805710. Rivaroxaban or aspirin in patients with CHD & GD undergoing PCI. clinicaltrials.gov/show/NCT04805710 (first received 18 March 2021).
NCT04838808 {published data only}
    1. NCT04838808. Rivaroxaban in type 2 myocardial infarctions. clinicaltrials.gov/show/NCT04838808 (first received 9 April 2021).
Nct 2012 {published data only}
    1. NCT01661101. Management of myocardial injury after noncardiac surgery trial. clinicaltrials.gov/show/NCT01661101 (first received 9 August 2012).
Schiele 2018 {published data only}
    1. Schiele F, Puymirat E, Ferrieres J, Simon T, Danchin N. Do randomized clinical trial selection criteria reflect real-life levels of risk in acute myocardial infarction survivors? the compass trial in light of the FAST-MI 2005-2010-2015 registries. Circulation 2018;138:Suppl 1.
Zannad 2015 {published data only}
    1. Zannad F, Greenberg B, Cleland JG, Gheorghiade M, Veldhuisen DJ, Mehra MR, et al. Rationale and design of a randomized, double-blind, event-driven, multicentre study comparing the efficacy and safety of oral rivaroxaban with placebo for reducing the risk of death, myocardial infarction or stroke in subjects with heart failure and significant coronary artery disease following an exacerbation of heart failure: the COMMANDER HF trial. European Journal of Heart Failure 2015;17(7):735-42. - PMC - PubMed
Zannad 2018 {published data only}
    1. Zannad F, Anker SD, Byra WM, Cleland JG, Fu M, Gheorghiade M, et al. Rivaroxaban in patients with heart failure, sinus rhythm, and coronary disease. New England Journal of Medicine 2018;379(14):1332-42. - PubMed

References to ongoing studies

NCT03775746 {published data only}
    1. NCT03775746. Can very low dose rivaroxaban in addition to dual antiplatelet therapy (DAPT) improve thrombotic status in acute coronary syndrome (ACS) ACS (VaLiDate-R). clinicaltrials.gov/show/NCT03775746 (first received 14 December 2018).

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