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Meta-Analysis
. 2021 May 18;5(5):CD003336.
doi: 10.1002/14651858.CD003336.pub4.

Anticoagulation versus placebo for heart failure in sinus rhythm

Eduard Shantsila  1 , Monika Kozieł  2   3 , Gregory Yh Lip  4
Affiliations
Meta-Analysis

Anticoagulation versus placebo for heart failure in sinus rhythm

Eduard Shantsila et al. Cochrane Database Syst Rev. .

Abstract

Background: People with chronic heart failure (HF) are at risk of thromboembolic events, including stroke, pulmonary embolism, and peripheral arterial embolism; coronary ischaemic events also contribute to the progression of HF. The use of long-term oral anticoagulation is established in certain populations, including people with HF and atrial fibrillation (AF), but there is wide variation in the indications and use of oral anticoagulation in the broader HF population.

Objectives: To determine whether long-term oral anticoagulation reduces total deaths and stroke in people with heart failure in sinus rhythm.

Search methods: We updated the searches in CENTRAL, MEDLINE, and Embase in March 2020. We screened reference lists of papers and abstracts from national and international cardiovascular meetings to identify unpublished studies. We contacted relevant authors to obtain further data. We did not apply any language restrictions.

Selection criteria: Randomised controlled trials (RCT) comparing oral anticoagulants with placebo or no treatment in adults with HF, with treatment duration of at least one month. We made inclusion decisions in duplicate, and resolved any disagreements between review authors by discussion, or a third party.

Data collection and analysis: Two review authors independently assessed trials for inclusion, and assessed the risks and benefits of antithrombotic therapy by calculating odds ratio (OR), accompanied by the 95% confidence intervals (CI).

Main results: We identified three RCTs (5498 participants). One RCT compared warfarin, aspirin, and no antithrombotic therapy, the second compared warfarin with placebo in participants with idiopathic dilated cardiomyopathy, and the third compared rivaroxaban with placebo in participants with HF and coronary artery disease. We pooled data from the studies that compared warfarin with a placebo or no treatment. We are uncertain if there is an effect on all-cause death (OR 0.66, 95% CI 0.36 to 1.18; 2 studies, 324 participants; low-certainty evidence); warfarin may increase the risk of major bleeding events (OR 5.98, 95% CI 1.71 to 20.93, NNTH 17). 2 studies, 324 participants; low-certainty evidence). None of the studies reported stroke as an individual outcome. Rivaroxaban makes little to no difference to all-cause death compared with placebo (OR 0.99, 95% CI 0.87 to 1.13; 1 study, 5022 participants; high-certainty evidence). Rivaroxaban probably reduces the risk of stroke compared to placebo (OR 0.67, 95% CI 0.47 to 0.95; NNTB 101; 1 study, 5022 participants; moderate-certainty evidence), and probably increases the risk of major bleeding events (OR 1.65, 95% CI 1.17 to 2.33; NNTH 79; 1 study, 5008 participants; moderate-certainty evidence).

Authors' conclusions: Based on the three RCTs, there is no evidence that oral anticoagulant therapy modifies mortality in people with HF in sinus rhythm. The evidence is uncertain if warfarin has any effect on all-cause death compared to placebo or no treatment, but it may increase the risk of major bleeding events. There is no evidence of a difference in the effect of rivaroxaban on all-cause death compared to placebo. It probably reduces the risk of stroke, but probably increases the risk of major bleedings. The available evidence does not support the routine use of anticoagulation in people with HF who remain in sinus rhythm.

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Conflict of interest statement

Dr E Shantsila declares no conflict of interest.

Dr M Kozieł declares no conflict of interest.

Dr GYH Lip has served as a consultant for Bayer, Astellas, Merck, Sanofi, BMS/Pfizer, Daiichi‐Sankyo, Biotronik, Medtronic, Portola, and Boehringer Ingelheim, and has been on the speakers' bureau for Bayer, BMS/Pfizer, Boehringer Ingelheim, Daiichi‐Sankyo, Medtronic, and Sanofi Aventis.

Figures

1
1
PRISMA flowchart
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
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: Warfarin versus control, Outcome 1: All‐cause death
1.2
1.2. Analysis
Comparison 1: Warfarin versus control, Outcome 2: Cardiovascular death (including sudden death)
1.3
1.3. Analysis
Comparison 1: Warfarin versus control, Outcome 3: Myocardial infarction
1.4
1.4. Analysis
Comparison 1: Warfarin versus control, Outcome 4: Major bleeding events
2.1
2.1. Analysis
Comparison 2: Rivaroxaban versus placebo, Outcome 1: All‐cause death
2.2
2.2. Analysis
Comparison 2: Rivaroxaban versus placebo, Outcome 2: Cardiovascular death (including sudden death)
2.3
2.3. Analysis
Comparison 2: Rivaroxaban versus placebo, Outcome 3: Stroke
2.4
2.4. Analysis
Comparison 2: Rivaroxaban versus placebo, Outcome 4: Myocardial infarction
2.5
2.5. Analysis
Comparison 2: Rivaroxaban versus placebo, Outcome 5: Pulmonary embolism
2.6
2.6. Analysis
Comparison 2: Rivaroxaban versus placebo, Outcome 6: Major bleeding events
See this image and copyright information in PMC

Update of

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