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Clinician Article

Antiplatelet versus anticoagulation treatment for patients with heart failure in sinus rhythm.



  • Shantsila E
  • Lip GY
Cochrane Database Syst Rev. 2016 Sep 15;9(9):CD003333. doi: 10.1002/14651858.CD003333.pub3. (Review)
PMID: 27629776
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Disciplines
  • Cardiology
    Relevance - 6/7
    Newsworthiness - 5/7
  • Internal Medicine
    Relevance - 6/7
    Newsworthiness - 5/7
  • Hematology
    Relevance - 6/7
    Newsworthiness - 4/7
  • Hemostasis and Thrombosis
    Relevance - 5/7
    Newsworthiness - 5/7
  • Family Medicine (FM)/General Practice (GP)
    Relevance - 5/7
    Newsworthiness - 3/7
  • General Internal Medicine-Primary Care(US)
    Relevance - 5/7
    Newsworthiness - 3/7

Abstract

BACKGROUND: Morbidity in patients with chronic heart failure is high, and this predisposes them to thrombotic complications, including stroke and thromboembolism, which in turn contribute to high mortality. Oral anticoagulants (e.g. warfarin) and antiplatelet agents (e.g. aspirin) are the principle oral antithrombotic agents. Many heart failure patients with sinus rhythm take aspirin because coronary artery disease is the leading cause of heart failure. Oral anticoagulants have become a standard in the management of heart failure with atrial fibrillation. However, a question remains regarding the appropriateness of oral anticoagulants in heart failure with sinus rhythm. This update of a review previously published in 2012 aims to address this question.

OBJECTIVES: To assess the effects of oral anticoagulant therapy versus antiplatelet agents for all-cause mortality, non-fatal cardiovascular events and risk of major bleeding in adults with heart failure (either with reduced or preserved ejection fraction) who are in sinus rhythm.

SEARCH METHODS: We updated the searches in September 2015 on CENTRAL (The Cochrane Library), MEDLINE and Embase. We searched reference lists of papers and abstracts from cardiology meetings and contacted study authors for further information. We did not apply any language restrictions. Additionally, we searched two clinical trials registers: ClinicalTrials.gov (www.ClinicalTrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) Search Portal apps.who.int/trialsearch/) (searched in July 2016).

SELECTION CRITERIA: We included randomised controlled trials comparing antiplatelet therapy versus oral anticoagulation in adults with chronic heart failure in sinus rhythm. Treatment had to last at least one month. We compared orally administered antiplatelet agents (aspirin, ticlopidine, clopidogrel, prasugrel, ticagrelor, dipyridamole) versus anticoagulant agents (coumarins, warfarin, non-vitamin K oral anticoagulants).

DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and assessed the risks and benefits of antithrombotic versus antiplatelet therapy using relative measures of effects, such as risk ratios (RR), accompanied with 95% confidence intervals (CI). The data extracted included data relating to the study design, patient characteristics, study eligibility, quality, and outcomes. We used GRADE criteria to assess the quality of the evidence.

MAIN RESULTS: This update identified one additional study for inclusion, adding data for 2305 participants. This addition more than doubled the overall number of patients eligible for the review. In total, we included four randomised controlled trials (RCTs) with a total of 4187 eligible participants. All studies compared warfarin with aspirin. One RCT additionally compared warfarin with clopidogrel. All included RCTs studied patients with heart failure with reduced ejection fraction.Analysis of all outcomes for warfarin versus aspirin was based on 3663 patients from four RCTs. All-cause mortality was similar for warfarin and aspirin (RR 1.00, 95% CI 0.89 to 1.13; 4 studies; 3663 participants; moderate quality evidence). Oral anticoagulation was associated with a reduction in non-fatal cardiovascular events, which included non-fatal stroke, myocardial infarction, pulmonary embolism, peripheral arterial embolism (RR 0.79, 95% CI 0.63 to 1.00; 4 studies; 3663 participants; moderate quality evidence). The rate of major bleeding events was twice as high in the warfarin groups (RR 2.00, 95% CI 1.44 to 2.78; 4 studies; 3663 participants; moderate quality evidence). We generally considered the risk of bias of the included studies to be low.Analysis of warfarin versus clopidogrel was based on a single RCT (N = 1064). All-cause mortality was similar for warfarin and clopidogrel (RR 0.93, 95% CI 0.72 to 1.21; 1 study; 1064 participants; low quality evidence). There were similar rates of non-fatal cardiovascular events (RR 0.85, 95% CI 0.50 to 1.45; 1 study; 1064 participants; low quality evidence). The rate of major bleeding events was 2.5 times higher in the warfarin group (RR 2.47, 95% CI 1.24 to 4.91; 1 study; 1064 participants; low quality evidence). Risk of bias for this study can be summarised as low.

AUTHORS' CONCLUSIONS: There is evidence from RCTs to suggest that neither oral anticoagulation with warfarin or platelet inhibition with aspirin is better for mortality in systolic heart failure with sinus rhythm (high quality of the evidence for all-cause mortality and moderate quality of the evidence for non-fatal cardiovascular events and major bleeding events). Treatment with warfarin was associated with a 20% reduction in non-fatal cardiovascular events but a twofold higher risk of major bleeding complications (high quality of the evidence). We saw a similar pattern of results for the warfarin versus clopidogrel comparison (low quality of the evidence). At present, there are no data on the role of oral anticoagulation versus antiplatelet agents in heart failure with preserved ejection fraction with sinus rhythm. Also, there were no data from RCTs on the utility of non-vitamin K antagonist oral anticoagulants compared to antiplatelet agents in heart failure with sinus rhythm.


Clinical Comments

Family Medicine (FM)/General Practice (GP)

The authors draw a clear conclusion concerning mortality: no difference between oral anticoagulants and aspirin. Non-fatal cardiovascular events is a different matter. I think that the evaluation of the difference between non-fatal cardiovascular events (20% reduction with oral anticoagulants) versus major bleeding (two-fold increase with OAC) remains a matter of opinion. In the abstract, no final conclusions are drawn; however, in the plain language summary, they state that there is no evidence to suggest advantages of warfarin over antiplatelet drugs.

General Internal Medicine-Primary Care(US)

This well done review shows that overall warfarin is not superior to antiplatelet strategy in sinus rhythm. There is no reason to change the current practice of providing antiplatelet treatment to those who are likely to have coronary disease as an underlying cause of heart failure.

Hematology

Simple and clear.

Hemostasis and Thrombosis

This study confirms what we already knew.

Hemostasis and Thrombosis

This is useful evidence, though not completely unexpected. It's more relevant for cardiology than thrombosis. It is not common practice to anticogulate these patients, at least with warfarin, but I would expect that for many of these patients being considered for NOACS, it is a better and safer alternative to warfarin. In this perspective, it's good to know that there is no role for warfarin and therefore, no role for a safer alternative. Before choosing something different from aspirin in these patients, we would need new direct evidence.

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