Problem

There is wide consensus that low molecular weight heparins are part of the standard treatment for many patients with venous thromboembolic disease. Traditionally they are administered twice daily. However, a single daily dose could increase patient’s comfort, reduce costs and facilitate ambulatory treatment. However, it is not clear if this dosification has a similar benefit and safety profile. 

Methods

We used Epistemonikos database, which is maintained by screening more than 30 databases, to identify systematic reviews and their included primary studies. With this information we generated a structured summary using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), meta-analysis of the total of studies, a summary of findings table following the GRADE approach and a table of other considerations for decision-making.

About the body of evidence for this question

Summary of findings

The information is based on five randomized studies which included 1508 patients. Four studies reported all-cause mortality, three studies reported symptomatic recurrence at 3 months of follow up and five studies presented information on major bleeding during treatment with low molecular weight heparin. 

• It is not clear whether a daily dose of low molecular weight heparin modifies the risk of recurrence compared with two daily doses because the certainty of the evidence is very low.
• One daily dose of low molecular weight heparin could result in little or minimal increase in the risk of major bleeding. The certainty of the evidence is low.
• One daily dose of low molecular weight heparin might not increase mortality. The certainty of the evidence is low.

Other considerations for decision-making

To whom this evidence does and does not apply

Applies to patients with venous thromboembolism (pulmonary embolism, deep venous thrombosis or both) who initiate anticoagulation with subcutaneous low molecular weight heparin.   The majority of the included patients in the randomized studies had deep vein thrombosis, so there is some degree of uncertainty about its applicability to patients with pulmonary embolism. It does not apply to patients with contraindication to low molecular weight heparin, such as massive events or advanced chronic kidney disease.

About the outcomes included in this summary

This summary includes outcomes that according to the author’s criteria are critical for decision making in these patients, and that are also considered in trials and clinical guidelines [8],[9],[10]..

Balance between benefits and risks, and certainty of the evidence

Given the low and very low certainty of the evidence, it is not possible to make an adequate balance between the risks and benefits of the one daily dose scheme over the conventional two daily doses scheme.

What would patients and their doctors think about this intervention

The use of one daily dose could improve patient’s comfort and eventually could facilitate ambulatory treatment, so some patients would prefer this option. It is especially relevant in these cases to warn about the existing uncertainty.

Resource considerations

It is not possible to make an adequate balance between costs and benefits because there is a high degree of uncertainty about the latter. More information is needed to make an estimation of the costs associated to recurrence, bleeding and mortality. The proposed intervention could contribute to decrease the overburden of nursing teams and to reduce supplies needed for the administration. The costs could decrease in the case of enoxaparin, since the total daily dose is lower for once daily administration. In selected cases, the outpatient treatment would reduce the costs associated to hospitalization for once daily administration.

Differences between this summary and other sources

The conclusions of this summary are consistent with the included systematic reviews.  Our summary is in partial agreement with the main guidelines. The guideline of the American College of Chest Physicians [8] recommends a single daily dose over two daily doses provided that the total daily dose is not altered. The guidelines of the American Heart Association [9] and the European Society of Cardiology [10], although also supportive of the use of once daily dose, for enoxaparin they recommend a dosification of 1 mg/kg every 12 hours or 1.5 mg/kg every 24 hours (75% of the total daily dose of reference).

Could this evidence change in the future?

The probability that new studies change the information presented in this summary is high, because the certainty of the evidence is low or very low.

How we conducted this summary

Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and we present it as a matrix of evidence.

Follow the link to access the interactive version: Low molecular weight heparin administered once versus twice daily for venous thromboembolism

Notes

The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary. Even though the project considers the periodical update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence and the summary should be updated earlier. After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.

The details about the methods used to produce these summaries are described here http://dx.doi.org/10.5867/medwave.2014.06.5997.

Epistemonikos foundation is a non-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is Epistemonikos database (www.epistemonikos.org).

These summaries follow a rigorous process of internal peer review.

Conflicts of interest
The authors do not have relevant interests to declare.