Blood thinners for pulmonary hypertension

Background

The heart has four chambers: two upper and two lower chambers. The lower right chamber, also known as the right ventricle, pumps blood through the pulmonary artery to the lungs, where the blood receives oxygen. Pulmonary hypertension occurs when pressure in the pulmonary arteries is increased to above normal (8 to 25 mmHg). When this happens over time, inflammation of the pulmonary artery occurs. The arteries may then become stiff and tighten. These changes make it difficult for the heart to pump blood to the lungs. The heart becomes weaker as it tries to push against this pressure; the resulting disturbance to blood flow can lead to blood clots. These clots can travel to the lungs, which can worsen the person's condition and may result in death.

People with pulmonary hypertension may complain of tiredness, chest pain and shortness of breath during normal activities like walking and running, which may progress to affect all physical activities. Prospects of survival depend on several factors, but pregnancy is strongly associated with poor survival.

Treatment of this disease is multi-faceted and includes rehabilitation, psychosocial support and surgical and medical treatment. Medical treatment includes the use of blood thinners such as warfarin, heparin, fondaparinux, argatroban, dabigatran, apixaban and rivaroxaban. Blood thinners work by preventing the formation of clot. The blood thinner of choice, warfarin, needs close monitoring with daily to weekly laboratory testing to maintain the therapeutic target; this monitoring may be difficult to keep up with. The major side effect of blood thinners is bleeding, which can manifest as easy bruising, bleeding in the digestive tract and bleeding into the brain; severe cases can be fatal.

Review question

We set out to evaluate the effectiveness of blood thinners in the treatment of pulmonary hypertension. No eligible studies (randomised controlled trials) were found. Review of other studies (non-randomised controlled trials) shows the effectiveness of this intervention. However, these findings should be interpreted with caution because of the low quality of evidence provided by these studies.

Conclusion

No randomised evidence is available. We decided to look at the results of other studies (non-randomised control trials). They provide only poor quality evidence of effectiveness of this intervention, and the results should be interpreted with caution. We are uncertain as to how far the results of studies with this design can be believed, and our own approach was not designed to properly look for them and incorporate them in our systematic review. This review therefore highlights the need for appropriately designed randomised controlled trials.

Authors' conclusions: 

No eligible studies were identified for inclusion in this review. Although our review of available non-randomised studies shows beneficial effect, this finding should be interpreted with caution since there are likely to be biases associated with their design and our methods were not designed to identify, appraise and summarise evidence from them. So that better decisions can be made regarding the effectiveness of this intervention, well-designed randomised controlled trials are needed.

Read the full abstract...
Background: 

Elevation of pulmonary pressure is no longer a rare disease, given its multifactorial etiology. However data on the actual incidence of this condition are still limited, and controversies regarding its management are ongoing. Use of anticoagulation in the management of pulmonary hypertension is based on the presence of in situ thrombosis in the patient with pulmonary arterial hypertension (PAH) and on retrospective evidence of clinical benefit. Current practice is dependent mostly on expert opinion and individualised experience. The real benefit of its use in different types of pulmonary hypertension is still debatable, and the therapeutic target of the international normalised ratio (INR) among treated patients remains inconclusive. Adverse outcomes associated with anticoagulants are significant and can include fatal haemorrhage. Justification for the use of this intervention requires critical evaluation of randomised controlled trials.

Objectives: 

1. To evaluate the effectiveness of, and potential adverse events associated with, anticoagulation in the management of pulmonary hypertension (PH).

2. To evaluate the effective therapeutic INR in pulmonary hypertensive patients receiving anticoagulants (North American centres 1.5 to 2.5, European centres 2.0 to 3.0).

Search strategy: 

We identified trials through searches of the following databases.

Cochrane Airways Group Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL), part of The Cochrane Library; MEDLINE (Ovid); EMBASE (Ovid); CINAHL (EBSCOhost); Clinical trials.gov and the World Health Organization (WHO) trials portal. The trial search date was 28 March 2014.

Selection criteria: 

We planned to include only randomised controlled trials. Participants with PH with co-morbidities including medical conditions requiring long-term anticoagulation were to be included. We also planned to include trials comparing any anticoagulant with placebo.

Data collection and analysis: 

Review authors (IE and HE) independently appraised all identified citations to establish their relevance for inclusion in the review. IE and HE independently screened the titles and abstracts of all identified potential studies for inclusion.

Main results: 

No eligible trials were identified for inclusion in this review.

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