ASPIRE study


Aspirin a viable treatment for serious blood clots

Australian-led international study shows low-dose aspirin is a cheap and effective way to prevent potentially deadly deep vein thrombosis and pulmonary embolus (serious blood clots) in patients who have had a previous blood clot.

An international study published on 4th November 2012 in The New England Journal of Medicine has found people who have suffered blood clots in the veins of the leg (deep vein thrombosis or DVT) or the lungs (pulmonary embolism or PE), also known as venous thromboembolism (VTE) are less likely to suffer a recurrence of the serious blood clots or a cardiac event if they take low-dose aspirin. Read the article here.

The results of this study were also presented at the Late Breaking Clinical Trials session at the American Heart Association meeting of over 30,000 delegates.

Operating since 2003, the ASPIRE study completed recruitment of 822 participants from five countries including Australia, New Zealand, Singapore, India and Argentina. All the participants had previously suffered a DVT or PE that occurred for no particular reason (called "unprovoked VTE") and had completed on average 6 months of anti-coagulant treatment (generally with  warfarin). In the ASPIRE study participants were randomly allocated to receive either low dose enteric coated aspirin 100mg daily or a matching placebo. On average participants were followed for three years.

 Dr Tim Brighton, a Haematologist in Sydney and Principal Investigator of the study, explained:

"Many patients discontinue warfarin therapy after 6 or 12 months of treatment due to the inconvenience of regular blood tests and the increased risks of serious bleeding.  However if warfarin therapy is stopped these patients are at high risk of recurring thrombosis. The ASPIRE study found that aspirin reduces the risk of important blood clotting event including recurrent VTE, myocardial infarction, stroke, or cardiovascular death. We now have clear evidence that aspirin is of benefit for patients who are unable or do not wish to continue warfarin in the long term."

Importantly the study results are consistent with the findings of an Italian study, called WARFASA, reported in the The New England Journal of Medicine earlier this year. The protocols of both studies were harmonised and have similar eligibility criteria and outcomes.  The WARFASA study results showed a significant benefit with aspirin.   The combined results of the 2 trials show clear and consistent evidence that aspirin prevents recurrent blood clots and this is likely to be adopted into future international practice.  

Professor John Simes, Director of the NHMRC Clinical Trials Centre at the University of Sydney and Study Chair said:

"These results suggest that aspirin prevents about one third of recurrent blood clot events. For every 1000 patients treated for 1 year, aspirin can be expected to prevent about 20 to 30 episodes of recurrent major thrombotic events at the cost of about 3 significant bleeding episodes."
and
"The results of this study suggest the simple, inexpensive treatment of low-dose aspirin could prevent thousands of patients from experiencing recurrent clots each year and may make substantial healthcare savings in Australia and worldwide."

 

Background

  • Blood clots in the veins of the leg (deep vein thrombosis or DVT) or the lungs (pulmonary embolism or PE), also known as venous thromboembolism, or VTE, are a common condition and affect approximately 1 per 1,000 persons in Australia  and New Zealand each year. The usual risk factors for developing VTE include surgery, admission to hospital, leg injuries with immobility, and cancer. Anticoagulation treatment, generally with heparin and warfarin, is very effective to prevent further blood clots (called recurrent VTE).
  • Sometimes VTE occurs for no obvious reason (for example without preceding surgery, admission to hospital, leg injury or prolonged immobility) and is called 'unprovoked VTE'. Patients with unprovoked VTE are very prone to further episodes of VTE (called recurrent VTE) once anticoagulant therapy is discontinued. The chance of recurrent VTE are 1 in 10 in the first year after warfarin is discontinued, and then ~5% for every year thereafter.  
  • Many patients are unable or do not wish to continue anticoagulant treatment in the long-term after their first episode of unprovoked VTE. Anticoagulant treatment (like warfarin) increases the risks of serious (and occasionally fatal) bleeding. Warfarin is an inconvenient therapy requiring regular blood tests, dose adjustments, and caution with other medications. Consequently many patients discontinued warfarin after 6 months and hope they do not experience recurrent VTE. While initial treatment with warfarin for at least 6 months is recommended, alternatives to warfarin for long-term prevention of recurrent VTE therapy are required.
  • Aspirin is a simple and safe treatment that is of proven benefit to prevent vein thrombosis that may follow surgery or other illness. However, there remains uncertainty about whether aspirin would prevent recurrent vein thrombosis in patients with recent DVT or PE. The ASPIRE study was designed to determine more clearly the effects of aspirin in these patients.

Collaboration

  • The study was conducted by NHMRC Clinical Trials Centre at University of Sydney and investigators in Australia, New Zealand, India, Singapore and Argentina (trial registered on ANZCTR (ACTRN12605000004662)).
  • The study was conducted as an investigator-initiated study with support from government and industry and conducted independently of all funders. National Co-ordinating centres in India (St John's Medical College and Research Institute, Bangalore) and Argentina (Estudios Clínicos Latinoamérica International, (ECLA) Rosario) were responsible for the co-ordination of the study in these countries.
  • The study was supported by project grants from NHMRC (301911 and 570967), NZ HRC (05/080R), the Australasian Society of Thrombosis and Haemostasis (ASTH) and Bayer HealthCare, Germany.  Aspirin and matching placebo were provided without charge by Bayer HealthCare Pharmaceuticals who played no other role in the study.
  • There is also a similar study in Italy called WARFASA (the Warfarin and Aspirin trial), the protocols of both studies were harmonised and have similar eligibility criteria and outcomes.  The WARFASA study results showed a significant benefit with aspirin.   It is planned to pool the individual patient data from each study in a subsequent combined meta-analysis called the INSPIRE collaboration.

Contacts