[Physician Comment] Low dose aspirin shows net clinical benefit in patients with first unprovoked venous thromboembolism

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Study author, Dr. Tim Brighton, M.D. talks to 2 Minute Medicine: *Senior Staff Haematologist at Prince of Wales Hospital in Sydney, AU. 

a)     Why is this study clinically important to physicians?

I think the study is important. While aspirin is not as effective as therapeutic anticoagulation for preventing recurrent VTE, many patients are either unable or not willing to continue anticoagulation long-term after a first episode of unprovoked VTE. Previously we had no useful therapies to recommend. Many physicians gave low-dose aspirin in this situation with no good evidence of benefit. Now with the combined WARFASA and ASPIRE data we have 

b)    Why the medical student should care?consistent evidence of efficacy in prevention of recurrent VTE, as well as evidence of prevention of arterial vascular vents at little cots of bleeding.

Preventing recurrent VTE is really important. Recurrent VTE has a case fatality rate of ~5-10% and increases the risks of post-thrombotic syndrome by 6-fold.

c)     Future implications?

I believe the use of aspirin while make a significant difference. However it is not ideal therapy. Current research is trying to further stratify the risk of recurrent VTE amongst patients experiencing a first episode of unprovoked VTE. We know that the risk of recurrent VTE in this group is high (10% in first 12 months after ceasing anticoagulation and then 5% per year) but after 10 years the majority of patients have not experienced recurrent VTE. If we could identify within all patients with first episode of unprovoked VTE those at low, intermediate and high risk of recurrence then we could more appropriately target the patients for observation, low-dose aspirin or ongoing anticoagulation respectively.

Key study points:

1. Daily aspirin, in comparison to placebo, did not reduce recurrent venous thromboembolism in patients after first episode of venous thromboembolism.

2. Daily aspirin, in comparison to placebo, was associated with statistically significant decrease the secondary outcomes: i.e. the rate of major vascular events in patients after first episode of venous thromboembolism.

Primer: Prior studies have demonstrated that an episode of venous thromboembolism places one at a markedly increased risk of recurrence following the end of anticoagulant therapy. The standard option for patients after initial unprovoked venous thromboembolism is to go on warfarin therapy although the duration of this initial therapy is variable. Given warfarin’s role in anticoagulating, patients on such these treatments are at an increased risk of bleeding and maintaining therapeutic levels can be a hassle and challenge for many. For this reason, many patients are incompliant with it. While anticoagulation is done initially, lifelong anticoagulation has not been shown to improve survival despite its known efficacy in reducing venous thromboembolisms. The authors of this study hypothesized that low dose aspirin, a low risk and widely available drug, can be used to prevent recurrent venous thromboembolism events in patients with a first unprovoked venous thromboembolism event after an initial regimen of warfarin.

Background Reading:

1. Prandoni P, Lensing AWA, Cogo A, et al. The long term clinical course of acute deep venous thrombosis. Ann Intern Med 1996.125:1-7
2. Becattini C, Agnelli GA, Schenone A, et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med 2012. 366:1959-1967

This [prospective cohort] study: A total of 822 patients were recruited for this Aspirin to Prevent Recurrent Venous Thromboembolism (ASPIRE) study. The study was double blind, randomized, and placebo-controlled. Patients were randomly assigned to daily aspirin at a dose of 100mg daily or placebo for 2-4 years. 18% of those assigned to placebo and 14% of those assigned to aspirin demonstrated a recurrent venous thromboembolism event (95% CI, P=0.09). In 77% of cases the venous thromboembolism was unprovoked.

The significant net clinical benefit of aspirin was demonstrated as a 33% composite reduction in the rate of venous thromboembolism, myocardial infarction, stroke, major bleeding, or death (95% CI, P=0.01).

In sum: Daily low dose aspirin is known for its beneficial cardiovascular effects. This study suggests that aspirin can be used not only to help prevent major cardiovascular effects but also may be beneficial in patients with their first episode of unprovoked venous thromboembolism. One drawback to this study was a 22% nonadherence rate among enrolled patients. While the authors argue that combining data with a related study would provide adequate statistical powering to show a significant result in the primary outcome, this will need to be investigated further. Despite lacking the efficacy in preventing recurrent thromboembolism in comparison to warfarin, low dose aspirin represents an attractive option for some patients, especially given the reduction of major vascular events and its known safety profile.    

Click here to read this article in NEJM

By [JP] and [RR]

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