ASPIRE: Using Aspirin to Prevent Recurrence of VTE

Rita Buckley

doi:10.1177/155989771218007

Summary

Venous thrombosis, which manifests mainly as deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common and serious disorder; it occurs in 1 per 1000 individuals per year worldwide, and patients who suffer from DVT or PE are at risk of recurrent events [Rosendaal FR. PLoS Med 2012]. There is limited information on safe and effective long-term preventive strategies. This article discusses results from the Aspirin to Prevent Recurrent Venous Thromboembolism [ASPIRE; ACTRN12605000004662] trial.

Cardiology Clinical Trials
Thrombotic Disorders

Venous thrombosis, which manifests mainly as deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common and serious disorder; it occurs in 1 per 1000 individuals per year worldwide, and patients who suffer from DVT or PE are at risk of recurrent events [Rosendaal FR. PLoS Med 2012]. There is limited information on safe and effective long-term preventive strategies. Timothy Brighton, MBBS, South Eastern Area Lab Services, Prince of Wales Hospital, Sydney, Australia, presented results from the Aspirin to Prevent Recurrent Venous Thromboembolism [ASPIRE; ACTRN12605000004662] trial.

ASPIRE was a double-blind, randomized, placebo-controlled study that evaluated the efficacy of low-dose aspirin versus placebo in preventing a recurrence of venous thromboembolism (VTE) [Brighton TA et al. N Engl J Med 2012]. The primary endpoint was the composite of recurrent symptomatic objectively confirmed DVT, nonfatal PE, or fatal recurrence of VTE.

A total of 822 patients aged ≥18 years were randomized to receive 100 mg/day of aspirin or placebo for up to 4 years following initial anticoagulation therapy. Inclusion criteria were completion of initial anticoagulation therapy after a first unprovoked proximal DVT and/or PE, and commencement of study medication within 6 weeks (and as soon as possible) after the end of initial anticoagulant therapy.

During a median follow-up period of 37.2 months, VTE recurred in 73 of 411 (18%) patients assigned to placebo and in 57 of 411 (14%) assigned to aspirin (6.5% per year vs 4.8% per year; HR aspirin, 0.74; 95% CI, 0.52 to 1.05; p=0.09).

Although there was no significant reduction in the primary endpoint of recurrent VTE, treatment with aspirin was associated with a lower rate of the prespecified secondary broad composite outcomes combing venous and arterial thrombotic events as well as bleeding, including the rate of VTE, myocardial infarction (MI), stroke, or cardiovascular death (HR aspirin, 0.66; 95% CI, 0.48 to 0.92); The rate of VTE, MI, stroke, major bleeding, or death from any cause was reduced by 33% (HR, 0.67; 95% CI, 0.49 to 0.91; p=0.01). There was no significant difference in the rates of major or clinically relevant nonmajor bleeding episodes (0.6%/year with placebo vs 1.1%/year with aspirin; p=0.22) or serious adverse events.

Although the primary hypothesis that aspirin would significantly reduce the rate of recurrent VTE was not demonstrated, the presenter speculated that this may have been due to a lack of sufficient statistical power limitation. When combined with earlier data [WARFASA; Becattini CN et al. N Engl J Med 2012], Dr. Brighton suggested that the ASPIRE study adds to evidence that long-term, low-dose aspirin reduces the risk of recurrent VTE and major vascular events in patients with a first unprovoked VTE compared with placebo (Table 1) [Brighton TA et al. N Engl J Med 2012].

View this table:

Table 1.

Meta-analysis ASPIRE and WARFASA.

Dr. Brighton said that aspirin is an effective option for patients who are unable or do not wish to continue anticoagulation beyond their initial therapy. Unlike warfarin therapy aspirin is simple, widely available, low cost, and well tolerated, with low risks of bleeding and benefits that extend beyond the prevention of recurrent VTE.

Science Advisors' Statement

The clinical impact of these two trials should be interpreted carefully. While administration of aspirin may result in a modest reduction in VTE, trials of prolonged anticoagulant therapy—including those at reduced intensity—have shown benefit of greater magnitude [Ridker PM et al. N Engl J Med 2003; Schulman S et al. N Engl J Med 1997; Kearon C et al. N Engl J Med 1999; Kearon C et al. Chest 2012]. Clinicians should carefully consider treatment guidelines, prior data, and individual patient risks when advising patients with regard to appropriate antithrombotic therapy after VTE, and should not consider aspirin an alternative therapy with equivalent efficacy in patients with a clear indication for anticoagulation for VTE.

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