Salicylates hold an enduring place in the history of medical therapeutics. Hippocrates suggested salicin-rich preparations of willow bark and myrtle for the treatment of pain and fever in the 5th century B.C.E., and acetylsalicylic acid (aspirin) was first marketed as a purified drug by Friedrich Bayer & Co. as far back as 1899. From the 1950s onwards, researchers have explored aspirin’s powerful role in the prevention and treatment of myocardial infarction and stroke, and more recent efforts suggest aspirin reduces the risk of colorectal adenomas. As published in this week’s issue of NEJM, Dr. Cecilia Becattini (University of Perugia, Perugia, Italy) and colleagues think that the next chapter written in the aspirin story may be about the secondary prevention of venous thromboembolism (VTE).
Dr. Becattini and colleagues report on the multi-center WARFASA trial, which recruited 403 adult patients completing 6 to 18 months of vitamin K antagonist therapy for a first-ever, unprovoked, symptomatic, objectively-confirmed proximal deep venous thrombosis (DVT) and/or pulmonary embolism (PE). These patients were randomized in a double-blind fashion to daily aspirin (100 mg/d) or placebo, and followed for VTE recurrence and bleeding events for about two years.
The results suggest that aspirin’s ability to prevent recurrent VTE may be substantial. Compared to placebo, treatment with aspirin significantly reduced the risk of VTE recurrence (6.6% versus 11.2% of patients per year; hazard ratio, 0.58, 95% confidence interval 0.36 – 0.93; p=0.02), with a risk of non-fatal major bleeding that was about 0.3% per patient-year in both groups.
These trial results are consistent with prior findings, notes editorialist Dr. Richard C Becker (Duke Clinical Research Institute, Durham, NC), though the observed effect is “perhaps greater than one might have anticipated”. What’s more, many questions remain: In which patients does a transition to aspirin clearly trump extended-duration anticoagulant therapy? If aspirin is prescribed, for how long should it be continued? Dr. Becker argues that further study is needed to better define aspirin’s role in VTE prevention before it becomes part of usual VTE care.
After 113 years on the market, will acetylsalicylic acid find yet another indication for its use? Only time (and further study) will tell. Fortunately, this is one drug that’s willing to wait.
Diarmuid Jeffreys. Aspirin: The Remarkable Story of a Wonder Drug. New York: Bloomsbury Publishing, 2005.