New Studies Examine Prolonged Anticoagulation For VTE Recurrence Reply

Three studies published in the New England Journal of Medicine provide important new information about the risks and benefits of extended prophylaxis using two of the new oral anticoagulants in patients who have had venous thromboembolism (VTE).

In an accompanying editorial, Jean Connors writes that “deciding how to balance the risks and benefits of extended anticoagulation is difficult” in patients with unprovoked VTE, since the risk of recurrent VTE may reach 40% at 5 years. Patients at low-to-moderate risk of recurrence may benefit from aspirin, which “may be safer than the newer agents,” though “it appears to have less efficacy in reducing recurrent events.” For patients at higher risk, “the new targeted anticoagulants are attractive alternatives to warfarin. The finding that a low prophylactic dose of apixaban has the same efficacy as the full therapeutic dose, with no increased risk of major bleeding, may tip the risk-to-benefit ratio in favor of extended treatment for this patient population. The wide therapeutic window of this agent enables use of a lower dose that retains great efficacy with no or only a minimal increase in bleeding.”

Click here to read the entire post in Forbes.

The New England Journal of Medicine

 

 

 

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Prolonged Anticoagulation With Apixaban Found Beneficial In Venous Thromboembolism Reply

A new study suggests that extending anticoagulant therapy for an additional year may be beneficial after patients with venous thromboembolism complete their initial course of therapy. The results of AMPLIFY-EXT (Apixaban after the Initial Management of Pulmonary Embolism and Deep Vein Thrombosis with First-Line Therapy-Extended Treatment) were presented at the annual meeting of the American Society of Hematology meeting in Atlanta and published simultaneously in the New England Journal of  Medicine.

After completing a standard anticoagulation regimen for 6-12 months, 2,486 VTE patients were randomized to either placebo or apixaban (2.5 or 5 mg twice daily) for an additional 12 months. At both doses, apixaban treatment was associated with a large reduction in clinical events and no increase in major bleeding events.

The primary endpoint, the composite of death or symptomatic recurrent VTE, was significantly reduced in the apixaban groups, from  11.6% in the placebo group to 3.8% in the low-dose apixaban and 4.2% in the high-dose apixaban groups (p<0.001 for both comparisons).

There were very few major bleeding events: 4 (0.5%) in the placebo group, 2 (0.2%) in the low dose apixaban group and 1 ((0.1%) in the high dose apixaban group. Clinically relevant non-major bleeds occurred in 2.3% of the placebo group, 3% of the low dose apixaban group, and 4.2% of the high dose apixaban group.

The investigators concluded that the results of the study “provide a rationale for continuing anticoagulation therapy” in VTE patients for whom there is uncertainty about the worth of continued anticoagulant therapy. They calculated that 14 patients would need to be treated to prevent one VTE case.

ASPIRE: Aspirin An Attractive Alternative After First VTE Reply

It is unclear what the best approach is for the long-term treatment of people who have had a first unprovoked episode of venous thromboembolism (VTE). Although warfarin is effective at preventing a recurrence, it is inconvenient and raises the risk for bleeding. Newer anticoagulants have not been tested or approved for this population.

The ASPIRE (Aspirin to Prevent Recurrent Venous Thromboembolism) trial randomized 822 patients who had finished an initial course of anticoagulant therapy after a first unprovoked case of VTE to either aspirin (100 mg daily) or placebo for 4 years. Although the reduction in the rate for recurrent VTE with aspirin did not reach statistical significance, there were significant reductions in secondary outcomes of clinical events:

26% reduction in the yearly rate of VTE recurrence (primary endpoint):

  • 6.5% for placebo and 4.8% for aspirin (HR 0.74, CI 0.52-1.05, p=0.09)

34% reduction in the yearly rate of major vascular events (VTE, MI, stroke, or CV death):

  • 8.0% versus 5.2% (HR 0.66, CI 0.48-0.92, p=0.01)

33% reduction in the yearly rate of VTE, MI, stroke, major bleeding, or all-cause mortality (net clinical benefit):

  • 9.0% versus 6.0% (HR 0.67, CI 0.49-0.91, p=0.01)

The ASPIRE investigators calculated that for every 1000 patients treated for 1 year, aspirin would prevent 17 episodes of VTE and 28 major thrombotic events, at a cost of 5 nonfatal bleeding episodes.

Reporting in the New England Journal of Medicine, the investigators write that although aspirin is “substantially less effective than warfarin,” it is “an attractive alternative because it is simple and inexpensive and its safety profile is well documented.”

In an accompanying editorial, Theodore Warkentin combined the ASPIRE results with findings from the recent WARFASA trial and calculated that aspirin results in a 32% reduction in the rate of recurrent VTE and a 34% reduction in the rate of major vascular events. He concludes that aspirin is “a reasonable option” for patients who wish to stop anticoagulation:

Aspirin is inexpensive, does not require monitoring (in contrast to warfarin), and does not accumulate in patients with renal insufficiency (in contrast to dabigatran and rivaroxaban); in addition, if major bleeding occurs or the patient requires urgent surgery, the antiplatelet effects of aspirin can be reversed…”

Aspirin Found To Prevent Recurrent Venous Thromboembolism 1

Aspirin can help prevent the recurrence of venous thromboembolism (VTE) after discontinuation of anticoagulation therapy, according to results of the WARFASA (the Warfarin and Aspirin) study published in the New England Journal of Medicine.

Following 6 to 18 months of oral anticoagulation, 403 patients with first-time unprovoked VTE were randomized to aspirin (100 mg daily) or placebo for two years. Aspirin therapy resulted in a significant reduction in VTE but did not cause an increase in the risk of bleeding:

  • VTE recurrence: 6.6% per year in the aspirin group versus 11.2% in the placebo group (hazard ratio 0.58, CI 0.36 to 0.93, p=0.02).
  • Major bleeding occurred in one patient in each treatment group.

In an accompanying editorial, Richard Becker writes that the results of WARFASA “are compelling and may signal an important step in the evolution of care” but calls for additional studies to more precisely define the role of aspirin in preventing recurrent VTE. The results of a larger trial, the Aspirin to Prevent Recurrent Venous Thromboembolism (ASPIRE) study, will be reported this year, according to Becker, and, in conjunction with WARFASA, “may provide more reliable evidence of the effect of aspirin in patients with first unprovoked venous thromboembolism.”