Continuing anticoagulation indefinitely in patients with a first unprovoked venous thromboembolism (VTE) may have benefits for certain patients but is unlikely to be cost effective, say authors of a new study.
Continued anticoagulation for such patients “has little chance of improving life expectancy but might provide a mortality benefit in certain subgroups including patients with an initial PE (pulmonary embolism) or those at a very low risk for major bleeding,” wrote the authors, led by Faizan Khan, PhD, with the O’Brien Institute for Public Health, University of Calgary (Alta.).
Therefore, shared decision-making between patients with unprovoked VTE and physicians that includes discussion of preferences and values and use of validated prediction tools is important.
The authors noted that some patients might value avoiding morbidities of recurrent VTE the most and want to have lifelong anticoagulation. Some might be more fearful of major bleeding than VTE repercussions or don’t want the inconveniences of taking anticoagulants for a lifetime.
The findings were published in Annals of Internal Medicine.
Current guidelines recommend indefinite anticoagulation
Clinical practice guidelines now recommend indefinite anticoagulation for a first unprovoked VTE.
The authors did a modeling study in a hypothetical cohort of 1,000 patients aged 55 years with a first unprovoked VTE who had completed 3-6 months of initial anticoagulation. The study found indefinite anticoagulation, compared with discontinuing anticoagulation, on average, resulted in 368 fewer recurrent VTE events and 14 fewer fatal PE events.
At the same time, indefinite coagulation in the hypothetical group induced an additional 114 major bleeding events, 30 intracerebral hemorrhages, and 11 fatal bleeding events over 40 years.
As for cost effectiveness, from the perspective of Canada’s health care system, continuing anticoagulation indefinitely, on average, increased costs by $16,014 Canadian dollars per person ($12,140 USD) without improving quality-adjusted life-years (incremental difference, 0.075 per person; 95% uncertainty interval, –0.192 to 0.017).
The authors noted that cost is a prime consideration as the estimated annual health care costs of VTE and its complications is $600 Canadian dollars ($7 billion–$10 billion USD).
High probability of small benefit
The authors spelled out the small benefit in patients with an initial PE.
According to the study, indefinite anticoagulation would result in an 80% probability of a marginal added clinical benefit (average increase of 57 days of perfect health over a lifetime) in patients with an initial PE (but with only a 24% chance of being cost effective).
“This high probability of an additional clinical benefit is plausible due to the higher proportion of recurrent VTE events presenting as PE (approximately 70% of episodes) in patients initially presenting with PE, in turn, resulting in a two- to threefold higher case-fatality rate of recurrent VTE in this patient subgroup.”
Tools to estimate bleeding risk imprecise
Scott Woller, MD, an internal medicine specialist and chair of medicine at Intermountain Medical Center, Murray, Utah, said in an interview that these results should help physicians’ discuss with their patients about duration of anticoagulation after the treatment phase.
He noted that the authors suggest that a low estimated annual risk for major bleeding should be assumed (< 0.67%) to make the choice for indefinite anticoagulation.
“This is a sticky wicket,” he said, “as tools to estimate bleeding risk among VTE patients are presently imprecise. For these reasons PCPs should take into account patient risk estimates – and the limitations that exist surrounding how we calculate these estimates – in addition to their values and preferences. This is really key in electing duration of anticoagulation.”
A limitation of the study is that the model assumed that risks for recurrent VTE and major bleeding in clinical trials at 1 year remained constant during extended anticoagulation.
Dr. Woller said about that limitation: “One might argue that this is unlikely; age is a risk factor for major bleeding and therefore risks may be underestimated. However, in the ‘real world’ those that are perceived at lowest risk and demonstrate good tolerance to anticoagulation might likely preferentially continue anticoagulants and therefore risks may be overestimated.”
One coauthor reported being a clinical investigator for trials sponsored by Pfizer and Bristol-Myers Squibb and receiving honoraria from Pfizer, Sanofi and Aspen Pharma. The other authors disclosed no other relevant financial relationships. Dr. Woller is cochair of the CHEST guidelines on the treatment of venous thromboembolic disease.