0
Correspondence |

Duration of Warfarin in Pulmonary Embolism FREE TO VIEW

Andrew Miller, MD, FCCP; Ian Campbell, MD; Tony Fennerty, MD
Author and Funding Information

Affiliations: British Thoracic Society, London, UK,  University of Oklahoma Health Sciences Center, Oklahoma City, OK,  University of Amsterdam, Amsterdam, the Netherlands

Correspondence to: Andrew Miller, MD, FCCP, Mayday University Hospital, Croydon Chest Clinic CR7 74E, UK; e-mail: andrew.miller@mayday.nhs.uk



Chest. 2006;130(1):299-300. doi:10.1378/chest.130.1.299
Text Size: A A A
Published online

To the Editor:

Like numerous physicians, we always look forward to seeing the latest American College of Chest Physicians guidelines on antithrombotic therapy, and the latest (Seventh) edition is of the same superb quality as its predecessors. For several years,1 the British Thoracic Society has advised that 3 months of therapy is sufficient for the first episode of pulmonary embolism, including idiopathic cases, whereas our North American colleagues have interpreted the same available data to conclude that the traditional 6-month approach is preferable. This difference of opinion partly arose because, until recently, the only relevant studies included a high proportion of patients with deep vein thrombosis alone.

As members of the British Thoracic Society working party who recently updated our guidelines,2we understood that the issue had been resolved by an excellent large multicenter study3that only recruited patients with a first episode of proven clinical pulmonary embolism, and showed that continuing warfarin beyond 3 months merely deferred proven recurrence, both in idiopathic cases and in patients with a temporary risk factor (interestingly, the same group4 had previously reached similar conclusions in deep vein thrombosis). The interpretation of this is that in such cases there are only two logical alternatives: (1) stop at 3 months, but review in the event of a proven recurrence; or (2) use lifelong treatment, but review in the event of a significant iatrogenic bleed.

This important study was analyzed by the six international experts, one of whom was Professor Agnelli himself. For first-episode idiopathic pulmonary embolism, an option that can be “considered” (Recommendation 5.1.3 - Grade 2A) is indefinite treatment, the same as (2) above. However, we were very surprised that, for such cases, their preference (“we recommend”) is “at least 6 to 12 months” (Recommendation 5.1.2). Can the latter really still be considered Grade 1A? Why is there no recommendation for 3 months, which should certainly justify the same grade as that proposed?

Leaving out such guidance means that patients will receive anticoagulation for much longer than the evidence suggests, which is inconvenient and expensive. More worryingly, there will be some (not many, but some) patients who will experience a catastrophic bleed due to treatment unnecessarily prolonged beyond 3 to “at least 6 to 12 months” as a result of this selective advice.

Could we please be enlightened?

The authors have no conflicts of interest to disclose.

The authors have no conflicts of interest to disclose.

. British Thoracic Society. (1997) Suspected acute pulmonary embolism: a practical approach.Thorax52(suppl 4),S1-S24. [PubMed]
 
British Thoracic Society.. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism.Thorax2003;58,470-483. [CrossRef] [PubMed]
 
Agnelli, G, Prandoni, P, Becattini, C, et al Extended oral anticoagulant therapy after a first episode of pulmonary embolism.Ann Intern Med2003;139,19-25. [PubMed]
 
Agnelli, G, Prandoni, P, Santamaria, MG, et al Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis.N Engl J Med2001;345,165-169. [CrossRef] [PubMed]
 
Büller, HR, Agnelli, G, Hull, RD, et al Antithrombotic therapy for venous thromboembolic disease.Chest2004;126(suppl),401S-428S
 
To the Editor:

We appreciate the comments of Dr. Miller and colleagues, and also the efforts of the British Thoracic Society. Our recommendations were developed using the following key principles: a transparent link to the strength of the relevant evidence, evaluation of the balance between risks and benefits, and explicit identification of the underlying values and preferences.1Our recommendation that patients with a first episode of idiopathic pulmonary embolism receive treatment for 6 to 12 months was supported by the aggregate evidence available at the time for patients with idiopathic venous thromboembolism.25 This evidence supported three conclusions: (1) stopping treatment at 3 months resulted in a high incidence of recurrent thromboembolism, (2) an extended duration of anticoagulant treatment was effective for preventing recurrent thromboembolism while patients continued therapy, and (3) the optimal duration of anticoagulant therapy remained uncertain. The study by Professor Agnelli and colleagues4in patients with pulmonary embolism did not include sufficient patients with idiopathic pulmonary embolism to definitively conclude that 1 year of treatment was not more effective than 3 months, since the 95% confidence interval for the relative risk of recurrent thromboembolism in this subgroup ranged from 0.45 to 2.16. A similar conclusion applied to the study by Pinede and colleagues,5 in which the 95% confidence interval for the relative risk of recurrent venous thromboembolism for 6 months vs 3 months of treatment ranged from 0.47 to 1.87 in the subgroup with idiopathic venous thromboembolism. The aggregate evidence available at the time, and particularly the study by Kearon et al,2 suggested strongly that 3 months was an insufficient duration of treatment for idiopathic venous thromboembolism. We therefore recommended treatment for at least 6 to 12 months (grade 1A), providing the clinician some flexibility to tailor the duration of treatment to the patient’s specific clinical situation. We also made a separate recommendation to consider patients with idiopathic venous thromboembolism for indefinite anticoagulant treatment (grade 2A).6 Finally, we also included an explicit statement of the values and preferences underlying our recommendation, namely, “This recommendation ascribes a relatively high value to preventing recurrent thromboembolic events and a relatively low value on bleeding and cost.”6 Therefore, by including this explicit statement, we acknowledged that our recommendation was weighted toward preventing recurrent thromboembolism, and that clinicians may select a shorter duration of treatment, such as 3 months, for those patients who place a relatively higher value on avoiding bleeding than on preventing recurrent thromboembolism.

References
Schunemann, H, Munger, H, Brower, S, et al Methodology for guideline development for the seventh American College of Chest Physicians conference on antithrombotic and thrombolytic therapy: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.Chest2004;126(suppl),174S-178S
 
Kearon, C, Gent, M, Hirsh, J, et al A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism.N Engl J Med1999;340,901-907. [CrossRef] [PubMed]
 
Agnelli, G, Prandoni, P, Santamaria, MG, et al Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis.N Engl J Med2001;345,165-169. [CrossRef] [PubMed]
 
Agnelli, G, Prandoni, P, Becattini, C, et al Extended oral anticoagulant therapy after a first episode of pulmonary embolism.Ann Intern Med2003;139,19-25. [PubMed]
 
Pinede, L, Ninet, J, Duhaut, P, et al Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep-vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis.Circulation2001;103,2453-2460. [CrossRef] [PubMed]
 
Buller, H, Agnelli, G, Hull, R, et al Antithrombotic therapy for venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.Chest2004;126(suppl),401S-428S
 

Figures

Tables

References

. British Thoracic Society. (1997) Suspected acute pulmonary embolism: a practical approach.Thorax52(suppl 4),S1-S24. [PubMed]
 
British Thoracic Society.. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism.Thorax2003;58,470-483. [CrossRef] [PubMed]
 
Agnelli, G, Prandoni, P, Becattini, C, et al Extended oral anticoagulant therapy after a first episode of pulmonary embolism.Ann Intern Med2003;139,19-25. [PubMed]
 
Agnelli, G, Prandoni, P, Santamaria, MG, et al Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis.N Engl J Med2001;345,165-169. [CrossRef] [PubMed]
 
Büller, HR, Agnelli, G, Hull, RD, et al Antithrombotic therapy for venous thromboembolic disease.Chest2004;126(suppl),401S-428S
 
Schunemann, H, Munger, H, Brower, S, et al Methodology for guideline development for the seventh American College of Chest Physicians conference on antithrombotic and thrombolytic therapy: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.Chest2004;126(suppl),174S-178S
 
Kearon, C, Gent, M, Hirsh, J, et al A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism.N Engl J Med1999;340,901-907. [CrossRef] [PubMed]
 
Agnelli, G, Prandoni, P, Santamaria, MG, et al Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis.N Engl J Med2001;345,165-169. [CrossRef] [PubMed]
 
Agnelli, G, Prandoni, P, Becattini, C, et al Extended oral anticoagulant therapy after a first episode of pulmonary embolism.Ann Intern Med2003;139,19-25. [PubMed]
 
Pinede, L, Ninet, J, Duhaut, P, et al Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep-vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis.Circulation2001;103,2453-2460. [CrossRef] [PubMed]
 
Buller, H, Agnelli, G, Hull, R, et al Antithrombotic therapy for venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.Chest2004;126(suppl),401S-428S
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

CHEST Journal Articles
PubMed Articles
Guidelines
Venous thromboembolism (VTE).
University of Michigan Health System | 7/31/2009
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543