Taylor Wofford
EBM
5/15/09
Prandoni P, Prins MH, Lensing AWA, et al. Residual Thrombosis on Ultrasonography to Guide the Duration of Anticoagulation in Patients with Deep Venous Thrombosis. A Randomized Trial. Ann Intern Med. 2009;150:577-585.
Objective:
To determine whether tailoring the duration of anticoagulation therapy to the persistence of residual thrombi on ultrasound reduces the risk of recurrent VTE as compared to fixed duration of anticoagulation therapy in patients with proximal DVT.
Study Design:
Parallel randomized trial. No placebo. Consecutive patients enrolled. Study event adjudicators were blinded to patients’ randomization. Nine centers in Italy.
Selection Criteria:
Patients>18 years old with new onset symptomatic proximal DVT who had been treated uneventfully for 3 months with anticoagulation.
Exclusion Criteria:
Prior thromboembolism, cancer, immobilization from chronic medical disease, need for indefinite anticoagulation, poor followup, deficiency of natural anticoagulants or carriage of lupus-like anticoagulant (though Factor V Leiden and Prothrombin Gene Mutation allowed in trial), short life expectancy, pregnancy.
Methods:
-Randomization: At the end of 3 months anticoagulation, patients were randomized by center and placed into fixed or flexible duration of anticoagulation arms. For patients in the fixed-duration arm, warfarin was discontinued after an additional 3 months for idiopathic DVT and immediately in patients with secondary DVT. For patients in the flexible-duration arm, patients were reassessed with ultrasound at 3, 9, 15, and 21 months for idiopathic DVT and 3 and 9 months for secondary DVT. If vein was recanalized on ultrasound (<2mm fully compressed as single measurement or <3mm in consecutive measurements), anticoagulation was discontinued.
-Primary outcome measure: Recurrent venous thromboembolism. Patients and PCPs were told to present for evaluation if clinical manifestations of DVT or PE occurred.
-Statistical analysis: Intent-to-treat analysis using Cox proportional hazards modeling.
Results:
46 events occurred in the 268 patients in fixed-duration arm. Event rate: 17.2%
32 events occurred in the 270 patients in flexible-duration arm. Event rate: 11.9%
Adjusted hazard ratio 0.64 [95% CI, 0.39 to 0.99]
Subgroup analysis of idiopathic DVT: Adjusted hazard ratio 0.61 [95% CI, 0.36 to 1.02]
Subgroup analysis of secondary DVT: Adjusted hazard ratio 0.81 [CI 95%, 0.32 to 2.06]
Discussion:
Are the results of this therapeutic trial valid? No
Are the valid results of this randomized trial important? No
Can you apply this valid, important evidence about therapy in caring for your patient? Somewhat
Strengths:
-Exceptional followup
-Precise protocol
-Blinded adjudicators
Weaknesses:
-Study design flawed; variable is duration of anticoagulation more than compressibility of vein on ultrasound
-Lack of comparison of recanalization of vein to other risk factors in the multivariate analysis
-Underpowered
-Duration of followup limited
-Many exclusion criteria
Discussion:
What would be the optimal study design for this clinical question?