Use of D-dimer testing to determine duration of anticoagulation, risk of cardiovascular events and occult cancer after a first episode of idiopathic venous thromboembolism: the extended follow-up of the PROLONG study.
BACKGROUND
The PROLONG study showed that D-dimer (D-d) testing could help tailor the duration of anticoagulation after idiopathic venous thromboembolism (VTE). In this report the initial 18 month study follow-up was extended for 1 year.


METHODS
D-d was measured 1 month after anticoagulation withdrawal for a first episode of idiopathic VTE. Patients with a normal D-d did not resume anticoagulation, while patients with an abnormal D-d were randomized to either resume or not resume treatment. The primary outcome was the composite of recurrent VTE and major bleeding. Secondary end-points were cardiovascular events, newly diagnosed cancers and deaths.


RESULTS
D-d was abnormal in 222/608 (36.5%) patients. Average follow-up was 2.55 years. Twenty-eight events occurred in the 121 patients who stopped anticoagulation (23.1%, 9.6% person-years) and five in the 101 patients who resumed anticoagulation (5.0%, 2.0% person-years, adjusted hazard ratio-HR = 3.76; P = 0.008). Recurrence rate was higher in patients with abnormal D-d who stopped anticoagulation than in patients with normal D-d (51 events in 386 patients -13.2%; 5% person-years; adjusted HR 1.70; P = 0.045). The adjusted HR ratio associated with normal D-d versus abnormal D-d in patients who resumed anticoagulation was 2.7 (P = 0.042). An abnormal D-d was associated with a non significant higher risk of cardiovascular events and newly diagnosed cancers vs normal D-d.


CONCLUSIONS
Patients with an abnormal D-d at 1 month after withdrawal of VKA have a significant risk of recurrence over a 2.55 year follow-up and they benefit from resuming anticoagulation.
Cosmi
Benilde
B
Department Angiology and Blood Coagulation Marino Golinelli, S. Orsola-Malpighi University Hospital, Via Albertoni, 15, Bologna, Italy. benilde.cosmi@unibo.it
Legnani
Cristina
C
Tosetto
Alberto
A
Pengo
Vittorio
V
Ghirarduzzi
Angelo
A
Alatri
Adriano
A
Prisco
Domenico
D
Poli
Daniela
D
Tripodi
Armando
A
Palareti
Gualtiero
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology; D003955:Diagnostic Tests, Routine / Q000706:statistics & numerical data; D004334:Drug Administration Schedule; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000209:etiology; D009780:Occult Blood; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000097:blood* / Q000188:drug therapy*; D055815:Young Adult
D000925:Anticoagulants; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D