Extended oral anticoagulant therapy after a first episode of pulmonary embolism.
BACKGROUND
The optimal duration of oral anticoagulant treatment after a first episode of pulmonary embolism remains uncertain.


OBJECTIVE
To evaluate the long-term clinical benefit of extending a 3-month course of oral anticoagulant therapy to 6 months (pulmonary embolism associated with temporary risk factors) or to 1 year (idiopathic pulmonary embolism) in patients with a first episode of pulmonary embolism.


METHODS
Multicenter randomized study with independent, blinded assessment of the outcome events.


METHODS
19 Italian hospitals.


METHODS
326 patients who had had 3 months of oral anticoagulant therapy without experiencing recurrence or bleeding.


METHODS
The primary study outcome was recurrence of symptomatic, objectively confirmed venous thromboembolism.


RESULTS
Among 165 patients assigned to extended anticoagulant therapy, 15 patients (9.1%) had a recurrence of venous thromboembolism (3.1% per patient-year; average follow-up, 34.9 months), as compared with 18 of 161 patients (11.2%) assigned to discontinue treatment (4.1% per patient-year; average follow-up, 32.7 months); the rate ratio was 0.81 (95% CI, 0.42 to 1.56). All but one of the recurrences occurred after anticoagulant treatment was discontinued. Nineteen recurrences (57.6%) were episodes of pulmonary embolism, two of which were fatal. Three major bleeding episodes were observed during extended anticoagulation (1.8%). Among patients with idiopathic venous thromboembolism, 11 of 90 patients assigned to extended anticoagulation and 11 of 91 patients assigned to discontinue treatment experienced a recurrence (relative risk, 0.99 [CI, 0.45 to 2.16]).


CONCLUSIONS
Patients with pulmonary embolism have a substantial risk for recurrence after discontinuation of oral anticoagulation, regardless of treatment duration. Physicians should try to identify patients who are at high risk for recurrent venous thromboembolism and are therefore potential candidates for indefinite oral anticoagulant therapy.
Agnelli
Giancarlo
G
Sezione di Medicina Interna e Cardiovascolare, Dipartimento di Medicina Interna, Università di Perugia, Via Enrico Dal Pozzo, 06123 Perugia, Italy. agnellig@unipg.it
Prandoni
Paolo
P
Becattini
Cecilia
C
Silingardi
Mauro
M
Taliani
Maria Rita
MR
Miccio
Maddalena
M
Imberti
Davide
D
Poggio
Renzo
R
Ageno
Walter
W
Pogliani
Enrico
E
Porro
Fernando
F
Zonzin
Pietro
P
D000074:Acenocoumarol / Q000008:administration & dosage / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000517:prevention & control; D012307:Risk Factors; D055502:Secondary Prevention; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects; D028761:Withholding Treatment
D000925:Anticoagulants; D014859:Warfarin; D000074:Acenocoumarol