D-dimer and risk of venous thromboembolism recurrence: Comparison of two studies with similar designs but different laboratory and clinical results
Gualtiero Palareti a),*); Cristina Legnani a); Alberto Tosetto b); Daniela Poli c); Sophie Testa d); Walter Ageno e); Vittorio Pengo f); Benilde Cosmi g); Paolo Prandoni a)
a) Fondazione Arianna Anticoagulazione, Bologna, Italy
b) UOC Ematologia, Centro Malattie Emorragiche e Trombotiche (CMET), AULSS 8 Berica Ospedale S. Bortolo, Vicenza, Italy
c) Malattie Aterotrombotiche, AOU Careggi, Firenze, Italy
d) Centro Emostasi e Trombosi, UUOO Laboratorio Analisi chimico-cliniche e microbiologiche, ASST Cremona, Cremona, Italy
e) Dipartimento di Medicina e Chirurgia, Universit`a degli Studi dell’Insubria, UOC Pronto Soccorso, Medicina d’Urgenza e Centro Trombosi ed Emostasi, ASST dei Sette Laghi, Varese, Italy
f) Clinica Cardiologica, Azienda Ospedaliera di Padova, Padova, Italy
g) UO di Angiologia e Malattie della Coagulazione, Dipartimento Medicina Specialistica, Diagnostica e Sperimentale, Universit`a di Bologna, Azienda Ospedaliero Universitaria S. Orsola-Malpighi, I.R.C.C.S., Bologna, Italy
Abstract
Background:
D-dimer testing may help deciding the duration of anticoagulation in subjects at high risk of venous thromboembolism (VTE) recurrence. Two management studies on this issue have been published (DULCIS in 2014 and APIDULCIS in 2022). They had similar designs but had important different results. Aim of this article is to compare their results.
Methods:
Both studies were finalized to extend anticoagulation [with vitamin K anticoagulants (VKAs) in DULCIS or apixaban 2.5 mg BID (kindly provided by BMS-Pfizer Collaboration) in APIDULCIS] only in patients with positive D-dimer results.
Results:
More D-dimer assays resulted positive in APIDULCIS than in DULCIS (61.1 % vs 47.7 %, respectively; p < 0.0001). While only 4 (0.5 %) refused low dose apixaban in APIDULCIS, the 22.6 % of patients with positive Ddimer refused to resume VKAs in DULCIS; their rates of recurrence were 187 and 8.8 per 100 person-years, respectively (incidence rate ratio [IRR]: 21.2). The incidence of bleeding was low in those receiving apixaban vs those who resumed VKAs (0.4 vs 2.3 per 100 person-years, respectively; IRR 0.17;). While the recurrence rate was low and similar in the studies in subjects who resumed anticoagulation, it was significantly higher in APIDULCIS than in DULCIS in those who stopped anticoagulation for negative D-dimer (5.6 vs 3.0 per 100 person-years, respectively; IRR 1.9).
Conclusion:
The low dose Apixaban for extended VTE treatment is effective and safe, and well accepted by patients. Why subjects who stopped anticoagulation for negative D-dimer had a higher recurrence rate in APIDULCIS than in DULCIS remains to be explained.