BMJ Open (Nov 2020)

Bleeding and thrombotic complications during treatment with direct oral anticoagulants or vitamin K antagonists in venous thromboembolic patients included in the prospective, observational START2-register

  • Daniela Poli,
  • Emilia Antonucci,
  • Vittorio Pengo,
  • Niccolò Maggini,
  • Sophie Testa,
  • Antonio Insana,
  • Carmelo Paparo,
  • Pasquale Pignatelli,
  • Gualtiero Palareti,
  • Paolo Prandoni,
  • Elvira Grandone,
  • Cristina Legnani,
  • Daniela Mastroiacovo,
  • Alberto Tosetto,
  • Walter Ageno,
  • Rossella Marcucci,
  • Oriana Paoletti,
  • Giovanna Colombo,
  • Benilde Cosmi,
  • Giuliana Guazzaloca,
  • Ludovica Migliaccio,
  • Anna Falanga,
  • Teresa Lerede,
  • Luca Barcella,
  • Gentian Denas,
  • Elisa Bison,
  • Lucia Ruocco,
  • Paolo Chiarugi,
  • Giuliana Martini,
  • Simona Pedrini,
  • Federica Bertola,
  • Lucilla Masciocco,
  • Pasquale Saracino,
  • Angelo Benvenuto,
  • Claudio Vasselli,
  • Marco Marzolo,
  • Antonietta Piana,
  • Francesco Cibecchini,
  • Andrea Toma,
  • Pietro Barbera,
  • Donatella Colaizzo,
  • Domizio Serra,
  • Daniele Pastori,
  • Serena Rupoli,
  • Giuseppe Malcangi,
  • Giovanni Nante,
  • Rosella Sangiorgio

DOI
https://doi.org/10.1136/bmjopen-2020-040449
Journal volume & issue
Vol. 10, no. 11

Abstract

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Objective The proportion and characteristics of Italian patients affected by venous thromboembolism (VTE) treated with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs), and complications occurring during follow-up.Design A prospective cohort of 2728 VTE patients included in the Survey on anticoagulaTed pAtients RegisTer (START2-Register) from January 2014 to June 2018 was investigated. Characteristics of patients, type of treatment and complications occurring during 2962 years of follow-up were analysed.Setting About 60 Italian anticoagulation and thrombosis centres participated in the observational START2-RegisterParticipants 2728 adult patients with VTE of a lower limb and/or pulmonary embolism (PE), with a follow-up after the initial phase treatment.Interventions Patients could receive DOACs or VKAs; both prescribed by the National and Regional Health Systems for patients with VTE.Outcomes measures Efficacy: rate of VTE recurrence (all thrombotic complications were also recorded). Safety: the rate of major and clinically relevant non-major bleeding events.Results Almost 80% of patients were treated with DOACs. The prevalence of symptomatic PE and impaired renal function was higher in patients receiving VKAs. Duration of anticoagulation was >180 days in approximately 70% of patients. Bleeding events were similar in both treatment groups. The overall eventuality of recurrence was significantly higher in DOAC cohorts versus VKA cohorts (HR 2.15 (1.14–4.06), p=0.018); the difference was almost completely due to recurrences occurring during extended treatment (2.73% DOAC vs 0.49% VKA, p<0.0001). All-cause mortality was higher in VKA-treated (5.9%) than in DOAC-treated patients (2.6%, p<0.001).Conclusion Italian centres treat most patients with VTE with DOACs and prefer VKA for those with more serious clinical conditions. Recurrences were significantly more frequent in DOAC-treated patients due to increased incidence after 180 days of treatment, probably due to reduced adherence to treatment. These results underline the importance of structured surveillance of DOAC-treated patients with VTE to strengthen treatment adherence during extended therapy.