On-treatment Comparative Effectiveness of Vitamin K Antagonists and Direct Oral Anticoagulants in GARFIELD-VTE, and Focus on Cancer and Renal Disease

Abstract

Background Direct oral anticoagulants (DOACs) provide a safe, effective alternative to vitamin K antagonists (VKAs) for venous thromboembolism (VTE) treatment, as shown via intention-to-treat comparative effectiveness analysis. However, on-treatment analysis is imperative in observational studies because anticoagulation choice and duration are at investigators' discretion. Objectives The aim of the study is to compare the effectiveness of DOACs and VKAs on 12-month outcomes in VTE patients using on-treatment analysis. Methods The Global Anticoagulant Registry in the FIELD - VTE (GARFIELD-VTE) is a world-wide, prospective, non-interventional study observing treatment of VTE in routine clinical practice. Results In total, 8,034 patients received VKAs ( n = 3,043, 37.9%) or DOACs ( n = 4,991, 62.1%). After adjustment for baseline characteristics and follow-up bleeding events, and accounting for possible time-varying confounding, all-cause mortality was significantly lower with DOACs than VKAs (hazard ratio: 0.58 [95% confidence interval 0.42-0.79]). Furthermore, patients receiving VKAs were more likely to die of VTE complications (4.9 vs. 2.2%) or bleeding (4.9 vs. 0.0%). There was no significant difference in rates of recurrent VTE (hazard ratio: 0.74 [0.55-1.01]), major bleeding (hazard ratio: 0.76 [0.47-1.24]), or overall bleeding (hazard ratio: 0.87 [0.72-1.05]) with DOACs or VKAs. Unadjusted analyses suggested that VKA patients with active cancer or renal insufficiency were more likely to die than patients treated with DOAC (52.51 [37.33-73.86] vs. 26.52 [19.37-36.29] and 9.97 [7.51-13.23] vs. 4.70 [3.25-6.81] per 100 person-years, respectively). Conclusion DOACs and VKAs had similar rates of recurrent VTE and major bleeding. However, DOACs were associated with reduced all-cause mortality and a lower likelihood of death from VTE or bleeding compared with VKAs.

Keywords: anticoagulation; direct oral anticoagulants; on-treatment comparative effectiveness; venous thromboembolism; vitamin K antagonists.

Fig. 1

Treatment patterns over 12-months follow-up. No OAC includes end of study from death, termination of treatment or loss to follow-up. DOAC, direct oral anticoagulant; OAC, oral anticoagulant; VKA, vitamin-K antagonist.

Fig. 2

Kaplan-Meier curves for (A) all-cause mortality, (B) recurrent VTE, and (C) major bleeding. The number of patients at risk at each time point is shown below each curve.

Fig. 3

Adjusted hazard ratios between DOAC and VKA (reference) treatment groups. Values <1 favor DOAC treatment over VKA because they are indicative of a reduction in the hazard rate. HRs were adjusted for major bleeding and dropout at follow-up in addition to the following baseline characteristics: age, gender, ethnicity, BMI, previous aspirin usage, VTE type (DVT alone, PE alone, DVT, and PE), site of DVT (upper limb, lower limb, caval vein inferior or superior), care setting, physician specialty, treatment funding source, country, creatinine clearance, active cancer, recent bleeding or anemia, pregnancy or postpartum, family history of VTE, history of cancer, known thrombophilia, prior VTE episodes, and renal insufficiency. DOAC, Direct oral anticoagulants; DVT, deep vein thrombosis; PE, pulmonary embolism.