Efficacy and safety of direct oral anticoagulants for secondary prevention of cancer associated thrombosis: a meta-analysis of randomized controlled trials

Abstract

Direct oral anticoagulants (DOACs) may be good alternatives to low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) for treatment of cancer associated thrombosis (CAT). We conducted a meta-analysis of ten randomized clinical trials to evaluate the efficacy and safety of DOACs in patients with CAT. All had study populations composed in entirety or in part of patients with CAT. The primary outcome (efficacy) was recurrent VTE and the secondary outcomes (safety outcomes) included major bleeding, clinically relevant non-major bleeding (CRNMB), and all bleeding (major bleeding + CRNMB). Participants treated with DOACs had lower risk of recurrent VTE, overall (RR 0.63; 95% CI 0.51-0.79; p < 0.0001), compared to LMWH (RR 0.57; 95% CI 0.40-0.83; p = 0.003), but not compared to VKA (RR 0.69; 95% CI 0.44-1.06; p = 0.09). Compared to LMWH, DOACs showed no difference in major bleeding risk (RR 1.31; 95% CI 0.78-2.18; p = 0.31), though had higher risk of CRNMB (RR 1.60; 95% CI 1.13-2.26; p = 0.008) and all bleeding (RR 1.49; 95% CI 1.10-2.01; p = 0.010). These results indicate that DOACs are more effective than LMWH for prevention of recurrent VTE with CAT though carry an increased risk for non-major bleeding compared to standard of care, LMWH.

Figure 1

Prisma flow diagram of selection of studies.

Figure 2

Cochrane Collaboration risk of bias summary.

Figure 3

Efficacy (VTE recurrence) of DOAC. Forest plots show risk ratio (RR) of VTE recurrence of pooled data from all studies and subgroup analyses of studies evaluating DOAC compared to LMWH and DOAC compared VKA. Boxes superimposing RR estimates are proportional to the weight of the included study. Heterogeneity between RCT is assessed by the I² statistic.

Figure 4

Safety (bleeding risk) of DOAC. (a) Major bleeding (MB), (b) clinically relevant non major bleeding (CRNMB), (c) all bleeding (composite MB and CRNMB). Forest plots show risk ratio (RR) of VTE recurrence of pooled data from all studies and subgroup analyses of studies evaluating DOAC compared to LMWH and DOAC compared to VKA. Boxes superimposing RR estimates are proportional to the weight of the included study. Heterogeneity between RCT is assessed by the I² statistic.