Efficacy and safety of direct oral anticoagulants vs. low molecular weight heparin for cancer-related venous thromboembolism: a meta-analysis of randomized trials

Abstract

Aims To examine the efficacy and safety of direct oral anticoagulants (DOAC) versus low molecular weight heparin (LMWH) in patients with cancer-related venous thrombo-embolism (VTE). Methods and Results An electronic search of MEDLINE, SCOPUS and COCHRANE without language restrictions was performed through April 2020 for randomized controlled trials that compared the effects of DOACs versus LMWH on patients with cancer-related VTE. Summary estimates were reported using random effects model. The main efficacy outcome was VTE recurrence while the main safety outcome was major bleeding events. The final analysis included 4 randomized trials with a total of 2,907 patients. The weighted mean follow-up was 6.1 months. Compared with LMWH, DOACs were associated with lower risk of VTE recurrence (5.7% vs. 9.1%, risk ratio [RR] 0.62; 95% confidence interval [CI] 0.44 to 0.87; P = 0.01), driven by lower deep venous thrombosis (P = 0.02). There was no difference between DOACs and LMWH in major bleeding events (4.8% vs. 3.6%, RR 1.33; 95% CI 0.84 to 2.11; P = 0.23). The incidence of all-cause mortality was similar (RR 0.99; 95% CI 0.84 to 1.16; P = 0.91). Subgroup analysis suggested no differences according to the type of DOAC in recurrent VTE or major bleeding (Pinteraction= 0.53 and Pinteraction= 0.11, respectively). Conclusion Among patients with cancer-related VTE, DOACs were associated with lower risk of VTE recurrence and similar risk of major bleeding compared with LMWH. Future studies examining the subset of cancer patients who drive the most benefit are encouraged.

“direct Oral Anticoagulants Versus Low-molecular-weight Heparin for Acute Treatment of Venous Thromboembolism in Patients With Gastrointestinal Cancer: a Systematic Review and Meta-analysis”

“…The results of the meta-analysis are consistent with those of previous meta-analyses of DOAC use in cancer patients that reported higher CRNMB [27], but similar major bleeding events [28,29] in DOAC users compared to those taking LMWH. Although major bleeding in the present metaanalysis was not signi cantly different between GI cancer patients receiving DOACs and GI cancer patients receiving LMWH, there was a trend towards increased major bleeding in the DOACs group.…”

“…DOACs have become an alternative to LMWH for the treatment of CAT. Despite the non-inferior e cacy of DOACs to LMWH for preventing recurrent VTE, a higher bleeding risk was found in certain DOACs in a subgroup analysis of patients with GI and genitourinary tract cancers compared to that of LMWH [25][26][27]. However, previous randomized controlled trials enrolled patients with various kinds of cancer.…”

An epidemic of redundant meta‐analyses

“…At the time the search was ended (October 6, 2020), 46 records were identified, of which 26 were discarded on title and abstract ( n = 24) or full‐text ( n = 2). The 20 remaining meta‐analyses were published in nonpredatory peer‐reviewed journals: five studies pooled the data of two RCTs, 6‐10 four studies pooled the data of three RCTs, 11‐14 and 11 studies pooled the data of four RCTs 15‐25 . The main characteristics of the 20 meta‐analyses are described in Table 1 and the results of the 20 meta‐analyses for efficacy and safety endpoint are shown Figure 1.…”

“…The 20 remaining meta-analyses were published in nonpredatory peer-reviewed journals: five studies pooled the data of two RCTs, 6-10 four studies pooled the data of three RCTs, [11][12][13][14] and 11 studies pooled the data of four RCTs. [15][16][17][18][19][20][21][22][23][24][25] The main characteristics of the 20 meta-analyses are described in Table 1 and the results of the 20 meta-analyses for efficacy and safety endpoint are shown Figure 1. Within each category of meta-analysis (two, three, or 4 RCTs), the results were similar regarding the risks of VTE recurrence (differences in pooled relative…”

Current status of treatment of cancer-associated venous thromboembolism

“…In recent years, with respect to DOACs vs LMWH, besides SELECT-D trial [ 37 ], six meta-analyses indicated that DOACs were more efficacious in the treatment of cancer-associated VTE with an increase of bleeding risk, compared with LMWH [ 11 , 20 , 38 – 41 ], whereas a retrospective study [ 7 ] and another five meta-analyses [ 10 , 15 , 16 , 42 , 43 ] indicated that DOACs were more efficacious with a comparable bleeding risk, compared with LMWH. In the ADAM VTE trial, major bleeding and VTE recurrence rates were both lower in cancer patients with VTE receiving oral apixaban than those receiving dalteparin [ 44 ].…”