Direct oral anticoagulant for the prevention of thrombosis in ambulatory patients with cancer: A systematic review and meta‐analysis

Abstract

Background It is unclear if direct oral anticoagulant (DOAC) is efficacious and safe for prophylaxis of venous thromboembolism (VTE) in ambulatory patients with cancer. Methods We performed a systematic review using EMBASE, MEDLINE, and CENTRAL. Inclusion criteria included adult ambulatory patients with cancer, prophylactic use of DOAC, and randomized controlled trials. Exclusion criteria included pediatric patients, inpatient or postoperative setting, therapeutic indication of DOAC, or non‐phase III randomized controlled trial. Two authors screened/reviewed articles and abstracted the data. Meta‐analysis was performed using random‐effects model. Efficacy outcome included overall and symptomatic VTE incidence during the first 6 months. Safety outcomes included major bleeding and clinically relevant non‐major bleeding (CRNMB) incidence during the on‐treatment period. Subgroup analysis was performed for intermediate‐ and high‐risk Khorana score. Results A total of 202 records were identified and 28 full‐text articles were assessed. Two studies with 1415 participants were included for meta‐analysis. For DOAC vs placebo, the relative risks for overall and symptomatic VTE incidence by 6 months were 0.56 (0.35‐0.89) and 0.58 (0.29‐1.13), respectively. The relative risks for major bleeding and CRNMB while on‐treatment were 1.96 (0.80‐4.82) and 1.28 (0.74‐2.20), respectively. Patients with high‐risk Khorana score (3+) derived the largest absolute risk reduction of VTE. Conclusions Low‐dose DOAC reduces the rate of overall VTE in higher risk cancer patients starting systemic chemotherapy. It may reduce the rate of symptomatic VTE but increase the likelihood of bleeding.

SEOM clinical guideline of venous thromboembolism (VTE) and cancer (2019)

“…Considered together, these trials showed a significant benefit of the oral anticoagulants for the prevention of VTE with an acceptable incidence of major bleeding. Recently, at least two meta-analyses have assessed the role of DOACs in this setting [36,48]. Beccatini et al [36] included three randomized clinical trials and describe a significant reduction of VTE with DOACs [odds ratio (OR) 0.49; 95% CI 0.33-0.74].…”

Cost‐effectiveness analysis of low‐dose direct oral anticoagulant (DOAC) for the prevention of cancer‐associated thrombosis in the United States

“…A similar pattern of clinical outcomes was observed over 6 months and over 5 years (see Supporting Table 5). The absolute differences in all clinical outcomes, including overall VTE, PE, DVT, MB, CRNMB, and mortality, were all within the 95% CI of previously reported outcomes from the meta‐analysis at 6 months . Minor variations in outcomes were likely driven by the inclusion of a drug nonadherence/discontinuation factor in the Markov model, which led to small attenuations of the absolute risk reductions of the primary outcomes.…”

“…Subgroup meta-analyses were performed for patients with Khorana scores ≥3 and 2 after outcomes were obtained directly from the trial authors. 13 Because of the low case fatality associated with PE, MB, and ICH, pooled estimates were derived from 2 prophylaxis trials and 1 treatment trial (Hokusai-VTE Cancer). 15…”

“…The absolute differences in all clinical outcomes, including overall VTE, PE, DVT, MB, CRNMB, and mortality, were all within the 95% CI of previously reported outcomes from the meta-analysis at 6 months. 13 Minor variations in outcomes were likely driven by the inclusion of a drug nonadherence/discontinuation factor in the Markov model, which led to small attenuations of the absolute risk reductions of the primary outcomes. Over a lifetime, the intervention group had a mean total cost of $9899 per person, 6.51 life-years, and 4.79 QALYs.…”

Preventing Venous Thromboembolism in Ambulatory Patients with Cancer: A Narrative Review

“…A pooled analysis of the two studies has nevertheless been performed and showed a 6-month VTE risk reduction of 0.56 (95%CI 0.35-0.89) on DOACs, with a non-significant increase in major bleeding (1.96; 95%CI 0.80-4.82) [53]. In terms of absolute difference, this corresponded to a VTE risk reduction of 4% (95%CI 0.01-0.07, NNT 25) at the cost of a 1% (95%CI 0.0-0.02) increase (albeit statistically non-significant) in major bleeding (NNH 100).…”