Introduction: Thrombosis is the second leading cause of death in cancer patients and patients with APC are categorized as high-risk of developing venous thromboembolism (VTE). Many trials had failed to demonstrate improvement in survival with PATP. Despite decreasing VTE events, PATP in solid cancer patients is not routinely recommended. We conducted an updated meta- analysis of RCTs to determine the benefit and risk of PATP with low-molecular weight heparins (LMWH) and direct oral anticoagulants (DOAC) in patients with APC receiving chemotherapy.
Methods: We performed a comprehensive literature search using MEDLINE and EMBASE databases through June 30, 2019. The references of all potential studies were also reviewed for any additional relevant studies. The RCTs with reduction in VTE as a primary or secondary endpoint and the major bleeding (MB) as a safety outcome were incorporated in the analysis. The primary meta- analytic approach was a random effects model using the Mantel-Haenszel (MH) method. It was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q- statistic.
Results: A total of 1,013 patients with APC from two RCTs and a subgroup of another three RCTs were included in our meta-analysis. The prophylactic, intermediate and therapeutic doses of LMWH and prophylactic dose of DOAC (rivaroxaban) were used in the studies. The duration of LMWH and DOAC ranged from 3 to 6 months. The randomization ratio was 2 to 1 in PROTECHT study and 1 to 1 in all other studies. The I2statistic for heterogeneity was 60, suggesting some heterogeneity among RCTs. The VTE incidence was 28 (5.43%) in PATP group and 60 (12.07%) in control group with a RR of 0.44 (95% CI: 0.20 to 0.99, P = 0.05) and RD of -0.06 (95% CI: -0.11 to -0.01, P = 0.01). In fixed effects model, the pooled RR was 0.45 (95% CI: 0.29 to 0.70, P = 0.0003) and the absolute RD in VTE was -0.07 (95% CI: -0.10 to -0.03, P = 0.0002) with an estimate of the number needed to treat (NNT) of 15 to prevent one VTE event. MB events were reported in 9 (4.11%) patients in PATP group compared to 7 (3.27%) in control group according to an analysis of 2 RCTs. The pooled relative risk for MB was statistically non-significant at 1.25 (95% CI: 0.47 to 3.31, P = 0.65).
Conclusions: In our study, PATP in APC may statistically significantly decrease VTE events, approximately with relative risk reduction of 55% and a NNT of 15, without increasing MB events. Proper selection of patients who are high risk for VTE in outpatient setting is important. More RCTs are required to further define high risk subsets of APC patients receiving chemotherapy who may benefit from PATP.
Oo:Medical Education Speakers Network: Honoraria; Janssen and Janssen: Other: Research: site co-investigator .
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