P569Efficacy and safety of direct Xa oral inhibitors versus warfarin in patients with atrial fibrillation and cancer: a meta-analysis of randomized controlled trials
Authors: Casula M , Fortuni F , Fabris F , Leonardi S , Gnecchi M , Greco A , Sanzo A , Rordorf R 
Published: June 2020

Background

Patients with cancer are at higher risk of atrial fibrillation (AF) compared with the general population. Furthermore, cancer per se and anti-cancer treatments have been associated with thromboembolic complications and increased bleeding risk. Considering that only 12% of cancer patients can achieve a stable International Normalized Ratio target and the frequent need for invasive procedures, warfarin is not an ideal option. Direct oral anticoagulants may theoretically represent a valid alternative although their use in this population has been scarcely investigated.

Purpose

To compare efficacy and safety of direct oral Xa inhibitors (DOXaI) versus warfarin in patients with atrial fibrillation and cancer.

Methods

We searched electronic databases for randomized controlled trials (RCTs) that analyzed the use of DOXaI versus warfarin in patients with AF and cancer. The primary efficacy outcome was stroke or systemic embolism (SE). The secondary efficacy outcomes were ischemic stroke, myocardial infarction and all-cause death. The primary safety outcome was major bleeding; secondary safety outcomes were major or clinically relevant non-major bleeding, intracranial bleeding and any bleeding. The net clinical benefit was estimated as the composite of the two primary outcomes. A sensitivity analysis was performed to better define the incidence of these outcomes in patients with active cancer. The statistical software ProMeta 3 was used to estimate the risk ratio with a random-effect model.

Results

3 RCTs counting a total of 3029 cancer patients (1682 on DOXaI and 1347 on warfarin), 1354  of whom with active cancer (856 on DOXaI and 502 on warfarin), were included in the analysis. Mean age was 75.6 ± 1.2 years, and 32% were female. Mean follow-up period was 2.2 ± 0.6 years. The most common cancer sites were prostate (23%), gastrointestinal tract (22.2%), breast (12.1%) and genitourinary tract (10.6%). The mean CHADS2 score was 2.9 ± 0.6 and the mean HAS-BLED score was 2.6 ± 0.4.

There were no significant differences in the risk of stroke or SE (RR 0.76; 95% CI 0.52-1.10) as well as for all the other secondary efficacy outcomes. DOXaI significantly reduced the incidence of major bleeding in the overall cancer population (RR 0.79; 95% CI 0.63-0.99; p = 0.039); this finding was consistent also in patients with active cancer (RR 0.79; 95% CI 0.59-1.05) although the effect was not statistically significant.  DOXaI also significantly reduced intracranial bleeding in overall cancer population (RR 0.12; 95% CI 0.02-0.63; p = 0.013) and any bleeding in active cancer patients (RR 0.87; 95% CI 0.77-0.98; p = 0.026). Furthermore, DOXaI significantly reduced the composite endpoints of major bleeding and stroke or SE in overall cancer population (RR 0.78; 95% CI 0.64-0.94; p = 0.008).

Conclusions

Our metanalysis shows that, in patients with atrial fibrillation and cancer, DOXaI are safer and have a similar efficacy compared with warfarin.

Abstract Figure. Primary efficacy and safety outcomes