To perform a systematic review and network meta-analysis evaluating the efficacy and safety of low-molecular-weight heparins (LMWHs), vitamin K antagonists (VKAs), and direct-acting oral anticoagulants (DOACs) for the treatment of cancer-associated thrombosis (CAT). We searched MEDLINE, Cochrane Central Register of Controlled Trials, and conference abstracts through March 2018. Randomized controlled trials (RCTs) enrolling adults with CAT comparing 2 or more full-dose anticoagulants (LMWH, VKA, and DOAC) and evaluating recurrent venous thromboembolism (VTE), major bleeding, and/or all-cause mortality were included. Reviewers identified studies, extracted data, and assessed the quality of the evidence in duplicate. A frequentist network meta-analysis, which uses direct and indirect evidence to simultaneously compare multiple interventions, was performed using a random-effects approach. Results are reported as pooled relative risks (RRs) with 95% confidence intervals (CIs). We included 13 RCTs (n = 6292): 7 compared LMWHs with VKAs, 4 compared DOACs with VKAs, and 2 compared DOACs with LMWHs. The risk of recurrent VTE was significantly reduced by 28% and 54% with a DOAC compared to an LMWH and a VKA, respectively. Low-molecular-weight heparins significantly reduced the risk of recurrent VTE by 36% versus VKAs. The risk of major bleeding was 14% higher with DOACs compared to LMWHs and 15% and 25% lower with DOACs and LMWHs versus VKAs, although 95% CIs included unity for each. The risk of all-cause mortality appeared similar for all 3 comparisons (RR = 1.0 for each comparison). Direct-acting oral anticoagulants appeared superior in reducing recurrent VTE in patients with CAT compared to LMWH and VKAs, but an increased risk of major bleeding versus LMWH cannot be ruled out.

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The objective of this study was to evaluate the electrocardiographic effects of hawthorn in healthy adult volunteers. It was double-blind cross-over trial randomized 20 healthy adult volunteers to receive either a single oral 160-mg dose of hawthorn or matching placebo. Triplicate 12-lead electrocardiograms were taken before treatment and at 1-, 2-, 4-, and 6-hr post-dose. Following at least a 7-day washout period, participants were crossed over to the opposing treatment arm and had the measurements repeated. The primary endpoint was the change in corrected (Fridericia) QT intervals (QT I) at 4 and 6 hr. Maximum post-dose QT I and changes in PR and QRS intervals were measured. No significant differences in 4- or 6-hr QT I were seen between hawthorn and placebo. Maximum post-dose QT I in the hawthorn and placebo groups were similar (346 ± 35 vs 346 ± 40 ms; p = .979). No significant adverse events were seen. In conclusion, a single dose of oral hawthorn had no effect on electrocardiographic parameters in healthy volunteers.