Recurrent venous thromboembolism (VTE) is uncommon but associated with poor short-term survival among patients with cancer-associated thrombosis on extended apixaban therapy after at least six months of anticoagulation treatment, according to a post-hoc analysis of the API-CAT trial published July 13 in Circulation.

The prospective, double-blind trial found that a reduced dose of apixaban (2.5 mg twice daily) was noninferior to a standard full dose (5.0 mg twice daily) for VTE prevention over an additional 12 months of treatment among patients with active cancer who had completed at least six months of anticoagulation treatment. The reduced dose regimen was associated with fewer clinically relevant bleeding events.

Of 1,766 patients randomized at a median of eight months after an index VTE, 42 patients had a recurrent VTE over 12 months, translating to a cumulative incidence of 2.5%, of which 1.5% was pulmonary embolism (PE) and 1.1% was deep vein thrombosis (DVT). Notably, the index event was PE for most patients (n=34, 81%), of those, 24 (57%) had incidental index PE.

In their analysis, Isabelle Mahé, MD, PhD, et al., found that the 12-month cumulative incidence of all-cause death was higher among patients with than without recurrent VTE (55% vs. 19%). The mortality rate was higher following recurrent PE, whether symptomatic (65%) or incidental (64%), than following DVT (37%).

Of the 42 patients who developed recurrent VTE, 21 (50%) died during follow-up. The median time from recurrent VTE to death was 24 days (interquartile range, 2-64 days), and most deaths were attributed to cancer progression (n=14).

"These findings support similar management of incidental and symptomatic VTE in cancer-associated thrombosis during extended therapy as for initial therapy," write the authors.

"The practical implications are clear: regardless of whether cancer-associated VTE is symptomatic or incidental, or if it is [DVT] or [PE], recurrent VTE is rare but extremely ominous," writes Philippe Gabriel Steg, MD, FACC, in an accompanying editorial. "Further work developing clinical care pathways is needed for this small but highly vulnerable patient subgroup."