For patients with cancer, the oral blood thinner apixaban is at least as effective as dalteparin, a low–molecular-weight heparin given by injection, in preventing a repeat venous thromboembolism (VTE), with no excess in major bleeding events. These findings from the phase III Caravaggio study were presented by Agnelli et al at the American College of Cardiology's Annual Scientific Session (Abstract 406-09).

It is estimated that one in five blood clots occur in people with cancer. This population has a much higher risk of developing dangerous VTEs, including deep-vein thrombosis (DVT) and pulmonary embolism.

Experts say there are many reasons why people with cancer are more susceptible to clotting; for example, cancer itself can thicken the blood, and many cancer therapies and surgeries can inflame blood vessels and limit patients' movement so clots can form more easily.

Caravaggio Study

The aim of the Caravaggio study—the largest study to evaluate the treatment of VTE in the cancer setting—was to assess whether the direct oral anticoagulant apixaban is noninferior to subcutaneous dalteparin for preventing a recurrent VTE in people with cancer and to evaluate the risk of bleeding.

The trial enrolled 1,170 patients with a cancer-associated VTE at the time of diagnosis at 119 sites in nine European countries, Israel, and the United States. Participants were consecutively randomly assigned to receive the oral factor-Xa inhibitor apixaban at 10 mg twice daily for 7 days followed by 5 mg twice daily, or subcutaneous dalteparin at 200 units/kg once daily for 1 month followed by 150 units/kg once daily thereafter for a total of 6 months. The primary study outcome of recurrent VTE was confirmed by an independent adjudication committee unaware of the treatment patients received.

Enrolled patients were 68 years old on average. Pulmonary embolism with or without DVT was present in 55% of patients, while 45% had an isolated DVT. Most patients (80.3%) had symptoms suggestive of a blood clot, but 20% had unsuspected VTE that was found through imaging tests performed for reasons other than clinical suspicion of VTE.

Most patients (97%) in both the apixaban and dalteparin arms had active cancer at the time of enrollment; 94.3% of patients in the apixaban arm and 91% in the dalteparin arm had a solid tumor, of which 32.6% and 32.3% were located in the gastrointestinal tract. This was of interest to the investigators, given that major bleeding events from blood thinners often occur in the gastrointestinal tract.

Results

The data revealed that recurrent VTE occurred in 32 of 576 patients (5.6%) in the apixaban group and 46 of the 579 patients (7.9%) in the dalteparin group over 6 months of follow-up—a difference that was not statistically significant. Moreover, major bleeding events, as defined by International Society on Thrombosis and Haemostasis guidelines, were similar in the apixaban and dalteparin groups, occurring in 22 patients (3.8%) compared with 23 patients (4.0%), respectively. The proportion of patients who were free of a recurrent VTE, major bleeding events, and death during the study period was 73.3% in the apixaban group and 68.6% in the dalteparin group.

“VTE is a major cause of complications and death in these patients, and the high risk of recurrent blood clots and bleeding in patients with cancer make anticoagulant treatment challenging. Therefore, specific studies in these patients are necessary,” said lead study author Giancarlo Agnelli, MD, Professor of Internal Medicine at the University of Perugia, Italy. “Our data show that apixaban is at least as effective as dalteparin … without any excess in major bleeding, which is a common concern when giving blood thinners. These results should expand the proportion of patients with cancer-associated VTE who can be treated with oral apixaban, which is less cumbersome for patients because it's a pill, not a daily injection.”

Dr. Agnelli said that while previous studies have shown other direct oral anticoagulants (like edoxaban and rivaroxaban) to be as effective as low–molecular-weight heparin, there is a trade-off given the observed increase in bleeding, particularly in people with gastrointestinal cancers. He said, for this reason, the most recent guidelines, which have long recommended low–molecular-weight heparin for cancer-associated VTEs, added the use of these agents with the exception of patients with gastrointestinal cancers.

Dr. Agnelli said that in Caravaggio, apixaban was not associated with an increase in gastrointestinal bleeding compared to dalteparin; major gastrointestinal bleeding occurred in 1.9% of apixaban-treated and 1.7% of dalteparin-treated patients.

Dr. Agnelli also reported that apixaban was more effective than dalteparin at preventing recurrent VTE in patients younger than age 65. He and his and team will be conducting several subgroup analyses to determine if certain patients benefit more from one approach.

Disclosure: For full disclosures of the study authors, visit accscientificsession.acc.org.