Apixaban Linked to Large Reductions in Major Bleeding, Recurrent VTE in Active Cancer

Patients with cancer who took apixaban to prevent blood clots had a 37% reduction in major bleeding (MB) and a 39% reduction in recurrent venous thromboembolism (VTE) compared with low-molecular weight heparin (LMWH), according to data presented at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Florida. Apixaban also had large reductions in VTE (32%) relative to warfarin.¹

A subgroup analysis presented alongside the main study found that apixaban’s benefits relative to LMWH held up across different types of cancer regardless of the risk level they present for VTE.² Apixaban is sold as Eliquis by Bristol-Myers Squibb/Pfizer.

Patients with active cancer—for this study, defined as cancer diagnosis or treatment in the 6 months before or 30 days after a VTE diagnosis—have a 4 to 7 times greater risk of developing VTE. To gain more real-world evidence on the effectiveness and safety of LMWH compared with vitamin K antagonists (VKAs), which emerged in the last decade as a treatment of VTE, and non-VKA anticoagulants (NOACs), a team of researchers led by Alexander T. Cohen, MBBS, MSc, MD, evaluated the efficacy of apixaban, LMWH, and warfarin among patients with active cancer.

They examined 3 groups of patients who started treatment within 30 days of their first VTE: 3393 apixaban users, 6108 LMWH users, and 4585 warfarin users. The mean ages were 65, 64, and 64 years, respectively. To evaluate rates of MB, clinically relevant non-MB (CRNMB), and recurrent VTE, the patients were followed to the earliest of 1 of 6 time points: health plan disenrollment, death, index therapy discontinuation, switch to another anticoagulant, study end, or a maximum of 6 months.¹

The following results were reported:

• Apixaban had lower risks of MB, CRNMB, and recurrent VTE compared with LMWH, with a hazard ratio (HR) of 0.63 (95% CI: 0.47-0.86, P = .003) for MB, HR of 0.81 (95% CI: 0.70-0.94, P = .006) for CRNMB, and HR of 0.61 for recurrent VTE (95% CI: 0.47-0.81, P = .001).
• Apixaban had lower rates of recurrent VTE and modest reductions of MB and CRNMB compared with warfarin, with HR of 0.68 (95% CI: 0.52-0.90, P = .007) for recurrent VTE, and HR of 0.73 (95% CI: 0.53-1.0, P = 0.51) for MB and HR of 0.89 (95% CI: 0.77-1.04, P = 0.145) for CRNM.

“Real-world evidence analyses such as this have the potential to provide additional insights into complex patient populations such as those with VTE and active cancer,” Cohen said in a statement. “Results from these analyses are a welcomed addition to the growing body of data around recurrent VTE in patients with active cancer.”

In the second presentation, results from the subgroup analysis examined how apixaban affected recurrent VTE, MB, and CRNMB risk across different cancer types relative to warfarin and LMWN. Hematologic cancer, as well as those of the brain, pancreas, stomach, liver, lungs, and kidneys, are associated with higher risk of VTE. Researchers used the Khorana risk score based on cancer type, blood counts, and body mass index to evaluate risk level and assess the safety of each therapy based on cancer type. Patients were categorized as having a very high risk of VTE, high risk of VTE, or other.

Results from the same real-world data set as the first abstract showed that those taking apixaban had a lower risk of recurrent VTE compared with warfarin and a lower risk of MB, CRNMB and recurrent VTE compared with LMWH, consistent with the overall results. Researchers called for more studies to evaluate the role of anticoagulants in high-risk subgroups of VTE cancer patients.²

Besides risk of VTE, real-world evidence (RWE) can be evaluated for other factors. Asked if the patient data could be evaluated to see whether those with comorbidites had different responses, Danny Wiederker, HEOR team lead at Pfizer, said, “Comorbidities are always an important consideration in RWE given some may be important confounders that impact both the treatment decision and the outcomes of interest. That’s why the Pfizer/BMS Alliance leverages the best research practices recommended by organizations like the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) that look to adjust for both comorbidities and patient factors, like age, gender, etc., that may impact outcomes."

He said the study being presented ises the inverse probability of treatment weighting (IPTW) to adjust for confounding while including the broadest possible patient population.

“Our approach generally is to start with the broad population and then drill down into subgroups as we are also highly interested in better understanding in which patient populations there is even more unmet need and more opportunity to improve outcomes,” Wiederker said. “We have conducted the first subgroup analysis presented as the second oral presentation stratifying based on the risk of recurrent VTE level, but we also have interest in other subgroups and are exploring opportunities for additional analyses.”

References

1. Cohen AT, Keshishian A, Lee T, et al. Safety and effectiveness of apixaban, LMWH, and warfarin among venous thromboembolism patients with active cancer: a retrospective analysis using four US claims databases. Presented at: 61st American Society of Hematology Annual Meeting & Exposition; December 7-10, 2019; Orlando, Florida. Abstract 326. ash.confex.com/ash/2019/webprogram/Paper121769.html.

2. Cohen AT, Keshishian A, Lee T, et al. Safety and effectiveness of apixaban, LMWH and warfarin among venous thromboembolism (VTE) patients with active cancer: a subgroup analysis of VOTE risk scale. Presented at: 61 American Society of Hematology Annual Meeting & Exposition; December 7-10, 2019; Orlando, Florida. Abstract 327. ash.confex.com/ash/2019/webprogram/Paper126931.html