Blood clot made of red blood cells, platelets and fibrin protein strands. Thrombus
Credit: Dr_Microbe/getty Images

Direct acting oral anticoagulants (DOACs) are more cost-effective than low molecular weight heparin (LMWH) injections for the treatment of cancer-associated thrombosis, shows a new study published in the Annals of Internal Medicine.

The findings “should help policymakers and clinicians with decision-making,” when considering the most suitable treatment for these patients, said corresponding author Shuchi Gulati, oncologist and assistant professor of Medicine at UC Davis Comprehensive Cancer Center in Sacramento.

She told Inside Precision Medicine that it is not entirely clear why patients with cancer are at increased risk for blood clots. “While mechanisms may overlap non-malignant situations, there are some unique cancer related pathways that may be involved. There is speculation that cancer may cause the activation of the coagulation cascade and platelets. In addition, treatments rendered for cancer may also further enhance this risk—again mechanisms are not very clear.”

Nonetheless, individuals who develop cancer-associated thrombosis are almost twice as likely to die as matched patients with cancer without venous thromboembolism (VTE). In addition, VTE has an economic impact on patients and the health care system, with one large population-based study, showing that total health care costs were approximately 80% higher in patients with cancer and VTE relative to those with cancer but no VTE ($74,959 vs $41,691).

Yet, treatment cost “is generally an issue not discussed in the guidelines,” said co-author Mark Eckman, professor emeritus of Clinical Medicine at the University of Cincinnati.

He explained that LMWH was the standard treatment for cancer-associated thrombosis until the development of DOACs in 2016. These drugs, commonly apixaban, edoxaban, and rivaroxaban, now provide a non-inferior alternative first-line treatment and are recommended, alongside LMWH, by major guideline organizations such as The International Initiative on Thrombosis and Cancer, the American College of Chest Physicians, and the American Society of Hematology.

Eckman noted that “the costs of anticoagulants can be quite high. When the differences in efficacy and risks between agents is small, cost and cost-effectiveness become very important in decision-making.”

To explore differences in cost-effectiveness of these agents, Gulati and Eckman constructed a computer model that simulates major health events that happen over time to a cohort of patients with cancer who have experienced a blood clot. These events included recurrent pulmonary emboli, recurring deep-vein thrombosis without pulmonary emboli, major bleeds, and clinically relevant non-major bleeds as well as mortality. Then, over the course of the lifetime of the patient cohort, the study examined the accumulating lifetime costs and lifetime effectiveness measured in a metric called quality-adjusted life years (QALYs).

“QALYs are basically years lived by the members of the cohort but adjusted for the quality of life in the different health states they experience over that time,” Gulati said. “If you were to have a recurrent blood clot or a major bleed for instance, you would have a decrease in your quality of life.”

In the base-case analysis, which used the cost of drugs purchased from the U.S. Department of Veterans Affairs Federal Supply Schedule (VA-FSS), apixaban was found to be more effective and less costly than either the LMWH enoxaparin or edoxaban, whereas rivaroxaban was not cost-effective.

However, because drug costs noted in the VA-FSS may not be reflective of real-world costs to patients, the researchers conducted a second analysis using the average costs of enoxaparin and the three DOACs from the major pharmacies as reported in GoodRx, a free online service that provides drug coupons for discounts on medications.

In this scenario, if decision makers were unwilling to spend more than $50,000 per QALY, edoxaban was favored, and using the contemporary threshold for societal willingness to pay, rivaroxaban was cost-effective, with an incremental cost-effectiveness ratio of just more than $50,000 per QALY.

The two analyses also showed “a stark difference in the cost-effectiveness between the VA-FSS setting and the real-world setting, and this could have implications for value-based price benchmarks in the United States,” the researchers write.

Specifically, rivaroxaban had an incremental cost-effectiveness ratio (ICER) of $493,246 per QALY in the base case analysis, compared with $50,053 per QALY in the analysis using average prices from GoodRx.

“This large difference is due to a couple of factors,” said Eckman. “First, the cost difference for apixaban in the federal system ($90.45/month) and GoodRx ($548.22/month) is tremendous. In addition, apixaban is much less costly than rivaroxaban using the VA-FSS cost data ($90.45 vs $342.30/month). This is important because in the analysis using the VA-FSS costs, the ICER for rivaroxaban is being calculated vs apixaban, resulting in a very large ICER of $493,246 for rivaroxaban.”

He continued: “In the real-world analysis using drug prices from GoodRx, the ICER for rivaroxaban is being calculated against edoxaban instead of apixaban, due to the phenomenon of extended dominance, resulting in a lower ICER for rivaroxaban.”

“Most importantly, all the DOACs are more effective and have a better side-effect profile than low molecular weight heparin,” Eckman concluded. “Which of those is the most cost-effective is going to depend for any given patient on what the cost of those drugs will be for them. That decision can be one that is made in concert with the oncologist and the patient.”

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