Use of the anticoagulant warfarin may protect against a broad range of cancers in people over age 50, according to a large observational study from Norway[1].
"We were surprised first by the breadth of the cancer-protective association, and second that this association was stronger in our subgroup analysis of patients taking warfarin for abnormal heart rhythms (atrial fibrillation or flutter)," Dr James B Lorens (University of Bergen, Norway) told theheart.org | Medscape Cardiology.
The findings "could have important implications for the selection of medications for patients needing anticoagulation," the researchers say.
The study was published online November 6, 2017 in JAMA Internal Medicine.
Implications for Switch to NOACS?
Among about 1.25 million adults aged 52 to 82 years identified in Norwegian national registries, 92,942 (7.4%) were classified as warfarin users and about 1.1 million were warfarin nonusers. Warfarin use was defined as taking at least 6 months of a warfarin prescription and at least 2 years from first prescription to any cancer diagnosis.
During the 7-year observation period, 132,687 participants (10.6%) were diagnosed with cancer. Compared with nonusers of warfarin, users of warfarin had significantly lower age- and sex-adjusted rates of all cancers and of cancer of the lung, prostate, and breast, but not the colon.
Incidence Rate Ratio of Cancer in Warfarin Users vs Nonusers
| Cancer site | IRR (95% CI) |
|---|---|
| All cancers | 0.84 (0.82–0.86) |
| Prostate | 0.69 (0.65–0.72) |
| Lung | 0.80 (0.75–0.86) |
| Breast | 0.90 (0.82–1.00) |
| Colon | 0.99 (0.93–1.06) |
A subgroup analysis of patients with atrial fibrillation or flutter showed significantly lower rates of cancer overall (IRR 0.62; 95% CI 0.59–0.65) and cancer of the lung (IRR 0.39, 95% CI 0.33–0.46), prostate (IRR 0.60, 95% CI 0.55–0.66), breast (0.72, 95% CI 0.59–0.87) and colon (IRR 0.71, 95% CI 0.63–0.81).
The association between warfarin use and lower cancer incidence in this subgroup was "stronger compared with that in groups in the main analysis," the researchers report.
They note that the "well-known challenges of warfarin dosing that necessitate regular monitoring have fueled a transition to new oral anticoagulants. An unintended consequence of this switch to new oral anticoagulants may be an increased incidence of cancer, which is an important consideration for public health," the authors write.
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Lorens cautioned that this was a large observational study using data from Norwegian national registries, which can't prove a cause-and-effect relationship, and there are significant limitations.
"However, preclinical studies show that warfarin has antitumor activity at doses that do not inhibit coagulation. This suggests that the antitumor effects of warfarin are not related to anticoagulation but rather are due to the vitamin K antagonist mechanism of action. We and others have shown in experimental cancer models that warfarin inhibits the activity of a receptor (AXL) found on tumor and immune cells. Studies are ongoing to better understand this mechanism," Lorens said.
"Important Study, Rigorous and Impactful"
"This is a very important study, rigorous and impactful," Dr Rolf A Brekken (UT Southwestern, Dallas), told theheart.org | Medscape Cardiology. "The team did a really nice job of breaking down the effect of warfarin on cancer incidence in the population. There are some confounders to the study; for instance . . . it is likely that this cohort of patients probably are not smokers, so that would also affect cancer incidence," he said.
"However, the data are a strong indicator that warfarin reduces cancer development," Brekken said, "and support preclinical work from my group that warfarin inhibits cancer metastasis in an AXL-dependent manner."
Brekken noted that his group and others have shown that low-dose warfarin doses that do not affect coagulation are capable of inhibiting AXL.
"This is exciting, as it suggests that you treat cancer patients with a low dose of warfarin, thereby reducing worries about toxicity, and have an anticancer benefit. This of course needs to be investigated in a clinical trial. Hopefully this will happen soon," Brekken said.
The study had no specific funding. Lorens reported ownership interest in BerGenBio ASA, which is developing AXL inhibitors. No other disclosures were reported.
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