SAN DIEGO -- Patients diagnosed with chronic obstructive pulmonary disease (COPD) patients taking vitamin K antagonists (VKAs) such as warfarin for prevention of blood clots and strokes seemed to be at a greater risk of mortality than COPD patients not on oral anti-coagulants, researchers said here.
The corrected hazard ratio of mortality was significantly higher in COPD patients using VKAs compared with those who did not (HR 1.533, 95% CI 1.344-1.748, P<0.0005), reported Ianthe Piscaer, MD, of Maastricht University Medical Center in the Netherlands, and colleagues.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
In addition, age, male gender, cardiovascular disease, and diabetes were significantly associated with mortality, they reported at the American Thoracic Society annual meeting.
"Our work suggests that the combination of vitamin K antagonists can be harmful in people with COPD," Piscaer told ľֱ. "It is plausible that the underlying pathogenic mechanism are stimulation of both elastin degradation and vascular calcification by vitamin K antagonists."
While Piscaer cautioned that "our present results are currently insufficient to issue a negative advice against the use of vitamin K antagonists in patients with COPD, the [findings] should not be neglected and deserve further investigations."
Steven Lommatzsch, MD, of the National Jewish Hospital/University of Colorado Denver, agreed. He told ľֱ that the findings were interesting but "I wouldn't change anything about my practice based on this single study. It is still way too early to make recommendations."
Piscaer's group retrospectively reviewed the records of 31,137 COPD patients at Canisius-Wilhelmina Hospital in (Nijmegen, the Netherlands) from January 2018 to April 2017. Of those, 4,184 COPD patients (53.8% men; mean age 69.8) were included, and 1,013 COPD patients used VKAs while 3,171 did not.
Almost all of the patients (97%) treated with vitamin K antagonists were diagnosed with cardiovascular disease versus 61% of those not on vitamin K antagonists. Also, about 32% of the patients on vitamin K antagonists were diagnosed with diabetes versus 16% of those who were not.
The mean follow-up time was 4.4 years for the non-VKA users and 3.3 years for the VKA users. During the study period, 22.1% of non-VKA users and 41.6% of VKA users died.
The researchers suggested that interaction between medication and the disease process might be responsible for the higher mortality risk.
"Elastin degradation is accelerated in COPD patients and is related to mortality," they wrote. "Vascular calcification is also enhanced and inversely related to survival in COPD. Matrix Gla protein is a Vitamin-K dependent inhibitor of arterial calcification and elastin degradation. Vitamin K antagonists inhibit Vitamin K recycling, thereby inducing Vitamin K deficiency leading to insufficient Matrix Gla protein activation, and, consequently promotion of both arterial calcification and elastin degradation."
Lommatzsch, who was not involved in the study, said the researchers need "to drill down ... and find out why this is this trend." He added that that knowing the cause of death in the patients -- "was it bleeding or something else?" -- could help identify why there is a relationship between vitamin K antagonists and higher mortality.
"I would wait for more publications on this situation before I would take a well-controlled patient off vitamin K therapy," he said.
Disclosures
Piscaer disclosed no relevant relationships with industry.
Lommatzsch disclosed relevant relationships with AstraZeneca.
Primary Source
American Thoracic Society
Piscaer I, et al "Use of vitamin K antagonists is associated with increased mortality in chronic obstructive pulmonary disease" ATS 2018; Abstract A4234.