Three months of warfarin is the usual standard of care following bioprosthetic aortic valve replacement (AVR), although the supporting evidence base for this practice is limited. Now a large new registry study published in JAMA suggests that more prolonged warfarin therapy may be beneficial.
Danish researchers identified 4,075 patients who underwent bioprosthetic AVR. As expected, warfarin treatment between 30 and 90 days after AVR was associated with significant reductions in stroke, thromboembolic events and cardiovascular deaths compared with patients not taking warfarin. The benefits continued between 3 and 6 months, though the reduction in stroke was no longer statistically significant. The authors calculated that for every 23 patients not being treated with warfarin between 3 and 6 months, there was one additional cardiovascular death, at a cost of 1 bleeding complication requiring hospital admission for every 74 patients.
“With no randomized trials to guide the length of warfarin treatment, our results call for a review of guidelines in the field to consider an extension of the treatment to 6 months after surgery, especially in patients with an increased risk of cardiovascular death,” the authors wrote.
In an accompanying editorial, Shamir Mehta and Jeffrey Weitz write that, despite the limitations of an observational study, the results support a change in clinical practice in favor of prolonged warfarin therapy for as long as 6 months. They observe that the trial does not provide information about the possible role for the newer oral anticoagulants or about the role of adjunctive aspirin.
Here is the press release from JAMA:
Anticoagulation Treatment For Longer Than Three Months After Aortic Valve Replacement Associated With Decreased Risk of Cardiovascular Death
CHICAGO – Although current guidelines recommend 3 months of anticoagulation treatment after bioprosthetic aortic valve replacement surgery, a study that included more than 4,000 patients found that patients who had warfarin therapy continued between 3 and 6 months after surgery had a lower rate of cardiovascular death, according to a study in the November 28 issue of JAMA.
“Biological prostheses are preferred to mechanical valves for aortic valve replacement (AVR) surgery in elderly patients older than 65 years because of shorter life expectancy and lack of a need to use anticoagulation treatment in the long-term. Especially in these patients, the tradeoff between thromboembolic complications due to the valve implant and bleeding events as adverse effects from anticoagulation therapy must be balanced. Nevertheless, appropriate duration of anticoagulation treatment postoperatively is yet to be established because the risk of complications when the treatment is discontinued is unknown,” according to background information in the article. The current recommendation of 3 months of warfarin treatment after bioprosthetic AVR surgery is primarily based on results from 1 retrospective study with a limited number of events.
Charlotte Merie, M.D., of the Copenhagen University Hospital Gentofte, Copenhagen, Denmark and colleagues investigated whether discontinuation of warfarin treatment within prespecified periods after bioprosthetic AVR surgery was associated with increased risk of thromboembolic complications, cardiovascular death, and bleeding incidents. Through a search in the Danish National Patient Registry, 4,075 patients were identified who had bioprosthetic AVR surgery performed between January 1997 and December 2009. The researchers determined the incidence rate ratios (IRRs) of strokes, thromboembolic events, cardiovascular deaths, and bleeding incidents by discontinuing warfarin as opposed to continued treatment at 30 to 89 days, 90 to 179 days, 180 to 364 days, 365 to 729 days, and at least 730 days after surgery. Average age of the patients was 75 years; 41 percent were women.
Overall, 361 patients (8.9 percent) experienced a stroke, 615 (15.1 percent) had a thromboembolic event, and 364 (8.9 percent) encountered a bleeding incident after the date of surgery. During the observation period, 1,156 patients (28.4 percent) died, with 879 (76.0 percent) of these deaths related to cardiovascular disease. The IRRs for patients not treated with warfarin compared with those treated with warfarin were 2.46 for stroke; 2.93 for thromboembolic events; 2.32 for bleeding incidents; and 7.61for cardiovascular deaths within 30 to 89 days after surgery; and 3.51 for cardiovascular deaths within 90 to 179 days after surgery.
“Our study demonstrates that discontinuing warfarin therapy within the first 3 months after surgery is associated with a significant increase in the risk of stroke, thromboembolic complications, and cardiovascular death. The novelty of our study is the finding that discontinuing warfarin therapy within 90 to 179 days after surgery is associated with a significant increase in the risk of cardiovascular death,” the authors write.
“International guidelines on anticoagulation after a bioprosthetic AVR have been written with limited data on the appropriate duration of warfarin treatment after surgery. Consequently, our study challenges current guidelines on the duration of antithrombotic treatment after AVR surgery with biological valves by presenting results suggesting that these patients will gain from an additional 3 months of warfarin treatment in terms of reduced cardiovascular death without risking a significant increase in bleeding events.”
Editor’s Note: This work was supported by the Research Fund of the Department of Cardiology at Copenhagen University Hospital Gentofte, Gentofte, Denmark. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.