Patients who undergo bioprosthetic aortic valve replacement surgery likely will benefit from anticoagulation therapy that is extended three months beyond the duration recommended in guidelines, researchers report in the Nov. 28 issue of the Journal of the American Medical Association. The results offer compelling evidence to change practice, according to the researchers and authors of a companion editorial.
Guidelines published by both the American College of Cardiology/American Heart Association and the European Society of Cardiology recommend that physicians prescribe warfarin treatment for three months after a patient is implanted with a bioprosthetic aortic valve to reduce the risk of thromboembolism. The well-known tradeoff is the increased risk of bleeding events.
“However, this recommendation is primarily based on results from one retrospective study with limited number of events hampered by the observational design as well as low power like all other studies within this scope,” wrote Charlotte Merie, MD, of Copenhagen University Hospital Gentofte in Denmark, and colleagues.
The authors of an accompanying editorial reiterated the paucity of clear evidence, and added that yet another set of guidelines from the American College of Chest Physicians calls for aspirin alone unless the patient has risk factors for thromboembolism, such as atrial fibrillation. “The differences in the guidelines highlight the lack of consensus regarding the role of anticoagulation therapy after bioprosthetic aortic valve implantation and underscore the need for more information,” wrote Shamir R. Mehta, MD, MSc, and Jeffrey I. Weitz, MD, both of McMaster University in Hamilton, Ontario.
Merie and colleagues used data from a variety of registries in Denmark, which are considered to be mostly complete and linkable. Their goal was to study whether discontinuing warfarin treatment after bioprosthetic aortic valve replacement surgery was associated with an increased risk of thromboembolic events, cardiovascular death and bleeding events. They identified 4,075 patients through a patient registry who had bioprosthetic aortic valve implantation surgery performed between 1997 and 2009 and who did not have atrial fibrillation. They also obtained comorbidity and medication data for these patients.
Primary endpoints included of thromboembolic incidences and cardiovascular death. For the analysis, Merie et al calculated and compared rates of the primary endpoint for the 3,186 patients who received warfarin and the 881 who did not. The analysis omitted events from the first 30 days after surgery to account for the lag in which patients picked up their prescribed medications.
Patients were followed for a mean 6.57 person-years. The mean age of the total group was 74.6 years and 41 percent were women.
They found that overall 8.9 percent of patients experienced stroke; 15.1 percent, a thromboembolic incident; and 8.9 percent, a bleeding incident. Thirty days post-surgery, 2.7 percent experienced a stroke, 5 percent a thromboembolic events and 1.8 percent a bleeding incident. Thirty-day mortality was 6 percent and one-year mortality was 10.9 percent.
Looking out to 90 to 180 days post-surgery, the researchers calculated the number needed to treat/number needed to harm and determined that for every 23 patients not treated with warfarin, one patient died from cardiovascular cause. For every 74 patients treated with warfarin, one patient experienced bleeding episodes requiring hospital admission.
“We demonstrated a clear benefit associated with warfarin during the initial three months after surgery, and furthermore our data suggest that extension of warfarin treatment to six months postoperatively may reduce the risk of cardiovascular death,” Merie and colleagues wrote.
They added that the results give weight to the need to review existing guidelines to consider whether anticoagulation therapy should be extended to six months after surgery, especially for patients with heightened risk of cardiovascular death. They wrote that follow-up monitoring for bleeding events could be ratcheted up as well, if warranted.
They acknowledged several limitations, including lack of information on international normalized ratios to assess patients’ time in the therapeutic range; questions concerning adherence; lack of information about bleeding events outside the hospital setting, which may lead to potential underestimates of bleeding events; the lack of clinical information in registries; and the potential for bias.
Editorial writers Mehta and Weitz also highlighted limitations but repeated that the results showed not only benefits from warfarin treatment at three months but beyond to six months. “Despite these limitations, this study provides important information that will likely change treatment approaches for patients undergoing implantation of a bioprosthetic aortic valve,” they wrote. “Warfarin probably will be used more frequently and likely for six months instead of for three months.”
Mehta and Weitz pointed out that other novel agents such as factor Xa inhibitors and direct thrombin inhibitors offer benefits such as convenience. They recommended that in the future these drugs be studied in patients who undergo valve replacement surgery as well.