COPENHAGEN, Denmark — Patients who have had a bioprosthetic aortic valve implanted should receive anticoagulation with warfarin for six months after surgery, new epidemiological data suggest . The findings should inform current guidelines on this issue, which are muddled due to a lack of randomized trials in this area, say Dr Charlotte Mérie (Copenhagen University Hospital Gentofte, Denmark) and colleagues in their paper in the November 28, 2012 issue of the Journal of the American Medical Association.
"We have a very striking message here, and it is not to be overlooked when considering guidelines," Mérie told heartwire . Although she stresses that this type of study can point at strong associations only, rather than cause and effect, she notes the difficulty of performing randomized controlled trials in this area: "They need to be very large to investigate rare events such as stroke, and they are very costly."
In an accompanying editorial , Drs Shamir R Mehta and Jeffrey I Weitz (McMaster University, Hamilton, ON) say the study by Mérie and colleagues provides "important information to help clinicians understand the benefits and risks of warfarin use after bioprosthetic-valve implantation.
"Should all of these patients receive warfarin for three months, or even for six months, as the authors suggest? Although there are limitations to this study, the answer to both of these questions is yes. The rates of stroke and thromboembolic events in the first six months after bioprosthetic aortic-valve replacement are substantial. Use of warfarin was associated with a reduction in this risk and a reduction in cardiovascular mortality; the benefits are difficult to ignore," the editorialists state.
Warfarin appears to be "of benefit for three months after bioprosthetic-valve implantation, and its benefits appear to persist for up to six months."
Lack of Consensus on Role of Anticoagulation After Bioprosthetic Valve
Mehta and Weitz say that among the 170 000 patients who undergo surgical aortic-valve replacement annually in North America, the majority receive a bioprosthetic rather than a mechanical valve because they are elderly and frail and have comorbid conditions that put them at increased risk of bleeding with the prolonged anticoagulation required with a mechanical valve.
A three-month course of warfarin with or without concomitant aspirin is frequently given after bioprosthetic aortic-valve implantation because observational studies have suggested there is a risk of thromboembolism until the valve support structures are endothelialized, they explain. But although the rates of thromboembolism among those given warfarin or warfarin plus aspirin appear to be lower than the event rates for those given aspirin alone, warfarin is associated with more bleeding, and the trade-off between reduced thromboembolic events with warfarin and increased bleeding "remains uncertain," they point out.
This uncertainty has led to confusion in the current guidance on this issue. For example, the ACC/AHA guidelines recommend a three-month course of warfarin after bioprosthetic aortic-valve implantation and adjunctive aspirin. But the American College of Chest Physicians recommends aspirin alone unless there are other 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," they stress.
Discontinuing Warfarin Before Six Months Ups Cardiovascular Deaths
In the new study, using the Danish National Registry, Mérie and colleagues identified 4075 patients without AF who underwent bioprosthetic aortic-valve implantation between 1997 to 2009 and who were followed up for a median of 6.57 person-years.
The rates of stroke, other thromboembolic events, cardiovascular mortality, and bleeding among those who received warfarin (n=3186) were compared with rates among patients who were not given warfarin (n=881). Because few of the patients received aspirin alone, comparisons were performed independently of concomitant aspirin use.
At 30 days, 6% of patients had died, 2.7% had had a stroke, 5.0% had thromboembolic events, and 8.9% had a bleeding event. These findings "highlight that the first month after surgery represents a high-risk period," observe Mehta and Weitz. The events that occurred in the first month were not included in the analysis to ensure that all patients had an equal chance to obtain their prescriptions for antithrombotic drugs, they point out.
From days 30 to 89 after the valve-replacement surgery, patients taking warfarin had experienced 4.3 fewer strokes per 100 person-years (p=0.03), 9.1 fewer thromboembolic events per 100 person-years (p<0.001), and 27.9 fewer cardiovascular deaths per 100 person-years (p<0.001) than those not taking warfarin.
Between three and six months after surgery, those taking warfarin had 3.2 fewer thromboembolic events per 100 person-years (p=0.03) and 4.4 fewer cardiovascular deaths per 100 person-years (p=0.003) compared with those not taking warfarin; there was no difference in the rate of stroke.
There was weaker evidence for a benefit associated with warfarin use between six months and one year.
The authors found no significant differences in the rates of bleeding between three months and one year after surgery between patients taking warfarin and those not taking the drug. This is important when physicians are considering extending warfarin treatment further than the three months currently recommended in some guidelines, they say.
Mérie told heartwire : "The most important message of our study is that discontinuing warfarin treatment after bioprosthetic aortic-valve implantation seems to be associated with increased cardiovascular death for at least six months after surgery. This is quite different from what we have been thinking previously."
New guidelines should consider an extension of warfarin treatment to six months after surgery, "especially in patients with an increased risk of cardiovascular death," she and her colleagues conclude.
No Information on Adjunctive Aspirin, or Newer Anticoagulants
The editorialists point out that the study does not provide sufficient information to determine whether adjunctive aspirin is of benefit in this setting, nor does it inform on the efficacy of novel anticoagulants for this indication.
They note that a study is ongoing with dabigatran (Pradaxa, Boehringer Ingelheim) in patients with newly or previously implanted mechanical aortic valves. "Similar studies are needed in patients with bioprosthetic aortic valves and in those who undergo transcatheter aortic-valve replacement," they conclude.
Mérie reports no conflicts of interest; disclosures for the coauthors are listed in the paper. Mehta reports serving as a consultant for AstraZeneca, Eli Lilly, and Sanofi. Weitz reports serving as a consultant for Boehringer Ingelheim, Bayer, Pfizer, and Bristol-Myers Squibb.
Heartwire from Medscape © 2012 Medscape, LLC
Cite this: Warfarin for Six Months Should Be Norm for Bioprosthetic Aortic Valves - Medscape - Nov 27, 2012.