The report is a product of the VA/HSR Evidence Synthesis Program.

Comparing Antithrombotic Strategies after Aortic Valve Replacement

The use of bioprosthetic (containing animal tissue) aortic valves placed surgically – and with a transcatheter approach is a common treatment for valvular heart disease. While most patients are treated with anticoagulant and/or antiplatelet therapy for a period of time after the procedure, the optimal antithrombotic regimen and duration after bioprosthetic aortic valve replacement (bAVR) is unclear, and both guideline recommendations and practice patterns vary significantly. This systematic review sought to summarize the comparative benefits and harms for various anticoagulation strategies following surgical or transcatheter implantation of a bioprosthetic aortic valve, and to determine whether effects differed according to thromboembolic risk profile or concomitant procedure.

Investigators with VA's Evidence-based Synthesis Program (ESP) Center in Portland, OR searched MEDLINE, PubMed, EMBASE, EMB Reviews, and grey literature (unpublished or published in non-commercial form) sources from database inception through January 2017, with a search for new/in-process citations in June 2017. They also examined the bibliographies of relevant articles to identify additional studies. After reviewing more than 4,500 titles and abstracts, ESP investigators included 23 primary studies reported in 22 publications, which included 4 randomized controlled trials (RCTs) and 11 cohort studies that compared antithrombotic strategies in bAVR patients, as well as 3 RCTs and 5 cohort studies assessing various antiplatelet and anticoagulation strategies in patients who have undergone a transcatheter aortic valve replacement (TAVR).

Summary of Findings
Moderate-strength evidence shows that the use of aspirin or warfarin after surgical bAVR is associated with similar effects on mortality, thromboembolic events and bleeding rates. Observational data suggest the combination of warfarin plus aspirin may be associated with lower mortality and thromboembolic events compared to aspirin alone after surgical bAVR, but the effect size is small and the combination is associated with a substantial increase in bleeding risk. Insufficient evidence was found for all other treatment comparisons in surgical bAVR.

There also was insufficient evidence to draw conclusions about the optimal anticoagulation strategy according to thromboembolic risk or receipt of concomitant procedures. In TAVR patients, the strategy of adding a second antiplatelet agent to aspirin for 3 to 6 months had similar effects as aspirin alone on mortality, stroke, and major cardiac events (moderate strength evidence), though use of aspirin alone was associated with a non-significantly lower rate of bleeding (low-strength evidence).

Current Practice and Clinical Outcomes in VA
In a companion project, ESP investigators partnered with PRISM QUERI to complete a retrospective cohort study to better understand practice patterns in the VA healthcare system, how practice differs across VA facilities, and to describe post-bAVR outcomes in VA patients. A detailed report explaining the study's methods and describing all findings can be found alongside this ESP report. In brief, the VA cohort study found:

• The number of bAVR procedures doubled between 2005 and 2015.
• Nearly half of all Veterans received aspirin alone, but practice patterns differed substantially across facilities. For example, the use of aspirin and warfarin together varied from 10% to about 70% of patients across facilities.
• There were clinical differences among groups of patients receiving different anticoagulation, but the variation in practice was not entirely attributable to comorbidities, i.e., atrial fibrillation.
• Outcomes in VA patients were similar to non-VA cohorts:
  • 90-day mortality after bAVR was 1.5%,
  • 90-day thromboembolism was 1.6%, and
  • 90-day major bleeding ranged 0.6 to 2.2% depending on the anticoagulation strategy.

Implications and Future Research
Event rates in most of the included studies were fairly low, and it is possible that the lack of difference reflects lack of power to detect a difference rather than true similarity in effect. However, given the low event rates and lack of demonstrable difference in available studies, it is reasonable to argue that the discovery of a significant effect in a large trial might have uncertain clinical importance, as the number of patients to treat to achieve benefit would likely be large and, as the available studies suggest, offset by the risk of bleeding seen with more aggressive anticoagulation strategies. Larger trials of TAVR are underway, and their findings may have a significant impact on clinical management.

**A cyberseminar session titled "Comparing Antithrombotic Strategies after Bioprosthetic Aortic Valve Replacement: A Systematic Review" will be held on Monday, May 21 from 1:00pm to 2:00pm (ET). Register for this session.**

Reference
Papak J, Chiovaro J, Noelck N, Healy L, Freeman M, Paynter R, Low A, Kondo K, McCarty O, Kansagara D. Comparing Antithrombotic Strategies after Bioprosthetic Aortic Valve Replacement: A Systematic Review. VA ESP Project #05-225; 2017.

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