The report is a product of the VA/HSR&D Evidence Synthesis Program.
Dual Antiplatelet Management in the Perioperative Period:
A Systematic Review
Takeaway: The evidence base is extremely thin to inform management strategies for dual antiplatelet therapy in the perioperative period.
Antiplatelet agents are central in the management of cardiovascular and cerebrovascular disease. Dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y12 antagonist (i.e., ticlopidine and clopidogrel) is protective against recurrent myocardial infarction, coronary stent thrombosis after percutaneous coronary intervention (PCI), and cerebrovascular ischemic events. However, the benefits of DAPT in terms of thromboembolic prevention must be weighed against bleeding risk. This balance is especially critical in patients undergoing both cardiac and non-cardiac surgery. Further, the optimal perioperative management of antiplatelet agents for patients on DAPT is not clear. These issues pose a particular challenge to clinicians who must consider the consequence of delaying surgery, the hazard of periprocedural bleeding, and the risk of thrombotic events in patients with known cardiovascular disease.
VA’s Evidence Synthesis Program (ESP) Center located at the VA Greater Los Angeles Healthcare System recently conducted a systematic review to examine evidence on the occurrence of major adverse events associated with continuing, suspending, or varying DAPT in the perioperative period. PubMed and Cochrane were searched for relevant articles from November 30, 2015 through May 16, 2021, and Embase was searched from January 1, 2016 through May 17, 2022. From 3,565 potentially relevant articles, investigators identified 66 publications, which included 18 observational studies that met inclusion criteria. Among the 18 included studies, the majority involved CABG (coronary artery bypass graft) surgery. No randomized clinical trials (RCTs) were identified, and no studies were judged to be at low risk of bias.
Summary of Findings
The most important finding from this review is how thin the evidence base is for this consequential decision that must be made many times every day at surgical centers around the country. The strongest signal, which was still judged as low certainty evidence, is that suspension of DAPT for more than two days prior to CABG surgery is associated with less bleeding, transfusions, and re-explorations, however, its association with other outcomes of interest, such as MACE (major adverse cardiac event), is uncertain.
All of the evidence examined for this review came from observational studies with methodologic limitations, chiefly the concern for confounding in patient selection for the different DAPT strategies. All study outcomes were judged to have serious limitations due to study design and execution issues. Further, although investigators found a signal that suspending DAPT therapy for >2 days was associated with less bleeding in CABG surgery, the clinical significance of this blood loss is uncertain, as the quantity of average blood loss across DAPT strategies amounted to <300 mL of blood. They also were unable to find any conclusive evidence about that strategy’s association with cardiac outcomes. Without this information, it is difficult to determine whether the risks of suspending DAPT therapy outweigh its benefits.
Implications for VA
This ESP review was conducted in response to a request from the Surgical Quality Improvement Program (VASQIP) in VA’s National Surgery Office to review the evidence on the occurrence of major adverse events associated with continuing, suspending, or varying dual antiplatelet therapy in the perioperative period. Findings from this review will be used to inform guidance on the management of DAPT in the perioperative period for Veterans undergoing major elective, urgent, or emergent surgeries.
In the absence of randomized trials of different DAPT strategies, it is left to observational studies of sufficient size and rigor to help provide evidence about major adverse events associated with continuing, suspending, or varying DAPT in the perioperative period. The attributes of such an observational study would include:
- A very large sample, to facilitate risk adjusting and support subgroup analyses;
- Periodic auditing of the accuracy of data collection;
- Multiple data sources from many institutions and surgical teams; and
- The ability for the collected data to be used to create standardized composite endpoints such as BARC (Bleeding Academic Research Consortium) and MACE.
One possible data source for such a study would be the VASQIP. It would be worth an exploratory assessment of whether there is sufficient variation in DAPT strategies among patients in the VASQIP database such that an analysis as outlined above is feasible. If the VASQIP data are unable to provide clinically useful conclusions regarding the above questions, the VA Corporate Data Warehouse (CDW) could be evaluated as another potential data source for an epidemiologic analysis, although this would likely require far more time in building and cleaning the data than VASQIP.
Shekelle P, Maggard-Gibbons M, Girgis MD, et al. Dual Antiplatelet Management in the Perioperative Period: A Systematic Review. Washington, DC: Evidence Synthesis Program, Health Services Research and Development Service, Office of Research and Development, Department of Veterans Affairs. VA ESP Project #05-226; 2023.
To view the full report, go to https://www.hsrd.research.va.gov/publications/esp/antiplatelet-mgt.cfm.
ESP is currently soliciting review topics from the broader VA community. Nominations will be accepted electronically using the online Topic Submission Form. If your topic is selected for a synthesis, you will be contacted by an ESP Center to refine the questions and determine a timeline for the report.
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