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

Management of Antiplatelet Therapy among Patients with Coronary or Cerebrovascular Disease: A Systematic Review

The perioperative management of antiplatelet therapy (APT) for patients with coronary stents remains unclear. Patients who have coronary stents placed are at risk of stent thrombosis and, therefore, are nearly all recommended to receive prolonged antiplatelet therapy: dual antiplatelet therapy (aspirin plus a P2Y12 inhibitor) followed by indefinite single antiplatelet therapy (almost always aspirin). Historically, clopidogrel and aspirin have been prescribed; however, the use of newer agents (i.e., ticagrelor and prasugrel) is increasing. Patients undergoing non-cardiac surgery with a prior history of percutaneous coronary intervention (PCI) and placement of coronary stents or balloon angioplasty are at increased risk of perioperative cardiac events. The risk of perioperative adverse events (i.e., major adverse cardiac event, bleeding) is associated with time from PCI, operative urgency, and antiplatelet therapy.

Current guidelines from the American College of Cardiology (ACC) and American Heart Association (AHA) recommend elective non-cardiac surgery be delayed one year after drug-eluting stent placement, and 30 days after bare metal stent placement. When considering urgent non-cardiac operative intervention, ACC/AHA recommendations are to continue dual antiplatelet therapy in the perioperative period for four to six weeks after PCI, unless the risks of bleeding outweigh the risks of stent thrombosis.

To help clinicians, patients, and policymakers with this important decision, investigators with VA's Evidence-based Synthesis Program Center located at the West Los Angeles VA Medical Center conducted a systematic review of the literature (PubMed, Web of Science, and Scopus) from inception to December 17, 2015. From more than 4,000 citations, 14 publications (several studies, including the largest, specifically assessed Veterans) were used to answer the following key questions.

• What are the risks and benefits of APT in the perioperative period after PCI?
• Do the risks and benefits vary by timing of discontinuation and resumption of APT?
• Do the risks and benefits vary by operative intervention, or do they vary by type of APT?

Summary of Review
Published studies of the association between perioperative APT management and outcomes in patients with coronary stents undergoing non-emergent surgery have challenging methodologic limitations and heterogeneous results, and do not provide sufficient evidence to moderately or strongly support any clinical recommendation. This heterogeneity, combined with small sample sizes, limits the ability to assess the impact of the different aspects of APT: timing of cessation, bridging, restarting therapy, and type of APT. Additionally, the varied range of invasiveness of the procedure – from skin excisions to major thoracic cases – contributes to the operative bleeding risk and MACE risk, yet many studies lack sufficient detail to assess the impact of procedure on the outcomes. The results also suggest that clinical factors other than perioperative APT management may be partly responsible for MACE (all-cause mortality, myocardial infarction, or coronary revascularization) and bleeding outcomes. It is likely that a clinical trial of large size would be needed to more definitely provide evidence about this clinical decision. Specific findings include:

• Eleven observational studies reported the details of preoperative APT, perioperative APT management, and outcomes, in sufficient detail to assess their association. However, the majority of studies were small (less than 100 patients), and the results were heterogeneous, with MACE rates and bleeding rates varying many-fold between studies reporting outcomes for the same combination of preoperative APT and perioperative management.
• Evidence for the impact of timing of APT discontinuation consisted of very small case reports within larger studies, and demonstrated no identifiable trend. In one VA case control study, there was no association between stopping dual APT for at least five days versus some other strategy.
• Few studies reported results stratified by type of surgical procedure, and among those that did there was no clear signal of differences in outcomes depending on perioperative APT strategy.
• One large VA study did not find any evidence that the type of APT (single or dual) was associated with differences in MACE outcomes.
• Evidence for the impact of timing of resuming APT following a surgical procedure was absent from the identified literature.

Future Research
There is a very large research gap, as investigators were unable to find evidence sufficient to reach conclusions for any of the key questions. This is particularly notable, as it is not uncommon for patients on APT following cardiac stent placement to require elective operations and the optimal management is unclear. The evidence does suggest that differences in outcomes due to perioperative antiplatelet management are likely to be smaller than differences in outcomes due to other clinical factors. This suggests that definitive answers to these questions are going to require clinical trials, and since the differences in outcomes are likely to be small, the trials must be very large, on the order of many hundreds or even >1000 patients in each arm of the trial.

Reference
Maggard Gibbons M, Ulloa JG, Macqueen I, Childers CP, Miake-Lye IM, Shanman R, Beroes JM, Shekelle PG. Management of Antiplatelet Therapy among Patients on Antiplatelet Therapy for Coronary or Cerebrovascular Disease or with Prior Percutaneous Cardiac Interventions Undergoing Elective Surgery: A Systematic Review. VA ESP Project #05-226; 2017.

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This report is a product of VA/HSR&D's Quality Enhancement Research Initiative's (QUERI) Evidence-Based Synthesis Program (ESP), which was established to provide timely and accurate synthesis of targeted healthcare topics of particular importance to VA managers and policymakers – and to disseminate these reports throughout VA.

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