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 [Internet]

INTRODUCTION The perioperative management of antiplatelet therapy for patients with coronary stents remains unclear. This review was requested to assess the evidence for the following key questions: METHODS Data Sources and Searches We conducted searches in PubMed, Web of Science, and Scopus from inception of each database to 12/17/2015. Study Selection Studies were included if: 1.) The patients underwent elective, non-cardiac surgery, either entirely or in the great majority of reported cases; 2.) The patients were post-percutaneous coronary intervention with stent placement; 3.) The article presents original data (eg, not a review, commentary, or duplicate publication using the same data as another included publication); 4.) The article reports major adverse cardiac events (MACE) as a composite or any of the individual components (such as stent closure) or bleeding outcomes; 5.) The details of the preoperative and perioperative antiplatelet therapy were presented in sufficient detail to identify outcomes by management strategy; and 6.) The article was published in the English language. We did not exclude studies based on the type of APT management (ie, all P2Y12 agents were eligible). Data Synthesis and Analysis Data extraction was completed in duplicate. Data abstracted included the study design and data sources, details of the patient and the stent type, preoperative and perioperative antiplatelet therapy, type of surgery, outcomes, and statistical methods used. RESULTS Results of Literature Search Our literature searches and reference mining identified 4,068 potentially relevant citations, of which 491 were included by at least one reviewer at the title screening stage. Of these, 100 abstracts were included and obtained as full-text publications. A total of 14 publications were identified that contributed as includes to our final sample. Summary of Results for Key Questions Key Question 1 Thirteen observational studies reported the details of preoperative APT, perioperative APT management, and outcomes, in sufficient detail to assess their association. The majority of studies were small, with less than 100 patients included, and the results were quite heterogeneous, with MACE rates and bleeding rates varying many-fold between studies reporting outcomes for the same combination of preoperative APT and perioperative management (such as preoperative dual antiplatelet therapy, holding both prior to surgery). In general, within studies the bleeding outcomes were reported at higher rates than the MACE outcomes. Key Question 2 Evidence for the impact of timing of discontinuation of APT consists 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 5 days versus some other strategy. Key Question 3 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. Key Question 4 One large VA study did not find any evidence that the type of APT was associated with differences in MACE outcomes. Key Question 5 Evidence for the impact of timing of resuming antiplatelet therapy was absent from the identified literature. DISCUSSION Key Findings and Strength of Evidence The overarching finding from this systematic review is that the available evidence regarding perioperative antiplatelet management in patients with cardiac stents undergoing non-emergent surgery is insufficient to conclusively guide clinical practice. The heterogeneity observed limited the ability to adequately assess the impact of APT management for the wide range of procedures. It is likely that factors other than the perioperative management of APT play a role in differences in bleeding and MACE rates observed between studies. The strength (or quality) of the evidence was insufficient for all key questions. Applicability Several studies specifically assessed Veterans, including the largest study. Even though the remaining studies were not in VA populations, we judged these results as being moderately or even strongly applicable to VA since the enrolled patients with cardiac stents were very likely to moderately or strongly resemble VA patients, except with respect to gender. Research Gaps/Future Research There is obviously a very large research gap, as we were unable to find evidence sufficient to reach conclusions for any of the key questions. 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. Conclusions 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 lacks 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 in part responsible for MACE 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.