BACKGROUND: Guideline-recommended strategies to interrupt chronic anticoagulation with warfarin or direct oral anticoagulants (DOAC) during the perioperative period of cardiac implantable electronic device (CIED) surgery differ worldwide. There is uncertainty concerning the benefits and harms of interrupted and uninterrupted anticoagulation in patients undergoing CIED surgery. OBJECTIVES: To assess the benefits and harms of interrupted anticoagulation (IAC) with either warfarin or DOAC in the perioperative period of CIED surgery versus uninterrupted anticoagulation (UAC), with or without heparin bridging, during an equivalent time frame, for CIED surgery. SEARCH METHODS: CENTRAL, MEDLINE, Embase, Web of Science, and two trials registers were searched on 26 November 2021 together with reference checking, citation searching and contact with study authors to identify additional studies. We plan to update this review imminently. SELECTION CRITERIA: We included randomized controlled trials (RCTs) evaluating IAC vs. UAC in adults with a diagnosed cardiac rhythm disorder, who underwent elective CIED surgery and received at least one month of warfarin or DOAC anticoagulation. Comparisons of interest were: (1) continued warfarin vs. interrupted warfarin anticoagulation, with or without heparin bridging
and (2) continued DOAC (apixaban, betrixaban, dabigatran, edoxaban, or rivaroxaban) vs. interrupted DOAC, with or without heparin bridging. DATA COLLECTION AND ANALYSIS: Primary outcomes were composite thromboembolic events (transient ischemic attack, ischemic stroke, deep vein thrombosis, pulmonary embolism, peripheral embolism, or valve thrombosis) and device-pocket hematoma. Secondary outcomes included individual components of composite thromboembolic events, composite bleeding events, all-cause mortality, adverse events, quality of life and days of hospitalization. Two authors independently selected studies, extracted data, and assessed the risk of bias. We assessed the certainty of evidence using GRADE. The inverse variance random-effects model was used for meta-analyses, and the DerSimonian and Laird method was used for calculating the between-study variance Tau MAIN RESULTS: We identified 10 eligible studies (2221 participants), of which one is ongoing. Of these 10 studies, six compared IAC vs. UAC with warfarin (1267 participants) and four compared IAC vs. UAC with DOAC (954 participants). Follow-up duration ranged between 0.5 to three months. The mean age of participants ranged from 68 to 76 years. Definitions of thromboembolic events, device-pocket hematoma, and bleeding events varied across studies. IAC vs. UAC with warfarin IAC with warfarin may result in little to no difference in composite thromboembolic events (RR 0.85, 95% CI 0.18 to 4.11
5 RCTs, n = 1266
low-certainty evidence). The evidence is very uncertain about the effect of IAC on device-pocket hematoma (RR 1.87, 95% CI 0.83 to 4.22
5 RCTs, n = 1266
very low-certainty evidence), ischemic stroke (RR 0.70, 95% CI 0.11 to 4.40
5 RCTs, n = 1266
very low-certainty evidence) and composite bleeding events (RR 1.92, 95% CI 0.84 to 4.43
5 RCTs, very low-certainty evidence). IAC with warfarin likely results in little to no difference in deep vein thrombosis or pulmonary embolism (0 events in both groups
2 RCTs, n = 782
moderate-certainty evidence). IAC may result in a slight reduction of all-cause mortality (RR 0.35, 95% CI 0.04 to 2.93
3 RCTs, n = 953
low-certainty evidence). IAC vs. UAC with DOAC IAC with DOAC may result in little to no difference in composite thromboembolic events (RR 0.98, 95% CI 0.06 to 15.63
3 RCTs, n = 843
low-certainty evidence) and ischemic stroke (RR 0.98, 95% CI 0.06 to 15.63, 2 RCTs, n = 763
low-certainty evidence). The evidence is very uncertain about the effect of IAC with DOAC on device-pocket hematoma (RR 1.07, 95% CI 0.55 to 2.11
4 RCTs, n = 954
very low-certainty evidence) and composite bleeding events (RR 1.07, 95% CI 0.55 to 2.06
4 RCTs, n = 954
very low-certainty evidence). IAC may result in little to no difference in ischemic stroke (RR 0.98, 95% CI 0.06 to 15.63, 2 RCTs, low-certainty evidence). IAC likely results in little to no difference in deep vein thrombosis or pulmonary embolism (0 events in both groups
2 RCTs, n = 763
moderate-certainty evidence). IAC may result in a slight reduction of all-cause mortality (RR 0.49, 95% CI 0.04 to 5.39
2 RCTs, n = 763
low-certainty evidence). AUTHORS' CONCLUSIONS: Interrupted anticoagulation in people undergoing elective CIED surgery had similar outcomes to uninterrupted anticoagulation with either warfarin or DOAC medications. Certainty of evidence was judged to be low to very low for most of the assessed outcomes. Further RCTs are particularly needed to help identify whether IAC significantly impacts the risks of thromboembolic events and device-pocket hematoma.