Clinical events after interruption of anticoagulation in patients with atrial fibrillation: An analysis from the ENGAGE AF-TIMI 48 trial. (15th April 2018)

• Record Type: Journal Article
• Authors: Cavallari, Ilaria; Ruff, Christian T.; Nordio, Francesco; Deenadayalu, Naveen; Shi, Minggao; Lanz, Hans; Rutman, Howard; Mercuri, Michele F.; Antman, Elliott M.; Braunwald, Eugene; Giugliano, Robert P.
• Is Part Of: International journal of cardiology. Volume 257(2018)
• Page Start: 102
• Page End: 107
• Publication Date: 2018-04-15
• Subjects: Oral anticoagulation -- Interruption -- Atrial fibrillation -- Stroke; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2018.01.065
• Languages: English
• ISSNs: 0167-5273

Abstract

Abstract: Background: Patients with atrial fibrillation (AF) who interrupt anticoagulation are at high risk of thromboembolism and death. Methods and results: Patients enrolled in the ENGAGE AF-TIMI 48 trial (randomized comparison of edoxaban vs. warfarin) who interrupted study anticoagulant for >3 days were identified. Clinical events (ischemic stroke/systemic embolism, major cardiac and cerebrovascular events [MACCE]) were analyzed from day 4 after interruption until day 34 or study drug resumption. During 2.8 years median follow-up, 13, 311 (63%) patients interrupted study drug for >3 days. After excluding those who received open-label anticoagulation during the at-risk window, the population for analysis included 9148 patients. The rates of ischemic stroke/systemic embolism and MACCE post interruption were substantially greater than in patients who never interrupted (15.42 vs. 0.26 and 60.82 vs. 0.36 per 100 patient-years, respectively, p adj < .001). Patients who interrupted study drug for an adverse event (44.1% of the cohort), compared to those who interrupted for other reasons, had an increased risk of MACCE (HRadj 2.75; 95% CI 2.02–3.74, p < .0001), but similar rates of ischemic stroke/systemic embolism. Rates of clinical events after interruption of warfarin and edoxaban were similar. Conclusion: Interruption of study drug was frequent in patients with AF and was associated with a substantial risk of major cardiac and cerebrovascular events over the ensuing 30 days. This risk was particularly high in patients who interrupted as a result of an adverse event; these patients deserve close monitoring and resumption of anticoagulation as soon as it is safe to do so. Highlights: OAC interruption occurred in ~2/3 of patients in 3 years being significantly more frequent with warfarin than edoxaban Adverse events and physician decision, mainly driven by planned procedures, were the most common reasons for OAC interruption OAC interruptions were associated with poor outcomes and an elevated thromboembolic risk through 30 days