6 Table 2: Recommendations for the management of acute coronary syndromes in the RE-LY and RELY-ABLE studies [47]. (1) Dabigatran should be temporarily discontinued (2) Aspirin, clopidogrel and glycoprotein IIb/IIIa inhibitors may be administered according to usual clinical practice (3) Heparin can be started 12 or more hours after the last dose of dabigatran or as soon as the aPTT is <1.5 × baseline value (4) Reperfusion with primary PCI is preferable to ﬁbrinolysis (5) During PCI the ACT should be measured and heparin administered as needed according to usual practice Dabigatran can be restarted after the discontinuation of heparin, which generally occurs after coronary revasculariza- tion or after at least 48 hours of heparin therapy. In the RE-LY trial, the annual rate of myocardial infarction (MI) was slightly higher in the dabigatran groups (0.82%/year for 110 mg and 0.81%/year for 150 mg) when compared with the warfarin group (0.64%/year) [51, 52]. This result may represent a play of chance or a more protec- tive eﬀect of warfarin against MI in patients with AF [53]. Nevertheless, in the RE-LY trial, this potential advantage of warfarin was exceeded by the beneﬁt of dabigatran on cerebrovascular events, as reﬂected in the lower annual rate of vascular mortality observed in the dabigatran groups [1]. One meta-analysis of 7 trials found an increased risk of MI and ACS associated with dabigatran [54], but in clinical trials of primary prevention of venous thromboembolism, in patients undergoing major orthopedic surgery, no increase in ACS was detected in patients treated with dabigatran when compared to those treated with enoxaparin [55]. In the RE-LY platelet function substudy, no evidence of platelet activation was observed in the group of patients with AF receiving dabigatran when compared to warfarin [56]. 2.14. How to Manage Anticoagulant Therapy in a Patient Treated with Dabigatran and Submitted to Percutaneous Abla- tion of AF? In a recent study, administration of dabigatran to 123 consecutive patients after percutaneous ablation of AF was found to be well tolerated and safe in terms of bleeding complications and thromboembolic events, leading to the conclusion that dabigatran could be a good alternative to warfarin in this context [57]. In this study, periprocedural anticoagulation was based on a predetermined algorithm. Patients on dabigatran prior to AF ablation stopped this drug 36 hours before the procedure if estimated glomerular ﬁltration rate (GFR) was >60 mL/min, 48 hours before the procedure if GFR was 40 to 60 mL/min, and 60 hours before the procedure if estimated GFR was <40 mL/min. Patients receiving dabigatran before ablation did not receive preprocedural enoxaparin. Intraprocedural anticoagulation consisted on a weight- based bolus of unfractionated heparin administered when the transseptal sheath entered the left atrium, followed by a 1,000 units/hour infusion running through the transseptal sheath. Additional heparin administration depended on the ACT, targeted at 225 seconds. At the end of the procedure, Thrombosis heparin was reversed with protamine and all sheaths were removed. After ablation patients received two doses of enoxaparin (0.5 mg/kg), the ﬁrst one immediately at the end of the procedure and the second 12 hours later. Dabigatran was started 10 hours after the last enoxaparin dose (22 hours after the procedure) at a dose of 150 mg bid if the estimated GFR was >30 mL/min and 75 mg bid if the estimated GFR was between 15 and 30 mL/min (in Europe, the 75 mg bid dose is not approved for stroke prevention in patients with nonvalvular AF). Patients with a GFR <15 mL/min were not considered for dabigatran. Dabigatran was maintained for at least 30 days after ablation. No postablation strokes, transient ischemic attacks, or systemic thromboembolic events were reported [57]. The Dabigatran for Peri Procedural Anticoagulation During Radiofrequency Ablation of Atrial Fibrillation (DAP- PAR AF) trial, a prospective, open-label study, will start in a near future. In this trial, periprocedural anticoagulation will be managed in a similar way to that which is described in the previous study and this trial’s primary outcome will be the incidence of periprocedural major bleeding complications [58]. 2.15. How to Manage Cardioversion in a Patient Treated with Dabigatran? Cardioversion to sinus rhythm (pharmacolog- ical or electrical) can be safely considered in AF patients treated with dabigatran. According to the ESC guidelines [14], in patients with AF of 48 h or longer duration (or AF of unknown duration) undergoing cardioversion, oral anticoagulants should be given for at least 3 weeks prior and 4 weeks after cardioversion. This recommendation is also valid for dabigatran. Despite the fact that with dabigatran eﬀective anticoagu- lation is obtained within 2 hours of administration, the possibility of a thrombus being already present in the left atrial appendage must be considered. There is no prospective data on the safety of cardiover- sion under dabigatran treatment, but a post hoc analysis of the RE-LY trial revealed a low and comparable rate of cardioversion-related strokes in patients treated with dabiga- tran versus VKA [59]. In this study, the largest cardioversion study to date and the ﬁrst evaluating dabigatran in this setting, more dabigatran patients underwent prior trans- esophageal echocardiography (TEE) (25.5% for dabigatran 110 mg, 24.1% for dabigatran 150 mg, and 13.3% for warfarin, P < 0.0001 for comparisons between dabigatran and warfarin) and although the prevalence of left atrial thrombus was not signiﬁcantly higher in the dabigatran patients (1.8% for dabigatran 110 mg, 1.2% for dabigatran 150 mg, and 1.1% for warfarin, P = NS for comparisons between dabigatran and warfarin), it may still be prudent to recommended a TEE before a planned cardioversion in patients taking dabigatran. It is important to point out that the routinely performed INR test, prior to cardioversion, is of no use in patients treated with dabigatran and noteworthy that the dabigatran- speciﬁc coagulation assay (diluted assay) will inform if the