Thrombosis patient took dabigatran that particular morning, but gives no information on treatment compliance over the preceding 3 week period. Therefore, compliance of drug intake in the preceding 3 to 4 weeks should be speciﬁcally inquired and documented in the patient’s ﬁle. Finally, it is also important to recall that long-term anticoagulation is required for patients with a high throm- boembolic risk, even if sinus rhythm is restored [14]. 2.16. Is It Safe to Perform Thrombolysis for an Acute Ischemic Stroke in a Patient Treated with Dabigatran? Despite the fact that there are no evidence-based data to answer this question, thrombolytic therapy is not recommended for anticoag- ulated patients with dabigatran [17]. There is only one reported case of thrombolytic treatment with intravenous rt- PA performed just below 4.5 h after the onset of symptoms and 7 hours after the last administration of dabigatran (aPTT 34.8 seconds, normal range 22.2–34.4 seconds; TT not reported) [60]. In this case, no hemorrhagic complica- tions were observed. The Interventional Management Stroke (IMS) III trial proposed that administration of rt-PA or endovascular treatment could be considered 48 h after the last intake of dabigatran or within 48 h of last intake with a normal aPTT [61]. Future studies are needed in order to answer this question, until then the use of ﬁbrinolytic agents for the treatment of acute ischemic stroke can probably be considered if the patient presents with a diluted TT or aPTT not exceeding the upper limit of normal, according to the local reference range, but careful evaluation of patient eligibility is strongly encouraged. 2.17. In a Patient with AF and an Acute Ischemic Stroke, or Transient Ischemic Attack, When Should Therapy with Dabi- gatran Be Initiated? A substudy of the RE-LY trial showed that there was no increase in adverse events, including intracranial bleeding, with the two doses of dabigatran when compared to warfarin, between patients with and without previous stroke or transient ischemic attack [62]. Never- theless, this trial excluded patients with transient ischemic attack or ischemic stroke in the two weeks before enrollment. Thus, while initiation of dabigatran seems safe after the ﬁrst two weeks, further data on earlier initiation of dabigatran after stroke or transient ischemic attack is needed. However, it is important to underline that, in these settings, data concerning initiation of other anticoagulant drugs, including VKAs, is also lacking. An ongoing observational multicenter study, the Risk of early stroke recurrence in patients with Atrial Fibrillation (RAF) study, is currently evaluating timing of initiation of diﬀerent anticoagulant drugs in patients with transient ischemic attack or acute ischemic stroke and AF (Paciaroni et al., unpublished data, 2011). Early intro- duction of dabigatran in transient ischemic attacks or minor ischemic stroke cases seems attractive, in view of its rapid anticoagulant action, and is probably feasible, but more data is needed in order to identify the optimal time for treatment initiation. Delaying introduction of anticoagulant therapy in patients with extensive ischemic lesions, as proposed by 7 current guidelines [63], should also be advocated in the case of dabigatran, to avoid hemorrhagic transformation. 2.18. How Should Intracranial Bleeding Be Managed in a Patient Treated with Dabigatran? Fewer intracranial hemor- rhagic events are expected in patients under treatment with dabigatran than in patients treated with warfarin. In the RE-LY trial, in comparison with warfarin treatment, there was a marked reduction of intracranial bleeding with both doses of dabigatran (69% reduction with dabigatran 110 mg bid and 60% reduction with dabigatran 150 mg bid, P < 0.001 for comparisons between dabigatran and warfarin) [1]. Nevertheless, it is important to understand how to manage these situations in case they do occur. As there is no antidote for dabigatran, currently avail- able, supportive treatment in order to stop bleeding is the mainstay of management of intracranial hemorrhagic events. Dabigatran should be stopped immediately and symptomatic treatment should be initiated. Further attitudes should be individualized according to the severity of the hemorrhage [64, 65], and measures described in Section 2.8 should be taken into account. 3. Conclusion The questions answered in this paper represent some of the relevant issues clinicians will face when asked to manage nonvalvular AF patients treated with dabigatran. Informa- tion about these and other management issues should be easily and widely available, in order to improve correct patient and drug dosage selection, taking into account variables such as age, renal function, and comorbidities. “Real-world” experience with dabigatran and further evidence from ongoing clinical trials will dictate the need for adjustments to the recommendations in this paper. Disclosure J. Ferreira, D. Ferreira, M. Viana-Baptista, P. Bettencourt, and R. Cernadas report receiving consulting fees from Boehringer Ingelheim Portugal. F. Crespo reports receiving grant support from Boehringer Ingelheim Portugal and Roche Portugal. Acknowledgment The authors would like to acknowledge Dra. Katya Reis Santos, who provided medical writing services, supported by an unrestricted grant from Boehringer Ingelheim Portugal. References [1] S. J. Connolly, M. D. Ezekowitz, S. Yusuf et al., “Dabigatran versus warfarin in patients with atrial ﬁbrillation,” The New England Journal of Medicine, vol. 361, no. 12, pp. 1139–1151, 2009. [2] U.S. Food and Drug Administration, “FDA approves Pradaxa to prevent stroke in people with atrial ﬁbrillation,” 2010,