Thrombosis Patients should be provided with a phone contact for support. The frequency of follow-up appointments in these patients must consider multiple factors: presence of comor- bidities; previous treatment with VKAs; age and respective degree of autonomy; disease chronicity. Patients should have a ﬁrst visit within 3 to 6 months after starting dabigatran and thereafter according to their medical condition: in general, these patients should have biannual visits (AR). In elderly patients (>75 years) or patients with some degree of impaired renal function, quarterly visits are recommended (AR). Since dabigatran is eliminated primarily in urine and since it is contraindicated in patients with severe renal failure [17], renal function should be assessed in the ﬁrst appointment and every 6 months when mild-to-moderate renal dysfunction is present or whenever a decline of renal function is suspected. 2.4. How Can Adherence Be Checked and Improved? The success of a clinical intervention depends not only on an accurate diagnosis and appropriate treatment, but also on the patient’s commitment to comply with the prescribed therapy. Nonadherence is a major challenge for clinicians, especially in elderly patients, and, as with other chronic diseases (such as hypertension), AF patients should be monitored for compliance [19]. In view of the short half-life of dabigatran (12 to 14 hours after multiple doses) [3], no coagulation test can ascertain long-term compliance. As such, the evaluation of continued adherence must be clinically assessed. To improve adherence, patient education should be rein- forced. Prior to dabigatran prescription, clinicians should explain to patients and caregivers what an anticoagulant is; why it is being prescribed; what are its risks and beneﬁts; what adverse events can occur and how to identify and deal with them. Patients and caregivers should be alerted of the importance of immediately contacting the physician in the event of bleeding or other adverse events and a special emphasis should be given to the risks of noncompliance. These measures should be complemented with educational brochures and easy access to nonscheduled appointments. For reassurance, prescribing physicians should provide a phone contact to all patients starting dabigatran, especially those switching over from VKAs. Other healthcare providers should be aware that the patient is anticoagulated, particularly if there is a possibility of surgery. In this respect, patient alert cards are useful tools, reinforcing patient adherence and providing other health professionals with information on the prescribing drug. 2.5. How to Deal with Dyspepsia? Dyspepsia is a frequently reported adverse event with drugs commonly prescribed in primary care settings, such as NSAIDs or ticlopidine [20]. In the RE-LY trial, dyspepsia was observed in 11.3% and 11.8% of patients in the dabigatran arms and in 5.8% of patients in the warfarin arm [1]. Dabigatran- related gastrointestinal (GI) symptoms were most commonly 3 of an esophageal/gastroesophageal reﬂux nature, typically occurring soon after drug initiation with a mild-to-moderate presentation and, in most cases, did not require drug discontinuation. Patients with GI symptoms had a higher risk of GI bleeding, irrespective of whether they were treated with dabigatran or warfarin [21], but the rate of GI bleeding was increased with dabigatran 150 mg bid versus warfarin (annual rate 1.51% versus 1.02%, P = 0.007) [1]. It is important to inform patients that dyspepsia may occur. The administration of dabigatran within meals (breakfast and dinner) can mitigate this eﬀect [22]. The value of proton pump inhibitors in the management of dyspepsia, in this speciﬁc scenario, is not yet clear. However, it is known that a ﬁfth of the patients enrolled in the RE-LY trial were on pantoprazole and although the bioavailability of dabigatran was reduced by about 12.5% in this subpopulation, a negative impact on clinical outcomes was not observed [17]. This data supports the use of pantoprazole for the management of dabigatran related dyspepsia. 2.6. In Which Patients Treated with Dabigatran Should Coag- ulation Be Monitored? The RE-LY trial showed that dabi- gatran, when compared to warfarin, is an eﬀective and safe treatment that obviates the need for routine laboratory monitoring. The vast majority of patients will not beneﬁt from routine and scheduled coagulation monitoring. In patients with an increased risk of bleeding, careful dose selection is advised. If available, the lower 110 mg bid dose should be used in patients aged at least 80 years; with high risk of bleeding; in patients with concomitant dabigatran and verapamil therapy [17]. In patients with moderate renal impairment, close clinical surveillance is recommended, including periodical assessment of renal function. Only in exceptional situations may patients treated with dabigatran require anticoagulation status assessment. These situations are (1) cases of suspected overdose; (2) patients presenting to the emergency departments with acute bleeding, and (3) indication for urgent surgery (see also Section 2.7). 2.7. How Can the Anticoagulant Eﬀect of Dabigatran Be Measured? There is a close correlation between plasma dabi- gatran concentration and the degree of anticoagulant eﬀect evaluated by the ecarin clotting time (ECT) and thrombin time (TT) [23]. To assess the risk of bleeding, qualitative tests such as activated partial prothrombin time (aPTT) or TT (other than the dabigatran calibrated Hemoclot thrombin inhibitor assay) may be used [24]. For a quantitative measurement of dabigatran plasma concentrations, only the dabigatran calibrated Hemoclot thrombin inhibitor assay (a diluted TT) is available [17]. Importantly, anticoagulant parameters depend on the time when the blood sample is taken relative to the time when the previous dose was given. A blood sample taken 2 hours after dabigatran ingestion (∼peak level) will have diﬀerent (higher) result in all clotting tests compared to a blood