There was a 71% increase in the risk of stroke during the first 30 days of warfarin treatment in patients with atrial fibrillation compared with those who had not used antithrombotic therapy during the previous year, based on a nested case-control analysis of 70 766 evaluable adult patients with atrial fibrillation in the UK Clinical Practice Research Datalink (CPRD) database. The increased risk of stroke with warfarin use was most marked during the first week of warfarin therapy (peaked at 3 days; adjusted relative risk [RR] 2.33; 95 % CI 1.50, 3.61) and in those with a history of ischaemic stroke prior to cohort entry (2.45; 1.72, 3.79). Moreover, these results remained robust in sensitivity analyses. Of note, following this initial 30-day treatment period, the risk of stroke was significantly reduced in those taking warfarin. This large population based study had a number of strengths and limitations. Strengths of the study included its size, the duration of patient follow-up (≤ 16 years) and CPRD information is collected prospectively thereby eliminating recall bias. Conversely, limitations of the study included classifying patients as exposed rather than unexposed, since the CPRD represents warfarin prescriptions written and some of these may not have filled and/or taken, and the potential under-reporting of strokes in the CPRD leading to a potential under-estimation of treatment effects. The authors conclude "while one hypothesis is that warfarin may induce a transient hypercoagulable state at the start of treatment, additional well-conducted studies are needed to confirm these findings and determine whether a heparin bridging strategy at the initial phase of the treatment reduces the risk".