Dabigatran vs. Aspirin for Secondary Prevention After Embolic Stroke of Undetermined Source　- Japanese Subanalysis of the RE-SPECT ESUS Randomized Controlled Trial.

BACKGROUND: The international Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the EfficaCy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate versus Acetylsalicylic Acid in Patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS) trial did not demonstrate superiority of dabigatran over aspirin for reduction of recurrent strokes in patients with embolic strokes of undetermined source (ESUS). Based on pre-defined subanalyses, the safety and efficacy of dabigatran vs. aspirin in Japanese patients was assessed.Methods and Results:ESUS patients were randomized to receive either dabigatran (150 or 110 mg twice daily) or aspirin (100 mg once daily). Of 5,390 patients randomized, 594 were Japanese. Most Japanese patients (99.8%) underwent brain magnetic resonance imaging for trial screening, compared to 76.8% of non-Japanese (P<0.0001). In the Japanese cohort, over a 19.4-month median follow-up period, recurrent stroke as the primary outcome occurred in 20/294 patients (4.3%/year) in the dabigatran group and 38/300 (8.3%/year) in the aspirin group (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.32-0.94). Major bleeding occurred in 12 patients (2.5%/year) and 17 patients (3.5%/year), respectively (HR, 0.72; 95% CI, 0.34-1.52). In contrast, in the non-Japanese cohort, recurrent stroke occurred in 4.1%/year and 4.3%/year, respectively, showing no apparent difference in recurrent stroke for dabigatran vs. aspirin (HR, 0.91; 95% CI, 0.74-1.14). The P-interaction for treatment and region did not reach statistical significance (P=0.09). CONCLUSIONS: Dabigatran was putatively associated with a lower relative risk of recurrent stroke compared with aspirin in Japanese ESUS patients.

Intracellular aquaporins: clues for intracellular water transport?

Aquaporins (AQPs) are usually present at the plasma membrane to regulate influx and outflow of water and small molecules. They are important for the regulation of water homeostasis for the cells and organisms. AQPs are also present inside the cell, at the membranes of intracellular organelles. The roles of such AQPs have not yet been established. They will be clues to clarify the mechanisms of water and small solutes movements inside the cell. Recently, a new AQP subfamily has been identified with highly deviated asparagine-proline-alanine boxes, signature sequences for AQP. With limited homology less than 20%, this subfamily will be a superfamily of AQPs. Accordingly, it was tentatively named "superaquaporin subfamily," which is so far only present in multicellular organisms including plants, insects, nematodes, and vertebrates. Some superaquaporins are functionally water channels and localized intracellularly. AQP11, one of the two superaquaporins in mammals, has been shown to be important for the development of the proximal tubule as its disruption produced neonatally fatal polycystic kidneys in mice. Hence, recent identification of intracellular AQPs will open new areas of research on cell biology and expand the scope of AQPs.