br Discussion We evaluated and determined the
Discussion We evaluated and determined the incidence and severity of subjective reports of dyspepsia symptoms due to dabigatran. Based on the results of the RE-LY trial , the AE that was significantly more common with dabigatran than with warfarin was dyspepsia. In the sub-group (326 Japanese patients) analysis of the RE-LY trial , the incidence of dyspepsia symptoms in Japanese patients increased to approximately 25%. Therefore, based on this information regarding dyspepsia, care for gastrointestinal symptoms should be required to use dabigatran for stroke prevention in daily clinical practice in Japan. Sobieraj et al.  reported on the mechanisms that might be responsible for GI symptoms attributable to antithrombotic agents used for stroke prevention in AF. Aspirin directly irritates the gastric mucosa and impairs the ability of prostaglandins to provide mucosal protection . Dabigatran is formulated in pellets containing a tartaric vasopressin receptor antagonist core as a low pH is required to enhance absorption, which may lead to higher rates of dyspepsia and the increased risk of GI bleeding with the 150mg dose . Generally, drug-induced esophageal or upper GI ulcers develop because of contact of drugs with the upper GI mucosa and their subsequent retention there . The mechanism of injury resulting from bisphosphonates includes destruction of the phospholipid layer . Okada et al.  found exfoliative esophagitis or esophageal ulcers in the middle-lower esophagus with white membraniform attachments in the endoscopic examination of patients with AF who complained of symptoms suggestive of GI irritation. This finding supports a role for dabigatran׳s galenic formulation, and, therefore, the incidence of dyspepsia does not differ with differing doses of dabigatran. The observed incidence of dyspepsia symptoms was 17.2% (95% CI: 13.1–21.8%) and this incidence was considerably lower than the approximately 25% reported in the sub-group analysis of Japanese patients in the RE-LY study. Nonetheless, in the original analysis of the RE-LY study, dyspepsia occurred in 707 patients (11.8%) and 688 patients (11.3%) in the 110-mg and 150-mg dabigatran groups, respectively (P<0.001 for both comparisons), and these incidences were lower than our result of 17.2%. Therefore, the incidence of dyspepsia symptoms due to dabigatran may vary from 10% to 20%.
Conflict of interest
Acknowledgments The study was supported by the Waksman Foundation of Japan Inc. We are grateful to Mebix, Inc. for data management, statistics, and preparing the manuscript. We are also grateful to Prof. Hideyuki Hiraishi, Dokkyo Medical University, for the special advice in the evaluation of dyspepsia.
Introduction Ventricular fibrillation (VF) is the most common cause of sudden cardiac death . Survivors of VF require more careful post-resuscitation care, because this arrhythmia is associated with a high rate of recurrence and a poor prognosis after successful resuscitation. Therefore, the implantable cardioverter-defibrillator (ICD) for the secondary prevention of VF has already become an essential treatment to reduce the risk of sudden cardiac death and improve survival [2–4]. On the other hand, it has been shown that ICD shock therapy itself is linked with a deterioration in cardiac function, and may lead to high cardiac mortality . Thus, the recurrence of ventricular tachyarrhythmias after ICD implantation is a critical problem in patients who have previously experienced lethal ventricular tachyarrhythmias. In order to improve patients׳ survival after ICD implantation, an effective means of predicting which of them are at high risk for sudden cardiac death is required in the clinical setting. Recently, T-wave alternans (TWA) has been shown to be useful for predicting the prevalence of fatal ventricular tachyarrhythmias and sudden cardiac death in various heart diseases [6–9]. TWA is analyzed by the conventional power spectral method, using an exercise stress protocol, or by the time-domain modified moving average method, using Holter monitoring . From the point of view of risk assessment, TWA by the time-domain modified moving average method has been demonstrated to be equivalent to the conventional spectral method in the long-term prediction of cardiac death . However, the clinical significance of TWA measurement in survivors of VF or hemodynamically unstable ventricular tachycardia (VT) has not been fully elucidated.