vitamin-k-semiquinone-radical and darexaban

Insomnia is an important adverse event of mechanical thromboprophylaxis. This sleep disorder has been reported as one of the commonest adverse events of the new oral anti-Xa anticoagulant darexaban, with similar rates to mechanical thromboprophylaxis in a randomized controlled trial (RCT). However, the perceived effect could have been biased because it was an open-label RCT. Therefore, we aimed to review the incidence of insomnia with non-vitamin K antagonist oral anticoagulants (NOACs).. We performed a systematic review and meta-analysis of Phase III RCTs. Electronic databases MEDLINE and CENTRAL (inception to September 2013) were searched as well as review articles and references of included studies. We included phase III RCTs which compared NOACs with any other control group. Data were analyzed and pooled to estimate risk ratio (RR) with 95% confidence intervals (95%CI) for insomnia using inverse variance method. Statistical heterogeneity was evaluated with I(2) test.. We included seven studies (two apixaban RCTs, two dabigatran RCTs, one darexaban RCTs, and two rivaroxaban RCTs), enrolling a total of 23,023 patients. Overall, NOACs were not associated to an increased risk of insomnia: RR 0.94 (95%CI 0.83-1.08; I(2) = 0%). In blinded studies (six studies), NOACs also did not show increased risk of insomnia (RR 0.94, 95%CI 0.83-1.08; I(2) = 0%). Results were similar irrespective of the comparators.. NOACs (apixaban, dabigatran, darexaban, rivaroxaban) did not show increased risk of insomnia. Results according to study design (blinded vs. open-label trials) overlap the main analysis.

Topics: Administration, Oral; Anticoagulants; Azepines; Benzamides; Clinical Trials, Phase III as Topic; Humans; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Thrombosis; Vitamin K

Despite widespread adoption of acetylsalicylic acid and P2Y12 receptor inhibitor therapy as the standard of care for secondary event prevention in patients with acute coronary syndrome (ACS), the rate of cardiovascular death or myocardial infarction following discharge is approximately 24-31% over five years, indicating an important unmet need to reduce further the risk of recurrent ACS events. Because thrombin has a role in arterial thrombus generation, a mechanistic rationale exists for adding an anticoagulant to dual antiplatelet therapy to reduce cardiovascular event rates and mortality. The direct thrombin inhibitor dabigatran and the direct Factor Xa inhibitors rivaroxaban and apixaban have been investigated for this application, with only rivaroxaban successfully completing a phase III trial. These results suggest that dose selection is of paramount importance in this indication, with lower anticoagulant doses (relative to those used in other indications, such as stroke prevention in atrial fibrillation) plus low-dose acetylsalicylic acid potentially improving cardiovascular outcomes. This article reviews clinical trial data of anticoagulants for secondary event prevention in patients with ACS; it also discusses the mechanistic reasons that may underlie these observations and looks towards the potential impact of findings from the ATLAS ACS 2 TIMI 51 trial on clinical practice.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Azepines; Azetidines; Benzamides; Benzimidazoles; Benzylamines; beta-Alanine; Dabigatran; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thrombin; Vitamin K