A retrospective study of nearly 32,000 elderly veterans (mean age 81) treated with anticoagulants suggests that fall-related traumatic intracranial hemorrhage (ICH) rates in this population may be much higher than clinicians realize.

The incidence of hospitalization for traumatic ICH, the primary outcome, was 4.8 per 1,000 person-years over a median follow-up of three years. The strongest adjusted risk factor for traumatic ICH was comorbid dementia.

More than half the patients (59%) had labile international normalized ratios (INRs). A secondary analysis showed that 30.9% of patients who experienced either traumatic or nontraumatic ICH had multiple episodes.

The authors concluded that, when considering anticoagulation, the risk of ischemic stroke must be balanced with the risk of adverse outcomes such as ICH and that decisions around anticoagulation need to be individualized and patient-centered.

Source: Dodson JA, Petrone A, Gagnon DR, et al. Incidence and determinants of traumatic intracranial bleeding among older veterans receiving warfarin for atrial fibrillation. JAMA Cardiol. Published online March 9, 2016. http://cardiology.jamanetwork.com/article.aspx?articleid=2499815. Accessed April 2, 2016.

Adherence rates low with all anticoagulants

Despite the improvements in convenience with novel anticoagulants, fewer than half of patients with atrial fibrillation adhere to their anticoagulant regimen in a real-world clinical practice setting. These findings were obtained from a recent cohort study of 64,661 patients identified from a U.S. insurance database.

Warfarin was prescribed in 59% of patients, apixaban in 6% of patients, dabigatran in about 16% of patients, and rivaroxaban in 19% of patients. End points included first hospital admission for either ischemic stroke or systemic embolism and major gastrointestinal bleeding, intracranial hemorrhage, or bleeding from other sites. Almost 90% of patients had a CHA₂DS₂-VASc score of 2 or more.

At the yearlong median follow-up, 47.5% of patients taking one of the non-vitamin K oral anticoagulants had adhered to treatment for 80% or more of the study interval. That was modestly better than adherence among patients taking warfarin.

During follow-up, 1,150 patients were admitted for either an ischemic stroke or a systemic embolism. The risk of stroke in patients who did not take an oral anticoagulant for six months or more was 2.7-fold greater among those with a CHA₂DS₂-VASc score of 2 to 3 compared with the risk of those who were nonadherent for less than a week.

Nonadherence in routine clinical practice was largely due to failure to refill medications.

Ayabe K, Goto S, Goto S. Persistence and discontinuation of oral anticoagulant: Remaining issues not addressed by phase III clinical trials. J Am Heart Assoc. 2016;5:e003258.

Evening administration of rivaroxaban suppresses morning hypercoagulability

The endogenous coagulation system has circadian variation with hypercoagulability and hypofibrinolysis, and a corresponding peak of cardiovascular thromboembolic events in the morning. The best time to dose once-daily rivaroxaban is unknown.

Sixteen volunteers with a mean age of 26 years were included in a small trial that measured the circadian rhythms of prothrombin fragment 1+2, plasminogen activator inhibitor, and plasmin-antiplasmin complex before and after three morning and three evening doses of 10 mg of rivaroxaban.

Concentrations of rivaroxaban were higher 12 hours after evening administration than they were 12 hours after morning intake. Morning hypercoagulability factors were also lower when the drug was given in the evening and the hypercoagulability suppression lasted longer after evening administration.

Source: Brunner-Ziegler S, Jilma B, Schörgenhofer C, et al. Comparison between the impact of morning and evening doses of rivaroxaban on the circadian endogenous coagulation rhythm in healthy subjects.
J Thromb Haemost. 2016;14:316-323.