BackgroundAtrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions.Methods and ResultsIn the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS 2 score was 3.5. Over 1.9 years of median follow‐up, 1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677).ConclusionsIn a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.

Objective: To assess the impact on stroke outcome of statin use in the acute phase after IV thrombolysis.Methods: Multicenter study on prospectively collected data of 2,072 stroke patients treated with IV thrombolysis. Outcome measures of efficacy were neurologic improvement (NIH Stroke Scale [NIHSS] # 4 points from baseline or NIHSS 5 0) and major neurologic improvement (NIHSS # 8 points from baseline or NIHSS 5 0) at 7 days and favorable (modified Rankin Scale [mRS] # 2) and excellent functional outcome (mRS # 1) at 3 months. Outcome measures of safety were 7-day neurologic deterioration (NIHSS $ 4 points from baseline or death), symptomatic intracerebral hemorrhage type 2 with NIHSS $ 4 points from baseline or death within 36 hours, and 3-month death. Statins are recommended for primary and secondary stroke prevention in patients at risk of cerebrovascular events. Results1 In addition to reducing the risk of first and recurrent ischemic stroke, statin treatment may also improve outcome through pleiotropic non-cholesterol-dependent effects. 2An association between statin use before stroke and favorable outcome has been previously reported.3-5 Moreover, a prospective clinical trial showed that statin withdrawal during the first 3 days after a stroke event was associated with increased risk of death or dependency at 3 months. 6 To date, very few studies have investigated the effect of statin use in the acute phase on ischemic stroke outcome.7-9 The Stroke Prevention with Aggressive Reductions in Cholesterol Levels (SPARCL) trial showed a trend toward less severity for outcome 90 days after stroke with atorvastatin administration (80 mg), compared with placebo, in patients having a stroke during the trial. 10So far, few studies have assessed the efficacy and safety of statin treatment in ischemic stroke patients treated with IV thrombolysis. Two recent meta-analyses showed that prior statin use may increase the risk of symptomatic intracerebral hemorrhage (sICH) within 36 hours after IV recombinant tissue plasminogen activator (rtPA), though without influencing 3-month functional outcome. 11,12 Two large observational studies reported that previous treatment with statin was not an independent predictor of functional outcome or of ICH. 13,14 The aim of the THRombolysis and STatins (THRaST) study was to assess the impact of statin use in the acute phase of ischemic stroke on clinical outcome in patients treated with IV thrombolysis.Authors' affiliations are listed at the end of the article. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

NIHSS is a reliable tool of clinical monitoring and correlates with 30-day and 3-month mortality and functional outcome in subjects with ICH.

Arginine vasopressin (AVP) may play a role in the development of ischemic brain edema and/or cerebral vasospasm. Data available on AVP plasma levels in ischemic stroke are few and discordant. In order to ascertain whether changes in AVP plasma levels occur in ischemic stroke, plasma AVP levels, plasma osmolality and mean arterial pressure were determined in 24 patients with unprecedented ischemic cerebral infarction and in 15 controls over a 24-hour period. In stroke patients, mean 24-hour plasma AVP levels (7.2 ± 0.8 ng/l) were higher (p < 0.05) than in control subjects (2.4 ± 0.3 ng/l), and correlated with the severity score of the neurologic deficit and the mean size of the lesion. In patients with a more severe neurologic deficit, the mean 24-hour plasma AVP levels (8.7 ± 1.0 ng/l) were higher than in patients with a less severe neurologic deficit (5.2 ± 0.8 ng/l). Data indicate that in ischemic stroke an increased AVP secretion occurs independently of osmotic or baroreceptorial mechanisms. The possibility that AVP may play a role in neuronal cell damage following cerebral ischemia warrants further attention.

Delirium is an acute neuropsychiatric syndrome, very common in hospitalized people with medical and neurological conditions. The identification of delirium after stroke is not an easy task and validated psychometric instruments are needed to correctly identify it. We decided to verify if (1) formal training in DSM-V criteria is needed to correctly identify post-stroke delirium, (2) if the use of a brief psychometric instrument such as 4AT improves its identification, (3) the applicability of these scales in the stroke setting. In the first phase of this study we retrospectively studied 102 acute stroke patients in Stroke Units of San Martino Hospital (Genova, Italy) to evaluate delirium with clinical criteria, first by a neurologist without a formal training in DSM-V criteria and after training. Then, we enrolled 100 new acute stroke patients who underwent screening for delirium using 4AT scale and DSM-V criteria. In the first phase, DSM-V criteria training significantly increased the ability to capture delirium (5 vs. 15%). In the second phase, the 4AT was used for delirium screening revealing a 52% of cases of delirium, the same observed by the consensus diagnosis of two senior neurologists (that was 50%). In the second phase, the use of 4AT scale allowed to capture post-stroke delirium as well as the consensus diagnosis by two neurologists. The identification of post-stroke delirium is not an easy task and requires both formal training in DSM-V criteria as well as the application of brief scales, such as the 4AT.