Background— Patients with atrial fibrillation usually are elderly and may have cognitive dysfunction. These patients may receive less effective oral anticoagulation, resulting in more vascular events and bleeding. Methods and Results— In an analysis of cognitive function associated with the time in therapeutic range (TTR) in the Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events, 2510 patients (mean age, 71±9.5 years) from 27 countries completed the Mini-Mental State Examination (MMSE). Of these patients, 171 (6.8%) had an MMSE score <24, suggesting dementia, and 194 (7.7%) had intermediate scores of 24 to 25. Low MMSE scores were correlated with a low TTR. Even mild cognitive impairment was associated with a TTR below the median (<65%). Patients with an MMSE score <26 had more vascular events (6.7% versus 3.6% per 100 patient-years; P =0.002) and more bleeding (9.6% versus 7% per 100 patient-years; P =0.04). After controlling for TTR, the MMSE no longer conferred increased risk, suggesting that if improved anticoagulation was provided, vascular events and bleeding would be reduced. Other independent factors associated with a TTR <65% were region of the world, recent initiation of vitamin K antagonist, type of anticoagulant, and concurrent use of amiodarone or insulin. After adjustment for these factors, lower MMSE scores still predicted a reduced TTR. Conclusions— Cognitive dysfunction is common in elderly patients with atrial fibrillation and is related to less effective anticoagulation and more vascular events. The MMSE identifies patients with atrial fibrillation in whom extra efforts are needed to maintain effective anticoagulation and improve outcomes. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00243178.

Background and Purpose—: Apixaban reduces stroke with comparable bleeding risks when compared with aspirin in patients with atrial fibrillation who are unsuitable for vitamin k antagonist therapy. This analysis explores patterns of bleeding and defines bleeding risks based on stroke risk with apixaban and aspirin. Methods—: The Apixaban versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin k Antagonist Treatment (AVERROES) trial randomized 5599 patients with atrial fibrillation and risk factors to receive either apixaban or aspirin. Bleeding events were defined as the first occurrence of either major bleeding or clinically relevant nonmajor bleeding. Results—: The rate of a bleeding event was 3.8%/year with aspirin and 4.5%/year with apixaban (hazard ratio with apixaban, 1.18; 95% CI, 0.92–1.51; P =0.19). The anatomic site of bleeding did not differ between therapies. Risk factors for bleeding common to apixaban and aspirin were use of nonstudy aspirin >50% of the time and a history of daily/occasional nosebleeds. The rates of both stroke and bleeding increased with higher CHADS ₂ scores but apixaban compared with aspirin was associated with a similar relative risk of bleeding ( P interaction 0.21) and a reduced relative risk of stroke ( P interaction 0.37) irrespective of CHADS ₂ category. Conclusions—: Anatomic sites and predictors of bleeding are similar for apixaban and aspirin in these patients. Higher CHADS ₂ scores are associated with increasing rates of bleeding and stroke, but the balance between risks and benefits of apixaban compared with aspirin is favorable irrespective of baseline stroke risk. Clinical Trial Registration Information—: www.clinicaltrials.gov . Unique identifier: NCT 00496769.

Atherosclerosis remains a leading cause of cardiovascular diseases. Although the mechanism for atherosclerosis is complex and has not been fully understood, inflammation and oxidative stress play a critical role in the development and progression of atherosclerosis. N-acetylcysteine (NAC) has been used as a mucolytic agent and an antidote for acetaminophen overdose with a well-established safety profile. NAC has antioxidant and anti-inflammatory effects through multiple mechanisms, including an increase in the intracellular glutathione level and an attenuation of the nuclear factor kappa-B mediated production of inflammatory cytokines like tumor necrosis factor-alpha and interleukins. Numerous animal studies have demonstrated that NAC significantly decreases the development and progression of atherosclerosis. However, the data on the outcomes of clinical studies in patients with atherosclerosis have been limited and inconsistent. The purpose of this review is to summarize the data on the effect of NAC on atherosclerosis from both pre-clinical and clinical studies and discuss the potential mechanisms of action of NAC on atherosclerosis, as well as challenges in the field.