Aligning health care policy with evidence-based medicine: the case for funding direct oral anticoagulants in atrial fibrillation.

Misalignment between evidence-informed clinical care guideline recommendations and reimbursement policy has created care gaps that lead to suboptimal outcomes for patients denied access to guideline-based therapies. The purpose of this article is to make the case for addressing this growing access barrier to optimal care. Stroke prevention in atrial fibrillation (AF) is discussed as an example. Stroke is an extremely costly disease, imposing a significant human, societal, and economic burden. Stroke in the setting of AF carries an 80% probability of death or disability. Although two-thirds of these strokes are preventable with appropriate anticoagulation, this has historically been underprescribed and poorly managed. National and international guidelines endorse the direct oral anticoagulants as first-line therapy for this indication. However, no Canadian province has provided these agents with an unrestricted listing. These decisions appear to be founded on silo-based cost assessment-the drug costs rather than the total system costs-and thus overlook several important cost-drivers in stroke. The discordance between best scientific evidence and public policy requires health care providers to use a potentially suboptimal therapy in contravention of guideline recommendations. It represents a significant obstacle for knowledge translation efforts that aim to increase the appropriate anticoagulation of Canadians with AF. As health care professionals, we have a responsibility to our patients to engage with policy-makers in addressing and resolving this barrier to optimal patient care.

Changes in intracortical excitability after transient ischemic attack are associated with ABCD² score.

BACKGROUND AND PURPOSE: A transient ischemic attack (TIA) is a brief ischemic episode characterized by rapid clinical resolution and not associated with permanent cerebral infarction. Whether changes in intracortical excitability persist and are related to clinical predictors of stroke risk after TIA remains unknown. METHODS: Participants were individuals with clinically resolved motor TIA with no structural lesions and healthy age-matched control participants. Single and paired-pulse transcranial magnetic stimulation was used to measure intracortical excitability. Recruitment curves for percent inhibition and facilitation were used to derive excitability thresholds. Correlations between threshold asymmetries and ABCD(2) score were performed. RESULTS: Results showed a significant 3-way interaction with reduced inhibition and enhanced facilitation in the affected compared with unaffected hemisphere after TIA. No significant differences were present in healthy participants. Asymmetries in intracortical inhibition and facilitation were significantly correlated with ABCD(2) score. CONCLUSIONS: The present study is the first, to our knowledge, to demonstrate altered intracortical inhibition and facilitation in the affected hemisphere after TIA. These changes occurred on average 2 weeks after clinical signs of TIA resolved and in the absence of structural lesions and were not present in healthy age-matched control participants. Furthermore, this study is the first, to our knowledge, to report that changes in intracortical excitability after TIA are associated with ABCD(2) score.

Delayed detection of atrial fibrillation after ischemic stroke.

BACKGROUND: Detection of atrial fibrillation (AF) after ischemic stroke is important because anticoagulation is indicated to reduce the risk of recurrent stroke. However, no consensus exists about the optimum method for detecting underlying paroxysmal AF not apparent on presentation with stroke. The aim of this study was to characterize the rate, timing, and predictors of delayed detection of AF after stroke. METHODS: The Virtual International Stroke Trials Archive provided data from 3464 patients in the placebo arms of 4 clinical trials of therapies for acute ischemic stroke. Patients who had AF by history or on the baseline electrocardiogram were excluded. Electrocardiograms were obtained routinely and as clinically indicated. The time to detection of AF was evaluated using Kaplan-Meier survival statistics. Cox proportional hazards analysis was used to evaluate risk factors for AF. RESULTS: Among 2504 qualifying patients, AF was detected in 174 (6.9%; 95% confidence interval [CI] 6.0%-8.0%). In 68% of patients, AF was detected more than 48 hours after presentation. Detection of AF was associated with increasing age (hazard ratio [HR] 1.6/decade; 95% CI 1.4-1.9; P < .005), female sex (HR 1.7; CI 1.2-2.4; P < .005), congestive heart failure (HR 1.9; CI 1.1-3.4; P = .02), and the absence of hypertension (HR 1.6; CI 1.1-2.2; P = .01). CONCLUSIONS: Delayed detection of AF was common in this large cohort of patients carefully monitored after ischemic stroke. Current methods of screening may fail to detect underlying paroxysmal AF in a substantial proportion of patients.

Recent clinical trial results with antiplatelet therapy: implications in stroke prevention.

Dual antiplatelet therapy that inhibits more than one pathway of platelet activation is appealing and biologically rational. The CURE study evaluated the efficacy and safety of clopidogrel on top of acetylsalicylic acid (ASA) versus standard therapy (including ASA) in over 12,000 patients with unstable angina or non-ST-segment elevation myocardial infarction (MI). Clopidogrel in combination with ASA reduced the relative risk of the combined atherothrombotic endpoint of cardiovascular death, MI or stroke by 20% (95% CI 0.72-0.90; p < 0.001) and the absolute risk of this composite endpoint by 2.1%. While the study was not powered or designed to demonstrate a reduction in stroke, there was a 14% reduction in stroke risk (p > 0.05). Dual antiplatelet therapy was associated with an acceptable 1% increase in the incidence of major bleeding events (p = 0.001). PCI-CURE, a prespecified substudy of patients who underwent percutaneous coronary intervention (PCI) during CURE, confirmed the early and sustained benefits of clopidogrel therapy seen in the overall CURE study. CREDO was a randomized, double-blind, placebo-controlled trial in more than 2,100 patients that evaluated the continuation of clopidogrel on top of standard therapy including ASA for 12 months after PCI, and the benefit of a preprocedural clopidogrel loading dose. The long-term results at 1 year showed that there was a 27% reduction in the risk of stroke, MI or death with long-term clopidogrel therapy (p = 0.02). There was a consistent benefit of extended clopidogrel therapy for each component of the composite endpoint, with a 25.1% relative risk reduction for all-cause stroke. In patients who received clopidogrel > or =6 h before PCI, there was a 39% reduction in the risk of death, MI or urgent target-vessel revascularization at 28 days (p = 0.051). These data suggest important implications in the future for the use of an early loading dose of clopidogrel in patients undergoing carotid stenting and, if proven in current or future trials, the use of a loading dose followed by long-term continuation of clopidogrel in other high-risk atherothrombotic patients such as those with transient ischaemic attack or ischaemic stroke.