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The health burden of ischemic stroke is high and will continue to increase with an aging population. Recurrent ischemic stroke is increasingly recognized as a major public health concern with potentially debilitating sequelae. Thus, it is imperative to develop and implement effective strategies for stroke prevention. When considering secondary ischemic stroke prevention, it is important to consider the mechanism of the first stroke and the related vascular risk factors. Secondary ischemic stroke prevention typically includes multiple medical and, potentially, surgical treatments, but with the shared goal of reducing the risk of recurrent ischemic stroke. Providers, health care systems, and insurers also need to consider the availability of treatments, their cost and patient burden, methods for improving adherence, and interventions that target lifestyle risk factors such as diet or activity. In this article, we discuss aspects from the 2021 AHA Guideline on Secondary Stroke Prevention as well as highlight additional information relevant to best practices for reducing recurrent stroke risk.

Background Medication adherence is one of the crucial attempts in primary stroke prevention. The available evidence lacks comprehensive reviews exploring the association of medication adherence with stroke prevention. Objectives To investigate the effects of non-adherence to medications used to treat the modifiable risk of diseases on stroke-associated outcomes in primary stroke prevention. Methods Study records were searched from PubMed, Embase, and CINAHL. Those studies reported risks relevant to stroke-associated outcomes and medication non-adherence for patients diagnosed with four modifiable stroke-related diseases (atrial fibrillation [AF], hyperlipidemia, hypertension, and type 2 diabetes mellitus) but without stroke history were included for meta-analysis and further subgroup, sensitivity, and publication bias analyses. A random effect model was performed to analyse the pooled risk estimates of relative risk (RR) and 95% confidence intervals (CIs). Results Thirty-nine studies (with 2,117,789 participants in total) designed as cohort or case–control studies were included. Those patients presenting with four stroke-related diseases and categorised as medication non-adherent tended to result in stroke and/or associated death (all pooled RR ≥ 1 and 95% CI did not include 1). The findings of stratification and sensitivity analysis for each stroke-related disease showed a similar trend. Non-adherent patients with AF were prone to stroke occurrence (RR 1.852; 95% CI 1.583–2.166) but inclined to reduced bleeding (RR 0.894; 95% CI 0.803–0.996). The existence of publication bias warrants further interpretation. Conclusions Non-adherence to medications for the four stroke-related diseases contributes to the development of stroke and/or mortality in primary stroke prevention. More efforts are needed to improve patients’ medication adherence.

Low-dose direct oral anticoagulant (DOAC) use is quite prevalent in clinical practice, but evidence of its effectiveness and safety compared with high-dose DOAC in patients with atrial fibrillation (AF) remains limited. We aimed to assess the effectiveness and safety of low-dose and high-dose DOACs in patients with AF with similar baseline characteristics. We used a cohort of hospitalized patients with a primary or secondary diagnosis of AF after discharge to the community, whose data were stored in the Quebec administrative databases, from 2011 to 2017. Older adults with AF newly prescribed with rivaroxaban (15 or 20 mg) or apixaban (2.5 mg or 5 mg) were classified as under treatment (UT) and intent to treat (ITT). We used an inverse probability treatment weighting study of new users of rivaroxaban and apixaban to address confounding by indication. The primary effectiveness outcome was ischemic stroke/systemic embolism (SE), while the primary safety outcome was major bleeding (MB). We used Cox proportional models to estimate the marginal hazard ratios (HRs). A total of 1,722 and 4,639 patients used low-dose and standard-dose rivaroxaban, respectively, while 3,833 and 6,773 patients used low-dose and standard-dose apixaban, respectively. No significant difference was observed in the incidence of comparative stroke/SE and MB between low-dose and standard-dose rivaroxaban, except for the risk of acute myocardial infarction (AMI), which was increased with the low dose in the UT analysis. For apixaban, no difference was found in the bleeding rates, but the risk of stroke/SE (HR: 1.95; 95% confidence interval (CI): 1.38-2.76) and death (HR: 1.99; 95% CI: 1.46-2.70) were greater in the low-dose group than in the standard-dose group in the UT analysis. Similar results were observed for the ITT analysis. No significant differences were observed in the effectiveness or safety outcome between low-dose and standard-dose rivaroxaban, except for AMI. However, low-dose apixaban was associated with a greater risk of stroke/SE and death without a reduction in the bleeding rates.

Acute stroke is the leading cause of disability in the UK and a leading cause of mortality worldwide. The majority of patients with ischaemic stroke present with minor deficits or transient ischaemic attack (TIA), and are often first seen by patient-facing clinicians. Urgent evaluation and treatment are important as many patients are at high risk of major vascular events and death within hours to days after the index event. This narrative review summarises the evidence on four antiplatelet treatments for non-cardioembolic stroke prevention: aspirin, clopidogrel, dipyridamole and ticagrelor. Each of these drugs has a unique mechanism and has been tested as a single agent or in combination. Aspirin, when given early is beneficial and short-term treatment with aspirin and clopidogrel has been shown to be more effective in high-risk TIA / minor stroke. This review concludes by highlighting gaps in evidence, including scope for future trials that could potentially change clinical practice.

Prevention and treatment of stroke are extremely important to reduce the incidence of stroke-related disability and the associated death. This study aimed to investigate the current ability of community doctors in stroke management in the Jinjiang district of Chengdu, China, and the effect of intensive education on stroke prevention and management ability of these doctors. A self-designed questionnaire was used to investigate the current status of stroke management by community doctors in the Jinjiang district. Subsequently, a series of intensive stroke management education courses for community doctors was designed according to the relevant guidelines for cerebrovascular accident prevention and treatment in China. All community doctors were trained, and their ability to treat and prevent stroke was reassessed using the self-designed questionnaire. Of the 450 questionnaires issued, 370 (82.2%) and 389 (86.4%) community doctors were enrolled before and after intensive education, respectively. The results showed that only 37.8% of the community doctors in the Jinjiang district knew the guidelines for the prevention and treatment of cerebrovascular diseases, and only 45.9% thought they had stroke management ability. The stroke management ability of community doctors improved after intensive education (p < 0.05), including pre-hospital identification and management of stroke, and management of its risk factors. The capacity of community doctors in the Jinjiang district of Chengdu is far from meeting the requirements of stroke prevention and treatment. However, the stroke management ability of the community doctors was greatly improved by promoting intensive education.

Background: Prospective population-based studies are important to accurately determine the incidence and characteristics of stroke associated with atrial fibrillation (AF), while avoiding selection bias which may complicate hospital-based studies. Methods: We investigated AF-associated stroke within the North Dublin Population Stroke Study, a prospective cohort study of stroke/transient ischaemic attack in 294,592 individuals, according to recommended criteria for rigorous stroke epidemiological studies. Results: Of 568 stroke patients ascertained in the first year, 31.2% (177/568) were associated with AF (90.4%, i.e. 160/177 ischaemic infarcts). The crude incidence rate of all AF-associated stroke was 60/100,000 person-years (95% CI = 52–70). Prior stroke was almost twice as common in AF compared to non-AF groups (21.9 vs. 12.8%, p = 0.01). The frequency of AF progressively increased across ischaemic stroke patients stratified by increasing stroke severity (NIHSS 0–4, 29.7%; 5–9, 38.1%; 10–14, 43.8%; ≥15, 53.3%, p < 0.0001). The 90-day trajectory of recovery of AF-associated stroke was identical to that of non-AF stroke, but Rankin scores in AF stroke remained higher at 7, 28 and 90 days (p < 0.001 for all). Discussion: AF-associated stroke occurred in one third of all patients and was associated with a distinct profile of recurrent, severe and disabling stroke. Targeted strategies to increase anticoagulation rates may provide a substantial benefit to prevent severe disabling stroke at a population level.

Background Prospectively collected, routine clinical practice-based data on antithrombotic therapy in non-valvular atrial fibrillation (AF) patients are important for assessing real-world comparative outcomes. The objective was to compare the safety and effectiveness of dabigatran versus vitamin K antagonists (VKAs) in patients with newly diagnosed AF. Methods and results GLORIA-AF is a large, prospective, global registry program. Consecutive patients with newly diagnosed AF and CHA 2 DS 2 -VASc scores ≥ 1 were included and followed for 3 years. To control for differences in patient characteristics, the comparative analysis for dabigatran versus VKA was performed on a propensity score (PS)-matched patient set. Missing data were multiply imputed. Proportional-hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest. Between 2014 and 2016, 21,300 eligible patients were included worldwide: 3839 patients were prescribed dabigatran and 4836 VKA with a median age of 71.0 and 72.0 years, respectively; > 85% in each group had a CHA 2 DS 2 -VASc-score ≥ 2. The PS-matched comparative analysis for dabigatran and VKA included on average 3326 pairs of matched initiators. For dabigatran versus VKAs, adjusted HRs (95% confidence intervals) were: stroke 0.89 (0.59–1.34), major bleeding 0.61 (0.42–0.88), all-cause death 0.78 (0.63–0.97), and myocardial infarction 0.89 (0.53–1.48). Further analyses stratified by PS and region provided similar results. Conclusions Dabigatran was associated with a 39% reduced risk of major bleeding and 22% reduced risk for all-cause death compared with VKA. Stroke and myocardial infarction risks were similar, confirming a more favorable benefit-risk profile for dabigatran compared with VKA in clinical practice. Clinical trial registration https://www.clinicaltrials.gov . NCT01468701, NCT01671007. Graphical abstract

Purpose of the Review The purpose of the study was to review the literature on cryptogenic stroke and embolic stroke of undetermined stroke (ESUS). Cryptogenic stroke according to TOAST criteria is a stroke which is not due to cardiogenic embolism, small vessel disease with lacunes or large vessel disease of brain supplying arteries. In the context of secondary stroke prevention studies, cryptogenic stroke is not operationally defined. Recent Findings The new concept of “embolic stroke of undetermined source” (ESUS) provides an operational definition. ESUS is diagnosed as a non-lacunar stroke on cerebral imaging and exclusion of large vessel atherosclerosis by CTA, MRA or ultrasound. Cardiogenic embolism is made less likely by ECG monitoring and echocardiography. At present, aspirin is used for secondary stroke prevention in patients with cryptogenic stroke. Summary Based on the construct that ESUS might be caused by undetected atrial fibrillation or other embolic mechanisms, ongoing randomised secondary stroke prevention trials are comparing non-vitamin K oral anticoagulants (NOACs) with aspirin.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a growing public health epidemic. In the UK, over 1.3 million people have a diagnosis of AF and an estimated 400,000 remain undiagnosed. AF-related strokes account for a quarter of all strokes and, as AF episodes are often asymptomatic, are still often the first manifestation of AF. Early diagnosis and initiation of oral anticoagulation, where appropriate, may prevent some of these thromboembolic strokes. Public Health England is committed to decrease the incidence of AF-related strokes and has sponsored initiatives aimed at improving AF detection by promoting the uptake of wearable technologies. However, the National Institute for Health and Care Excellence (NICE) has not recommended wearable technology in their recent AF diagnosis and management guidelines (NG196). Diagnostic accuracy of single-lead electrocardiography (ECG) generated by the latest iteration of wearable devices is excellent and, in many cases, superior to general practitioner interpretation of the 12-lead ECG. High-quality ECG from wearable devices that unequivocally shows AF can expedite AF detection. Otherwise, there is a real risk of delaying AF diagnosis with the potential of devastating consequences for patients and their families.

Summary Background The mechanisms by which hypertension causes vascular events are unclear. Guidelines for diagnosis and treatment focus only on underlying mean blood pressure. We aimed to reliably establish the prognostic significance of visit-to-visit variability in blood pressure, maximum blood pressure reached, untreated episodic hypertension, and residual variability in treated patients. Methods We determined the risk of stroke in relation to visit-to-visit variability in blood pressure (expressed as standard deviation [SD] and parameters independent of mean blood pressure) and maximum blood pressure in patients with previous transient ischaemic attack (TIA; UK-TIA trial and three validation cohorts) and in patients with treated hypertension (Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm [ASCOT-BPLA]). In ASCOT-BPLA, 24-h ambulatory blood-pressure monitoring (ABPM) was also studied. Findings In each TIA cohort, visit-to-visit variability in systolic blood pressure (SBP) was a strong predictor of subsequent stroke (eg, top-decile hazard ratio [HR] for SD SBP over seven visits in UK-TIA trial: 6·22, 95% CI 4·16–9·29, p<0·0001), independent of mean SBP, but dependent on precision of measurement (top-decile HR over ten visits: 12·08, 7·40–19·72, p<0·0001). Maximum SBP reached was also a strong predictor of stroke (HR for top-decile over seven visits: 15·01, 6·56–34·38, p<0·0001, after adjustment for mean SBP). In ASCOT-BPLA, residual visit-to-visit variability in SBP on treatment was also a strong predictor of stroke and coronary events (eg, top-decile HR for stroke: 3·25, 2·32–4·54, p<0·0001), independent of mean SBP in clinic or on ABPM. Variability on ABPM was a weaker predictor, but all measures of variability were most predictive in younger patients and at lower (

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