Prevention Of Embolic Stroke Research Articles

Patients with stable, therapeutic INR values should remain on warfarin

The second decade of the 21st century will be remembered as a significant milestone in the treatment and prevention of thromboembolic diseases. The approval of target-specific oral anticoagulants (TSOACs) means that patients with atrial fibrillation (AF) have, for the first time ever, multiple treatment options for the prevention of embolic stroke. Evidence from the landmark registration trials convincingly shows that the TSOACs are at least as safe and effective as warfarin in this setting. Because the new agents do not require routine coagulation monitoring and have very few drug or dietary interactions, they offer both convenience and, possibly, a public health benefit if they are used by patients who otherwise would have declined to take warfarin. However, patients on a highly stable, therapeutic dose of warfarin should not expect better health outcomes if switching to a TSOAC.

Systematic review and meta-analysis of incidence, prevalence and outcomes of atrial fibrillation in patients on dialysis

The reported incidence, prevalence and outcomes of atrial fibrillation (AF) in patients with end-stage renal disease (ESRD) are variable. The risks and benefits of warfarin anticoagulation need to be defined as the risk of bleeding in ESRD patients may overwhelm the benefits of embolic stroke prevention. We undertook a systematic literature review to clarify these issues. A literature search was undertaken using Medline and EMBASE from 1990 to September 2011. Studies that reported incidence, prevalence or selected outcomes in ESRD patients with AF were included. Cross-sectional, cohort and randomized controlled trials with >25 participants were included. The lists of authors and abstracts from the search were reviewed by two investigators to determine the manuscripts for full text review. Data were abstracted to a form designed specifically for this study. The quality of the studies was assessed using the Newcastle-Ottawa scale. Event rates were calculated using a random-effects model. Twenty-five studies met our inclusion criteria. The prevalence of AF was 11.6% and the overall incidence was 2.7/100 patient-years. The risk of mortality and stroke was increased in ESRD patients with AF at 26.9 and 5.2/100 patient-years versus 13.4 and 1.9/100 patient-years compared with ESRD patients without AF. The majority of studies do not support a protective effect for warfarin in ESRD patients with AF. The incidence and prevalence of AF in ESRD patients are higher than in the general population and are associated with an increased risk of stroke and mortality. An appropriately designed randomized controlled trial is required to determine whether anticoagulation is an appropriate therapeutic strategy in patients with end-stage renal disease and atrial fibrillation.

Prevention of Embolic Strokes: The Role of the American College of Chest Physicians

Patients with atrial fibrillation (AF) face an annual stroke risk of about 5%. Evidence that anticoagulants reduce the risk of stroke has evolved over the 20th century. The American College of Chest Physicians (ACCP) has played a critical role in presenting guidelines for stroke prevention in AF. This commentary highlights the role that the ACCP guidelines have played, from their inception to the ninth edition. The first ACCP Conference on Antithrombotic and Thrombolytic Therapy in 1986 developed evidence-based guidelines for the indications, dosage, and monitoring of antithrombotic therapy. The conference recommended that anticoagulants be monitored by the international normalized ratio, and the appropriate dosage was to increase the international normalized ratio to two to three times control. This recommendation was widely accepted. Anticoagulants were recommended for AF with mitral valve disease and for nonvalvular AF with a history of embolism. No recommendations were made for nonvalvular AF without a history of embolism. These recommendations stimulated numerous randomized controlled trials (RCTs). By the third ACCP conference in 1992, RCTs had demonstrated a dramatic 69% stroke reduction in patients with nonvalvular AF. The third ACCP conference was the first to strongly recommend anticoagulation for primary and secondary stroke prevention in nonvalvular AF. ACCP conferences since 1992 have refined recommendations for nonvalvular AF on the basis of associated risk factors. The most recent conference, in 2011, recommended a direct thrombin inhibitor, dabigatran, rather than warfarin as the anticoagulant of choice. These ACCP guidelines have played a critical role in changing physicians' practice patterns. In 1980 only 7% of patients with AF in the United States received OA; by 2007, this had increased to 57%.

Dabigatran: Review of Pharmacology and Management of Bleeding Complications of This Novel Oral Anticoagulant

Dabigatran (Pradaxa) is a competitive direct thrombin inhibitor approved by the US FDA for prevention of embolic stroke in patients with nonvalvular atrial fibrillation. Dabigatran has a pharmacokinetic profile that produces predictable anticoagulation responses, does not undergo CYP 450 metabolism, has few drug-drug and drug-food interactions, and does not require frequent laboratory monitoring of clotting parameters. Clinicians are rapidly prescribing this agent as a replacement for warfarin therapy. However, no therapeutic agent has been accepted to reliably reverse the hemorrhagic complications of dabigatran. As of yet, there is no solid evidence to guide management of bleeding complications; management should start with local control of bleeding when possible and transfusion of pRBCs if needed. Transfusion of FFP would not be expected to help control bleeding. Limited and mixed data exist for transfusion of factor VIIa and prothrombin complex concentrates; these therapies should be considered as well as dialysis, which will increase elimination in patients with life-threatening or closed-space bleeding due to dabigatran. We present an article that reviews the pharmacokinetics, clinical trial literature, and consensus guidelines regarding this novel oral anticoagulant.

New Options in Anticoagulation for Atrial Fibrillation

The presence of atrial fibrillation significantly increases the risk and burden of thromboembolic stroke.1 Warfarin is the reference standard treatment for the primary prevention of embolic stroke during atrial fibrillation.2 However, the long-term use of warfarin has its limitations. Although guidelines suggest a target international normalized ratio (INR) of 2.5 (range, 2.0 to 3.0) for this indication,2 only about 60% of patients have an INR within the recommended range at a given time in usual clinical practice. This is the reason that is most often given for the search for other oral antithrombotic agents that could be simpler to manage . . .

Carotid artery disease: stenting vs endarterectomy

Several multicentre, randomized trials have validated the efficacy of carotid endarterectomy (CEA). Comparative randomized trials are also currently developing insight into the role of carotid angioplasty and stenting (CAS), and identifying factors for optimal patient selection. Although these interventions are aimed at embolic stroke prevention, anaesthetic management might prevent the subset of strokes that are haemodynamic in nature by maintaining tight physiological control. The perioperative risk of myocardial events is increased in this population. Hence, preoperative attention to cardiovascular disease, hypertension, renal insufficiency, and diabetes mellitus might reduce neurological and cardiovascular complications. During carotid artery cross-clamping, the risk of cerebral ischaemia can be decreased by maintaining normal to high perfusion pressure. Although there is no demonstrable advantage of a specific anaesthetic technique for patients undergoing CEA, it is imperative that cerebral blood flow is optimized, that there is minimal cardiac stress, and that anaesthetic recovery is rapid. Carotid angioplasty and stenting is performed under light sedation with antithrombotic therapy and vigilance for bradycardia and hypotension. Tight haemodynamic control remains a priority in the immediate postoperative period for both interventions.

Prevention of embolic stroke by catheter ablation of atrial fibrillation

Radiofrequency-catheter-ablation of atrial fibrillation is now commonly performed. Aim of this short review is to summarize questions and uncertainties concerning radiofrequency ablation of atrial fibrillation with respect to therapeutic mechanisms, long-term efficacy and stroke-prevention. The majority of atrial fibrillation patients is too old for radiofrequency ablation. Candidates for radiofrequency ablation belong to a subgroup with a low embolic risk. The radiofrequency ablation procedure itself may increase the embolic risk, and at present it is uncertain how long this embolic risk persists after the procedure. We doubt if radiofrequency ablation prevents embolism in atrial fibrillation.

The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage.

Warfarin sodium is highly effective for prevention of embolic stroke, particularly in nonvalvular atrial fibrillation, but its expected benefit can be offset by risk of intracerebral hemorrhage (ICH). We studied the determinants of ICH outcome to quantify the independent effect of warfarin. Consecutive patients with supratentorial ICH treated in a tertiary care hospital with a neurointensive care unit were prospectively identified during a 7-year period, and data on hemorrhage location, clinical characteristics, and warfarin use were collected. Independent predictors of 3-month mortality were determined using multiple logistic regression analysis. Of 435 consecutive patients aged 55 years or older, 102 (23.4%) were taking warfarin at the time of ICH. Three-month mortality was 25.8% for those not taking warfarin and 52.0% for those taking warfarin. Independent predictors of death were warfarin use (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.3-3.8), age 70 years or older (OR, 2.4; 95% CI, 1.4-4.0), and presence of diabetes mellitus (OR, 1.8; 95% CI, 1.0-3.3). Although 68.0% of all warfarin-related hemorrhages occurred at an international normalized ratio (INR) of 3.0 or less, increasing degrees of anticoagulation were strongly associated with increasing risk of death compared with no warfarin use. Patients taking warfarin had a doubling in the rate of intracerebral hemorrhage mortality in a dose-dependent manner. The data suggest that careful control of the INR, already known to limit the risk of warfarin-related ICH, may also limit its severity.

Large variations in the use of oral anticoagulants in stroke patients with atrial fibrillation: a Swedish national perspective.

To explore nation-wide use of anticoagulation in stroke patients with atrial fibrillation, in routine clinical practice in Sweden. Cross-sectional cohort study. Patients included in Riks-Stroke, the Swedish national quality register for stroke care, during 2001. Hospitals with incomplete coverage were excluded, leaving 4538 stroke patients with atrial fibrillation amongst 18 276 stroke patients from 75 hospitals in six health care regions. Treatment with oral anticoagulants. At stroke onset, the proportion of patients with atrial fibrillation and first-ever stroke, receiving oral anticoagulants as primary prevention was 11.0% (range 8.4-13.5% between regions and 2.5-24.4% between hospitals). Younger age, male sex and diabetes at stroke onset independently predicted primary prevention with oral anticoagulants. The proportion of stroke patients with atrial fibrillation receiving oral anticoagulants as secondary prevention at discharge was 33.5% (range 29.9-40.6% between regions and 16.4-61.9% between hospitals). Independent predictors for secondary prevention were younger age, male sex and independent activities of daily life (ADL) function before the stroke, being discharged to home, being fully conscious on admission and health care region. There were variations between hospitals and regions that differences in age, sex, functional impairments and comorbidities could not fully explain. This indicates that evidence-based primary and secondary prevention of embolic stroke is insufficiently practised. Local factors seem to determine whether patients with atrial fibrillation gain access to optimal prevention of stroke or not.

Anticoagulant treatment in primary health care in Sweden - prevalence, incidence and treatment diagnosis: a retrospective study on electronic patient records in a registered population.

BackgroundThe indications for warfarin treatment in primary health care are increasing. An undertreatment with warfarin is reported in the prevention of embolic stroke in patients with chronic atrial fibrillation, and can be suspected for other indications. Information on the prevalence and incidence of diseases treated with warfarin would reveal useful data for audits concerning management of anticoagulant treatment. We aimed to assess warfarin treatment in primary health care with regard to prevalence, incidence, treatment diagnosis and patient characteristics.MethodsA one-year retrospective study of electronic patient records up to May 2000 in primary health care in Stockholm, Sweden. Five primary health care centres with a registered population of 75 146. Main outcome measures were prevalence, incidence and treatment diagnosis.ResultsFive hundred and seven patients, mean age 71.9 years, were on warfarin treatment. The prevalence was 0.67% (age-adjusted 0.75%), and it was significantly higher for men (0.78%) than for women (0.58%) (p = 0.01). In the age group 75–84 years the prevalence was 4.54%. The most prevalent treatment diagnosis was chronic atrial fibrillation (0.28%), which was more predominant for males (p = 0.02), followed by cerebrovascular disease (0.13%) and deep venous thrombosis (0.13%). The yearly incidence of warfarin treatment was 0.17%, with chronic atrial fibrillation as the predominant treatment diagnosis.ConclusionWarfarin treatment in primary health care is prevalent among the elderly. Chronic atrial fibrillation is the main treatment diagnosis. There is a gender difference favouring men in general and chronic atrial fibrillation as the treatment diagnosis.

EFFECTIVE EMBOLI DIVERSION BY A NOVEL PERMANENT DEVICE FOR PREVENTION OF EMBOLIC STROKE

Purpose: To test the efficacy of a new embolic stroke prevention device (the Diverter) to be implanted at the carotid bifurcation using a mock circulation and animal model. The Diverter is designed to divert emboli away from the internal into the external carotid artery. We hypothesized that emboli smaller than the Diverter pores could be diverted. Methods: A compliant transparent silicon tubes model of the carotid bifurcation was used to investigate the capacity of the Diverter (pore size 450μm) to redirect polystyrene particles sized 50–700 μm. Subsequently, a swine model was used to validate the in-vitro findings. After implantation of the Diverter between the Right Carotid (RC) and bicarotid arteries (diverting the particles away from the Left carotid) the particles were injected (4 boluses) and collected at both carotids using shunts with bleed valves. The weight of the diverted and non-diverted particles was compared. Results: The particles larger than 450μm were fully diverted. Within the particles smaller than pore size, 98.4±0.9, 92.0±7.1 and 81.6±15.1% of the 350–420, 250–300 and 210–250μm particles, respectively, were diverted into RC. Post deployment injection of contrast material demonstrated Diverter patency. Pre-deployment injections showed that the particles were distributed according to the flow regardless of their size. Conclusions: The novel Diverter was found highly effective for redirecting emboli smaller than its pore size. Our in-vitro and in-vivo data support the clinical use of this novel permanent protective device for prevention of embolic stroke.

Surgical management of atherosclerotic aortic arch aneurysms using selective cerebral perfusion: 7-year experience in 52 patients.

Patients with atherosclerotic aortic arch aneurysms are at greater risk for brain complication. We report our techniques and results of operation using selective cerebral perfusion. We retrospectively analyzed 52 consecutive patients with atherosclerotic aortic arch aneurysms (mean age, 70 years, range, 53-86 years), who underwent operation between April 1992 and March 1999. The operation was non-elective in 11 patients (21.1%). Concomitant operations included eight coronary artery bypass grafting and one aortic valve replacement. Simultaneous distal aortic reconstruction was performed in three patients. The operation was performed through median sternotomy. To avoid brain embolism, total arch replacement with a branched prosthesis was performed in 48 patients, in an attempt to exclude affected segments of aorta. In addition, retrograde femoral artery perfusion was avoided and cerebral circulation was isolated before aortic manipulation. To achieve even blood flow distribution, we employed perfusion and continuous pressure monitoring of all the three arch vessels. The perfusion rate was 12+/-2 ml/kg per min and the pressure was kept around 50 mmHg. Deep hypothermic arrest of the lower torso (bladder temperature, 22 degrees C) was used during open distal aortic anastomosis. The hospital mortality rate was 11.5% (six of 52), and 7.3% (three of 41) for elective cases. Only one patient (1. 9%) developed permanent focal neurological deficit. Six other patients showed temporary brain complications, which was global (delirium) in three and focal in three others. Selective cerebral perfusion is a safe brain protection method, and our strategy seems effective for embolic stroke prevention.

Decision analysis concerning the application of echocardiography to the diagnosis and treatment of mural thrombi after anterior wall acute myocardial infarction

The diagnostic and therapeutic approach to the problem of mural thrombi after acute myocardial infarction is uncertain. it is clear that the main therapeutic goal is the prevention of embolic strokes. Although it is known that the incidence of thrombi is greatest after anterior wall infarctions, there is uncertainty concerning (1) the probability of a mural thrombus; (2) the sensitivity and specificity of echocardiography in making the diagnosis; (3) the probability that a thrombus will embolize and result in a cerebrovascular accident (CVA); (4) the efficacy of warfarin in preventing embolization; and (5) the probability of bleeding with and without warfarin. To study this problem in patients who have had an anterior wall myocardial infarction, a model was created in which reasonable estimates for the unknown parameters were determined from published medical studies. The model was designed to consider patients if they were or were not treated during the initial hospitalization with heparin. The probability of thrombus was estimated at 0.30, sensitivity and specificity of echocardiography at 0.85 and 0.85, probability that a thrombus will embolize at 0.15, efficacy of anticoagulation of 0.75, probability of bleeding with warfarin at 0.03 and probability of bleeding without warfarin at 0.005. Probabilities of a CVA and of bleeding with and without warfarin were determined if all patients were anticoagulated, if patients with positive echocardiographic results were treated, if patients with negative echocardiographic results were treated and if echocardiographically guided therapy was instituted in which patients with positive echocardiographic results are treated and patients with negative results are not treated. The results revealed that the baseline probability of a CVA will be reduced from 0.045 to 0.011 with anticoagulation for all patients and to 0.016 for echocardiographically guided therapy. These models translate into anticoagulation of 30 patients to prevent 1 stroke if all patients are anticoagulated versus “treatment” of 35 patients to prevent 1 stroke if echocardiography is used to guide anticoagulation. There is a net savings in major bleeding events for echocardiographically guided therapy, allowing 111 patients to be treated for 1 bleeding event compared with 40 for the strategy in which all patients are treated. Sensitivity analysis permitted these results to be expanded and amplified. Echocardiographically guided therapy prevents most CVAs at considerable savings in bleeding episodes. This strategy is especially safe if the sensitivity is high.