Efficacy In Stroke Prevention Research Articles

Role of Endovascular Closure of the Left Atrial Appendage in Stroke Prevention for Atrial Fibrillation.

The pathophysiologic mechanism of thromboembolic stroke in the setting of non-valvular atrial fibrillation (AF) resides in the left atrial appendage (LAA). In this setting, approximately 90 % of all strokes originate from this structure. Percutaneous left atrial appendage occlusion (LAAO) therapy has recently emerged as an important strategy for prevention of stroke and systemic embolism in patients with non-valvular AF. Systemic anticoagulation therapy in this AF population, while effective, is associated with a significant bleeding risk, drug compliance issues, and limited reversal strategies. In this manuscript, we will review the percutaneous devices and techniques that allow endovascular closure of the LAA, including their efficacy in stroke prevention, the safety profile of these local site-specific therapies, comparison of the multiple approaches being studied, the index patient populations involved, and long-term follow-up in comparison with systemic anticoagulation therapy. The percutaneous LAAO approach indeed represents an exciting and revolutionary advance in the field of stroke prevention in AF.

Use of non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients: insights from a specialist atrial fibrillation clinic.

Non-vitamin K antagonist oral anticoagulants (NOACs) are broadly preferable to vitamin K antagonists (VKAs) for stroke prevention in non-valvular atrial fibrillation (AF) given their overall net clinical benefit. We report an audit of the profile of OAC usage and adverse events in patients attending a specialist AF clinic. Patients attending our specialist AF clinic who were commenced on NOACs for SPAF between January 2013 and August 2014 were included and electronic medical records were retrospectively reviewed between August 2014 and November 2014, to collect demographic, clinical and outcome data. Outcomes included cerebrovascular and bleeding events, death, switching between NOACs or to VKA, dose changes, cessation of NOACs and the reasons for these. To provide perspective, descriptive comparisons were made with a historical cohort of warfarin users attending the specialist AF clinic prior to the introduction of NOACs. We report data on 813 patients as follows: (i) 233 consecutive patients (mean (standard deviation) age 74 (10) years, 45.1% female) initiated on NOACs, with median (interquartile range) CHA2 DS2 -VASc score 3 (2-5) and HAS-BLED score 1 (1-2); and (ii) a historical cohort of 580 patients on warfarin (mean (SD) age 75 (10) years, 42.1% female) with broadly similar demographics. Overall, 54.5% (127/233) were started on rivaroxaban, 22.7% (53/233) on dabigatran and 22.7% on apixaban. Two patients experienced a transient ischaemic attack; 31 patients (13%) contributed to 37 documented bleeding events of which five bleeds (in four patients, 1.7%) were classified as major. There were seven deaths; cause of death was not available for three and the others were not related to NOACs. Eighteen (7.7%) patients switched NOACs, 2 (0.9%) patients switched to warfarin and 8 (3.4%) had their NOACs stopped. There were no ischaemic strokes in the NOAC cohort, compared with nine in the warfarin cohort, with a similar rate of major bleeding (1.7% for NOACs and 1.6% for warfarin). There were more gastrointestinal haemorrhages in the NOAC cohort (3.4% vs. 0.7% with warfarin). In this specialist AF clinic, patients prescribed NOACs had a favourable adverse event profile with good efficacy for stroke prevention, with a low rate of cessation or switch to warfarin.

Efficacy of stroke prevention in atrial fibrillation: a way of improvement.

Improve stroke prevention in atrial fibrillation (AF) patients. AF patients on warfarin who visited Bradford Anticoagulation Clinic between January and December 2013 were listed randomly, then the first 200 patients were selected. Time in therapeutic range (TTR) over that year was calculated for each patient using the Rosendaal method. Exclusion criteria: 1. Patients recently started on warfarin (within 6 weeks). 2. Patients with a target international normalised ratio (INR) range other than 2.0–3.0. …

Efficacy of stroke prevention in atrial fibrillation: a way of improvement

Improve stroke prevention in atrial fibrillation (AF) patients. AF patients on warfarin who visited Bradford Anticoagulation Clinic between January and December 2013 were listed randomly, then the first 200 patients were selected. Time in therapeutic range (TTR) over that year was calculated for each patient using the Rosendaal method. Exclusion criteria: 1. Patients recently started on warfarin (within 6 weeks). 2. Patients with a target international normalised ratio (INR) range other than 2.0–3.0. …

Comparing Patient and Physician Risk Tolerance for Bleeding Events Associated with Anticoagulants in Atrial Fibrillation—evidence from the United States and Japan

ObjectivesAtrial fibrillation (AF) is a factor in the development of thrombi that can lead to ischemic strokes. Anticoagulants are crucial in preventing strokes among patients with AF but are associated with bleeding risks. Recent studies have shown that despite anticoagulants’ efficacy in stroke prevention, many patients with AF receive subtherapeutic levels of anticoagulation because of concerns about bleeding. Of particular interest is to quantify the perceived relative importance of treatment-related benefits and risks and how these perceptions vary between patients and physicians in different countries. MethodsPatients’ and physicians’ preferences were elicited using a discrete-choice experiment. We evaluated disagreements in preferences for the benefits and risks of anticoagulants. ResultsA total of 186 patients with AF and 107 physicians in the United States completed the survey. In Japan, 152 patients and 164 physicians completed the same survey. Japanese patients were relatively less averse than US patients to bleeding risks. Physicians in both countries did not distinguish between nondisabling and disabling strokes. US patients were less tolerant than physicians of nonmajor clinically relevant bleeding risk when this risk was a consequence of preventing nondisabling strokes. Japanese patients were generally more tolerant than physicians of bleeding risks when the risks were consequences of preventing both nondisabling and disabling strokes. ConclusionsOverall, preferences for anticoagulant benefits and risks were not statistically different between patients and physicians in the United States, nor were there differences in preferences for different stroke risks between physicians in the United States and Japan; however, preferences were different between patients and physicians in Japan.

Relevance of P-glycoprotein in stroke prevention with dabigatran, rivaroxaban, and apixaban.

The new oral anticoagulants (NOAC) dabigatran etexilate, rivaroxaban, and apixaban show similar efficacy for stroke prevention in patients with atrial fibrillation (AF) as the vitamin K antagonist warfarin. Absorption of NOACs is dependent on the intestinal P-glycoprotein (P-gp) system and P-gp activity is modulated by a variety of drugs and food components. The aim of this review is to give an overview of P-gp-associated drug-drug and drug-food interactions with NOACs in AF patients. A literature search was carried out by screening MEDLINE for the terms dabigatran, rivaroxaban, apixaban, P-glycoprotein, and atrial fibrillation from 1998 to 2013. Randomized clinical trials, longitudinal studies, case series, and case reports were included. Concomitant medication with proton pump inhibitors, amiodarone, clarithromycin, and verapamil increased bioavailability whereas rifampicin decreased the bioavailability of dabigatran. Coadministration of erythromycin, clarithromycin, fluconazole, ketoconazole, and ritonavir increased rivaroxaban plasma concentrations. No data were found on apixaban and P-gp-modulating drugs or on NOACs and food components modulating P-gp. The clinical relevance of interactions between NOACs and P-gp-modulating drugs or food components is largely unknown as bleeding complications under NOACs and P-gp-inhibiting drugs are mainly reported from patients with concomitant renal failure. There is an urgent need to investigate the role of P-gp-modulating substances as potential sources of drug-drug and drug-food interactions. A thorough analysis of the data accumulated in the three large NOAC trials regarding the role of P-gp-modulating drugs in bleeding and embolic events is desirable. Pharmacological studies should investigate the influence of P-gp-modulating drugs and food on NOAC plasma concentrations and coagulation parameters. When prescribing NOACs, patients should be informed about the potential interactions with drugs and herbal drugs. Patients who develop bleeding or embolic events under treatment with NOACs should be investigated for co-medications as well as for over-the-counter drugs and dietary habits. In post-marketing surveillance of NOACs, the association with drug or food intake with complications, bleeding, and embolic events should be registered.

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

The Korean Heart Rhythm Society's 2014 Statement on Antithrombotic Therapy for Patients with Nonvalvular Atrial Fibrillation: Korean Heart Rhythm Society.

In patients with nonvalvular atrial fibrillation (AF), the risk of stroke varies considerably according to individual clinical status. The CHA2DS2-VASc score is better than the CHADS2 score for identifying truly lower risk patients with AF. With the advent of novel oral anticoagulants (NOACs), the strategy for antithrombotic therapy has undergone significant changes due to its superior efficacy, safety and convenience compared with warfarin. Furthermore, new aspects of antithrombotic therapy and risk assessment of stroke have been revealed: the efficacy of stroke prevention with aspirin is weak, while the risk of major bleeding is not significantly different from that of oral anticoagulant (OAC) therapy, especially in the elderly. Reflecting these pivotal aspects, previous guidelines have been updated in recent years by overseas societies and associations. The Korean Heart Rhythm Society has summarized the new evidence and updated recommendations for stroke prevention of patients with nonvalvular AF. First of all, antithrombotic therapy must be considered carefully and incorporate the clinical characteristics and circumstances of each individual patient, especially with regards to balancing the benefits of stroke prevention with the risk of bleeding, recommending the CHA2DS2-VASc score rather than the CHADS2 score for assessing the risk of stroke, and employing the HAS-BLED score to validate bleeding risk. In patients with truly low risk (lone AF, CHA2DS2-VASc score of 0), no antithrombotic therapy is recommended, whereas OAC therapy, including warfarin (international normalized ratio 2-3) or NOACs, is recommended for patients with a CHA2DS2-VASc score ≥2 unless contraindicated. In patients with a CHA2DS2-VASc score of 1, OAC therapy should be preferentially considered, but depending on bleeding risk or patient preferences, antiplatelet therapy or no therapy could be permitted.

Anticoagulation-related reduction of first-ever stroke severity in Chinese patients with atrial fibrillation

Atrial fibrillation (AF) is an independent risk factor for ischemic stroke and warfarin related anticoagulation has been recommended as an effective treatment for stroke prevention. We aimed to determine whether pre-stroke oral anticoagulation therapy would reduce initial stroke severity in AF patients with first-ever ischemic stroke. We identified consecutive patients who developed first-ever ischemic stroke and were eligible for anticoagulation therapy from the China National Stroke Registry. Multivariate logistic analysis was used to assess the association between warfarin usage and initial stroke severity, measured by the National Institutes of Health Stroke Scale (NIHSS) and the Glasgow Coma Scale (GCS). Of 9519 patients, 1140 (11.98%) had AF, including 440 (38.6%) without known AF before presentation, 561 (49.2%) with known AF but not taking warfarin, and 139 (12.2%) with known AF who were taking warfarin. Compared to patients with known AF but not on warfarin, the odds ratio (OR) of having a major stroke (NIHSS ⩾4) was lower in patients with known AF who were on warfarin (OR=0.68; 95% confidence interval [CI] 0.57–0.84). The OR of developing a severe coma (GCS 3–8) was also reduced in the warfarin group (OR=0.71; 95% CI 0.56–0.91). In conclusion, pre-stroke warfarin therapy lowered the severity of the first-ever ischemic stroke in patients with known AF. Considering its efficacy in stroke prevention and the significant under-usage of warfarin in China, the primary prevention of stroke in AF patients should be reinforced.

Ischaemic stroke prevention in patients with atrial fibrillation and high bleeding risk: opportunities and challenges for percutaneous left atrial appendage occlusion.

Patients with atrial fibrillation (AF) are at an increased risk of ischaemic stroke. The efficacy of stroke prevention with vitamin K antagonists in these patients has been well established. However, associated bleeding risks may offset the therapeutic benefits in patients with risk factors for bleeding. Despite improvements achieved by novel oral anticoagulants, bleeding remains a clinically relevant problem, especially gastrointestinal bleeding. Percutaneous occlusion of the left atrial appendage (LAA) may be considered as an alternative stroke prevention therapy in AF patients with a high bleeding risk. This paper explores patient groups in whom oral anticoagulation may be challenging and percutaneous LAA occlusion (LAAO) has a potentially better risk-benefit balance. The current status of LAAO and future directions are reviewed, and particular challenges for LAA occlusion requiring further clinical data are discussed. This article is a summary of the Third Global Summit on LAA occlusion, 15 March 2013, Barcelona, Spain.

New Alternative Anticoagulants in Atrial Fibrillation: The Move Beyond Warfarin.

Given the increasing prevalence of atrial fibrillation, the need for safe and effective stroke prophylaxis will continue to rise. Warfarin has been around for many years and has proven efficacy in preventing stroke, but it has major limitations due to its variable dosing, food and drug interactions, and requirement for regular monitoring. Newer agents which include dabigatran, rivaroxaban, and apixaban have recently or will soon be available and may provide an improved efficacy in stroke prevention, an improved safety profile, and improved user-friendliness. Dabigatran was the first of the agents to be widely available, and in the RE-LY study, dabigatran (150 mg dose) showed superiority to warfarin in preventing ischemic stroke and a significant reduction in intracranial bleeding. Rivaroxaban was studied in the ROCKETAF trial, and with once daily dosing, it showed noninferiority to warfarin in preventing stroke with a significant reduction in intracranial bleeding. The ARISTOTLE trial showed apixaban was superior to warfarin for stroke prevention, significantly reduced all major bleeding, and resulted in a significant reduction in all-cause mortality. While all three trials have important limitations, they were very large randomized trials with more than 14,000 patients each and show a clear overall net clinical benefit when compared with warfarin. Key features of the drugs as well as an individual's preferences and stability on warfarin will help guide the ultimate drug choice for any given patient, but these newer anticoagulant agents are likely to usher in a new era in stroke prevention in atrial fibrillation.

337-I * THORACOSCOPIC LEFT ATRIAL APPENDECTOMY

Objectives: In patients with non-rheumatic atrial fibrillation, the most common place for thrombosis is the left atrial appendage (LAA). The efficacy of stroke prevention with oral anticoagulant therapy (OAC) has been proved, but there are patients who are not candidates for long-term OAC, namely patients with a high risk of bleeding complications or previous haemorrhagic stroke. In those patients, percutaneous closure of the LAA has been demonstrated to be safe and efficacious in preventing cardioembolic events. However, some LAAs are too large or too fragile and they may not be suitable for occlusion. Methods: We present a film showing videothoracoscopic LAA excision in an 82-year-old male patient with lone atrial fibrillation, in whom the need to suppress OAC became obvious after an intracerebral haemorrhagic event. Percutaneous closure of LAA also failed because an additional LAA lobe precluded tight occlusion. Results: Following right selective pulmonary intubation, the patient was placed in a right anterolateral decubitus position. Transoesophageal echocardiography confirmed the absence of LAA thrombus. Three thoracoscopic incisions were made to introduce the video-assisted thoracoscopic instruments. The pericardial cavity was entered 1 cm above the phrenic nerve and the pericardial incision was enlarged to visualize the LAA. Then, a gentle traction was performed to show the appendiceal base where a row of staples was placed. The duration of the procedure was 40 min and the patient was discharged after four days without postoperative complications. Conclusions: This approach demonstrated feasibility, safety and effectiveness and should be considered as a possible alternative to percutaneous closure of the LAA. However, its effect on long-term prevention of stroke needs to be evaluated.

Anticoagulation Therapy for Atrial Fibrillation

Atrial fibrillation (AF) is the most common significant cardiac rhythm disorder, and its prevalence is increasing worldwide. Atrial fibrillation confers a fivefold increased risk of stroke, and these strokes are associated with significant mortality and disability. The vitamin K antagonist, warfarin, has been the mainstay of anticoagulant therapy for patients with AF, reducing the risk of stroke by 65%. Despite its efficacy, warfarin remains underused in clinical practice because of its variable dose response, diet and medication interactions, and need for frequent monitoring. Stroke prevention in AF has entered an exciting therapeutic era with new classes of targeted anticoagulants that avoid the many pitfalls of the vitamin K antagonists. Dabigatran, an oral thrombin inhibitor, and the factor Xa inhibitors, rivaroxaban and apixaban, have demonstrated efficacy for stroke prevention and a reduced risk of intracranial hemorrhage relative to warfarin. Translating the efficacy of clinical trials into effective use of these novel agents in clinical practice will require an understanding of their pharmacokinetic profiles, dose selection, and management in select clinical situations.

AHA 2012: Prevention a key focus of meeting

The American Heart Association (AHA) Scientific Sessions 2012 brought together leading experts from around the world to discuss successes and new initiatives aimed at reducing the burden of cardiovascular disease (CVD). A key focus of the meeting was on treatments aimed at preventing cardiovascular events. In addition, the meeting discussed the efficacy of novel therapies and safety of marketed treatments. A review of select late-breaking trials and other presentations will be covered in this article.

Spontaneous splenic hemorrhage after initiation of dabigatran (Pradaxa) for atrial fibrillation

Dabigatran etexilate (Pradaxa; Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT) is an oral anticoagulant that produces a reliable, dose-dependent anticoagulant effect without the need for routine laboratory monitoring. Dabigatran is a direct thrombin inhibitor, acting like other members in its class (bivalirudin, argatroban) to impede the clotting process through selective and reversible binding with both free and clot-bound thrombin. Dabigatran anticoagulates rapidly: plasma levels peak 2 hours after absorption, with a half-life that ranges between 12 and 17 hours. Dabigatran was approved by the Food and Drug Administration in October 2010 after it compared favorably with warfarin in a large clinical trial studying its efficacy in stroke prevention in atrial fibrillation. Currently, there is no laboratory test on the market by which a physician can quantify the anticoagulation effect of dabigatran, nor is there any antidote to reverse a life-threatening bleed should it occur. We present a case of a patient with splenic hemorrhagic soon after initiation of dabigatran.

Cilostazol, a phosphodiesterase inhibitor, prevents no-reflow and hemorrhage in mice with focal cerebral ischemia

Background and PurposeThe Cilostazol Stroke Prevention Study II has shown a similar efficacy in stroke prevention but markedly fewer hemorrhagic events with the phosphodiesterase inhibitor cilostazol versus aspirin. The purpose of this study is therefore to investigate how cilostazol affects cerebral hemodynamics and whether it prevents hemorrhagic transformation induced by recombinant tissue plasminogen activator (rtPA) in a mouse model of focal ischemia/reperfusion. Particular emphasis will be placed on the plasma-microvessel interface. MethodsAfter receiving food containing 0.3% cilostazol or standard food for 7days, adult C57BL/6J mice were subjected to middle cerebral artery occlusion/reperfusion with or without rtPA (10mg/kg) intravenously administered prior to reperfusion. Cerebral blood flow was monitored at several time points by laser speckle imaging in the 24 hour period post reperfusion, before neurobehavioral and histological assessment. The long-term effect of cilostazol on cerebral ischemia was analyzed in the non-rtPA cohort. ResultsIn the non-rtPA cohort, pretreatment by cilostazol significantly decreased the endothelial expression of adhesion molecules (P-selectin and intercellular adhesion molecule-1) and prevented platelet aggregation and leukocyte plugging in the microvessels after cerebral ischemia/reperfusion in the acute phase. Cilostazol significantly reduced mortality rate and improved motor function at 7days post-ischemia/reperfusion. In the rtPA cohort, cilostazol significantly suppressed edema formation and hemorrhagic transformation with reduced density of microglial cells positive for matrix metalloproteinase-9 in the cerebral cortex and the striatum. In both cohorts, cilostazol significantly suppressed focal no-reflow, mitigated cerebral infarct, and improved neurological outcome. ConclusionsCilostazol may possess protective properties against cerebral ischemic injury by preventing no-reflow and hemorrhagic transformation, via maintenance of microvascular integrity.

Carotid Surgery or Stenting Following Neck Irradiation: Time to Address the Assumptions

Magne et al. are to be congratulated for reviewing the outcomes of carotid surgery for their 24 patients with prior neck irradiation,1 adding one of the largest and longest followed case-series reported for such patients. This, and the other 17 case-series quoted by Magne et al. of patients with prior neck irradiation undergoing open carotid surgery2e9 or angioplasty/stenting,9e17 illustrate how these procedures are technically possible with low 30-day procedural stroke/death rates. Considering all 18 case-series, the periprocedural 30-day stroke/death rate was 0% in ten (56%).1,3e6,8,11,12,15,17 However, among these ten case-series, the average sample size was only 16 patients (range 4e28) with a mean followup of approximately 1.6 years (range 1e37 months). By contrast, in the remaining eight case-series, the 30-day perioperative stroke/death rate was >0% (range 1.5e10%). In these, the average sample size was over double, 35 patients (range 10e135), with a mean followup of approximately 2.7 years (range 18e58 months). Small sample sizes, brief followup and publication bias (good operative results more likely reported and published) are important reasons why routine practice procedural risk may be underestimated. It has taken prospective studies of thousands of patients to compare safety of carotid surgery versus stenting in patients without prior neck irradiation. Further, it is clear that procedural results from one centre cannot be assumed equivalent to another. Crucial elements in determining procedural complication rates are; operator experience, procedural technique, quality of vascular disease medical (non-invasive) intervention received, patient risk factor profile and method of followup to identify outcomes. It is also clear that the stroke prevention efficacy of vascular disease medical intervention has improved significantly over recent decades indicating that fewer patients are now likely to benefit from invasive carotid procedures.18e21 As medical intervention improves, invasive carotid procedures need to become more specialised. It is time for all carotid surgery and endovascular services to adopt ongoing audit activities, documenting use of current, optimal vascular disease medical intervention and procedural technique and incorporating independent, prospective identification of outcomes of

Role of Carotid Stenting in Management of Carotid Bifurcation Disease: Was the Revolution Overstated?

At its advent, carotid artery stenting (CAS) was widely touted by some as a revolution in the revascularization of severe carotid artery disease, destined to replace carotid endarterectomy (CEA). However, 15 years after the early phases of CAS, it still has only a limited role in carotid therapy in the US. This article will explore the reasons why, which are related to expert operator availability, early trials (largely EU based) that did not support the safety of CAS but which were confounded by a variety of factors which severely limited a true assessment of CAS outcomes, mandatory time-lines involved with regulatory approval, technique and patient selection, and Medicare non-coverage for the multiple FDA-approved devices except for a very select population of patients. The recent publication of the CREST study, and the subsequent FDA Devices Panel presentation of additional analyses, demonstrates equivalent safety and long-term stroke prevention efficacy. This, combined with the adjunct morbidity associated with CEA including cranial nerve injury and excess incisional site complications, suggests that, assuming FDA and CMS approvals, that CAS is poised to have a greater place in the management of the carotid patient.

Transient ischaemic attack clinics and management of transient ischaemic attacks

The aim is to review transient ischaemic attack (TIA) clinics, other service delivery models, and current TIA management. Urgent assessment of TIA patients by stroke specialist services reduces stroke risk and is cost-effective. Almost one-third of TIA patients wait more than 24 h before presenting to medical attention, with delay associated with higher stroke risk. Risk stratification following suspected TIA may be performed by clinical assessment of individual patient characteristics, combined with the validated ABCD2 score (pre-investigation), and the ABCD3-I score (postinvestigation) in secondary care settings. Brain MRI and transcranial Doppler ultrasound add information related to vascular territory, TIA mechanism, and prognosis. Variability in systolic blood pressure in treated and untreated patients is an important predictor of stroke risk, independently of mean blood pressure. Daily specialist-provided TIA services delivered in clinic or inpatient settings have proven efficacy for stroke prevention. In addition, a rapid-access, clinic-based service is associated with cost savings and reduced hospital bed-day utilization after TIA.

Clopidogrel Versus Dipyridamole in Addition to Aspirin in Reducing Embolization Detected With Ambulatory Transcranial Doppler

After stroke and transient ischemic attack there is a high early risk of recurrent stroke, particularly in large artery disease. It has been suggested more intensive antiplatelet regimens are required, but trial data are lacking. Treatment efficacy can be evaluated using transcranial Doppler detection of embolic signals. Ambulatory transcranial Doppler has recently been developed; prolonged recording may reduce subject numbers required to determine therapeutic efficacy. In a randomized trial (ISRCTN68019845) with blinded end point evaluation, we determined whether treatment with dipyridamole or clopidogrel, in addition to aspirin, was more effective at reducing embolization. Consecutive patients with recent symptomatic carotid stenosis were recruited. Ambulatory transcranial Doppler and platelet aggregometry were performed at baseline and 48 hours. Patients, all on aspirin, were randomized to dipyridamole or clopidogrel. Recordings were analyzed offline masked to subject identity. Sixty patients were recruited, 30 in each arm. The primary end point of change in embolic signal frequency did not differ between groups (P=0.36). In patients with embolic signals at baseline, there was no difference in reduction in embolic signal frequency: dipyridamole (75.5; SD 17.7%) versus clopidogrel (77.5; SD 20.5%; P=0.77). Baseline platelet aggregation was not different between regimens, but at 48 hours, adenosine 5'-diphosphate aggregation rate (but not collagen) was lower with clopidogrel (P<0.001). Both dipyridamole and clopidogrel reduced embolization to a similar extent. Embolic signals are strong predictors of future stroke rate in this patient group. Our results suggest these 2 treatment regimens have similar efficacy in early secondary prevention of stroke, although this now needs testing in large Phase III trials.