Antiplatelet Agents For Secondary Prevention Research Articles

АНТИАГРЕГАНТЫ В ЛЕЧЕНИИ И ВТОРИЧНОЙ ПРОФИЛАКТИКЕ ДЕТСКОГО АРТЕРИАЛЬНОГО ИШЕМИЧЕСКОГО ИНСУЛЬТА: СОСТОЯНИЕ ПРОБЛЕМЫ

Arterial ischemic stroke (AIS) in children is a potentially disabling disease with cumulative rates of relapse in the first year of 12–16%, necessitating secondary prevention of the disease. Both in adults and in pediatric clinical practice, acetylsalicylic acid is most commonly used, much less often – clopidogrel. However, the validity of the use of antiplatelet agents in children with ischemic stroke is still controversial, due to the low level of evidence-based studies and the paucity of publications. The article analyzes and summarizes data on the possibilities and limitations of the use of antiplatelet agents for secondary prevention of AIS in children.

A Clinical Update on Antiplatelet Therapy in Secondary Prevention of Ischemic Stroke.

Antiplatelet therapy remains the standard of care in secondary stroke prevention for non-cardioembolic ischemic stroke and transient ischemic attack. We aim to examine the use of antiplatelet agents in secondary prevention through highlighting relevant clinical trials and meta-analyses as well as providing commentary regarding our practice. In the POINT and CHANCE trials, dual antiplatelet therapy reduced recurrent stroke compared to aspirin monotherapy. Sub-analyses of these trials suggest that genetic polymorphisms could play a role in diminishing the effectiveness of clopidogrel. Similarly, THALES demonstrated better outcomes with ticagrelor-aspirin combination therapy over aspirin monotherapy. Combination antiplatelet therapy with aspirin and the P2Y12 inhibitors, clopidogrel and ticagrelor, reduced stroke recurrence in those presenting with mild ischemic stroke or high risk TIA. Genetic polymorphisms may play a role in determining the appropriate regimen. Questions remain regarding the optimal duration of combination antiplatelet therapy for various stroke etiologies.

Antiplatelet agents for the secondary prevention of ischaemic stroke in patients with or without renal dysfunction.

Studies on using antiplatelet agents for secondary prevention in ischaemic stroke patients with renal dysfunction are limited. The Taiwan Stroke Registry database was used to compare the efficacy of antiplatelet agents. From the Taiwan Stroke Registry data, 39174 acute ischaemic stroke patients were identified and were classified into three groups by antiplatelet agent: aspirin, clopidogrel and dual antiplatelet therapy (DAPT) with a combination of aspirin and clopidogrel. The re-stroke incidence and 1-year mortality were stratified by estimated glomerular filtration rate (eGFR) levels at admission: ≥90, 60-89 and <60ml/min/1.73m2 or on dialysis. Compared to the aspirin group, the re-stroke differences were not statistically significant for the clopidogrel group [adjusted subhazard ratio 0.95, 95% confidence interval (CI) 0.84-1.08] and the DAPT group (adjusted subhazard ratio1.03, 95% CI 0.77-1.39) after controlling for the competing risk of death. The mortality rate increased as the eGFR level declined. In addition, compared to patients taking aspirin, there was no statistically significant difference in overall 1-year mortality for the clopidogrel group (adjusted hazard ratio 1.11, 95% CI 0.95-1.29) and for the DAPT group (adjusted hazard ratio 1.01, 95% CI 0.67-1.54). The results were consistent in different subgroups stratified by eGFR levels. There was no difference in the risks of recurrent stroke and 1-year mortality amongst ischaemic stroke patients with or without renal dysfunction receiving antiplatelet agents with aspirin, clopidogrel or dual agents with a combination of aspirin and clopidogrel, regardless of their renal dysfunction status.

Efficacy of antiplatelet therapy for treating lacunar infarct: Meta-analysis

Objective To evaluate the efficacy of antiplatelet agents in secondary prevention of patients with lacunar infarct (LACI). Methods Retrieve relevant randomized controlled trials (RCTs) that reported antiplatelet therapy in patients with LACI from online databases (January 1, 1980-November 20, 2016) in PubMed, EMBASE/SCOPUS and Cochrane Online Library with key words: stroke, lacunar infarction, platelet aggregation inhibitors, antiplatelet, randomized controlled trial. Quality of studies was evaluated by using Jadad Scale and Cochrane Handbook for Systematic Reviews of Interventions. All data were pooled by RevMan 5.3 software for Meta-analysis. A network Meta-analysis was done by R software Gemtc and JAGS software. Results A total of 4068 articles were enrolled and 12 high - quality RCTs (Jadad ≥ 4 scores) with 24 969 eligible participants were finally included after excluding duplicates and those not meeting the inclusion criteria. Meta-analysis showed single antiplatelet therapy was more effective than placebo in reducing ischemic stroke recurrence rate ( RR = 0.480, 95%CI: 0.300-0.780; P = 0.003) and any stroke recurrence rate ( RR = 0.780, 95%CI: 0.630-0.970; P = 0.030). The efficacy of single antiplatelet therapy was not significantly different from that of dual antiplatelet therapy (ischemic stroke recurrence rate: RR = 0.900, 95%CI: 0.760-1.050, P = 0.170; any stroke recurrence rate: RR = 0.910, 95%CI: 0.820-1.010, P = 0.070). Network Meta-analysis (four interventions including aspirin, placebo, cilostazol and ticlopidine) showed that cilostazol was associated with a significant reduction in recurrence of any stroke compared with aspirin ( OR = 0.341, 95% CrI: 0.011-0.673) and placebo ( OR = 0.615, 95% CrI: 0.191-1.042). Conclusions Single antiplatelet therapy could significantly reduce the recurrence of any stroke, especially ischemic stroke in patients with LACI. There is no evidence showing that dual antiplatelet therapy is probably better than single therapy. Cilostazol is better than aspirin in reducing any stroke recurrence in the treatment of LACI. DOI: 10.3969/j.issn.1672-6731.2017.03.004

Managing acute stroke in low-resource settings.

Managing acute stroke in low-resource settings.

Antiplatelet Agents for the Secondary Prevention of Ischemic Stroke or Transient Ischemic Attack: A Network Meta-Analysis

Stroke can cause high morbidity and mortality, and ischemic stroke (IS) and transient ischemic attack (TIA) patients have a high stroke recurrence rate. Antiplatelet agents are the standard therapy for these patients, but it is often difficult for clinicians to select the best therapy from among the multiple treatment options. We therefore performed a network meta-analysis to estimate the efficacy of antiplatelet agents for secondary prevention of recurrent stroke. We systematically searched 3 databases (PubMed, Embase, and Cochrane) for relevant studies published through August 2015. The primary end points of this meta-analysis were overall stroke, hemorrhagic stroke, and fatal stroke. A total of 30 trials were included in our network meta-analysis and abstracted data. Among the therapies evaluated in the included trials, the estimates for overall stroke and hemorrhagic stroke for cilostazol (Cilo) were significantly better than those for aspirin (odds ratio [OR] = .64, 95% credibility interval [CrI], .45-.91; OR = .23, 95% CrI, .08-.58). The estimate for fatal stroke was highest for Cilo plus aspirin combination therapy, followed by Cilo therapy. The results of our meta-analysis indicate that Cilo significantly improves overall stroke and hemorrhagic stroke in IS or TIA patients and reduces fatal stroke, but with low statistical significance. Our results also show that Cilo was significantly more efficient than other therapies in Asian patients; therefore, future trials should focus on Cilo treatment for secondary prevention of recurrent stroke in non-Asian patients.

High-risk type-2 diabetes mellitus patients, without prior ischemic events, have normal blood platelet functionality profiles: a cross-sectional study.

BackgroundPatients with type 2 diabetes mellitus (DM) display a predisposition for vascular disease. Platelets taken from vasculopathic diabetic patients, show enhanced stimuli-induced activation and aggregation responses. Aspirin remains the cornerstone antiplatelet agent for secondary prevention of vascular complications among diabetic patients, yet evidence of its efficacy and safety in primary prevention are conflicting. Our aim was to assess whether high risk diabetic patients, without previous ischemic events, have abnormal platelet functionality profiles.MethodsThe study included 82 diabetic patients and 86 matched non-diabetic patients without prior ischemic events nor treatment with anti-platelet medications. Blood samples were analyzed for platelet markers of activation, turnover and leukocyte-platelet interactions.ResultsOur final analysis included 122 males (74 %), with a mean age of 61 years. Mean platelet volume (MPV) was similar between the diabetic patients and controls (9.2 fL for both). Following activation, PAC-1 binding and P-selectin expression were found comparable between the diabetic patients and controls (83 % versus 81 % and 76 % versus 74 %, respectively). Leukocyte-platelet aggregates (LPAs) were similar between the diabetic patients and controls (18 % versus 17 %, respectively). Neutrophil-platelet aggregates (NPAs) and monocyte-platelet aggregates (MPAs) were also found similar in the diabetic patients and controls. Elevated fasting plasma glucose was associated with increased LPAs rates.ConclusionsHigh risk type-2 diabetes mellitus patients, without prior ischemic events, have normal blood platelet functionality profiles.

Evaluation of Antiplatelet Agents for Secondary Prevention of Stroke Using Mixed Treatment Comparison Meta-analysis

BackgroundThe current guidelines recommend various antiplatelet agents used alone or in combination for secondary prevention of noncardioembolic stroke. ObjectiveThe purpose of this study was to conduct a mixed treatment comparison meta-analysis to determine which antiplatelet or combination of antiplatelet agents is most efficacious and tolerable in patients with prior stroke. MethodsA comprehensive literature search was conducted in MEDLINE (1945 through March 2012), EMBASE (1974 through March 2012), and the Cochrane Controlled Trials Registry (1975 through April 2012) to identify randomized trials evaluating the role of various antiplatelet agents and combinations for the secondary prevention of stroke. Key articles were cross-referenced for additional studies. Data were screened and evaluated to generate direct and indirect comparisons for recurrent stroke and overall hemorrhagic events. Data were reported as rate ratios (RRs) and 95% CIs. ResultsA total of 24 articles were included in the analysis. Eleven antiplatelet regimens were compared in >88,000 patients. The combination of acetylsalicylic acid (ASA) plus dipyridamole (DP) was more protective against recurrent stroke than ASA alone (RR = 0.78; 95% CI, 0.64–0.93), and no differences were found in all other direct and indirect comparisons with active treatment. ASA plus DP was associated with more overall hemorrhagic events than DP (RR = 1.83; 95% CI, 1.17–2.81), cilostazol (RR = 2.12; 95% CI, 1.21–3.48), and triflusal (RR = 1.67; 95% CI, 1.05–2.78) but fewer events than the combination of ASA plus clopidogrel (RR = 0.38; 95% CI, 0.25–0.56). The combination of ASA plus clopidogrel was associated with an excess of overall hemorrhagic events compared with clopidogrel (RR = 2.81; 95% CI, 1.96–4.10), cilostazol (RR = 5.56; 95% CI, 3.03–9.66), DP (RR = 4.78; 95% CI, 2.80–8.21), sarpogrelate (RR = 3.59; 95% CI, 1.96–6.45), terutroban (RR = 2.13; 95% CI, 1.21–3.61), ticlopidine (RR = 2.80; 95% CI, 1.69–5.00), and triflusal (RR = 4.36; 95% CI, 2.62–7.81). ConclusionWe found that ASA plus DP was more protective than ASA alone for preventing recurrent stroke; however, no difference was found between most direct and indirect comparisons of antiplatelet agents and combinations. More overall hemorrhagic events seemed to occur with the combination of ASA and clopidogrel than with other treatments. Selection of antiplatelet therapy for the secondary prevention of stroke must be individualized according to patient comorbidities, including risk of stroke recurrence and bleeding.

Use of Antiplatelet Agents in Patients With Atherosclerotic Disease

Platelets play a key role in the initiation of hemostatic mechanisms during vascular injury. When contemplating prescription of antiplatelet agents (APAs) for patients as primary prevention for cardiovascular events, the physician should carefully weigh the potential benefits of cardiovascular risk reduction with the likelihood of harm, related mostly to hemorrhagic complications. The role of APAs in secondary prevention of atherosclerosis and coronary artery disease is well established, however, optimal duration of therapy and intensity of patient treatment are not settled and probably need to be individualized per patient. We describe the data emerging from contemporary trials on the efficacy and safety of the use of oral APAs in various patient subpopulations. We also discuss the advantages and potential roles of new APAs during and following acute coronary syndromes, percutaneous coronary interventions, and symptomatic atherosclerosis. We propose certain strategies and directions for future research to enhance the safety and efficacy prevention by optimizing the beneficial effects of APAs along with other contemporary treatment modalities of primary and secondary prevention.

Secondary stroke prevention: misguided by guidelines?

Objectives Despite large clinical trials, there is no consensus about the best antithrombotic strategy for the secondary prevention of non-cardioembolic ischaemic stroke. This retrospective study is the fi rst to combine the results of the most important trials and to integrate data on study validity, eff ectiveness, adverse events, risk of non-compliance, and cost.Methods We searched MEDLINE, EMBASE, and the Cochrane Database (1996 to July 2011) and selected long-term secondary prevention trials with treatment with aspirin, dipyridamole, clopidogrel, aspirin plus dipyridamole, or aspirin plus clopidogrel. Subgroup analyses were included to explain diff erences in interpretations that could have led to the diff erences in guidelines.Results Two trials showed a small but signifi cant reduction with aspirin plus dipyridamole compared to aspirin (ARR 1.5%, P< 0.05 and ARR 1.0%, P< 0.05). There was no eff ect on vascular death. One trial showed a small but statistical signifi cant reduction with clopidogrel compared to aspirin (ARR 0.5%, P< 0.05). The association of clopidogrel with aspirin could not show any signifi cant benefi t compared to clopidogrel monotherapy, nor compared to aspirin monotherapy, but showed higher rates of adverse events. Signifi cantly more patients discontinued treatment with aspirin plus dipyridamole compared to aspirin monotherapy (34.5% versus 13.4% and 29.0% versus 22.2%, P< 0.001) and clopidogrel monotherapy (29.1% versus 22.6%, P< 0.001). Transposition of statistical signifi cant reductions in stroke recurrence into clinical signifi cance could not be supported.Conclusions Despite changes in international guidelines, aspirin monotherapy should retain its position as the main antiplatelet agent for secondary prevention of non-cardioembolic ischaemic stroke.

Improving Long‐Term ACS Management: Is There a Role for the New Antiplatelets?

Acute coronary syndrome (ACS) is a major health burden, resulting in increased hospital admissions and significant morbidity and mortality. Platelet activation, which leads to thrombin generation, is highly implicated in ACS, and antiplatelet agents represent the current standard of care. Established antiplatelet agents include acetylsalicylic acid (ASA), thienopyridines (clopidogrel, ticlopidine), and glycoprotein IIb/IIIa inhibitors. Recently, antiplatelet therapy for ACS has evolved to include more potent inhibitors (e.g., prasugrel, cangrelor, and ticagrelor). During the acute phase of an acute coronary event, both anticoagulation and dual antiplatelet therapy with aspirin and a thienopyridine are guideline recommended as first-line treatment. While anticoagulation is usually limited to the acute in-patient phase, dual antiplatelet therapy is recommended for 12 months. Despite the efficacy of antiplatelet agents in ACS, in many patients the residual risk of death from cardiac events, myocardial infarction, stroke, and refractory ischemia remains high. Dual therapy (i.e., ASA or clopidogrel plus a vitamin K antagonist [VKA]), and triple therapy (two antiplatelets plus a VKA) are associated with increases in bleeding complications. New oral anticoagulants that offer a novel mechanism of action may, when added to the current standard of care, provide a more comprehensive response to thrombin generation. In this review, we examine the pathology of ACS, investigate antiplatelet therapies and describe emerging anticoagulants that may be of benefit when used as combination therapy with antiplatelet agents for secondary prevention in ACS patients.

Evaluation of a Novel Antiplatelet Agent for Secondary Prevention in Patients with Atherosclerotic Disease: Results from the TRA 2P-TIMI 50 Trial

In stable patients with a history of atherosclerosis, the investigational protease-activated receptor (PAR)-1 antagonist vorapaxar was effective at reducing further atherothrombotic events. This article presents data from the Thrombin Receptor Antagonist in Secondary Prevention-TIMI 50 Trial [TRA 2P; NCT00526474] which showed that vorapaxar significantly reduced the risk of deaths from cardiovascular disease, myocardial infarction, or stroke compared with placebo.

Impact of preoperative maintenance or interruption of aspirin on thrombotic and bleeding events after elective non-cardiac surgery: the multicentre, randomized, blinded, placebo-controlled, STRATAGEM trial

Patients receiving anti-platelet agents for secondary cardiovascular prevention frequently require non-cardiac surgery. A substantial proportion of these patients have their anti-platelet drug discontinued before operation; however, there is uncertainty about the impact of this practice. The aim of this study was to compare the effect of maintenance or interruption of aspirin before surgery, in terms of major thrombotic and bleeding events. Patients treated with anti-platelet agents for secondary prevention and undergoing intermediate- or high-risk non-cardiac surgery were included in this multicentre, randomized, placebo-controlled, trial. We substituted non-aspirin anti-platelets with aspirin (75 mg daily) or placebo starting 10 days before surgery. The primary outcome was a composite score evaluating both major thrombotic and bleeding adverse events occurring within the first 30 postoperative days weighted by their severity (weights were established a priori using a Delphi consensus process). Analyses followed the intention-to-treat principle. We randomized 291 patients (n=145, aspirin group, and n=146, placebo group). The most frequent surgical procedures were orthopaedic surgery (52.2%), abdominal surgery (20.6%), and urologic surgery (15.5%). No significant difference was observed neither in the primary outcome score [mean values (SD)=0.67 (2.05) in the aspirin group vs 0.65 (2.04) in the placebo group, P=0.94] nor at day 30 in the number of major complications between groups. In these at-risk patients undergoing elective non-cardiac surgery, we did not find any difference in terms of occurrence of major thrombotic or bleeding events between preoperative maintenance or interruption of aspirin.

Current Guidelines on Antiplatelet Agents for Secondary Prevention of Noncardiogenic Stroke: An Evidence-Based Review

Antiplatelet therapy is a mainstay of secondary prevention of ischemic strokes. Recent studies, such as Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS), the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial, and the European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT), have added much to our understanding about how best to utilize the various antiplatelet agents available. Aspirin has been shown to reduce the risk of recurrent strokes, and the combination of aspirin and dipyridamole has repeatedly been shown to outperform aspirin alone. Recently, clopidogrel was demonstrated to be “noninferior” to an aspirin/dipyridamole combination, and can be considered as a first-line agent. The American Stroke Association and American Heart Association have clear recommendations on how to utilize these agents.

Evaluation of a novel antiplatelet agent for secondary prevention in patients with a history of atherosclerotic disease: Design and rationale for the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P)-TIMI 50 trial

Thrombin potently activates platelets via interaction with the protease-activated receptor 1. SCH 530348 is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin via antagonism of the protease-activated receptor 1. Because SCH 530348 does not interfere with other pathways for hemostasis, it is possible that SCH 530348 reduces thrombosis with less increase in bleeding than do other potent antiplatelet agents. TRA 2 degrees P-TIMI 50 is a phase III, randomized, double-blind, placebo-controlled, multinational clinical trial designed to evaluate the efficacy and safety of SCH 530348 during long-term treatment of patients with established atherosclerotic disease receiving standard therapy (up to 27,000). Eligible patients with a history of myocardial infarction, ischemic stroke, or peripheral arterial disease are randomized 1:1 to SCH 530348 2.5 mg daily or matched placebo until the end of study. Randomization is stratified by the qualifying disease and planned use of a thienopyridine. The primary end point is the composite of cardiovascular death, myocardial infarction, stroke, or urgent coronary revascularization. The major secondary end point is the composite of cardiovascular death, myocardial infarction, or stroke. The evaluation of long-term safety includes bleeding defined by the GUSTO and TIMI criteria. Recruitment began in September 2007. The trial will continue until 2,279 primary end points and 1,400 secondary end points are recorded with expected completion in 36 to 44 months from first enrollment. TRA 2 degrees P-TIMI 50 is evaluating whether a new approach to platelet inhibition via interruption of thrombin-mediated platelet activation reduces major cardiovascular events with a favorable safety profile in patients with established atherosclerosis.

The Use of Antiplatelet Agents for Secondary Prevention of Ischemic Stroke in U.S. Ambulatory Care Settings

We examined stroke prevention with antiplatelet agents by U.S. nonfederal office physicians and hospital outpatient departments from 2005-2006. The nationally representative dataset used a multistage (112 primary sampling units, physicians/ hospitals, patient medical records) random sample of 1,702 visits by patients 20 years or older with cerebrovascular disease (national estimate: 15.4 million annual visits). Dependent variable: use of antiplatelet agents for patients without contraindications. age, sex, race/ethnicity, payment, primary care provider, prior visits in last year, comorbidities. Logistic regression was used to investigate associations with recommended interventions. Antiplatelet agents were prescribed at 31.1% of visits. Positive predictors: seeing the patient's primary care provider and having five or more comorbidities. Negative predictors: non-Hispanic Black race/ethnicity and having six or more prior visits in the last year. Variations by visit characteristics suggest that improvement in using antiplatelet agents is possible, especially for non-Hispanic Black patients.

Combination Antiplatelet Agents for Secondary Prevention of Ischemic Stroke

Stroke is a leading cause of death and the primary cause of serious, long-term disability in the United States. Joint guidelines from the American Heart Association (AHA) and American Stroke Association (ASA), as well as recent guidelines from the Eighth American College of Chest Physicians (ACCP) Conference on Antithrombotic and Antiplatelet Therapy, recommend aspirin, clopidogrel, or extended-release dipyridamole plus aspirin as acceptable first-line options for secondary prevention of ischemic events in patients with a history of ischemic stroke or transient ischemic attack (TIA). The ACCP strongly recommends the combination of extended-release dipyridamole plus aspirin over aspirin monotherapy (highest level of evidence) and suggests clopidogrel monotherapy over aspirin monotherapy (lower level of evidence). The AHA-ASA guidelines suggest that either extended-release dipyridamole plus aspirin or clopidogrel monotherapy should be used over aspirin monotherapy. Both guidelines recommend avoiding the combination of clopidogrel and aspirin for most patients with previous stroke or TIA. Results from recent trials evaluating combination antiplatelet therapy have been published that enhance the AHA-ASA recommendations and provide the foundation for the updated ACCP guideline. To identify pertinent combination antiplatelet trials, a MEDLINE search of the literature from 1967-2007 was performed. Two trials were identified--the European-Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT) and Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA). The ESPRIT compared aspirin monotherapy with the combination of aspirin plus extended-release dipyridamole for prevention of secondary ischemic events in patients with a history of TIA or minor stroke. The CHARISMA trial compared aspirin plus clopidogrel with aspirin alone in a population at high risk for atherothrombotic events using the composite outcome of myocardial infarction, stroke, and death from cardiovascular causes. Data from ESPRIT add to evidence that the combination of aspirin plus extended-release dipyridamole is superior to aspirin alone. The findings of the CHARISMA trial reinforce recommendations from both AHA-ASA and ACCP that the combination of aspirin and clopidogrel be reserved for special populations requiring this antiplatelet combination (e.g., those who have had coronary artery stenting).

The role of antiplatelet therapy in the management of ischemic stroke: implementation of guidelines in current practice

Objective: To review and discuss evidence-based guideline recommendations for the use of antiplatelet agents for secondary prevention in patients with ischemic stroke or TIA.Methods: A literature search was conducted on PubMed through August 2007 using combinations of the following search terms: aspirin, clopidogrel, dipyridamole plus aspirin, transient ischemic attack, secondary prevention, stroke and guidelines.Results: Modification of risk factors such as hypertension, diabetes, hypercholesterolemia, cigarette smoking and obesity are fundamental to stroke management. Antiplatelet therapy is highly effective in reducing the risk of recurrent vascular events and is recommended over oral anticoagulants for non-cardioembolic stroke. Evidence from head-to-head comparative clinical trials versus aspirin monotherapy has shown that clopidogrel and the combination of aspirin plus dipyridamole are safe and effective therapeutic options.Discussion: Despite the availability of evidence-based guidelines, recommended interventions are largely underutilized. Quality improvement initiatives such as the ASA's Get with the Guidelines – Stroke and the UCLA stroke PROTECT Program have demonstrated effectiveness in increasing adherence to recommended therapies and thereby improving patient outcomes.

Antiplatelet agents for secondary prevention of stroke

Patients with recent ischemic stroke or transient ischemic attack (TIA) face a high risk of recurrent stroke as well as an increased risk of myocardial infarction and sudden cardiac death. In the absence of a clearly established indication for long-term anticoagulation, such as atrial fibrillation, antiplatelet agents are the antithrombotic drugs of choice for preventing recurrent vascular events. For many years, aspirin (ASA) has been the first-line therapy for patients at high risk of vascular ischemic events. Two large clinical trials have established the superiority of the combination of ASA and extended-release dipyridamole (ASA/ERDP) over ASA alone in patients with recent noncardioembolic ischemic stroke or TIA. Clopidogrel, another antiplatelet agent, is a reasonable alternative to ASA, but its superiority to ASA in patients with a history of stroke has not been as clearly established. The combination of ASA and clopidogrel, which is effective in patients with acute coronary syndrome, has not been shown to be either effective or safe, compared with either agent alone, in stroke patients, although there may be some benefit to this combination in patients with acute TIA. The results from a large randomized trial comparing ASA/ERDP with clopidogrel, anticipated soon, will further assist clinicians in choosing among available antiplatelet agents.

Emerging Therapies: ESPRIT

To the Editor: It was with great anticipation and interest that I read the ESPRIT results1 and the accompanying Editorial in Stroke .2 The study reports superiority of aspirin plus dipyridamole over aspirin alone in patients with minor or transient cerebral ischemic symptoms, for the composite outcome of vascular mortality, cerebrovascular event, myocardial infarction, and major hemorrhage.1 In reviewing the outcome measure details, several concerns arose regarding the interpretation of this study by the authors and by the editorialist. In recent cardiovascular trials, a beneficial effect of combination antiplatelet therapy for preventing myocardial ischemia greatly contributed to the benefit seen for cumulative vascular outcomes.3–5 Similarly, in ESPS-2 …