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E J Topol

Publications and source records attributed to E J Topol.

At least 127 records · Page 7Linked to original sources
PubMed2000

Inhibition of platelet aggregation with a glycoprotein IIb-IIIa antagonist does not prevent thrombin generation in patients undergoing thrombolysis for acute myocardial infarction.

Thrombin activity has been implicated as a mechanism for failed reperfusion and reocclusion following thrombolysis. Aggregating platelets provide a phospholipid surface on which prothrombin is cleaved to form thrombin. We examined markers of thrombin generation and activity in patients enrolled in a randomized, placebo-controlled, dose escalating trial of the platelet glycoprotein IIb-IIIa inhibitor eptifibatide (Integrilintrade mark) administered concomitantly with tissue plasminogen activator for the treatment of myocardial infarction. Measurements were obtained at baseline, at 90 minutes, and at 6, 12, and 24 hours after starting therapy. Eptifibatide inhibited platelet aggregation in response to 20 microM ADP. Levels of fibrinopeptide A (FPA), thrombin-antithrombin complexes (TAT), and prothrombin fragment 1.2 (F1.2) were not lower in patients treated with eptifibatide than in the control group. In the course of dose escalation, two groups of patients received the same 135 microg/kg bolus of eptifibatide, one with and one without a heparin bolus. FPA levels were dramatically lower in the heparin-treated patients. Levels of FPA, TAT, and F1.2 were not higher in patients with than in those without recurrent ischemia, or in patients without than in those with Thrombolysis in Myocardial Infarction (TIMI) grade 3 angiographic flow at 90 minutes. These data suggest that thrombin generation and activity persist following thrombolysis, despite inhibition of platelet aggregation, and that treatment with inhibitors of thrombin activity may be required even when glycoprotein IIb-IIIa inhibitors are used.

Cohort Studies↗
PubMed2000

Geographic variability in outcomes within an international trial of glycoprotein IIb/IIIa inhibition in patients with acute coronary syndromes. Results from PURSUIT.

AIMS: Variations in outcome of patients from different geographic regions have been observed in many large international trials. We analysed the factors that might contribute to the geographic variations in patient outcome and treatment effect as observed in the PURSUIT trial. METHODS: In PURSUIT, 9461 patients with acute coronary syndromes without persistent ST-elevation were randomized to the platelet inhibitor eptifibatide or placebo for 72 h in 27 countries in four geographic regions: Western (n=3697) and Eastern Europe (n=1541) as well as North (n=3827) and Latin America (n=396). The primary end-point was the 30-day composite of death or myocardial infarction. In the initial univariate analysis, the treatment effect appeared greater in N. America than in W. Europe, while no benefit was apparent in L. America and E. Europe. However, the confidence intervals were wide and overlapping. To study these differences, a subdivision in an early and late patient outcome and treatment effect was made. Accordingly, we analysed the rate of death or infarction at 72 h censored for percutaneous coronary intervention and the rate between 3 and 30 days, respectively. Additional analyses were performed with different definitions of myocardial infarction using progressively higher thresholds of CK(-MB) elevation. Multivariable analysis was used to evaluate the relation between region and outcome and to determine the adjusted odds ratios for the eptifibatide treatment effect. RESULTS: Major differences in baseline demographics were apparent among the four regions; in particular, more patients from E. Europe had characteristics associated with impaired outcome. Interventional treatment also varied considerably, with more patients from N. America undergoing revascularization. Despite differences in the 72 h event rate, eptifibatide showed a consistent trend towards a reduction in the composite end-point among all four regions and for all definitions of infarction. Relative reductions ranged from 17-42% in W. Europe, 23-35% in N. America, 0-33% in E. Europe, and 55-82% in L. America. After multivariable adjustment, the pattern of benefit with eptifibatide was consistent among the regions. In patients undergoing percutaneous coronary intervention during study drug infusion in W. Europe (n=266) and N. America (n=931), the relative reduction in myocardial infarction during medical therapy ranged from 56-75% in W. Europe and 14-67% in N. America, while the reduction in procedure-related events ranged from 12-44% and 25-61% for different definitions of infarction. After multivariable adjustment neither benefit nor rebound were apparent after study drug discontinuation, or after 3 days in all regions, except in L. America. In general, the differences in outcome and treatment effect were greatest when the protocol definition of myocardial infarction (CK(-MB) >1 upper normal limit) was applied. Under stricter definitions, these differences became smaller and disappeared with the investigator's assessment. CONCLUSION: The analysis suggests that the apparent differences in patient outcome and eptifibatide treatment effect can be explained largely by differences in baseline demographics and adjunctive treatment strategies as well as by the methodology of myocardial infarction definition and the adjudication process.

Aged↗
PubMed2000

Lack of progress in cardiogenic shock: lessons from the GUSTO trials.

AIMS: We used the GUSTO-I and GUSTO-III databases to evaluate our performance in treating cardiogenic shock patients over much of the 1990s. METHODS AND RESULTS: GUSTO-I (1990-1993) and GUSTO-III (1995-1997) prospectively identified all patients with cardiogenic shock complicating acute myocardial infarction. Demographics, clinical presentation and outcomes for cardiogenic shock patients in the two trials were compared. Only patients enrolled with cardiogenic shock in countries common to both trials were included in these analysis. The 695 patients with cardiogenic shock in GUSTO-III were compared with the 2814 patients with cardiogenic shock in GUSTO-I. GUSTO-III patients were older (P=0.0001) and more likely to be diabetic (P=0.009) and hypertensive (P=0.025). They had a higher Killip class (P=0.002) and significantly greater index anterior infarction than cardiogenic shock patients enrolled in GUSTO-I. Time to treatment, presentation heart rate, and diastolic blood pressure were similar; however, systolic blood pressure at presentation was higher among GUSTO-III patients (P=0.002). Rates of coronary angiography, pulmonary artery catheterization, and mechanical ventilation declined in GUSTO-III compared with GUSTO-I (P=0.001); rates of angioplasty and bypass surgery were similar. Cardiogenic shock mortality in GUSTO-III was significantly higher than in GUSTO-I (62 vs 54%, P=0.001), as were rates of reinfarction (14 vs 11%, P=0.013) and recurrent ischaemia (35 vs 27%, P=0.00001). Mortality at non-U.S. sites (68 and 64%) was higher than at U.S. sites (53 and 50%) in both GUSTO-I and GUSTO-III studies, respectively. Angioplasty, bypass surgery, and balloon pump rates were lower for non-U.S. patients. CONCLUSIONS: Cardiogenic shock continues to be associated with high mortality in thrombolytic-treated patients. Lower mortality observed in the U.S.A. supports consideration for percutaneous and surgical revascularization.

Aged↗
PubMed2000

Influence of diabetes mellitus on clinical outcomes across the spectrum of acute coronary syndromes. Findings from the GUSTO-IIb study. GUSTO IIb Investigators.

AIMS: We examined the characteristics, outcomes, and effects of hirudin vs heparin treatment of diabetic patients across the spectrum of acute coronary syndromes. METHODS AND RESULTS: We studied the 12,142 patients enrolled in the randomized GUSTO-IIb study. Diabetic patients (n=2175) were older, more often female, more often had prior cardiovascular disease, hypertension, and hyperlipidaemia, and less often were current smokers. Diabetic patients had a higher overall incidence of death or (re)infarction at 30 days (13.1% vs 8.5%, P=0.0001), whether they presented with ST-segment elevation (13.9% vs 9.9%, P=0.0017) or not (12.8% vs 7.8%, P=0.0001), and at 6 months (18.8% vs 11.4%, P=0.0001). Among diabetic patients, hirudin was associated with a tendency toward a lower risk of death or (re)infarction at 30 days (12.2% vs 13.9% with heparin) and 6 months (17.8% vs 20.2%). Diabetic patients had more major bleeding, stroke, heart failure, shock, atrioventricular block, and atrial arrhythmias, but no increased risk for ocular bleeding. CONCLUSIONS: Diabetic patients with acute coronary syndromes had worse 30-day and 6-month outcomes, particularly those without ST-segment elevation. The statistically non-significant trend toward improved outcomes with hirudin was similar among patients with and without diabetes, with a greater point estimate for the absolute difference in patients with diabetes.

Aged↗
PubMed2000

Design of the blockade of the glycoprotein IIb/IIIa receptor to avoid vascular occlusion (BRAVO) trial.

BACKGROUND: Platelets play a key role in the pathogenesis of atherosclerosis, thrombosis, and acute coronary and cerebrovascular syndromes. Inhibition of platelet function by acetylsalicylic acid (aspirin) has been shown to reduce the incidence atherothrombotic events in patients with coronary, cerebrovascular, or peripheral vascular disease. Thienopyridine agents, however, including ticlopidine and clopidogrel, inhibit the adenosine diphosphate receptor and have modestly superior effects compared with aspirin on reduction of death, myocardial infarction, and stroke among a broad group of patients with vascular disease. More effective antithrombotic agents are still required to treat patients at high risk for recurrent vascular events. METHODS: Lotrafiban, a selective, nonpeptide antagonist of the human platelet fibrinogen receptor (glycoprotein [GP] IIb/IIIa [alphaIIb/beta3 integrin]), blocks the binding of fibrinogen to the GP IIb/IIIa receptor, which is the final common pathway of platelet aggregation. Lotrafiban at doses of up to 50 mg twice daily was well-tolerated in a 12-week, double-blind, placebo-controlled, dose-ranging study in patients with recent myocardial infarction, unstable angina, transient ischemic attack, or stroke when added to aspirin therapy. On the basis of these results, a dosing regimen was selected for the phase III Blockage of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion (BRAVO) trial based on pharmacodynamics and drug tolerability. In the pivotal BRAVO study, lotrafiban therapy is being evaluated in patients who have had a recent myocardial infarction, unstable angina, transient ischemic attack, or ischemic stroke, or who present at any time after a diagnosis of peripheral vascular disease combined with either cardiovascular or cerebrovascular disease. RESULTS: The efficacy evaluation will be based on a composite end point of clinical events (death by any cause, myocardial infarction, stroke, recurrent ischemia requiring hospitalization, or urgent ischemia-driven revascularization). The target enrollment is 9200 patients worldwide. Approximately 700 centers will participate and will be distributed within 30 countries across North America, Europe, Australia, and Asia.

Administration, Oral↗
PubMed2000

Proteinuria is a key determinant of death in patients with diabetes after isolated coronary artery bypass grafting.

BACKGROUND: Proteinuria is a marker for underlying diabetic nephropathy and may be a surrogate marker for advanced atherosclerosis. It is unknown if proteinuria is a determinant of death in patients with diabetes after coronary artery bypass grafting. We hypothesized that diabetic patients with evidence of proteinuria would have increased mortality and clinical event rates after isolated coronary artery bypass grafting compared with nonproteinuric diabetic patients. METHODS AND RESULTS: We performed an observational of study of 905 diabetic patients with urinalysis and available follow-up data (nonproteinuria, n = 651; proteinuria, n = 254) after isolated coronary artery bypass grafting at the Cleveland Clinic Foundation between January 1989 and December 1992. The proteinuria group was further prospectively stratified into low-concentration (n = 225) and high-concentration (n = 29) groups. The end points of this study were all-cause mortality and the composite end point of death, nonfatal myocardial infarction, and need for repeat revascularization. The mean follow-up time was 66 months. The 5-year mortality rate for the nonproteinuria and proteinuria groups was 20.2% and 29.1% (P <.001), respectively. The 5-year rate of death, nonfatal myocardial infarction, and need for repeat revascularization for the nonproteinuria and proteinuria groups was 25.2% and 36.2% (P <.001), respectively. Significant multivariate predictors of 5-year mortality included age, not using a left internal mammary artery graft to the left anterior descending coronary artery, proteinuria, lower body weight, and increased creatinine level. CONCLUSIONS: Among diabetic patients, proteinuria appears to be an important predictor of death after isolated coronary artery bypass grafting.

Aged↗
PubMed2000

Hierarchy of risk based on history and location of prior myocardial infarction in the thrombolytic era. GUSTO-I Investigators.

BACKGROUND: Among patients receiving thrombolytic therapy for myocardial infarction, the outcome for those with a history of infarction is dramatically worse than for those with their first event. Methods And Results We performed a post hoc analysis of patients with a history of myocardial infarction enrolled in the Global Utilization of Streptokinase and TPA for Occluded arteries (GUSTO)-I trial, focusing on the impact of the location of their current and prior events on mortality rates. Within the first 24 hours, mortality rate was greatest among patients with a current infarction in a territory remote from their previous event. By 48 hours after examination, mortality rates among patients with a second anterior infarct had overtaken that among patients with a current inferior/prior anterior infarct. This hierarchy of risk persisted at both 30 days and 1 year (mortality rate at 1 year: current anterior/prior inferior 23.2% +/- 1.4%, current anterior/prior anterior 20% +/- 1.5%, current inferior/prior anterior 17% +/- 1.2%, current inferior/prior inferior 10.8% +/- 0. 9%). CONCLUSIONS: In patients with ST-elevation myocardial infarction on a background of prior infarction, the location of current and prior events predicts a hierarchy of short- and long-term risk of death.

Aged↗
PubMed2000

Clinical correlates and course of thrombocytopenia during percutaneous coronary intervention in the era of abciximab platelet glycoprotein IIb/IIIa blockade.

BACKGROUND: Thrombocytopenia is infrequently associated with abciximab therapy but may contribute to hemorrhagic risk. Factors associated with development of thrombocytopenia, the role of weight-adjustment in concomitant heparin administration, and clinical outcomes in patients with thrombocytopenia are not well defined. METHODS AND RESULTS: Pooled data from 3 placebo-controlled, randomized trials (EPIC, EPILOG, and EPISTENT) of abciximab therapy during percutaneous coronary intervention identified 178 patients (2. 4% of 7290 patients) in whom thrombocytopenia (platelet count <100 x 10(9)/L) developed after enrollment. Multivariate regression analysis identified age (>65 years; P <.001), weight (<90 kg; P =. 023), baseline platelet count (<200 x 10(9)/L; P <.001), abciximab therapy (P =.002), and enrollment into the EPIC trial (P <.001) to be associated with development of thrombocytopenia. Major and minor nonsurgical hemorrhage and transfusion were more frequent (all P <. 001) in thrombocytopenic patients. Although the primary composite clinical end point of these trials (death, myocardial infarction, or urgent revascularization to 30 days) was observed with similar frequency in patients with (11.2%) and those without (7.9%; P =.114) thrombocytopenia, 30-day mortality rate was higher in thrombocytopenic patients (8.4% vs 0.6%, respectively; P <.001). This excess mortality rate persisted after excluding patients in whom thrombocytopenia was first noted after the performance of coronary bypass surgery (4.8% vs 0.6%; P <.001). Among patients in whom thrombocytopenia developed during these trials, those who received prophylactic abciximab had fewer primary end point events (7.1% vs 23.1%; P =.056) and had a lower 30-day mortality rate (3.5% vs 15.4%; P =.048) than patients with thrombocytopenia who had received prophylactic placebo. CONCLUSIONS: Thrombocytopenia associated with abciximab therapy for percutaneous coronary intervention was more frequent in older, lighter-weight patients, those with lower baseline platelet counts, and in those patients who were enrolled into the EPIC trial. Both bleeding and transfusion events occur more frequently in patients with thrombocytopenia. Patients in whom thrombocytopenia developed during these trials had increased mortality rates to 30 days not attributable to the performance of coronary bypass surgery. Among patients with thrombocytopenia, those who received prophylactic abciximab had better clinical outcomes including survival than those who did not.

Abciximab↗
PubMed2000

Reduction in the need for hospitalization for recurrent ischemic events and bleeding with clopidogrel instead of aspirin. CAPRIE investigators.

BACKGROUND: Repeat hospitalizations of patients with atherosclerosis represent a considerable burden on the health care system. We sought to determine whether clopidogrel compared with aspirin decreases the need for rehospitalization for ischemia and bleeding. METHODS AND RESULTS: The Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial was a randomized, blinded, multicenter, trial of 19,185 patients with atherosclerotic disease manifested as recent ischemic stroke or myocardial infarction or symptomatic peripheral arterial disease. Without any double-counting of events, the number of rehospitalizations for ischemic events (defined as angina, transient ischemic attack, or limb ischemia) or bleeding events was determined for the entire cohort. There was a significant reduction in the total number of rehospitalizations for ischemic events or bleeding with clopidogrel use compared with aspirin (1502 vs 1673; P =.010) over an average of 1.6 years of treatment. This reduction in rehospitalization was consistent across individual outcomes of angina, transient ischemic attack, limb ischemia, and bleeding. Compared with aspirin, clopidogrel also resulted in a 7.9% relative risk reduction in a combined end point of vascular death, stroke, myocardial infarction, or rehospitalization for ischemic events or bleeding (15.1% to 13.7% at 1 year; P =.011). Adjusting for baseline prognostic variables, clopidogrel therapy was an independent predictor for reduction of vascular death, stroke, myocardial infarction, or rehospitalization for ischemic events or bleeding (P =.009). CONCLUSIONS: Treatment with clopidogrel results in a significant decrease in the need for rehospitalization for ischemic events or bleeding compared with aspirin. This meaningful end point tracks well with other, more traditional measures of outcome and has incremental value beyond such end points.

Aspirin↗
PubMed2000

Negative T waves shortly after ST-elevation acute myocardial infarction are a powerful marker for improved survival rate.

BACKGROUND: Recent studies have reported that negative T waves in the setting of acute coronary events are associated with Thrombolysis In Myocardial Infarction flow grade 3 in the infarct-related artery and with improved parameters of ventricular function rather than with ischemia. METHODS: Patients enrolled in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) angiographic substudy (ie, patients with acute infarction randomly assigned to one of 4 thrombolytic regimens who then underwent coronary angiography) were included in this study if they survived at least 24 hours and had no confounding electrocardiographic factors (n = 1505). RESULTS: More patients had negative T waves develop (NT group, n = 938 [62%]) than not (PT group, n = 567 [38%]). Peak creatine kinase MB, time to thrombolysis, and randomization to accelerated alteplase were no different between the groups. Thirty days after admission, 12 patients in the NT group had died versus 25 patients in the PT group (1.3% vs. 4.4%; P <.001; odds ratio for negative T waves 0.28; 95% confidence interval 0.14-0.56). The difference persisted when only patients who survived at least 3 days were analyzed. After adjusting for relevant covariates (including presence of new Q waves in the follow-up electrocardiogram), negative T waves were an independent predictor for survival (P =. 007; odds ratio for negative T waves 0.38; 95% confidence interval 0. 18-0.78). Patients in the NT group were 35% more likely to have achieved patency of the infarct-related artery, although this difference was not statistically significant. CONCLUSIONS: Negative T waves shortly after acute myocardial infarction treated with thrombolysis were markers for improved 30-day survival rate. This finding merits prospective testing.

Adult↗
PubMed2000

A direct comparison of tirofiban and abciximab during percutaneous coronary revascularization and stent placement: rationale and design of the TARGET study.

BACKGROUND: Trials testing intravenous platelet glycoprotein IIb/IIIa antagonists in the setting of percutaneous coronary revascularization and empirically during acute coronary syndromes have consistently demonstrated a reduction in ischemic events. These trials, however, have varied regarding patient population, type, duration and timing of IIb/IIIa therapy, adjunct therapies, and methods for collection and adjudication of end points. All trials were placebo-controlled, and none involved a direct comparison of IIb/IIIa inhibitors. Whether these agents produce a similar clinical outcome in the contemporary practice of coronary interventions is uncertain. METHODS AND RESULTS: To evaluate the efficacy of tirofiban in patients undergoing percutaneous revascularization with stent placement, a randomized, multicenter, double-blind, double-dummy, abciximab-controlled study is currently underway. All patients will receive preprocedural clopidogrel, weight-adjusted heparin, and aspirin. In 18 countries, 4750 patients undergoing nonemergency percutaneous coronary revascularization will be studied. The primary end point will be the composite 30-day occurrence of death, myocardial infarction, or urgent target vessel revascularization. Secondary end points will include 6-month death, myocardial infarction, or any myocardial revascularization and 1-year death. CONCLUSION: This is the first large-scale, head-to-head comparison of 2 established IIb/IIIa inhibitors in interventional cardiology. Enrollment is expected to be complete by mid-2000.

Abciximab↗
PubMed2000

New atrial fibrillation after acute myocardial infarction independently predicts death: the GUSTO-III experience.

BACKGROUND: Atrial fibrillation (AF) or flutter occurring after myocardial infarction may occur alone or in association with other complications. Whether the arrhythmia portends a poor prognosis independent of other complications with contemporary therapy is unknown. METHODS AND RESULTS: As part of the Global Use of Strategies To Open occluded coronary arteries (GUSTO-III) trial, we evaluated whether postinfarction complications were associated with the subsequent development of AF and whether AF independently predicted death over periods of 30 days and 1 year. Information including exact timing was collected on deaths and major in-hospital postinfarction complications up to 30 days. Of the 13,858 patients with sinus rhythm at enrollment, 906 later had AF or flutter and 12, 952 did not. We compared outcomes between these 2 groups, adjusting for differences in baseline characteristics and prefibrillation complications. Worsening heart failure, hypotension, third-degree heart block, and ventricular fibrillation were independent predictors of new-onset AF. The unadjusted odds ratio (OR) for death among patients with versus those without AF was 2.74 (95% confidence interval [95% CI], 2.56-3.34). After adjusting for baseline differences, the OR was reduced to 1.63 (95% CI, 1.31-2.02). Adjustment for other in-hospital complications before the onset of AF further reduced the OR to 1.49 (95% CI, 1.17-1.89). CONCLUSIONS: Atrial fibrillation or flutter occurs secondary to other postinfarction complications but independently portends a worse prognosis. Prevention and management may improve outcome.

Aged↗
PubMed2000

Importance of microembolization and inflammation in atherosclerotic heart disease.

Considerable evidence now exists that inflammation is a central component of events that initiate and propagate an acute coronary syndrome. This process evokes the potential for embolization, which occurs more often than previously suspected, and imparts poor cardiovascular prognosis. Recent development of techniques to detect inflammation and embolization represents an important advance. In addition, therapies that diminish occurrence of these phenomena such as aspirin, statins, angiotensin converting enzyme (ACE) inhibitors, and IIb/IIIa receptor antagonists have been shown to improve outlook.

Biomarkers↗
PubMed2000

Optimizing percutaneous coronary revascularization in diabetic women: analysis from the EPISTENT trial.

Clinical studies have demonstrated that diabetic women have an increased risk of death and nonfatal myocardial infarction (MI) after percutaneous coronary intervention (PCI). However, there have been few data regarding the outcome of diabetic women in the current era of percutaneous coronary revascularization. Using the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting Trial (EPISTENT) database, we determined morbidity and mortality for diabetic women undergoing PCT in the current era using stents and the glycoprotein IIb/IIIa inhibitor, abciximab. There were no mortality differences in the diabetic women treated with stent-placebo, stent-abciximab, or balloon-abciximab at 30 days and 6 months. However, the primary end point of 1-year death, MI, or target vessel revascularization (TVR) was lowered in the diabetic women from 34.5% in the stent-placebo group and 28.9% in the balloon-abciximab group to 13. 3% in the stent-abciximab group (p = 0.02 for stent-stent comparison, and p = 0.09 for stent-abciximab vs. balloon-abciximab comparison). Also, 1-year TVR rates were lowered from 21.1% in the stent-placebo group and 26.7% in the balloon-abciximab group to 4.5% in the stent-abciximab group (p = 0.02 for stent-stent comparison, and p = 0.004 for stent-abciximab vs. balloon-abciximab comparison). The combination of stenting and abciximab therapy among diabetic women resulted in a significant reduction in 1-year rate of death, MI, or TVR compared with stent-placebo or balloon-abciximab therapy.

Abciximab↗
PubMed2000

Update on clinical trials of antiplatelet therapy for cerebrovascular diseases.

Antiplatelet medications are an important part of the therapy of cerebrovascular diseases. Oral agents such as aspirin have an established role in the secondary prevention of stroke. An aspirin and dipyridamole combination has recently been approved. Ticlopidine has been proven to be more effective than aspirin, but its potentially serious side effect profile makes long-term use hazardous. Clopidogrel has been demonstrated to be both more effective than and at least as safe as aspirin. The combination of clopidogrel plus aspirin represents the likely future therapy for high-risk patients. The role of oral antiplatelet therapy in the acute treatment of stroke is beginning to be clarified. Aspirin treatment appears to be strongly indicated. Intravenous antiplatelet therapy with glycoprotein IIb/IIIa inhibitors for acute stroke and as an adjunct to carotid artery stenting appears promising.

Aspirin↗