Perioperative changes of response to antiplatelet medication in vascular surgery patients.

INTRODUCTION: Reduced antiplatelet activity of aspirin (ALR) or clopidogrel (CLR) is associated with an increased risk of thromboembolic events. The reported prevalence data for low-responders vary widely and there have been few investigations in vascular surgery patients even though they are at high risk for thromb-embolic complications. The aim of this prospective observational monocentric study was to elucidate possible changes in ALR or CLR after common vascular procedures. METHODS: Activity of aspirin and clopidogrel was measured by impedance aggregometry using a multiple electrode aggregometer (Multiplate®). Possible risk factors for ALR or CLR were identified by demographical, clinical data and laboratory parameters. In addition, a follow-up aggregometry was performed after completion of the vascular procedure to identify changes in antiplatelet response. RESULTS: A total of 176 patients taking antiplatelet medications aspirin and/or clopidogrel with peripheral artery disease (PAD) and/or carotid stenosis (CS) were included in the study. The prevalence of ALR was 13.1% and the prevalence of CLR was 32% in the aggregometry before vascular treatment. Potential risk factors identified in the aspirin group were concomitant insulin medication (p = 0.0006) and elevated C-reactive protein (CRP) (p = 0.0021). The overall ALR increased significantly postoperatively to 27.5% (p = 0.0006); however, there was no significant change in CLR that was detected. In a subgroup analysis elevation of the platelet count was associated with a post-procedure increase of ALR incidence. CONCLUSION: The incidence of ALR in vascular surgery patients increases after vascular procedures. An elevated platelet count was detected as a risk factor. Further studies are necessary to analyse this potential influence on patency rates of vascular reconstructions.

Age and Sex Differences in Ischemic Stroke Treatment in a Nationwide Analysis of 1.11 Million Hospitalized Cases.

Background and Purpose- To date, there is still uncertainty about age and sex differences in access to stroke unit treatment and use of intravenous thrombolysis (IVT), while age and sex differences have not been investigated for the new treatment option of mechanical thrombectomy (MT). We, therefore, undertook a complete nationwide analysis of all hospitalized ischemic stroke patients in Germany from 2013 to 2017. Methods- We used the nationwide administrative database of the German Federal Statistical Office and investigated access to stroke unit treatment, IVT, MT, and in-hospital mortality. Patients were subdivided into 6 predefined age groups (20-44, 45-59, 60-69, 70-79, 80-89, and >90 years). Pooled overall and age group estimates were calculated using the random-effects model. To evaluate potential sex disparities, we estimated odds ratios (ORs) with 95% CIs. Results- A total of 1 112 570 patients were hospitalized for first or recurrent ischemic stroke from 2013 to 2017. Overall, stroke unit treatment increased significantly from 66.8% in 2013 to 73.5% in 2017, as did IVT (from 12.4% to 15.9%) and MT (from 2.4% to 5.8%; all P<0.001). Although the difference became smaller over time, patients ≥80 years of age still received significantly less often treatments. Men of all age groups had a significantly higher probability receiving stroke unit treatment (OR, 1.11; 95% CI, 1.09-1.12) and lower in-hospital mortality (OR, 0.91; 95% CI, 0.89-0.93). No disparity was observed in the use of IVT (OR, 1.00; 95% CI, 0.98-1.01), while women of all ages were treated more often with MT (OR, 1.26; 95% CI, 1.22-1.30). Conclusions- Access to stroke unit treatment has to be increased in both older patients and women of all ages. While there was no sex difference in IVT use, it is important to further investigate the significantly higher frequency of MT in women with ischemic stroke irrespective of age.

Dagibatran Etexilate: Is There Any Need for Coagulation Monitoring After Initiation?

INTRODUCTION: Activated prothrombin time (aPTT) and thrombin time (TT) can serve as indicators for anticoagulation effect of dabigatran etexilate (Pradaxa), the new oral reversible, competitive inhibitor of thrombin. Further, a significant elevation of these coagulation parameters might demonstrate an increased risk of bleeding probably due to an accumulation of dabigatran. CASE REPORTS: We present 2 cases of patients with atrial fibrillation as well as mild and moderate renal impairment, which were treated with dabigatran. The patient with the mild renal impairment [creatinine clearance in 24-hour urine collection (CrCl) 50.2 mL/min] had a comorbid slightly disturbed liver synthesis and prolongation of aPTT. Increased risk of bleeding could be identified by significant elevated coagulation parameters (TT and aPTT) during dabigatran treatment. Further speculative in this case increased risk of bleeding might be due to an accumulation of dabigatran possibly caused by comorbid kidney and liver impairment and an effective gain of dabigatran caused by reduced hepatic synthesis of coagulation factors. CONCLUSIONS: Especially in multimorbid elderly patients with comorbid liver and kidney dysfunction, a measurement of coagulation parameters not only before but also soon after initiation of treatment might provide additional information about the risk of bleeding.

Multiple cerebral infarctions in a young patient with heroin-induced hypereosinophilic syndrome.

Hypereosinophilic syndrome represents a rare cause for cerebral infarctions and inflammatory neurological disorders. Various possible pathogenic mechanisms for cerebral infarctions have already been discussed. Complex mechanisms including a local hypercoagulability by eosinophilic granules as well as a direct damage to endothelial cells, leading to alterations of the microcirculation seem to be involved. The changing pattern of heroin use to inhalation/sniffing leading to an increasing abuse may cause a rise in the prevalence of Heroin induced eosinophilia, as it has been reported in a case of eosinophilic pneumonia associated with heroin inhalation. To our knowledge, the present case report displays the first description of stroke in the setting of heroin induced hypereosinophilia. Thus, besides usual vasoconstriction, HES should be considered in drug-induced cerebral infarctions.

Evaluation of CNS involvement in myotonic dystrophy type 1 and type 2 by transcranial sonography.

Myotonic dystrophies (DMs) are clinically similar but distinct multisystemic diseases related to different repeat expansion mutations. CNS involvement is one important aspect of both, myotonic dystrophy type 1 and type 2 (DM1, DM2). Transcran ial sonography (TCS) has become a reliable diagnostic tool in the evaluation of several CNS disorders. The aim of this study was to evaluate TCS-findings in DM-patients in correlation with their clinical status. Thirty-one DM-patients (DM1 = 17; DM2 = 14) were examined clinically and sonographically by independent physicians. Echogenicities of basal ganglia and mesencephalic regions were assessed according to the examination protocol for extrapyramidal disorders using a Toshiba Aplio(®) XG ultrasound system. TCS abnormalities were correlated to clinical findings and secondly compared to 31 controls. Ventricle diameters were additionally compared to 3T-MRI volumetry. Nine patients (29 %) showed hyperechogenicity of substantia nigra. Mesencephalic raphe was hypoechogenic in nine (29 %) DM-patients and was more frequently in DM1 patients (p = 0.021). Width of third ventricle was significantly larger in the patient group (p = 0.021) and correlated with MRI-based volumetry (R (2) = 0.756). Pathological raphe signal was observed mainly in patients suffering from daytime sleepiness (sensitivity = 42.1 %, specificity = 88.9 %, p = 0,044), while alterations did not correlate with symptoms of depression. As a novel finding, a relation between mesencephalic raphe echogenicity and excessive daytime sleepiness could be identified in our DM-patients. An alteration of serotonergic raphe structures might be involved in the pathogenesis of hypersomnia in DM. TCS allows for measurement of third ventricle enlargement as a feasible bedside test.

Echogenicity of basal ganglia structures in different Huntington's disease phenotypes.

In Huntington's disease (HD), a neurodegenerative-inherited disease, chorea as the typical kind of movement disorder is described. Beside chorea, however, all other kinds of movement disturbances, such as bradykinesia, dystonia, tremor or myoclonus can occur. Aim of the current study was to investigate alterations in the echogenicity of basal ganglia structures in different Huntington's disease phenotypes. 47 patients with manifest and genetically confirmed HD were recruited. All participants underwent a thorough neurological examination. According to a previously described method, classification into predominantly choreatic, mixed or bradykinetic-rigid motor phenotypes was performed depending on subscores of the Unified Huntington's Disease Rating Scale. In addition, findings in juvenile HD were compared to adult HD. Transcranial sonography was performed by investigators blinded to clinical classification. There were no significant differences in basal ganglia echogenicities between the three phenotypes. Size of echogenic area of substantia nigra (SN) correlated positively with CAG repeat and bradykinesia subscore, and negatively with age of onset and chorea subscore. Comparing juvenile and adult HD subtypes, SN hyperechogenicity was significantly more often detectable in the juvenile form (100 vs. 29.3 %, p = 0.002). Regarding echogenicity of caudate or lentiform nuclei, no significant differences were detected. HD patients with the juvenile variant exhibit marked hyperechogenicity of substantia nigra. No significant differences in basal ganglia echogenicities between predominantly choreatic, mixed or bradykinetic-rigid motor phenotypes were detected.

Monitoring ASA and P2Y12-specific platelet inhibition--comparison of conventional (single) and multiple electrode aggregometry.

OBJECTIVE: Several platelet function test systems exist for the evaluation of the platelet inhibitory effect in patients on P2Y12 inhibitors and/or acetylsalicylic acid (ASA, aspirin) therapy. Studies comparing different available assays found only a poor correlation. The objective of the present study was to evaluate the correlation and agreement between single electrode (SEA) and multiple electrode (MEA) aggregometry. METHODS AND RESULTS: In whole blood arachidonic acid (AA) and adenosine diphosphate (ADP)-induced platelet aggregation was measured simultaneously using SEA (Chrono-Log) and MEA (Multiplate). We analyzed a total of 226 measurements taken from 58 patients on single ASA therapy or dual antiplatelet therapy with ASA and a thienopyridine. A cut-off value for clopidogrel/prasugrel high on-treatment platelet reactivity (HPR) of > 47 units (U) was chosen for MEA testing using hirudin and > 5 Ohm for SEA with citrate anticoagulated blood samples. The respective cut-off values for ASA HPR were > 30 U for the MEA assay and > 1 Ohm for SEA testing. There was a good correlation of the prevalence of thienopyridine-HPR in both whole blood assays (Spearman rank correlation coefficient r = 0.698) and a good inter-rate accordance (Cohen's Kappa statistic κ = 0.648). For AA-induced aggregation, the correlation of the results obtained was significant (r = 0.536; p < 0.001) and detecting ASA-HPR revealed a moderate (κ = 0.482) correlation between both impedance aggregometry assays. CONCLUSION: Platelet function testing using SEA and MEA provided both good accordance and correlation and therefore study results obtained by these two assays similarly enabled the detection of HPR of thienopyridine (and ASA) therapy.

Clopidogrel high-on-treatment platelet reactivity in acute ischemic stroke patients.

BACKGROUND: During the first days following an acute ischemic stroke, a consistently good antiplatelet effect of clopidogrel is important due to the increased risk of recurrent ischemia. However, the platelet inhibitory effectiveness of clopidogrel is variable for multifactorial reasons. We investigated the prevalence and risk factors for clopidogrel high-on-treatment platelet reactivity (clopidogrel-HTPR) in acute ischemic stroke patients. METHODS: Using multiple-electrode impedance aggregometry (MEA), the antiplatelet effectiveness of clopidogrel in patients with acute ischemic stroke was prospectively evaluated. Measurements were performed 48 h after therapy was either initiated or continued after hospital admission. Clopidogrel-HTPR was defined as ADP-induced values>47 U. RESULTS: A total of 159 patients (71.8 ± 9.8 years, 69 female) were enrolled and 44% (n=70) patients were clopidogrel-HTPR. 35 of the clopidogrel-HTPR were retested within one week and 57.1% (n=20) showed a good clopidogrel response during subsequent testing. We identified diabetes mellitus (36.3% vs. 54.4%, p-value=0.003) and higher HbA1c values (6.3% vs. 6.8%, p=0.007) as risk factors for clopidogrel-HTPR. Multivariate regression analysis revealed that diabetes mellitus more than doubled the risk of clopidogrel-HTPR (OR 2.41; 95%-CI 1.19-4.88; p=0.015). CONCLUSIONS: Clopidogrel-HTPR was found in 44% of the patients with acute ischemic stroke. Besides time-dependency of the clopidogrel effect, major risk factors for clopidogrel-HTPR were diabetes mellitus and higher HbA1c values. Further investigations are required to analyse if a function test guided strategy has the potential to optimize the antiplatelet therapy of acute stroke patients.

Effectiveness of antiplatelet therapy in atherosclerotic disease: comparing the ASA low-response prevalence in CVD, CAD and PAD.

Although acetylsalicylic acid (ASA, aspirin) reduces the risk of ischemic events in patients with atherosclerosis, a substantial number of incidents continue to occur. As only limited data exist we evaluated the antiplatelet effectiveness of ASA in patients with different manifestations of atherosclerosis as in cerebrovascular, coronary artery and peripheral arterial disease (CVD, CAD, PAD). For the evaluation of the antiplatelet effectiveness of ASA we used whole blood aggregometry (Chrono-log Model 590). The patients in the different subgroups received ASA 100, 200 or 500 mg daily. We analysed 737 consecutive patients: 47.5 % with CVD, 33.6 % with CAD, and 18.9 % with PAD. We identified 28.0 % of the CVD, 18.1 % of the CAD and 21.6 % of the PAD patients to be ASA low-responder (ALR). Comparing subgroups treated with 100 mg ASA, 36.4 % were ALR in the CVD group as were 13.1 % of the CAD and 21.6 % of the PAD patients. Multivariate regression analysis revealed an odds ratio for being ALR of 4.50 (95 % confidence interval (CI) 1.70-11.9) when 100 mg and of 2.97 (95 % CI 1.58-5.60) when 200 mg ASA was taken compared to a dose of 500 mg. Despite the proven benefits of antiplatelet therapy in the secondary prevention of atherosclerotic disease, current antiplatelet management is suboptimal as up to 36 % of patients failed to achieve an adequate platelet inhibitory effect. Our findings may explain, at least in part, the high rates of cardiovascular events observed in the course of atherothrombotic disease and support the need to improve antiplatelet therapy.

Transcranial sonography in obsessive-compulsive disorder.

There is convergent evidence that basal ganglia structures are involved in the pathogenesis of obsessive-compulsive disorder (OCD). It has been also assumed that OCD is caused by a central serotonergic dysfunction. Transcranial sonography (TCS) has become a reliable, sensitive and non-invasive diagnostic tool concerning the evaluation of extrapyramidal movement disorders. This study used TCS to examine the alterations in different parenchymal regions, especially concerning serotonergic brainstem raphe nuclei as well as basal ganglia in OCD. Thirty-one OCD patients were compared with 31 matched healthy controls. Echogenecities were investigated according to the examination protocol for extrapyramidal disorders using a Siemens Sonoline(®) Elegra system. Obsessive-compulsive disorder patients showed reduced echogenity of the serotonergic brainstem raphe nuclei (32.3%) compared with healthy controls (16.1%). In nine OCD-patients (31%), but only in 2 control subjects (6.2%), a hyperechogenicity of the caudate nucleus was found. Patients with OCD significantly more often reveal a hypoechogenic brainstem raphe possibly reflecting altered serotonergic neurons there and a hyperechogenicity of caudate nucleus indicating structural or molecular cell changes. Further research is warranted to examine, whether TCS is useful in order to classify OCD and its subtypes.

Brainstem raphe alterations depicted by transcranial sonography do not result in serotonergic functional impairment.

In transcranial sonography (TCS), hypoechogenic signal of mesencephalic raphe structures has been described as a frequent finding in unipolar depression. It remains unclear if raphe hypoechogenicity represents a correlate for an altered serotonergic system. The loudness dependence of auditory evoked potentials (LDAEP) has been proposed as an indirect indicator of central serotonergic activity. Aim of this study was to evaluate TCS and LDAEP as independent variables of the human cerebral serotonergic system. Sonographic and electrophysiological investigations as well as psychometric assessment were performed blindly in 44 healthy subjects (28.7 ± 7.0 years; 24 females). Hypoechogenic raphe was detected in 6 subjects (13.6%). Three probands (6.8%) exhibit hyperechogenicity of Substantia nigra. LDAEP values ranged between -2.80 and 8.40 mVeff/10dB (2.31 ± 2.44). No correlations between LDAEP and sonographic findings were found. There were no significant correlations with the psychometric assessments. At least in healthy subjects, our findings do not support the hypothesis that abnormal structural finding of hypoechogenic BR in TCS is accompanied by a functional impairment of serotonergic system as assessed by LDAEP. Further multimodal studies on patients with depressive disorders are needed to elucidate the impact of the hypoechogenic raphe signal in the pathophysiology of depression.

Correlation between frequency of microembolic signals and efficacy of antiplatelet therapy in symptomatic carotid disease.

BACKGROUND AND PURPOSE: The detection of microembolic signals in transcranial-Doppler monitoring is associated with a higher stroke risk. We investigated the correlation between the frequency of microembolic signals and the efficacy of the antiplatelet therapy in patients with a recent symptomatic carotid-artery stenosis. SUBJECTS AND METHODS: Thirty-two patients (mean age: 70 years, 22 men) with a recent symptomatic carotid-artery stenosis underwent 30-minute TCD-monitoring. Twenty-three patients received acetylsalicylic-acid and 9 patients clopidogrel as antiplatelet-therapy. At the same day, the antiplatelet effect was measured with multiple-electrode-impedance aggregometry. RESULTS: In 20 cases, the qualifying event was a stroke and in 12 cases, a TIA. Twenty-six of the patients had a >50% degree of stenosis. More than one microembolic signals were detected in 13 (40.6%) of the subjects, while multiple-electrode-impedance aggregometry revealed eight low responders (6 acetylsalicylic-acid, 2 clopidogrel). More than one microembolic signals were detected in 6 of the 8 (75.0%) patients with low response, but in only 7 of the 24 subjects (29.2%) with an effective antiplatelet treatment (sensitivity 75%, specificity 70.8%; Fisher's exact test: P = .038). CONCLUSIONS: Our study suggests that in patients with recent symptomatic carotid-artery stenosis the detection of more than one microembolic signals might serve as a useful marker for the effectiveness of the antiplatelet treatment.

Clopidogrel load for emboli reduction in patients with symptomatic carotid stenosis undergoing urgent carotid endarterectomy.

BACKGROUND AND PURPOSE: Microembolic signals (MES) on transcranial Doppler are an independent risk factor for recurrent stroke in patients with extracranial symptomatic/asymptomatic carotid artery stenosis (CARAS). Clopidogrel load (300 mg) combined with dual antiplatelet therapy has been shown to reduce MES in patients with symptomatic CARAS. We sought to determine feasibility of clopidogrel load in decreasing asymptomatic embolization in patients with symptomatic CARAS undergoing urgent carotid endarterectomy within the first 2 weeks from the index event. Subjects and METHODS: Consecutive patients with symptomatic CARAS (70%-99%) and presence of MES on 1-hour baseline (<24 hours from the index event) transcranial Doppler monitoring of ipsilateral middle cerebral artery were treated with clopidogrel load followed by clopidogrel (75 mg)±aspirin (100 mg) during the elapsed time period between hospital admission and urgent carotid endarterectomy at 3 tertiary-care stroke centers. Repeat 1-hour transcranial Doppler monitoring was performed the day before surgery. Bleeding complications during surgery and recurrent strokes or transient ischemic attacks during the first month of ictus were prospectively recorded. RESULTS: A total of 11 symptomatic CARAS patients (mean age, 66±7 years; 73% men; 64% acute ischemic strokes) were treated with clopidogrel load followed by dual (67%) or single (33%) antiplatelet therapy. MES count was significantly reduced between baseline (median count, 8 MES/h; interquartile range, 6-19) and repeat transcranial Doppler monitoring (0 MES/h; interquartile range, 0-3; P=0.003). No bleeding complications, recurrent strokes, or transient ischemic attacks were documented. CONCLUSIONS: Our pilot observational study provides preliminary nonrandomized data regarding the potential efficacy of clopidogrel load to reduce asymptomatic embolization in patients with symptomatic CARAS before urgent carotid endarterectomy.

Which is the best anticoagulant for whole blood aggregometry platelet function testing? Comparison of six anticoagulants and diverse storage conditions.

Major hindrances of impedance aggregometry are caused by limited storage time and the requirement of ex vivo anticoagulation. Data on the influence of different anticoagulants and storage conditions are rare and incomplete. This study has systematically examined the influence of six different anticoagulants (sodium and lithium heparin, 20 µg/mL and 45 µg/mL r-hirudin, benzylsulfonyl-D-Arg-Pro-4-amidinobenzylamide (BAPA), and citrate) on the results of Adenosine 5'-diphosphate (ADP) and arachidonic acid (AA) induced measurements using multiple-electrode impedance aggregometer (MEA). Measurements were carried out in a time frame of 0 min up to 48 h after blood withdrawal. In addition, the influence of storage temperatures of 4°C and 37°C was evaluated. Results of ADP-induced tests significantly varied within the first 30 min in all tested anticoagulants, in citrated blood even within the first 60 min. They remained stable up to 2 h in 20 µg/mL r-hirudin and BAPA, 4 h in citrate, 8 h in 45 µg/mL r-hirudin, and lithium heparin and up to a maximum of 12 h in sodium heparin anticoagulated blood. The analysis of AA-induced tests revealed no significantly different results up to 6 h when BAPA was used, 8 h in lithium heparin, 20 µg/mL r-hirudin and citrate, 12 h in 45 µg/mL r-hirudin, and even 24 h in sodium heparin-anticoagulated samples. A storage temperature of either 4°C or 37°C in contrast to room temperature had a negative influence on the stability of results. In conclusion, sodium heparin and 45 µg/mL r-hirudin as anticoagulants guarantee the longest storage time for impedance aggregometry.

Dose-dependent effect of early antiplatelet therapy in acute ischaemic stroke.

Antiplatelet agents are essential in treating patients with acute ischaemic stroke (AIS) to prevent recurrent ischaemic events. The aim of this study was to evaluate the effectiveness of early antiplatelet therapy with different aspirin (ASA) dosages in patients with AIS. This observational study included 454 patients with AIS in whom antiplatelet treatment was initiated. The antiplatelet effect was determined by whole blood aggregometry within 48 hours after antplatelet therapy was initiated. An impedance change exceeding 0 W after stimulation with arachidonic acid was defined as ASA low response (ALR) and ≥5 Ω in ADP-stimulated specimen as clopidogrel LR. Of the study group 53.5% patients were treated with 200 mg ASA orally, 27.5% with 500 mg ASA intravenously, 8.6% with 100 mg ASA orally, and 7.7% with 75 mg clopidogrel. A dose-dependent antiplatelet effect of ASA treatment was found: 18.4% of patients with 500 mg ASA intravenously were ALR, in contrast to 32.5% on 200 mg and 35.9% on 100 mg ASA orally. Clopidogrel treatment without a loading dose resulted in a high proportion of LR (45.7%). Using the propensity score method revealed a three times higher risk for ALR for patients treated with ASA 200 mg [odds ratio 2.99 (1.55-5.79)] compared to treatment with ASA 500 mg. In conclusion, initiating antiplatelet therapy in patients with AIS resulted in a dose-dependent insufficient platelet inhibitory effect. Our findings suggest using a loading dose of 500 mg ASA intravenously as this seems to be favourable when a sufficient early platelet inhibitory effect is wanted.

Is there an ideal way to initiate antiplatelet therapy with aspirin? A crossover study on healthy volunteers evaluating different dosing schemes with whole blood aggregometry.

BACKGROUND: Guidelines recommend an early initiation of aspirin treatment in patients with acute cerebral ischemia. Comparative studies on the best starting dose for initiating aspirin therapy to achieve a rapid antiplatelet effect do not exist. This study evaluated the platelet inhibitory effect in healthy volunteers by using three different aspirin loading doses to gain a model for initiating antiplatelet treatment in acute strokes patients. METHODS: Using whole blood aggregometry, this study with a prospective, uncontrolled, open, crossover design examined 12 healthy volunteers treated with three different aspirin loading doses: intravenous 500 mg aspirin, oral 500 mg aspirin, and a course of 200 mg aspirin on two subsequent days followed by a five-day course of 100 mg aspirin. Aspirin low response was defined as change of impedance exceeding 0 Ω after stimulation with arachidonic acid. RESULTS: Sufficient antiplatelet effectiveness was gained within 30 seconds when intravenous 500 mg aspirin was used. The mean time until antiplatelet effect was 74 minutes for 500 mg aspirin taken orally and 662 minutes (11.2 hours) for the dose scheme with 200 mg aspirin with a high inter- and intraindividual variability in those two regimes. Platelet aggregation returned to the baseline range during the wash-out phase within 4 days. CONCLUSION: Our study reveals that the antiplatelet effect differs significantly between the three different aspirin starting dosages with a high inter- and intraindividual variability of antiplatelet response in our healthy volunteers. To ensure an early platelet inhibitory effect in acute stroke patients, it could be advantageous to initiate the therapy with an intravenous loading dose of 500 mg aspirin. However, clinical outcome studies must still define the best way to initiate antiplatelet treatment with aspirin.