Subsequent Ischemic Events Research Articles

Matrix metalloproteinase-2 of human carotid atherosclerotic plaques promotes platelet activation

Purified active matrix metalloproteinase-2 (MMP-2) is able to promote platelet aggregation. We aimed to assess the role of MMP-2 expressed in atherosclerotic plaques in the platelet-activating potential of human carotid plaques and its correlation with ischaemic events. Carotid plaques from 81 patients undergoing endarterectomy were tested for pro-MMP-2 and TIMP-2 content by zymography and ELISA. Plaque extracts were incubated with gel-filtered platelets from healthy volunteers for 2 minutes before the addition of a subthreshold concentration of thrombin receptor activating peptide-6 (TRAP-6) and aggregation was assessed. Moreover, platelet deposition on plaque extracts immobilised on plastic coverslips under high shear-rate flow conditions was measured. Forty-three plaque extracts (53%) potentiated platelet aggregation (+233 ± 26.8%), an effect prevented by three different specific MMP-2 inhibitors (inhibitor II, TIMP-2, moAb anti-MMP-2). The pro-MMP-2/TIMP-2 ratio of plaques potentiating platelet aggregation was significantly higher than that of plaques not potentiating it (3.67 ± 1.21 vs 1.01 ± 0.43, p<0.05). Moreover, the platelet aggregation-potentiating effect, the active-MMP-2 content and the active MMP-2/pro-MMP-2 ratio of plaque extracts were significantly higher in plaques from patients who developed a subsequent major cardiovascular event. In conclusion, atherosclerotic plaques exert a prothrombotic effect by potentiating platelet activation due to their content of MMP-2; an elevated MMP-2 activity in plaques is associated with a higher rate of subsequent ischaemic cerebrovascular events.

Value of High-Sensitivity Troponin in Assessing the Extent of Benefit Provided by Ticagrelor Versus Clopidogrel in Non–ST-Segment Elevation Acute Coronary Syndromes

There is considerable evidence supporting an aggressive approach to the management of non-ST-segment elevation acute coronary syndromes (NSTE-ACS). This includes intensive medical therapy and an early invasive strategy. These tactics, alone or in combination, can reduce the rate of subsequent ischemic events though increase bleeding events. The challenge for clinicians is to efficiently identify those patients (from among the very large number of patients presenting to the hospital with chest pain) who will receive the greatest net benefit from an aggressive approach. Numerous methods for risk stratification of NSTE-ACS patients have emerged. Clinical risk assessments such as the TIMI risk score have been shown to predict adverse outcomes and, perhaps more importantly, identify patients most likely to benefit from an early invasive strategy or intensive antithrombotics. 1-2 Elevated levels of serum troponin have been found separately to predict adverse events and identify patients likely to benefit from intensive antiplatelet therapy. 3 Other biomarkers, such as B-type natriuretic peptide (BNP) and N-terminal-proBNP (NT-proBNP) predict adverse outcomes in the setting of NSTE-ACS, but have not consistently been shown to predict a response to a specific treatment regimen. 4 In this issue of Circulation , Wallentin et al 5 report their analysis of baseline levels of high-sensitivity troponin T (hs-TnT), NT-proBNP, and growth-differentiation factor-15 (GDF-15) in NSTE-ACS patients enrolled in the Platelet Inhibition and Patient Outcomes (PLATO) trial. 6

Cardiac Rehabilitation and Outcome in Stable Outpatients With Recent Myocardial Infarction

ObjectiveTo compare the mortality rate and the rate of subsequent ischemic events (myocardial infarction [MI], ischemic stroke, or limb amputation) in patients with recent MI according to the use of cardiac rehabilitation or no rehabilitation. DesignLongitudinal observational study. SettingOngoing registry of outpatients. ParticipantsPatients (N=1043) with recent acute MI were recruited; of these, 521 (50%) participated in cardiac rehabilitation. InterventionsNot applicable. Main Outcome MeasuresSubsequent ischemic events and mortality rates were registered. ResultsOver a mean follow-up of 18 months, 50 patients (4.8%) died and 49 (4.7%) developed 52 subsequent ischemic events (MI: n=43, ischemic stroke: n=6, limb amputation: n=3). Both the mortality rate (.16 vs 5.57 deaths per 100 patient-years; rate ratio=.03; 95% confidence interval [CI], 0.0–0.1]) and the rate of subsequent ischemic events (1.65 vs 4.54 events per 100 patient-years; rate ratio=0.4; 95% CI, 0.2–0.7) were significantly lower in cardiac rehabilitation participants than in nonparticipants. Multivariate analysis confirmed that patients in cardiac rehabilitation had a significantly lower risk of death (hazard ratio=.08; 95% CI, .01–.63; P=.016) and a nonsignificant lower risk of subsequent ischemic events (hazard ratio=.65; 95% CI, .30–1.42). ConclusionsThe use of cardiac rehabilitation in patients with recent MI was independently associated with a significant decrease in the mortality rate and a nonsignificant decrease in the rate of subsequent ischemic events.

Repetitive Myocardial Ischemia Promotes Coronary Growth in the Adult Mammalian Heart

BackgroundCoronary artery disease and ischemic cardiomyopathy represent the leading cause of heart failure and continue to grow at exponential rates. Despite widespread availability of coronary bypass surgery and percutaneous coronary intervention, subsequent ischemic events and progression to heart failure continue to be common occurrences. Previous studies have shown that a subgroup of patients develop collateral blood vessels that serve to connect patent and occluded arteries and restore perfusion to ischemic territories. The presence of coronary collaterals has been correlated with improved clinical outcomes; however, the molecular mechanisms governing this process remain largely unknown.Methods and ResultsTo date, no mouse models of coronary arterial growth have been described. Using a closed‐chest model of myocardial ischemia, we have demonstrated that brief episodes of repetitive ischemia are sufficient to promote the growth of both large coronary arteries and the microvasculature. Induction of large coronary artery and microvascular growth resulted in improvements in myocardial perfusion after prolonged ischemia and protected from subsequent myocardial infarction. We further show that repetitive ischemia did not lead to increased expression of classic proangiogenic factors but instead resulted in activation of the innate immune system and recruitment of macrophages to growing blood vessels.ConclusionsThese studies describe a novel model of coronary angiogenesis and implicate the cardiac macrophage as a potential mediator of ischemia‐driven coronary growth.

Suboptimal platelet response to clopidogrel after percutaneous coronary intervention in patients with acute coronary syndrome is not associated with total platelet count and mean platelet volume

Cardiologia CROATICA Objectives: Responsiveness to clopidogrel is characterized by large variability in platelet inhibition among patients. Suboptimal response to clopidogrel is known to be associated with higher risk for subsequent cardiovascular ischaemic events such as in-stent thrombosis or recurrent acute coronary syndrome (ACS). We sought to evaluate correlation of platelet count and mean platelet volume (MPV) with low clopidogrel response in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). Patients and Methods: We enrolled 359 consecutive ACS patients in the study. Patients with thrombocytopenia, suboptimal PCI and those who received glycoprotein IIbIIIa antagonists during and/or after PCI were excluded (120 patients). Residual platelet activity specific to clopidogrel was measured using Multiplate function analyzer — a point of care instrument which determines platelet function in small quantities of whole blood. Results: Fifty-three patients (22.2%) had suboptimal response to clopidogrel. Average platelet number and MPV in patients with decreased response was 240.8x10/L (SD ± 52.40) and 9.63 fL (SD ± 1.00), respectively. Patients with normal or increased response had average platelet number of 226.6x10/L (SD ± 53.02) and average MPV 9.3 fL (SD ± 0,91). There was no statistically significant difference in total platelet number (P=0.07) nor MPV values (P=0.13) between low responders and other patients. Conclusion: MPV and total platelet number are not associated with low respond to clopidogrel after successful PCI in ACS.

Carotid Plaque MRI and Stroke Risk

MRI characterization of carotid plaque has been studied recently as a potential tool to predict stroke caused by carotid atherosclerosis. We performed a systematic review and meta-analysis to summarize the association of MRI-determined intraplaque hemorrhage, lipid-rich necrotic core, and thinning/rupture of the fibrous cap with subsequent ischemic events. We performed a comprehensive literature search evaluating the association of carotid plaque composition on MRI with ischemic outcomes. We included cohort studies examining intraplaque hemorrhage, lipid-rich necrotic core, or thinning/rupture of the fibrous cap with mean follow-up of ≥1 month and an outcome measure of ipsilateral stroke or transient ischemic attack. A meta-analysis using a random-effects model with assessment of study heterogeneity and publication bias was performed. Of the 3436 articles screened, 9 studies with a total of 779 subjects met eligibility for systematic review. The hazard ratios for intraplaque hemorrhage, lipid-rich necrotic core, and thinning/rupture of the fibrous cap as predictors of subsequent stroke/transient ischemic attack were 4.59 (95% confidence interval, 2.91-7.24), 3.00 (95% confidence interval, 1.51-5.95), and 5.93 (95% confidence interval, 2.65-13.20), respectively. No statistically significant heterogeneity or publication bias was present in the 3 main meta-analyses performed. The presence of intraplaque hemorrhage, lipid-rich necrotic core, and thinning/rupture of the fibrous cap on MRI of carotid plaque is associated with increased risk of future stroke or transient ischemic attack in patients with carotid atherosclerotic disease. Dedicated MRI of plaque composition offers stroke risk information beyond measurement of luminal stenosis in carotid atherosclerotic disease.

D-dimer levels predict ischemic and hemorrhagic outcomes after acute myocardial infarction: a HORIZONS-AMI biomarker substudy

D-dimer is a product of cross linked fibrin degradation and is a measure of the amount of fibrin turnover. As such, D-dimer might be of utility in the prediction of both thrombotic and hemorrhagic events. Therefore, the aim of the present study was to evaluate whether elevated D-dimer levels on admission and at discharge could predict subsequent ischemic and hemorrhagic events in patients with acute myocardial infarction (AMI). D-dimer was measured on admission and at discharge in 461 out of a total of 3,602 patients in the HORIZONS-AMI trial, as part of the formal prespecified biomarker substudy. The predictive value for major adverse cardiovascular events (MACE) and non-CABG major bleeding after 3year follow up was investigated by stratifying patients in groups of D-dimer level and comparing event rates using Kaplan-Meier and calculating hazard ratios using Cox proportional hazards models. D-dimer levels≥0.71μg/mL on admission were associated with an adjusted hazard ratio of 2.58 for MACE (p=0.0014) and 4.61 for major bleeding (p=0.0018). A discharge D-dimer level≥1.26μg/mL was associated with a higher risk for MACE by univariate analysis (HR 1.88, p=0.037), but lost its significance after multivariate adjustment (HR 1.77, p=0.070). High D-dimer levels on admission were associated with a higher risk of MACE and non-CABG major bleeding in STEMI patients undergoing pPCI.

Postoperative Neurocognitive Dysfunction in Patients Undergoing Cardiac Surgery after Remote Ischemic Preconditioning: A Double-Blind Randomized Controlled Pilot Study

BackgroundRemote ischemic preconditioning (RIPC) has been shown to enhance the tolerance of remote organs to cope with a subsequent ischemic event. We hypothesized that RIPC reduces postoperative neurocognitive dysfunction (POCD) in patients undergoing complex cardiac surgery.MethodsWe conducted a prospective, randomized, double-blind, controlled trial including 180 adult patients undergoing elective cardiac surgery with cardiopulmonary bypass. Patients were randomized either to RIPC or to control group. Primary endpoint was postoperative neurocognitive dysfunction 5–7 days after surgery assessed by a comprehensive test battery. Cognitive change was assumed if the preoperative to postoperative difference in 2 or more tasks assessing different cognitive domains exceeded more than one SD (1 SD criterion) or if the combined Z score was 1.96 or greater (Z score criterion).ResultsAccording to 1 SD criterion, 52% of control and 46% of RIPC patients had cognitive deterioration 5–7 days after surgery (p = 0.753). The summarized Z score showed a trend to more cognitive decline in the control group (2.16±5.30) compared to the RIPC group (1.14±4.02; p = 0.228). Three months after surgery, incidence and severity of neurocognitive dysfunction did not differ between control and RIPC. RIPC tended to decrease postoperative troponin T release at both 12 hours [0.60 (0.19–1.94) µg/L vs. 0.48 (0.07–1.84) µg/L] and 24 hours after surgery [0.36 (0.14–1.89) µg/L vs. 0.26 (0.07–0.90) µg/L].ConclusionsWe failed to demonstrate efficacy of a RIPC protocol with respect to incidence and severity of POCD and secondary outcome variables in patients undergoing a wide range of cardiac surgery. Therefore, definitive large-scale multicenter trials are needed.Trial RegistrationClinicalTrials.gov NCT00877305

Renal function and short-term outcome in stable outpatients with coronary, cerebrovascular or peripheral artery disease

BackgroundThe influence of renal function on outcome in stable outpatients with atherosclerotic disease has not been thoroughly studied. MethodsWe used the FRENA Registry data to compare the incidence of subsequent ischemic events (myocardial infarction [MI], ischemic stroke or limb amputation) in patients with coronary (CAD), cerebrovascular (CVD) or peripheral artery disease (PAD), according to their estimated glomerular filtration rate (eGFR) at baseline. ResultsAs of April 2012, 3860 patients were recruited in FRENA: 1439 with CAD, 1118 with CVD and 1303 with PAD. Over a mean follow-up of 14±12 months, 97 patients suffered subsequent MI, 93 had ischemic stroke and 46 underwent limb amputation. In all, 2699 patients (70%) had eGFR>60mL/min/1.73m2, 1022 (26%) had 30–60mL/min/1.73m2, and 139 (3.6%) had <30mL/min/1.73m2. Among patients with CAD, the rate of subsequent MI was: 1.38 (95% CI: 0.85–2.11), 5.79 (95% CI: 3.90–8.31) and 18.8 (95% CI: 9.14–34.4) events per 100 patient-years, respectively. On multivariable analysis, the hazard ratio for MI (compared with patients with eGFR>60mL/min/1.73m2) was of 1.77 (95% CI: 1.15–2.73) for patients with eGFR of 30–60mL/min/1.73m2, and 3.15 (95% CI: 1.61–6.14) for those with eGFR<30mL/min/1.73m2. Among patients with CVD or PAD, there was no increasing rate of subsequent ischemic events with decreasing renal function. ConclusionsAmong stable outpatients with CAD, there is an increasing rate of subsequent MI with decreasing renal function, independently of potentially confounding variables. These findings were not observed in patients with CVD or PAD.

Progression of Carotid Artery Stenosis Is Associated With the Occurrence of Subsequent Ipsilateral Ischemic Events and Stroke: Results From the ACSRS Study

Progression of Carotid Artery Stenosis Is Associated With the Occurrence of Subsequent Ipsilateral Ischemic Events and Stroke: Results From the ACSRS Study

Intraplaque stretch in carotid atherosclerotic plaque--an effective biomechanical predictor for subsequent cerebrovascular ischemic events.

BackgroundStretch is a mechanical parameter, which has been proposed previously to affect the biological activities in different tissues. This study explored its utility in determining plaque vulnerability.MethodsOne hundred and six patients with mild to moderate carotid stenosis were recruited in this study (53 symptomatic and 53 asymptomatic). High resolution, multi-sequence magnetic resonance (MR) imaging was performed to delineate various plaque components. Finite element method was used to predict high stretch concentration within the plaque.ResultsDuring a two-year follow-up, 11 patients in symptomatic group and 3 in asymptomatic group experienced recurrent cerebrovascular events. Plaque stretch at systole and stretch variation during one cardiac cycle was greater in symptomatic group than those in the asymptomatic. Within the symptomatic group, a similar trend was observed in patients with recurrent events compared to those without.ConclusionPlaques with high stretch concentration and large stretch variation are associated with increased risk of future cerebrovascular events.

Avoiding stent thrombosis: advances in technique, antiplatelet pharmacotherapy and stent design

Stent thrombosis (ST) is major complication that can occur any time following stent placement. Many studies have advanced our understanding of the risk factors and mechanisms contributing to ST. Beyond identifying high-risk characteristics, such as premature discontinuation of dual antiplatelet therapy or acute coronary syndrome on presentation, insights from these studies have led to refinements in procedural technique and stent design. Second-generation drug-eluting stents are commonly used in practice today, and have improved some of the characteristics found to promote ST with first-generation drug-eluting stents, and have resulted in lower rates of ST. In addition, the use of a novel and more potent antiplatelet therapy in high-risk patients has led to a reduction in subsequent ischemic events, including ST. Despite these important gains, several issues remain unresolved. Studies continue to evaluate the optimal duration of dual antiplatelet therapy following stent placement, which is challenged by s...

The role of urgent imaging in the diagnosis and management of patients with TIA and minor stroke

The diagnosis of patients with transient ischemic attack and minor stroke is challenging as patients have minimal or no neurological deficits related to their ischemic event on their clinical examination. Multiple clinical factors have been used in triaging these patients into high- and low-risk categories based on the estimated risk of having a recurrent ischemic event. However, the ability of clinical factors in isolation in predicting future ischemic events remains poor. The addition of urgent neuroimaging has substantially improved the diagnostic certainty and the accuracy of outcome prediction in this patient population. In this article, we briefly discuss the different forms of subsequent ischemic events that may occur in patients with transient ischemic attack and minor stroke. We review the role of different forms of parenchymal and vascular neuroimaging in the acute setting in establishing the correct diagnosis and predicting both radiographic and clinical outcomes in this patient population.

Age-related reduction of cerebral ischemic preconditioning: myth or reality?

Stroke is one of the leading causes of death in industrialized countries for people older than 65 years of age. The reasons are still unclear. A reduction of endogenous mechanisms against ischemic insults has been proposed to explain this phenomenon. The “cerebral” ischemic preconditioning mechanism is characterized by a brief episode of ischemia that renders the brain more resistant against subsequent longer ischemic events. This ischemic tolerance has been shown in numerous experimental models of cerebral ischemia. This protective mechanism seems to be reduced with aging both in experimental and clinical studies. Alterations of mediators released and/or intracellular pathways may be responsible for age-related ischemic preconditioning reduction. Agents able to mimic the “cerebral” preconditioning effect may represent a new powerful tool for the treatment of acute ischemic stroke in the elderly. In this article, animal and human cerebral ischemic preconditioning, its age-related difference, and its potential therapeutical applications are discussed.

Receptor Inhibitors in Acute Coronary Syndromes: What Is New on the Horizon?

Dual antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor represents the cornerstone therapy for patients with acute coronary syndromes or undergoing percutaneous interventions, leading to a reduction of subsequent ischemic events. Variable response to clopidogrel has received close attention, and pharmacokinetic, pharmacodynamic, and pharmacogenomic factors have been identified as culprits. This led to the introduction of newer, potentially safer, and more effective antiplatelet agents (prasugrel and ticagrelor). Additionally, several point-of-care assays of platelet function have been developed in recent years to rapidly screen individuals on antiplatelet therapy. While the routine use of platelet function testing is uncertain and not currently recommended, it may be useful in instances when the degree of platelet inhibition may be uncertain such as high-risk patients undergoing percutaneous coronary intervention or when there may be a suspected pharmacodynamic interaction with other drugs. The current paper focuses on the P2Y12 receptor inhibitors and their pharmacogenetics and indications in patients with acute coronary syndromes or receiving percutaneous coronary interventions as well as the applicability of platelet function testing in this clinical context.

Mean Platelet Volume and Long-Term Mortality in Patients Undergoing Percutaneous Coronary Intervention

Increased platelet activity is associated with adverse cardiovascular events. The mean platelet volume (MPV) correlates with platelet activity; however, the relation between the MPV and long-term mortality in patients undergoing percutaneous coronary intervention (PCI) is not well established. Furthermore, the role of change in the MPV over time has not been previously evaluated. We evaluated the MPV at baseline, 30 days, 60 days, 90 days, 1 year, 2 years, and 3 years after the procedure in 1,512 patients who underwent PCI. The speed of change in the MPV was estimated using the slope of linear regression. Mortality was determined by query of the Social Security Death Index. During a median of 8.7 years, mortality was 49.3% after PCI. No significant difference was seen in mortality when stratified by MPV quartile (first quartile, 50.1%; second quartile, 47.7%; third quartile, 51.3%; fourth quartile, 48.3%; p= 0.74). For the 839 patients with available data to determine a change in the MPV over time after PCI, mortality was 49.1% and was significantly greater in patients with an increase (52.9%) than in those with a decrease (44.2%) or no change (49.1%) in the MPV over time (p <0.0001). In conclusion, no association was found between the baseline MPV and long-term mortality in patients undergoing PCI. However, increased mortality was found when the MPV increased over time after PCI. Monitoring the MPV after coronary revascularization might play a role in risk stratification.

Predictors of outcome in stable outpatients with peripheral artery disease

Patients with peripheral artery disease (PAD) are at increased risk for subsequent ischemic events. We used data from the FRENA Registry to find predictors of subsequent myocardial infarction (MI), ischemic stroke, and limb amputation in stable outpatients with PAD. As of January 2012, 1,270 patients with PAD were recruited, of whom 1,042 (82%) had Fontaine stage II; 113 (8.9%) stage III; and 115 (9.1%) stage IV. Over a mean follow-up of 14months, 35 patients developed MI, 25 had stroke, 39 underwent limb amputation, and 91 died. Among patients with Fontaine stage II, the incidence of MI (2.09 events per 100 patient-years; 95% CI 1.43-2.97) or stroke (0.93; 95% CI 0.52-1.56) was similar to that of limb amputation (3.22; 95% CI 2.37-4.29). On multivariate analysis, patients with diabetes [hazard ratio (HR) 2.09; 95% CI 1.05-4.18], prior coronary disease (HR 5.35; 95% CI 2.24-12.8), or atrial fibrillation (HR 3.11; 95% CI 1.52-6.37) were at increased risk for MI; female (HR 2.94; 95% CI 1.32-6.67), those with prior stroke (HR 5.21; 95% CI 1.22-22.2) or atrial fibrillation (HR 3.37; 95% CI 1.45-7.85) at increased risk for stroke; and female (HR 2.38; 95% CI 1.23-4.55), those with diabetes (HR 3.50; 95% CI 1.58-7.73) or advanced stages of PAD were at increased risk for limb amputation. Prior coronary artery disease, diabetes and atrial fibrillation predicted subsequent MI; female gender, prior stroke and atrial fibrillation predicted stroke; and female gender, diabetes, and advanced stages of PAD predicted limb amputation.

Contrast-Enhanced 3T High-Resolution MR Imaging in Symptomatic Atherosclerotic Basilar Artery Stenosis

Contrast-enhanced 3T high-resolution MR imaging can be used to determine the wall enhancement pattern of the basilar artery in symptomatic atherosclerotic stenosis. We used this method to explore the relationship between wall enhancement and both recent infarction in the territory of the stenotic BA and subsequent ischemic events associated with the stenotic BA. Sixty patients with symptomatic atherosclerotic BA stenosis ≥70% were enrolled consecutively. HR-MRI of cross-sectional BAs was obtained before and after contrast media injection, and wall enhancement indices were calculated for sections proximal to, at, and distal to the site of maximal luminal narrowing. DWI of the brain was performed to determine the presence of recent infarction. Images from 56 patients were suitable for analysis. Thirty-three patients underwent stent placement for the stenotic BA, and 23 patients underwent conservative medical treatment with antiplatelet agents and risk-factor control. All 23 patients with medical treatment had a 12-month follow-up. Greater wall enhancement was seen in the section proximal to the MLN section in both patients with recent infarction (74 ± 65% versus 44 ± 44%; P = .046) and in patients with subsequent ischemic events (100 ± 57% versus 44 ± 44%; P = .014). Greater wall enhancement proximal to the MLN site correlates with recent infarction in the territory of the stenotic BA and subsequent ischemic events associated with the stenotic BA. Contrast-enhanced HR-MRI may serve as a noninvasive tool for risk stratification of BA atherosclerosis.

Rapid P2Y 12 Inhibition

Acute coronary syndrome (ACS) is still a serious condition associated with decreased quality of life, increased healthcare expenditures, and premature death. The prevalence of ACS is expected to increase with aging of the population and with the epidemics of obesity and diabetes. The short- and long-term mortality after an ACS has been dramatically reduced by the development of revascularization techniques and new antithrombotic agents. The past decade has seen many trials evaluating new oral and parenteral antiplatelet agents with greater potency than aspirin and clopidogrel. Several antiplatelet agents have been developed, with the ultimate goal to obtain optimal antiplatelet therapy for both the acute and the chronic phases of disease. Articles see p 336, 347 Ideally, efficiency requires several pharmacodynamic proprieties, such as a fast onset of action (immediate onset for emergency situations), a strong degree of platelet inhibition (at least stronger than the standard of care [aspirin and clopidogrel]), a narrow interindividual variability with no impact of genetic variants and no drug-to-drug interaction, and an easy administration (an oral drug for maintenance therapy and an intravenous formulation for rapid loading). Of course, this drug should also lead to a convincing reduction of recurrent ischemic events in an adequately powered phase 3 trial. With regard to safety, the illusion of having the same dose of a single antiplatelet drug to treat all clinical situations has passed. The degree of platelet activation and aggregation is different across clinical situations (eg, acute ST-segment–elevation myocardial infarction [STEMI] versus secondary prevention) and varies over time in the same patient. Recent large phase 3 trials have confirmed the importance of dosing and the target population treated with the new agents.1–4 From a safety standpoint, an ideal antiplatelet agent would also have an intravenous and oral formulation, with different doses tested in …

Abstract 3299: Can The Perfusion Status Predict The Subsequent Ischemic Events Following Acute Symptomatic Steno-occlusion Of Cerebral Arteries?

Background: Symptomatic steno-occlusion (SYSO) is associated with stroke progression and recurrence after acute ischemic stroke. And the perfusion status is believed to be an important determinant in this situation. However, the impact of perfusion status on progression or recurrence has not been studied yet in patients with acute SYSO. Method: Based on prospective stroke registry, a consecutive series of 1309 patients were identified who were hospitalized due to ischemic stroke within 24 hours of onset. Among them, we selected who had more than 50% of stenosis or occlusion of extracranial internal carotid artery (EICA), intracranial internal carotid artery (IICA), middle cerebral artery (M1 and M2), anterior cerebral artery (ACA), and posterior cerebral artery (PCA) with the corresponding ischemic lesions. Patients who did not undergo perfusion study, who had infratentorial stroke, or the quality of whose perfusion image was poor were excluded. The perfusion status was assessed by perfusion lesion volume (PLV) using geometric method of visually delineated area. Stroke progression and recurrence (subsequent ischemic event, SIE) were defined and captured prospectively up to 1 year as a part of the institution’s quality-of-care monitoring program for hospitalized stroke patients. Result: A total 385 patients (age: 69.7 ± 12.6 year-old) were enrolled in this study. The distribution of PLV according to the location of SYSO was presented in the figure below. A total 88 patients (22.9%) experienced SIE and 72.7% were ischemic progression. The SIE rates of EICA, IICA, M1, M2, ACA and PCA were 31.8%, 24.1%, 19.9%, 14.1%, 15.4% and 25.0%, respectively. The PLV was dichotomized at median value of each SYSO location and the SIE rate was 26.6% in patients with high PLV and 19.2% in those with low PLV (P=0.084). The SIE rate of patients with occlusion (N=282) was not different from those with stenosis (N=103) (P=0.672). In the multivariable model, the adjusted odds ratio of PLV was 1.64 (95% confidence interval, 0.98-2.74) for the risk of SIE. The adjustments were done for male, time from onset to admission, baseline NIHSS score, and thrombolysis. After additional adjustment for recanalization status, the odds ratio of PLV was 1.81 (1.06 to 3.08). Conclusion: This study shows that the initial perfusion status may predict the following stroke progression or recurrence in patients with acute symptomatic steno-occlusion of cerebral arteries.