Risk Of Recurrent Ischemic Events Research Articles

Association between GNAQ Gene DNA Methylation and Vascular Recurrence in Patients with Acute Ischemic Stroke or Transient Ischemic Attack

Purpose: We aimed to assess whether the aberrant methylation of GNAQ gene, which may involve in the clopidogrel resistance (CR), was associated with a higher risk of recurrent ischemic events in clopidogrel-treated acute ischemic stroke or transient ischemic attack (TIA) patients. Methods: This is a nested case-control study, 152 clopidogrel-treated acute ischemic stroke or TIA patients that were propensity-matched were included in the final analysis, including 36 patients with vascular recurrence set as cases. Methylation levels of GNAQ gene were identified with MassARRAY EpiTYPER assays. Univariate and multivariate logistic regression analyses were conducted to explore the predictive value of CpG units for recurrent ischemic events within 1 year.Mediation analysis was performed to assess the role of CR in describing the effect of GNAQ methylation on recurrent ischemic events. Results: A total of 16 differentially methylated CpG units were identified. Multivariate logistic analysis indicated that the average methylation of CpG 32–39 of GNAQ was associated with a significantly higher risk of ischemic events (p < 0.001). When transformed into dichotomous variables with the receiver operating characteristic curve, hypomethylation (<0.31) of CpG 32–39 of GNAQ significantly increased the risk of vascular recurrence (odds ratio 73.82, 95% confidence interval 20.33–268.01). The mediation effect of CR for recurrent ischemic events was not identified. Conclusions: Hypomethylation of CpG 32–39 of GANQ gene was associated with a higher risk of ischemic events for clopidogrel-treated acute ischemic stroke or TIA patients. Further studies were warranted to explain the possible mechanism.

Assessment of medical management in Coronary Type 2 Diabetic patients with previous percutaneous coronary intervention in Spain: A retrospective analysis of electronic health records using Natural Language Processing.

Introduction and objectivesPatients with type 2 diabetes (T2D) and stable coronary artery disease (CAD) previously revascularized with percutaneous coronary intervention (PCI) are at high risk of recurrent ischemic events. We aimed to provide real-world insights into the clinical characteristics and management of this clinical population, excluding patients with a history of myocardial infarction (MI) or stroke, using Natural Language Processing (NLP) technology.MethodsThis is a multicenter, retrospective study based on the secondary use of 2014–2018 real-world data captured in the Electronic Health Records (EHRs) of 1,579 patients (0.72% of the T2D population analyzed; n = 217,632 patients) from 12 representative hospitals in Spain. To access the unstructured clinical information in EHRs, we used the EHRead® technology, based on NLP and machine learning. Major adverse cardiovascular events (MACE) were considered: MI, ischemic stroke, urgent coronary revascularization, and hospitalization due to unstable angina. The association between MACE rates and the variables included in this study was evaluated following univariate and multivariate approaches.ResultsMost patients were male (72.13%), with a mean age of 70.5±10 years. Regarding T2D, most patients were non-insulin-dependent T2D (61.75%) with high prevalence of comorbidities. The median (Q1-Q3) duration of follow-up was 1.2 (0.3–4.5) years. Overall, 35.66% of patients suffered from at least one MACE during follow up. Using a Cox Proportional Hazards regression model analysis, several independent factors were associated with MACE during follow up: CAD duration (p < 0.001), COPD/Asthma (p = 0.021), heart valve disease (p = 0.031), multivessel disease (p = 0.005), insulin treatment (p < 0.001), statins treatment (p < 0.001), and clopidogrel treatment (p = 0.039).ConclusionsOur results showed high rates of MACE in a large real-world series of PCI-revascularized patients with T2D and CAD with no history of MI or stroke. These data represent a potential opportunity to improve the clinical management of these patients.

Abstract WP170: Hospital Course And Clinical Outcomes In Internal Carotid Versus Vertebral Artery Dissections

Background: Data regarding the differential clinical features of internal carotid artery dissection (CAD) versus vertebral artery dissection (VAD) are limited. We, therefore, aimed to evaluate the clinical course of cervical artery dissections (CeAD) presenting with acute ischemic stroke (AIS) or transient ischemic attack (TIA), according to the location of the dissection. Method: Hospitalizations with discharge diagnoses of CeAD and AIS/TIA were identified from the Nationwide Readmissions Database 2016-2018. Logistic regression analysis was used to compare the risk factors, interventions, and clinical outcomes of CAD and both CAD/VAD in reference to VAD alone. Survival analysis was used to study the risk of recurrent ischemic events after discharge. Results: There were 21402 hospitalizations with ischemic events due to CeAD (mean±SD age: 54.8±17.2 years, female: 40.7%). Of these, 10250 (47.9%) had VAD (reference group), 10813 (50.5%) had CAD, and 339 (1.6%) had both CAD/VAD. Patients with CAD were older, more likely to be female, more likely to have comorbidities like hypertension, atrial fibrillation, coronary artery disease, heart failure, tobacco use, head/neck vessel atherosclerosis, and previous stroke, and less likely to have migraines. Whereas patients with both CAD/VAD were younger, less likely to have hypertension, hyperlipidemia, and diabetes, and more likely to have Ehlers Danlos syndrome. Patients with CAD were more likely to receive intravenous thrombolysis and mechanical thrombectomy. Both groups had higher risk for intraparenchymal hemorrhage and in-hospital mortality and patients with CAD were less likely to discharge home as compared to those with VAD alone. Of 17925 patients with survival to discharge and known discharge disposition, 746 (4.2%) were readmitted due to recurrent ischemic events within 1 year of discharge (mean±SD time to readmission: 55.5±71.0 days). The risk of readmission did not vary by the location of dissection during the initial hospitalization. Conclusion: Carotid and vertebral artery dissections have different risk factor profiles. Although patients with CAD are more likely to get acute stroke interventions, they remain at a higher risk of worse clinical outcomes as compared to those with VAD.

Ticagrelor Monotherapy After PCI in High-Risk Patients With Prior MI: A Prespecified TWILIGHT Substudy.

The aim of this study was to evaluate if patients with prior myocardial infarction (MI) could benefit from ticagrelor monotherapy in terms of bleeding reduction without any compromise in ischemic event prevention. Patients with history of MI who undergo percutaneous coronary intervention (PCI) remain at risk for recurrent ischemic events. The optimal antithrombotic strategy for this cohort remains debated. In this prespecified analysis of the randomized TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, the authors evaluated the impact of history of MI on treatment effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients undergoing PCI with drug-eluting stent with at least 1clinical and 1 angiographic high-risk feature and free from adverse events at 3months after index PCI. The primary endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, and the key secondary endpoint was the composite of all-cause death, MI, or stroke, both at 12months after randomization. A total of 1,937 patients (29.7%) with and 4,595 patients (70.3%) without prior MI were randomized to ticagrelor and placebo or ticagrelor and aspirin. At 1 year after randomization, patients with prior MI experienced higher rates of death, MI, or stroke (5.7% vs 3.2%; P< 0.001) but similar BARC types 2 to 5 bleeding (5.0% vs 5.5%; P=0.677) compared with patients without prior MI. Ticagrelor monotherapy consistently reduced the risk for the primary bleeding outcome in patients with (3.4% vs 6.7%; HR: 0.50; 95%CI: 0.33-0.76) and without (4.2% vs 7.0%; HR: 0.58; 95%CI: 0.45-0.76; Pinteraction=0.54) prior MI. Rates of the key secondary ischemic outcome were not significantly different between treatment groups irrespective of history of MI (prior MI, 6.0% vs 5.5% [HR: 1.09; 95%CI: 0.75-1.58]; no prior MI, 3.1% vs 3.3% [HR: 0.92; 95%CI: 0.67-1.28]; Pinteraction=0.52). Ticagrelor monotherapy is associated with significantly lower risk for bleeding events compared with ticagrelor plus aspirin, without any compromise in ischemic prevention, among high-risk patients with history of MI undergoing PCI. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242).

Abstract TP197: Early Direct Oral Anticoagulants Therapy After Ischemic Stroke In Patients With And Without Atrial Fibrillation:A Pooled Analysis Of Five Studies

Introduction: Early anticoagulation after acute ischemic stroke is usually avoided due to the risk of hemorrhagic transformation (HT). We aimed to assess the rate of radiological HT associated with direct oral anticoagulant (DOAC) initiation within 48 hours vs. &gt; 48 hours in the post-stroke period. Methods: A pooled analysis of five studies of DOAC initiation within 14 days of ischemic stroke onset was conducted. The primary endpoint was incident radiographic HT on follow-up imaging. Secondary endpoints included symptomatic HT, new parenchymal hemorrhage (PH1 or asymptomatic PH2), recurrent systemic events, systemic hemorrhagic complications, mortality within the study period, final modified Rankin Scale score. The results were reported as odds ratio (OR) with 95% confidence interval (CI). Results: A total of 468 patients were enrolled. Median infarct volume was 1.35 (0-7.5) ml, and National Institutes of Health Stroke Scale was 1 (0-3). Incident radiographic HT was seen on follow-up scan in 29 patients. DOAC initiation within 48 hours from index event onset was not associated with incident HT (adjusted OR 0.67, [0.31 - 1.50] P =0.34). No patients developed symptomatic HT. Conversely, 25 patients developed recurrent ischemic events, 64% of which occurred within 14 days. Initiating DOAC within 48 hours of onset was not associated with a reduction in the risk of recurrent ischemic events (OR 0.47, [0.19 - 1.20] P =0.12). In contrast to HT, recurrent ischemic events were associated with poor functional outcomes (OR=6.8, [2.95 - 15.63], p&lt;0.0001). Conclusions: Early DOAC initiation after stroke was not associated with increased incident HT risk. Recurrent ischemic events were common and associated with poor outcomes. These data may be useful for estimating outcome rates and sample size calculations in future trials of early versus late DOAC initiation after AF-related stroke.

Characteristics and prognosis of patients with elevated triglycerides in acute myocardial infarction: Observational data from a large database over a 17y period

From a large database of a regional registry, we aimed to address the prevalence, characteristics and prognosis of patients with elevated triglycerides (TG) in patients with acute myocardial infarction (MI). From the multicenter database (RICO survey), all consecutive patients hospitalized for an acute MI (2001-2017) and alive at discharge were included. Patients with TG > 500 mg/dL, lost to follow-up (FU), or under chronic fibrate treatment were excluded. Patients with high TG (> 200 mg/dL) on admission were compared to those with TG ≤ 200 mg/dL. Endpoints were recurrent ischemic events (i.e. recurrent MI, angina, unstable angina, stroke or urgent revascularization (PCI or CABG)) at 1-year FU. Among the 10,667 patients included, 1,886 (17.7%) had elevated TG. When compared with patients with TG ≤ 200 mg/dL, patients with high TG were younger (59 vs. 69 y, P < 0.001), had a higher BMI (28 vs. 26 kg/m 2 , P < 0.001), were more frequently men (77 vs. 68%, P < 0.001), diabetic (27 vs. 21%, P < 0.001), and smokers (42 vs. 28%, P < 0.001). The rate of statin therapy at discharge was similar for the 2 groups (79 vs. 77%, P = 0.285), as well as SYNTAX score and rate of multivessel disease ( P = 0.368 and P = 0.791). In high TG group, LDL cholesterol was higher (130 vs. 120 mg/dL, P < 0.001) and HDL-cholesterol was lower (37 vs. 46 mg/dL). At 1-Y FU, recurrent ischemic events were more frequent in elevated TG patients (11.2 vs. 9.1%, P = 0.004). In multivariate logistic regression analysis, high TG (OR (95%CI): 1.356(1.095-1.679)) remains an independent estimate for recurrent ischemic event, even after adjustment for confounding (GRACE score, diabetes, obesity). In our large population-based cohort, elevated TG are common in acute MI, and associated with residual risk of recurrent ischemic events, beyond traditional prognostic markers. Our data may help to identify candidates for targeted therapies to reduce recurrent ischemic risk after MI.

Variability of mean platelet volume in patients with ischemic stroke in the early recovery period depending on comorbidity

High platelet reactivity in patients with ischemic noncardioembolic stroke is associated with an increased risk of recurrent ischemic events. However, their determinants are still poorly understood. The aim of our study was to examine changes in mean platelet volume in patients with ischemic stroke in the early recovery period depending on comorbidity.Material and methods. Clinical and laboratory analysis of 90 patients with acute noncardioembolic stroke of the early recovery period. Among those surveyed were 49 men and 41 women aged (60.42 ± 6.8) years. Platelet count (PLT) and mean platelet volume (MPV) were determined on an Abacus 30 hematology analyzer.Results. Significantly more often, the highest mean platelet counts were observed in patients with atherothrombotic subtype of ischemic stroke with greater neurological deficit. Patients with the highest MPV rates had a higher prevalence of diabetes, an elevated body mass index, and a degree of cerebral atherosclerosis compared with patients with lower MPV levels.Conclusion. The increase in MPV in patients with ischemic stroke is observed in parallel with the increase in the influence of known factors in the development of cardiovascular diseases that cause the progression of vascular endothelial damage and atherothrombosis and indicates an increased risk of recurrent stroke.

Antithrombotic Treatment in Lower Extremity Peripheral Arterial Disease.

Lower extremity arteries might be affected by atherosclerotic peripheral arterial disease (PAD), or by embolization causing ischaemic symptoms. Patients with PAD often have widespread atherosclerosis, and progression of PAD is associated with increased risk for both other cardiovascular events and cardiovascular mortality. Peripheral arterial disease patients should therefore be offered both non-pharmacological and pharmacological secondary prevention to reduce the risk for future ischemic arterial complications. This review is focussed on the rationale for recommendations on antiplatelet and anticoagulant treatment in PAD. Asymptomatic PAD does not warrant either anticoagulant or antiplatelet treatment, whereas patients with ischaemic lower extremity symptoms such as intermittent claudication or critical limb ischemia caused by atherosclerosis should be offered platelet antiaggregation with either low dose aspirin or clopidogrel. Combined treatment with aspirin and low-dose of the direct oral anticoagulant (DOAC) rivaroxaban should be considered and weighed against bleeding risk in symptomatic PAD patients considered at high risk for recurrent ischaemic events and in patients having undergone endovascular or open surgical intervention for PAD. Patiens with cardiogenic embolization to lower extremity arteries should be recommended anticoagulant treatment with either one of the DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban) or warfarin.

Associations of CYP2C19 and F2R genetic polymorphisms with platelet reactivity in Chinese ischemic stroke patients receiving clopidogrel therapy.

Genetic variation has been considered a major contributor to the high variability in the response to dual antiplatelet therapy in patients with acute ischemic stroke or transient ischemic attack. Recently, incidences of ischemic stroke are increasing rapidly in China. We aimed to evaluate the influence of potential determinants on the response of antiplatelet therapy and adverse events in Chinese ischemic stroke patients receiving clopidogrel-aspirin treatment. Based on the clopidogrel drug response pathway and the coagulation and anticoagulation function, we systematically selected 34 genetic polymorphisms in 12 candidate genes. Three hundred and eight patients were divided into 2 groups according to their degree of inhibition of platelet aggregation. Multivariate analysis was then performed to assess the influence of demographic, clinical and genetic factors on platelet reactivity in Chinese ischemic stroke patients. We found that polymorphisms in CYP2C19 and F2R genes were still significantly associated with platelet reactivity in Chinese ischemic stroke patients (P = 0.037 and 0.015). The newly identified rs168753 in F2R gene may influence the efficacy to clopidogrel-aspirin therapy for ischemic stroke patients. We also found that ischemic stroke patients with low level of inhibition of platelet aggregation had higher risk of recurrent ischemic events (P = 0.001). Together, these results emphasized the necessity of genotype-directed antiplatelet therapy and facilitated to minimize adverse ischemic events.

Rationale, Design and Methods of the Prospective Record of the Use of Dabigatran in Patients with Acute Stroke or TIA (PRODAST) Study.

BackgroundThe optimal timing of anticoagulation following acute ischaemic stroke or TIA in patients with atrial fibrillation (AF) is a frequent challenge. Early initiation of anticoagulation can reduce the risk for recurrent ischaemic events, but may lead to an increased risk for intracerebral haemorrhage.AimThe Prospective Record of the Use of Dabigatran in Patients with Acute Stroke or TIA (PRODAST) study was initiated to investigate outcome events under antithrombotic therapy after ischaemic stroke or TIA in patients with AF. The main objective is to compare the three-month rates of major haemorrhagic events between early (≤ 7 days) versus late (> 7 days) administration of dabigatran or treatment with vitamin-K antagonists started at any time. Occurrences of ischaemic and major haemorrhagic events will be evaluated to determine the optimal time point for initiation or resumption of anticoagulation.Design and MethodsPRODAST is a prospective, multicenter, observational, non-interventional post-authorization safety study. 10,000 patients with recent (≤ 1 week from index event) ischaemic stroke or TIA and non-valvular AF were recruited at 86 German sites starting in July 2015. The observational plan includes a baseline visit, documentation of data during hospitalization and a telephone-based, central follow-up at three months after the index event. The primary endpoint is the major bleeding rate within three months. Secondary endpoints include rates of recurrent ischaemic or haemorrhagic stroke, TIA, systemic embolism, myocardial infarction and death.SummaryPRODAST will provide important real-world data on safety and efficacy of antithrombotic therapy after acute stroke and TIA in patients with AF.

Abstract 1122‐000140: National Trends in Readmission after Mechanical Thrombectomy in Acute Ischemic Stroke

Introduction : Mechanical thrombectomy (MT) has become the standard of care in patients with large vessel occlusion after trials have demonstrated (MT) improved outcomes in acute ischemic stroke (AIS) as compared to medical therapy. Despite leading to high reperfusion rates, MT patients are at high risk for recurrent ischemic events and complications of stroke. We performed an analysis to evaluate temporal trends in readmission of post‐MT among stroke patients over a three‐year period. Methods : From the Healthcare Cost and Utilization Project Nationwide Readmission Database, we obtained in‐hospital adult patient data with a principal diagnosis of AIS in the US from 2016 to 2018. AIS, MT, thrombolysis treatment and other diagnosis were identified based on International Classification of Diseases, 10th Revision, Clinical Modification codes. We compared the trend of 30‐day readmission in AIS patients who received MT, thrombolysis only and neither treatment with linear regression. Using Clinical Classifications Software Refined tool, we categorized the readmission principal diagnoses of patients underwent MT into groups. All analyses were performed in Stata/SE 15.1 software. Results : Of the 1,271,958 patients admitted from throughout the US with AIS within the study period, 1,130,737 (88.90%) did not receive thrombolysis nor MT, 100,737 (7.92%) received thrombolysis only, and 40,849 (3.21%) underwent MT with or without thrombolysis. The endovascular treatment rate doubled from 2016 (2.40%) to 2018 (4.11%, p &lt; 0.0001). From 2016 to 2018, the readmission rate has significantly decreased from 15.00% to 12.04% (absolute risk reduction (ARR) 2.96%, p = 0.0001) in patients who underwent MT, decreased from 10.46% to 9.51% (ARR 0.95%, p = 0.0097) in patients who received thrombolysis only, and decreased from 11.96% to 11.56% (ARR 0.40%, p = 0.0130) in patients received neither therapy. Among all the patients who underwent MT during the three‐year period, sepsis (1.88%), cerebral infarction (1.59%), sequelae of cerebral infarction (0.82%), cardiac dysrhythmias (0.67%) and heart failure (0.49%) were the most common principal readmission diagnoses. From 2016 to 2018, there were significant decreases in rate of readmissions with septic infection (p = 0.0001), sequelae of cerebral infarction (p &lt; 0.0001), and heart failure (p = 0.0123), but no significant change in cerebral infarction (p = 0.4853) and cardiac dysrhythmias (p = 0.1834). Conclusions : Over three years, the rate of readmissions in AIS patients receiving MT significantly declined, particularly in rate of readmissions in sepsis, sequelae of cerebral infarction, and heart failure. Improved reperfusion rate and better outcomes may explain the reduction in post‐MT complication rate, which needs further studies.

Outcomes of patients with high bleeding risks characteristics presenting with acute coronary syndrome undergoing percutaneous coronary intervention

Abstract Background Patients with high bleeding risk characteristics (HBR) presenting with acute coronary syndrome (ACS) pose a clinical challenge to balance risk for recurrent ischemic events versus incurring bleeding with dual antiplatelet therapy. Purpose We seek to determine the incidence and predictors of short and long term ischemic and bleeding outcomes in patients with HBR factors presenting with ACS after percutaneous coronary intervention (PCI). Method Consecutive patients over a 1-year period, who underwent PCI for ACS were categorized as having HBR based on: age ≥75, anemia (hemoglobin&amp;lt;110g/L), thrombocytopenia (platelet&amp;lt;100x109/L), renal failure (eGFR&amp;lt;30umol/L) or concurrent use of oral anticoagulation. Primary outcome was major adverse cardiovascular event (MACE) defined as composite of cardiovascular death, myocardial infarction, and stroke at 1 year. Key secondary outcomes include significant bleeding defined as Bleeding Academic Research Consortium (BARC) type 3 or 5, and net adverse cardiovascular event (NACE), as a composite of MACE and significant bleeding. Results Of 1351 patients presented with ACS, 389 (28.8%) had at least one HBR criteria. At 1 year, patients with HBR, compared to those without, had increased MACE (11.1% vs 4.2%, p&amp;lt;0.001) and cardiovascular death (5.7% vs 1.7%, p&amp;lt;0.001). Patients with HBR had increased significant bleeding (3.6% vs 2.3%, p=0.011) and NACE (14.4% vs 5.4%, p&amp;lt;0.001). Multivariate analysis showed the presence of HBR and prior history of myocardial infarction were predictors for 1-year MACE (OR 2.67, CI [1.62–4.42], p&amp;lt;0.001 and OR 2.18, CI [1.29–3.70], p=0.004, respectively), whereas the use of second-generation antiplatelet agent was not. Increased MACE and NACE were observed in HBR patients beyond 1 month of DAPT. Conclusion Among patients with ACS undergoing PCI, those with HBR had higher risk for both ischemic and bleeding complications. Novel strategies need to be considered for this high-risk group. Current guidelines, recommending 1 year of DAPT for patients with ACS, should be re-evaluated among patients with HBR. Funding Acknowledgement Type of funding sources: None. Kaplan-Meier curve for 1 year MACEKaplan-Meier curve for 1 year death

Characteristics and prognosis of patients with elevated triglycerides in acute myocardial infarction: observational data from a large database over a 17 years period

Abstract Background and aim From a large database of a regional registry, we aimed to address the prevalence, characteristics and prognosis of patients with elevated triglycerides (TG) in patients hospitalized for an acute myocardial infarction (MI). Methods From the multicenter database (RICO survey), all consecutive patients hospitalized for an acute MI (2001–2017) and alive at discharge were included. Patients with TG &amp;gt;500 mg/dL, lost to follow-up (FU), or under chronic fibrate treatment were excluded. Patients with high TG (&amp;gt;200 mg/dL) on admission were compared to those with TG ≤200 mg/dL. Endpoints were recurrent ischemic events (i.e. recurrent MI, angina, unstable angina, stroke or urgent revascularization (PCI or CABG)) at 1-year FU. Results Among the 10667 patients included, 1886 (17.7%) had elevated TG. When compared with patients with TG ≤200 mg/dL, patients with high TG were younger (59 vs 69 y, p&amp;lt;0.001), had a higher BMI (28 vs 26 kg/m2, p&amp;lt;0.001), were more frequently men (77 vs 68%, p&amp;lt;0.001), diabetic (27 vs 21%, p&amp;lt;0.001), and smokers (42 vs 28%, p&amp;lt;0.001). The rate of statin therapy at discharge was similar for the 2 groups (79 vs 77%, p=0.285), as well as SYNTAX score and rate of multivessel disease (p=0.368 and p=0.791). In high TG group, LDL cholesterol was higher (130 vs 120 mg/dL, p&amp;lt;0.001) and HDL-cholesterol was lower (37 vs 46 mg/dL). At 1-Y FU, recurrent ischemic events were more frequent in elevated TG patients (11.2 vs 9.1%, p=0.004). In multivariate logistic regression analysis, high TG (OR (95% CI): 1.356 (1.095–1.679)) remains an independent estimate for recurrent ischemic event, even after adjustment for confounding (GRACE score, diabetes, obesity). Conclusions In our large population-based cohort, elevated TG are common in acute MI, and associated with residual risk of recurrent ischemic events, beyond traditional prognostic markers. Our data may help to identify candidates for targeted therapies to reduce recurrent ischemic risk after MI. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Amarin

Anticipating recurrent ischemic events after an acute coronary syndrome: validation and application of the SMART-REACH score

Abstract Background The SMART-REACH score (SRS) was developed to predict the risk of major adverse cardiovascular events in ambulatory patients with established cardiovascular disease, although it has not been extensively validated. Patients at higher risk of recurrent ischemic events may benefit from novel, more intensive treatment options, and earlier identification of these patients can potentially improve outcomes. Purpose We aimed to validate the SRS and evaluate its performance in a population recently admitted with acute coronary syndrome. Methods In this single-centre retrospective cohort, we included 320 patients aged 45 to 80 years, who were discharged following admission for an acute coronary syndrome between 2016 and 2018. To calculate the SRS for each patient, we considered clinical data on admission (age, gender, smoking, diabetes, prior history of vascular disease, heart failure or atrial fibrillation), lipid values obtained within the first 24 hours of hospitalization, serum creatinine level at baseline and once the patient was deemed clinically stable, and discharge medication. The outcome of interest was defined as stroke, myocardial infarction or cardiovascular death (MACE) at two years of follow-up. SRS was assessed for discrimination and calibration. Results Mean age was 63±9 years, and 240 (75%) were male. There was high prevalence of cardiovascular risk factors: 71% had hypertension, 32% had diabetes mellitus, 42% were active smokers and 25% had previously established cardiovascular disease. The outcome of interest was observed in 38 patients (22 cardiovascular deaths, 6 strokes and 14 myocardial infarctions). SRS showed good discrimination of the estimated MACE risk with overall C-statistic of 0.646 (95% CI, 0.554–0.737, p=0.004) (picture 1) and calibration (p-value for the goodness-of-fit test of 0.544). The global estimated risk of MACE at 2-years was 4.8% (3.8%-6.8%). The expected/ observed ratio was 0.56 for the occurrence MACE (picture 2). Conclusions Over the first two years after discharge from an acute coronary syndrome, one of every 8 patients developed a potentially fatal recurrent ischemic event. The SRS performed reasonably well in discriminating those at highest risk of MACE, suggesting that this score may help select patients at discharge for ad initium more intensive pharmacological therapy. Funding Acknowledgement Type of funding sources: None. ROC curve for the SMART-REACH scoreExpected versus observed MACE

Clinical and genetic factors associated with the risk of recurrent ischemic events in patients with stable stenocardia

The aimof the study was to assess the clinical and genetic factors associated with the risk of recurrent ischemic events in patients with stable stenocardia (SS).Materials and methods.A total of 100 patients with SS were examined and followed-up for 15.3±8.3 months. The patients were divided into subgroups (SG): SG1 (n=51) – persons without events, SG2 (n=49) persons with recurrent ischemic events (hospitalization due to the development of pain syndrome, re-stenting due to stent restenosis, myocardial infarction, cerebral infarction and death from cardiovascular causes), SGB (n=11) – persons with «major» recurrent ischemic events (re-stenting due to stent restenosis, myocardial infarction, cerebral infarction and death from cardiovascular causes) , SGG (n=89) – persons without «major» events. The obtained survey data (general clinical, aggregometry, polymor phism of genes of platelet fibrinogen receptor ITGB3 (T1565C), platelet collagen receptor ITGA2 (C807T), ADP platelet receptor P2RY12, H1/H2 (T744C)) were analyzed using the STATISTICA 10.0 software.Results.In SG2, men predominated (χ2=9.2; p&lt;0.01), past MI was more common (χ2=4.8; p&lt;0.05), more stents were implanted (2.4±1.9 versus 1.7±1.1, p&lt;0.05), TRAP-test values were higher (p&lt;0.05) compared to SG1. In SGB, greater number of stents were implanted (3.1±2.2 versus 1.61±1.57, p&lt;0.05), the carriage of the TC genotype of the ITGB3 gene was more common, (p&lt;0.05), a combination of gene mutations ITGB3 and P2RY12 was more common, (p&lt;0.05) compared to SGG. A logistic regression equation was constructed, including the presence of diabetes mellitus, the number of platelets in the blood test, the ASPI-test values, the carriage of the 1565C allele of the ITGB3 gene, the number of stents implanted, which makes it possible to determine the likelihood of developing «major» recurrent ischemic events with a cut-off threshold LP₀=0.0965, with sensitivity – 81.82 %, specificity – 78.48 %, overall accuracy – 78.89 %.Conclusions.The factors associated with the development of recurrent ischemic events are: male sex, previous MI, a greater number of implanted stents, and high TRAP-test values. The factors associated with the development of recurrent «major» ischemic events are: a greater number of implanted stents, carriage of the TC genotype of the ITGB3 gene, carriage of a combination of mutations of the H1/H2 polymorphic locus of the P2RY12 gene and the T1565C polymorphic locus of the ITGB3 gene, diabetes mellitus, the number of platelets in blood test, ASPI-test values.

Association of Lipoprotein(a) With Recurrent Ischemic Events Following Percutaneous Coronary Intervention.

This study evaluated the association between elevated levels of lipoprotein(a) [Lp(a)] and risk of recurrent ischemic events in patients who underwent percutaneous coronary intervention (PCI). Elevated levels of Lp(a) have been identified as an independent, possibly causal, risk factor for atherosclerotic cardiovascular disease in a general population study. A prospective single-center registry was used to identify 12,064 patients with baseline Lp(a) measurements who underwent PCI between 2003 and 2013. The primary outcomes were a composite of cardiovascular death, spontaneous myocardial infarction, and ischemic stroke. From the registry, 3,747 (31.1%) patients had high Lp(a) (>30mg/dL) and 8,317 (68.9%) patients had low Lp(a) (≤30mg/dL). During a median follow-up of 7.4 years, primary outcomes occurred in 1,490 patients, and the incidence rates of primary outcomes were 2.0 per 100 person-years in the high-Lp(a) group and 1.6 per 100 person-years in the low-Lp(a) group (adjusted hazard ratio [aHR]: 1.17; 95% confidence interval [CI]: 1.05-1.30; P = 0.004). Increased risk of recurrent ischemic cardiovascular events in the high-Lp(a) group was consistent in various subgroups including patients receiving statin treatment at discharge (aHR: 1.18; 95%CI: 1.03-1.34; P = 0.011). In addition, the risk of repeated revascularization was significantly higher in the high-Lp(a) group (aHR: 1.13; 95%CI: 1.02-1.25; P = 0.022). Elevated levels of Lp(a) were significantly associated with the recurrent ischemic events in patients who underwent PCI. This study provides a rationale for outcome trials to test Lp(a)-lowering therapy for secondary prevention in patients undergoing PCI.

Timing of Anticoagulation after Stroke in Patients with Non-Valvular Atrial Fibrillation Assessment of Provider Practices

BackgroundOptimal timing of oral anticoagulation (TOAC) in acute ischemic stroke (AIS) in patients with atrial fibrillation (AF) is unknown. The risk of recurrent ischemic events when treatment is delayed is often weighed against that of hemorrhagic transformation (HT) when anticoagulation is started in the subacute phase, especially in moderate to large infarctions. Despite substantial evidence for the benefit of oral anticoagulation (OAC) in reducing stroke recurrence, current nationally recognized practice guidelines do not provide clear recommendations on the TOAC after AF-related AIS. Materials and MethodsWe surveyed neurologists on therapeutic approaches to timing of anticoagulation after stroke in patients with AF (without moderate or severe mitral stenosis or a mechanical heart valve) using an online questionnaire. Several ischemic and hemorrhagic stroke scenarios with various stroke sizes, locations, and high-risk thrombotic complications were presented, and survey respondents were asked to provide post-stroke timeframe for TOAC. Practice background, specialty and years of experience of respondents were recorded. ResultsMajority of participants favored early initiation of OAC in small infarcts. In moderate to larger infarct burden, or when ischemia was complicated by HT, there was an overall trend to delay any initiation of OAC, irrespective of specialty or years of experience. The overt presence of an additional cardiac embolic source such as cardiac thrombus led decisions for early anticoagulation. ConclusionAlthough general practice trends were captured, optimal TOAC following AIS in AF remains unknown. Further research is warranted to determine optimal timing and anticoagulant selection.

Balancing Benefits and Risks of Long-Term Antiplatelet Therapy in Noncardioembolic Transient Ischemic Attack or Stroke.

Lifelong treatment with antiplatelet drugs is recommended following a transient ischemic attack or ischemic stroke. Bleeding complications may offset the benefit of antiplatelet drugs in patients at increased risk of bleeding and low risk of recurrent ischemic events. We aimed to investigate the net benefit of antiplatelet treatment according to an individuals’ bleeding risk. We pooled individual patient data from 6 randomized clinical trials (CAPRIE [Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events], ESPS-2 [European Stroke Prevention Study-2], MATCH [Management of Atherothrombosis With Clopidogrel in High-Risk Patients], CHARISMA [Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance], ESPRIT [European/Australasian Stroke Prevention in Reversible Ischemia Trial], and PRoFESS [Prevention Regimen for Effectively Avoiding Second Strokes]) investigating antiplatelet therapy in the subacute or chronic phase after noncardioembolic transient ischemic attack or stroke. Patients were stratified into quintiles according to their predicted risk of major bleeding with the S2TOP-BLEED score. The annual risk of major bleeding and recurrent ischemic events was assessed per quintile for 4 scenarios: (1) aspirin monotherapy, (2) aspirin-clopidogrel versus aspirin or clopidogrel monotherapy, (3) aspirin-dipyridamole versus clopidogrel, and (4) aspirin versus clopidogrel. Net benefit was calculated for the second, third, and fourth scenario. Thirty seven thousand eighty-seven patients were included in the analyses. Both risk of major bleeding and recurrent ischemic events increased over quintiles of predicted bleeding risk, but risk of ischemic events was consistently higher (eg, from 0.7%/y (bottom quintile) to 3.2%/y (top quintile) for major bleeding on aspirin and from 2.5%/y to 10.2%/y for risk of ischemic events on aspirin). Treatment with aspirin-clopidogrel led to more major bleedings (0.9%–1.7% per year), than reduction in ischemic events (ranging from 0.4% to 0.9/1.0% per year) across all quintiles. There was no clear preference for either aspirin-dipyridamole or clopidogrel according to baseline bleeding risk. Among patients with a transient ischemic attack or ischemic stroke included in clinical trials of antiplatelet therapy, the risk of recurrent ischemic events and of major bleeding increase in parallel. Antiplatelet treatment cannot be individualized solely based on bleeding risk assessment.

Agreement of novel hemodynamic imaging parameters for the acute and chronic stages of ischemic stroke: a matched-pair cohort study.

In symptomatic patients with cerebrovascular steno-occlusive disease, impaired blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR) and increased flow velocity of the P2 segment of the posterior cerebral artery (PCA-P2) on transcranial Doppler (TCD) ultrasonography have been introduced as emerging clinical imaging parameters to identify patients at high risk for recurrent ischemic events. Since hemodynamic physiology differs between the acute and chronic stages of ischemic stroke, the authors sought to investigate whether those parameters have merit for both the acute and chronic stages of ischemic stroke. From a prospective database, patients who underwent BOLD-CVR and TCD examinations in the acute stroke stage (< 10 days) were matched to patients in the chronic stroke stage (> 3 months). A linear regression analysis for both groups was performed between ipsilateral PCA-P2 systolic flow velocity and BOLD-CVR of the ipsilateral (affected) hemisphere, the ipsilateral middle cerebral artery (MCA) territory, and the ipsilateral steal volume (i.e., paradoxical BOLD-CVR response). The resulting slopes and intercepts were statistically compared to evaluate differences between groups. Forty matched patient pairs were included. Regression analysis showed no significant difference for either the intercept (p = 0.84) or the slope (p = 0.85) between PCA-P2 flow velocity and BOLD-CVR as measured for the ipsilateral (affected) hemisphere. Similarly, no significant difference was seen between PCA-P2 flow velocity and BOLD-CVR of the ipsilateral MCA territory (intercept, p = 0.72; slope, p = 0.36) or between PCA-P2 flow velocity and steal volume (intercept, p = 0.59; slope, p = 0.34). The study results indicated that the relationship between ipsilateral PCA-P2 systolic flow velocity and BOLD-CVR remains the same during the acute and chronic stages of ischemic stroke. This provides further support that these novel hemodynamic imaging parameters may have merit to assess the risk for recurrent ischemic events for a wide ischemic stroke population. PCA-P2 systolic flow velocity, in particular, may be a highly practical screening tool, independent of ischemic stroke stage.

Pharmacological secondary prevention of MI

Patients remain at high risk of recurrent ischaemic events following a myocardial infarction (MI), and the goal of secondary prevention therapy is to reduce the risk of cardiovascular events while reducing symptom burden and extending life expectancy. This article provides an overview of the recommended secondary prevention strategies post‐MI, focusing on pharmacological therapy.