Risk Of Recurrent Ischemic Events Research Articles

Physician Approaches to the Initial Management of an Intraluminal Thrombus in Recently Symptomatic Carotid Artery Stenosis: Results from the Hot Carotid Study (S20.005)

Physician Approaches to the Initial Management of an Intraluminal Thrombus in Recently Symptomatic Carotid Artery Stenosis: Results from the Hot Carotid Study (S20.005)

Debate on dual pathway inhibition: Antiplatelet and anticoagulant therapies in patients undergoing percutaneous coronary intervention at high risk for recurrent ischemic events. Focus on anticoagulation-based strategies

Debate on dual pathway inhibition: Antiplatelet and anticoagulant therapies in patients undergoing percutaneous coronary intervention at high risk for recurrent ischemic events. Focus on anticoagulation-based strategies

Efficacy, Safety, and Role of Antiplatelet Drugs in the Management of Acute Coronary Syndrome: A Comprehensive Review of Literature.

Acute coronary syndrome (ACS) is a complex condition characterized by myocardial ischemia or infarctionwhich can lead to significant morbidity and death. Antiplatelet drugs play a crucial role in the management of ACS and have been shown to minimize the incidence of significant adverse cardiovascular events and recurrent myocardial infarction (MI). This comprehensive literature review is intended to summarize current information on the effectiveness, safety, and function of frequently used antiplatelet medications in treating ACS. Aspirin, clopidogrel, prasugrel, ticagrelor, abciximab, tirofiban, dipyridamole, cilostazol, and novel antiplatelets are included in the review. Aspirin's effectiveness as a first-line antiplatelet medication in ACS is well established. It has significantly lowered the risk of serious adverse cardiovascular events. Clopidogrel, prasugrel, and ticagrelor are P2Y12 receptor inhibitors found to lower the incidence of recurrent ischemia episodes in ACS patients. Using glycoprotein IIb/IIIa inhibitors such as abciximab, tirofiban, and eptifibatide is effective in managing ACS, especially in high-risk patients. Dipyridamole effectively reduces the risk of recurrent ischemic events in patients with ACS, particularly when used with aspirin. Cilostazol, a phosphodiesterase III inhibitor, has also been shown to reduce the risk of major adverse cardiovascular events (MACE) in patients with ACS. Antiplatelet drugs' safety in managing ACS has also been well established. Aspirin is generally well-tolerated with a low risk of adverse effects, although the risk of bleeding events, particularly gastrointestinal bleeding, cannot be eliminated. The P2Y12 receptor inhibitors have been associated with a small increase in the risk of bleeding events, particularly in patients with a high risk of bleeding. The glycoprotein IIb/IIIa inhibitors are associated with a higher risk of bleeding than other antiplatelet drugs, especially in high-risk patients. To summarize, antiplatelet drugs play a crucial role in the management of ACS, and the efficacy and safety of these drugs have been well-established in the literature. The choice of antiplatelet drugs will depend on the patient's risk factors, including age, comorbidities, and bleeding risk. The novel antiplatelets may offer new therapeutic options for managing ACS, and further studies are needed to determine their role in managing this complex condition.

Secondary Cardiovascular Prevention after Acute Coronary Syndrome: Emerging Risk Factors and Novel Therapeutic Targets.

The control of cardiovascular risk factors, the promotion of a healthy lifestyle, and antithrombotic therapy are the cornerstones of secondary prevention after acute coronary syndrome (ACS). However, many patients have recurrent ischemic events despite the optimal control of traditional modifiable risk factors and the use of tailored pharmacological therapy, including new-generation antiplatelet and lipid-lowering agents. This evidence emphasizes the importance of identifying novel risk factors and targets to optimize secondary preventive strategies. Lipoprotein(a) (Lp(a)) has emerged as an independent predictor of adverse events after ACS. New molecules such as anti-PCSK9 monoclonal antibodies, small interfering RNAs, and antisense oligonucleotides can reduce plasma Lp(a) levels and are associated with a long-term outcome benefit after the index event. The inflammatory stimulus and the inflammasome, pivotal elements in the development and progression of atherosclerosis, have been widely investigated in patients with coronary artery disease. More recently, randomized clinical trials including post-ACS patients treated with colchicine and monoclonal antibodies targeting cytokines yielded promising results in the reduction in major cardiovascular events after an ACS. Gut dysbiosis has also raised great interest for its potential pathophysiological role in cardiovascular disease. This evidence, albeit preliminary and needing confirmation by larger population-based studies, suggests the possibility of targeting the gut microbiome in particularly high-risk populations. The risk of recurrent ischemic events after ACS is related to the complex interaction between intrinsic predisposing factors and environmental triggers. The identification of novel risk factors and targets is fundamental to customizing patient clinical management with a precision medicine perspective.

Abstract Number ‐ 231: Role of Anticoagulation in Recurrent Basilar Artery Thrombosis Secondary to Dolichoectasia, a Case Report

Introduction Basilar artery thrombosis accounts for a small part of ischemic strokes but contributes to one‐fifth of the posterior circulation strokes. Recurrent basilar artery thrombosis secondary to dolichoectasia is caused by abnormal flow in the dilated artery and can result in cerebral ischemia. We present a similar case of recurrent thrombosis with a missed dose of anticoagulation and dehydration on two separate occasions. Methods An 81‐year‐old man with a past medical history of ulcerative colitis with colostomy, provoked deep venous thrombosis presented as a transfer from an outside hospital with acute onset of dysarthria, nausea/vomiting, unsteadiness, and left hemiparesis. CT angiogram of head and neck revealed right vertebral thrombosis extending into the basilar artery with dolichoectasia involving distal right vertebral artery and basilar artery. He was started on heparin infusion with improvement in symptoms and a return to baseline. He was later transitioned to apixaban and discharged home. On a follow‐up office visit two months later, his repeat CT angiogram revealed resolution of the thrombus. He was advised to continue the medication due to the risk of recurrent occlusion secondary to vessel anomaly. After four months, the patient returned to the emergency department with acute onset dizziness, imbalance, nausea, and vomiting. CT angiogram of the head and neck was performed which revealed non‐occlusive thrombosis in the basilar artery. On evaluation by neurology, he admits to three missed doses of apixaban. Clinical and laboratory data were concerning for volume depletion. On further questioning about his symptoms, he mentions decreased oral intake on the day of colostomy change. He was advised to continue apixaban and stay hydrated. Results After fifteen months of the first presentation, the patient is symptom‐free but was continued on anticoagulation with apixaban to prevent recurrent events. Conclusions The role of short‐term and long‐term anticoagulation in basilar artery occlusion is less studied. No prospective trials were done so far to suggest that antithrombotic therapy lowers the risk of recurrent ischemic events and/or anticoagulation is superior to antiplatelets. Dolichoectasia by itself can increase the risk of recurrent thrombosis and dehydration likely facilitated the thrombosis in our patient during the event of missed anticoagulation.

Abstract Number ‐ 49: Risk of HT with Early DOACs after Acute Ischemic Stroke: A Pooled Analysis

Introduction The risk of hemorrhagic transformation (HT) in the early phase of acute ischemic stroke (AIS) remains unknown, leading to potential unnecessary delays in initiation of anticoagulation for secondary stroke prevention. We sought to assess the rate of HT associated withdirect oral anticoagulant (DOAC) initiation within and beyond 48 hours after AIS, using a pooled analysis of available published data. Methods A pooled analysis of 6 studies (4 prospective observational blinded outcome studies and2 randomized trials) of DOAC initiation within 14 days of AIS or transient ischemic attack (TIA) was conducted. The primary endpoint was incident radiographic HT on follow‐up imaging. Secondary endpoints included symptomatic HT, new parenchymal hemorrhage, recurrent ischemic events, extracranial hemorrhage, mortality within the study period, and follow‐up modified Rankin Scale score.The results were reported as odds ratio (OR) andhazard ratio (HR)with 95% confidence interval (CI). Results We evaluated 509 patients; median infarct volume was1.5 (0.1‐7.8) ml, andmedian National Institutes of Health Stroke Scale was2 (0‐3).Incident radiographic HT was seen on follow‐up scan in 34 (6.8%) patients.DOAC initiation within 48 hours from index event was not associated with incident HT (adjusted OR 0.67, [0.30 – 1.50]P = 0.32).No patients developed symptomatic HT.Conversely, 31 (6.1%) patients developedrecurrent ischemic events, 64% of which occurred within 14 days.Initiating a DOAC within 48 hours of onset was associated with a trend towards lower rates of recurrent ischemic events, but this was not statistically significant (HR 0.42, [0.17 – 1.008]P = 0.052). In contrast to HT,recurrent ischemic events were associated with poor functional outcomes (OR = 6.8, [2.84 – 16.24], p< 0.001). Conclusions Initiation of DOAC within 48 hours after stroke was not associated with decreased risk of recurrent ischemic events, or increasedincident risk of HT. Both recurrent ischemic events and incident HT occurred at similar rates.Unlike HT, however, recurrent ischemic events were associated with poor outcomes.

P2Y12 Inhibitor Monotherapy versus Conventional Dual Antiplatelet Therapy in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Meta-Analysis.

P2Y12 inhibitor monotherapy is a feasible alternative treatment for patients after percutaneous coronary intervention (PCI) in the modern era. Clinical trials have shown that it could lower the risk of bleeding complications without increased ischemic events as compared to standard dual antiplatelet therapy (DAPT). However, the efficacy and safety of this novel approach among patients with acute coronary syndrome (ACS) are controversial because they have a much higher risk for recurrent ischemic events. The purpose of this study is to evaluate the efficacy and safety of this novel approach among patients with ACS. We conducted a meta-analysis of randomized controlled trials that compared P2Y12 inhibitor monotherapy with 12-month DAPT in ACS patients who underwent PCI with stent implantation. PubMed, Embase, the Cochrane library database, ClinicalTrials.gov, and other three websites were searched for data from the earliest report to July 2022. The primary efficacy outcome was major adverse cardiovascular and cerebrovascular events (MACCE), a composite of all-cause mortality, myocardial infarction, stent thrombosis, or stroke. The primary safety outcome was major or minor bleeding events. The secondary endpoint was net adverse clinical events (NACE), defined as a composite of major bleeding and adverse cardiac and cerebrovascular events. Five randomized controlled trials with a total of 21,034 patients were included in our meta-analysis. The quantitative analysis showed a significant reduction in major or minor bleeding events in patients treated with P2Y12 inhibitor monotherapy as compared with standard DAPT(OR: 0.59, 95% CI: 0.46-0.75, p < 0.0001) without increasing the risk of MACCE (OR: 0.98, 95% CI: 0.86-1.13, p = 0.82). The NACE was favorable in the patients treated with P2Y12 inhibitor monotherapy (OR: 0.82, 95% CI: 0.73-0.93, p = 0.002). Of note, the overall clinical benefit of P2Y12 inhibitor monotherapy was quite different between ticagrelor and clopidogrel. The incidence of NACE was significantly lower in ticagrelor monotherapy as compared with DAPT (OR: 0.79, 95% CI: 0.68-0.91), but not in clopidogrel monotherapy (OR: 1.14, 95% CI: 0.79-1.63). Both clopidogrel and ticagrelor monotherapy showed a similar reduction in bleeding complications (OR: 0.46, 95% CI: 0.22-0.94; OR: 0.60, 95% CI: 0.44-0.83, respectively). Although statistically insignificant, the incidence of MACCE was numerically higher in clopidogrel monotherapy as compared with standard DAPT (OR: 1.50, 95% CI: 0.99-2.28, p = 0.06). Based on these findings, P2Y12 inhibitor monotherapy with ticagrelor would be a better choice of medical treatment for ACS patients after PCI with stent implantation in the current era.

Prognostic impacts of Lipoxin A4 in patients with acute myocardial infarction: A prospective cohort study

Lipoxin A4 (LXA4) is one of the specialized pro-resolving lipid mediators proved to suppress the progression of atherosclerosis in vivo, but its clinical impacts in atherosclerotic patients is unclear. In this study, we assessed the prognostic impacts of LXA4 in patients with acute myocardial infarction (AMI). A total of 1569 consecutive AMI patients were prospectively recruited from March 2017 to January 2020. Plasma samples of AMI patients were collected, and LXA4 levels were determined using enzyme-linked immunosorbent assay. The primary outcome was major adverse cardiovascular event (MACE), a composite of all-cause death, recurrent MI, ischemic stroke, or ischemia-driven revascularization. Cox regression was used to assess associations between LXA4 and clinical outcomes. Overall, the median level of LXA4 was 5.637 (3.047-9.014) ng/mL for AMI patients. During a median follow-up of 786 (726-1108) days, high LXA4 (≥ 5.637ng/mL) was associated with lower risk of MACE (hazard ratio [HR]: 0.73, 95% confidence interval [CI]: 0.60-0.89, P=0.002), which was sustained in propensity score matching (HR: 0.73, 95% CI: 0.60-0.90, P=0.004) and inverse probability weighting analysis (HR: 0.74, 95% CI: 0.61-0.90, P=0.002). Combined with pro-inflammatory biomarker, patients with high levels of LXA4 (≥ 5.637ng/mL) but low levels of high-sensitivity C-reactive protein (< 5.7mg/L) acquired the lowest risk of MACE (HR: 0.68, 95% CI: 0.51-0.92, P=0.012). In sum, high levels of LXA4 were associated with lower risk of recurrent ischemic events for AMI patients, which could serve as new therapeutic target to tackle cardiovascular inflammation.

1154 MYOCARDIAL INFARCTION IN A TRANSGENDER FEMALE UNDERGOING HORMONE THERAPY: THE IMPACT PROLONGED EXPOSURE TO HORMONE THERAPY

Abstract Background Gender Identity (GI) is defined by a complex interplay between biological, psychological, environmental, and cultural factors. Health care services provide counseling, hormone treatment, and gender-affirming surgery. Testosterone is used for cross-sex hormone therapy in female-to-male transgender persons. Previous evidence suggests that testosterone administration is associated with hypertension, decreased high-density lipoprotein (HDL), increased low-density lipoprotein (LDL), and obesity, thus increasing cardiovascular risk. Hereafter, we report the case of a patient female-to-male on testosterone therapy undergoing percutaneous coronary intervention (PCI) and stent implantation for acute myocardial infarction. Case Description A 44-year-old Italian transgender (female-to-male) without common cardiovascular risk factors and family risk was admitted to the local emergency room with a sudden onset of anterior chest pain. The electrocardiogram showed anterior ST-Segment Elevation, and accordingly, the patient was transferred to our Institution for emergency coronary angiography. Past medical history revealed breast reduction, osteosynthesis of the right femur, hemorrhoidal pathology, and iron deficiency anemia. Of interest, drug history revealed a hormonal therapy with intramuscular testosterone undecanoate over the from 2005 for gender conversion (250 mg every 3 weeks) and Tamoxifen 20 mg/die from 2006. The coronary angiography performed after 90 minutes to the symptom onset revealed a total occlusion of the proximal left anterior descending artery (LAD) and minimal atherosclerosis of the remaining vessels. Recanalization of the LAD was achieved by pre-dilatations with a 2.5×15mm balloon catheter, showing diffuse atherosclerosis of the middle and distal LAD involving the origin of a diagonal branch (Medina 1,1,1). Then the lesion was treated with the implantation of three drug-eluting stents in overlap, followed by POBA (Plain Old Balloon Angioplast) of the diagonal branch with a 2.5×12 mm balloon at the ostium (Final TIMI flow III). The patient was then moved to the intensive care unit. Laboratory tests showed an altered lipid panel (overall cholesterol 210 mg/dl and LDL-cholesterol 153 mg/dl), elevated levels of cardiac enzymes (CK-MB 92.5 ng/ml, myoglobin 1606 ng/ml, TnT hs 1014 ng/L and NTproBNP 1263 pg/ml) and anaemia (Hb 9,1 mg/dl). The echocardiogram revealed akinesia of the apex with thrombotic formation (2.0×1.0 mm) and mid-distal anterior wall, with a 40% ejection fraction. Accordingly, parenteral anticoagulant was started. No further complications were observed the day after the procedure, with a progressive reduction of the miocardionecrosis enzymes and thrombotic formation. Ten days after, at the resolution of the thrombotic formation, the patient was discharged. Discussion This case report highlights the importance of primary prevention in patients undergoing long-term testosterone therapy for gender conversion, regardless of age and risk factors. For instance, prior evidence about the risk of recurrent ischemic events in these high-risk patients is poor with a high heterogeneity across the studies. Accordingly, high quality prospective and multicentric studies are needed to assess if there is a correlation between hormonal therapy for gender conversion and cardiovascular disease.

342 TMAO PLASMA LEVELS PREDICT RECURRENT ISCHEMIC EVENTS IN SURVIVORS OF MYOCARDIAL INFARCTION

Abstract Background Recent studies have highlighted a direct link between dietary nutrients, microbiota and cardiovascular disease (CVD). In this context, trimethylamine-N-oxide (TMAO), a metabolite derived from the intestinal microbiota, stands out, paving its way as one of the important biomarkers associated with atherosclerosis, increased risk of CVD, recurrent events and adverse outcomes. Methods 81 patients who survived acute myocardial infarction (AMI), (both STEMI 50 / NSTEMI 31) were enrolled in this study together with 10 healthy individuals. Further, we evaluated the relationship between plasma TMAO levels and cardiovascular events during the follow-up. The measurement of plasma levels of TMAO was performed using liquid chromatography-tandem mass spectrometry (LC-MS). Results The median plasma concentration of TMAO were significantly higher in patients with AMI compared with healthy control (1.62 (1.37–2.25) µM. vs 0.55 (0.35–0.74) µM, p &amp;lt; 0.0001). During a median follow-up of 61.74 (59.34–64.24) months, 10 out of 81 patients (12.3%) had a re-infarction. Patients who had another ischemic event had higher TMAO values compared with individuals who did not (2.29 (1.60–6.49) µM vs 1.60 (1.34–2.09) µM, p = 0.026). Further, TMAO values positively correlate with CRP, a pro-inflammatory marker. However, at multivariate Cox regression analysis, plasma TMAO values were not predictive of re-infarction. Conclusions The data of our pilot study show that higher TMAO values are associated with the risk of recurrent ischemic event. A future prospective study, including larger cohort is necessary to analyze this issue.

Abnormal epicardial coronary vasomotor reactivity is associated with altered outcomes

The prevalence and significance of abnormal epicardial coronary vasomotor reactivity (ACVR) in patients with symptoms compatible with myocardial ischaemia remains ill-defined. Our diagnostic strategy is to perform a provocative test (PT) in every patient presenting with chest pain at rest, for whom coronary angiography does not reveal significant epicardial coronary artery disease (≥70% stenosis by visual assessment). To evaluate such a strategy in terms of incidence of ACVR, PT safety and patient outcomes. The present study was a retrospective observational study with a median clinical follow-up of 5years. The primary outcome was incidence of ACVR in patients with PT. Risk factors for ACVR and clinical follow-up were obtained, and the rate of major adverse cardiovascular and cerebrovascular events (MACCE; death, cardiovascular mortality, myocardial infarction, stroke and coronary revascularization) was reported. ACVR was documented in 294 (12.4%) of the 2379 patients with PT, out of the 13,654 patients undergoing angiography. Patients with ACVR were more often female (43.9% vs. 30.0%; P<0.0001), current smokers (37.4% vs. 8.7%; P<0.0001) and had a suspected acute coronary syndrome (36.7% vs. 29.1%; P=0.005) at admittance compared with patients without ACVR. During clinical follow-up, MACCE occurred more frequently in patients with (9.8%) than in those without (3.7%) ACVR (hazard ratio [HR] 4.15, 95% confidence interval [CI] 2.62-6.57; P<0.0001), including more myocardial infarctions (4.0% vs. 0.4%; HR 17.8, 95% CI 6.41-49.5; P<0.0001) and more myocardial revascularizations (6.1% vs. 1.1%; HR 9.36, 95% CI 4.67-18.74; P<0.0001) compared with patients with normal PT at baseline. ACVR is frequent in patients with symptoms compatible with myocardial ischaemia at rest, with no significant coronary stenosis. PT is a safe strategy to identify a population at high risk of recurrent ischaemic events.

Biomarker-Based Prediction of Recurrent Ischemic Events in Patients With Acute Coronary Syndromes

BackgroundIn patients with acute coronary syndrome (ACS), there is residual and variable risk of recurrent ischemic events. ObjectivesThis study aimed to develop biomarker-based prediction models for 1-year risk of cardiovascular (CV) death and myocardial infarction (MI) in patients with ACS undergoing percutaneous coronary intervention. MethodsWe included 10,713 patients from the PLATO (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome) trial in the development cohort and externally validated in 3,508 patients from the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trial. Variables contributing to risk of CV death/MI were assessed using Cox regression models, and a score was derived using subsets of variables approximating the full model. ResultsThere were 632 and 190 episodes of CV death/MI in the development and validation cohorts. The most important predictors of CV death/MI were the biomarkers, growth differentiation factor 15, and N-terminal pro–B-type natriuretic peptide, which had greater prognostic value than all candidate variables. The final model included 8 items: age (A), biomarkers (B) (growth differentiation factor 15 and N-terminal pro–B-type natriuretic peptide), and clinical variables (C) (extent of coronary artery disease, previous vascular disease, Killip class, ACS type, P2Y12 inhibitor). The model, named ABC-ACS ischemia, was well calibrated and showed good discriminatory ability for 1-year risk of CV death/MI with C-indices of 0.71 and 0.72 in the development and validation cohorts, respectively. For CV death, the score performed better, with C-indices of 0.80 and 0.84 in the development and validation cohorts, respectively. ConclusionsAn 8-item score for the prediction of CV death/MI was developed and validated for patients with ACS undergoing percutaneous coronary intervention. The ABC-ACS ischemia score showed good calibration and discrimination and might be useful for risk prediction and decision support in patients with ACS. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872; Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Participants With Acute Coronary Syndrome [TRACER]; NCT00527943)

Navigating Antiplatelet Treatment Options for Stroke: Evidence-Based and Pragmatic Strategies.

The benefit of using antiplatelet monotherapy in acute ischemic stroke and secondary stroke prevention is well established. In the last few years, several large randomized trials showed that the use of short-term dual antiplatelet therapy in particular stroke subtypes may reduce the risk of recurrent ischemic events. The aim of this article is to provide a critical analysis of the current evidence and recommendations for the use of antiplatelet agents for stroke prevention. Long-term therapy with aspirin, clopidogrel, or aspirin plus extended-release dipyridamole is recommended for secondary stroke prevention in patients with noncardioembolic ischemic stroke. Short-term dual antiplatelet therapy with aspirin and clopidogrel is superior to antiplatelet monotherapy in secondary stroke prevention when used in patients with mild noncardioembolic stroke or high-risk transient ischemic attack. Dual therapy, however, is associated with an increased risk of major bleeding, particularly when the treatment is extended for greater than 30days. Similarly, aspirin plus ticagrelor is superior to aspirin monotherapy for the prevention of recurrent ischemic stroke, although this combination is associated with a higher risk of hemorrhagic complications when compared to other dual antiplatelet regimens. Among patients who carry CYP2C19 genetic polymorphisms associated with a slow bioactivation of clopidogrel, short-term treatment with aspirin plus ticagrelor is superior to aspirin plus clopidogrel for the reduction of recurrent stroke; however, the use of ticagrelor is associated with a higher risk of any bleeding. In patients with symptomatic intracranial stenosis, aggressive medical management in addition to dual antiplatelet therapy up to 90days is recommended. Antiplatelet therapy has an essential role in the management of ischemic stroke. The specific antiplatelet regimen should be individualized based on the stroke characteristics, time from symptom onset, and patient-specific predisposition to develop hemorrhagic complications.

Clopidogrel monotherapy following dual antiplatelet therapy in patients with acute coronary syndrome post-drug-eluting stent implantation: a systematic review and direct/indirect treatment comparison

Abstract Background In patients with acute coronary syndromes (ACS) receiving a drug-eluting stent (DES), treatment with dual antiplatelet therapy (DAPT) reduces the risk of recurrent ischemic events. Optimal duration of DAPT depends on patient characteristics and switching to single antiplatelet therapy (SAPT) is recommended after the course of DAPT. Purpose The aim of this study was to evaluate the comparative efficacy and safety of switching to clopidogrel SAPT following DAPT in patients with ACS post DES-implantation. Methods A systematic literature review (SLR) was conducted by searching MEDLINE®, Embase, and CENTRAL up to July 27, 2021. Randomized controlled trials (RCTs) and observational studies that evaluated clopidogrel SAPT following DAPT in adults with ACS post-DES implantation were included. Heterogeneity of included studies was vetted in a feasibility assessment. Random effects meta-analyses were conducted using the metafor package for R. Direct comparisons were conducted for clopidogrel vs. aspirin and clopidogrel vs. DAPT. Using the Bucher method, aspirin vs. DAPT was indirectly compared by taking the difference between their respective pooled treatment effects vs. clopidogrel. A sensitivity analysis was conducted by including studies with a follow-up of 12 months. Results Of 5,349 records identified, seven unique studies (four RCTs and three observational studies) were eligible to be included in the SLR and quantitative treatment comparison. Risk of major adverse cardiovascular events (MACE) was lower in patients who switched to clopidogrel SAPT after DAPT compared with those who switched to aspirin monotherapy (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.54, 0.98), and this difference was significant. No significant difference in risk of MACE was found between switching to clopidogrel SAPT after DAPT and continuation of DAPT (HR: 0.90; 95% CI: 0.65, 1.25). This finding was consistent with the sensitivity analysis representing studies with follow-up of 12 months (HR: 0.95; 95% CI: 0.69, 1.31). Risk of bleeding was not analysed due to insufficient data across included studies for patients with ACS. However, within-study findings from one RCT of 4,136 patients demonstrated a significantly lower risk of bleeding, defined as thrombolysis in myocardial infarction (major and/or minor, for switching to clopidogrel SAPT following DAPT compared with continuation of DAPT (0.54% vs. 1.17% of patients had bleeding [HR: 0.46; 95% CI: 0.23, 0.94]). Conclusion Findings from this SLR suggest switching to clopidogrel SAPT after DAPT in ACS post-DES implantation has a lower risk of MACE compared with switching to aspirin monotherapy, and no difference in the risk of MACE compared with continuation of DAPT. There was insufficient data across the included studies to evaluate the bleeding risk, however, a single study indicated a lower bleeding risk with switching to clopidogrel SAPT. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Sanofi

Short dual antiplatelet therapy duration in high bleeding risk patients undergoing PCI for non-ST-elevation acute coronary syndrome

Abstract Background Patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remain at increased risk of recurrent ischemic events. An abbreviated dual antiplatelet therapy (DAPT) duration as short as 1 month has been suggested for those at high bleeding risk (HBR). Whether the benefits of 1-month DAPT are preserved in HBR patients presenting with non-ST-elevation ACS (NSTE-ACS) is subject of debate. Purpose To assess the impact of NSTE-ACS presentation on the ischemic and bleeding outcomes of HBR patients undergoing PCI with a cobalt-chromium everolimus-eluting stent followed by a 1-month versus 3-month DAPT. Methods The XIENCE Short DAPT Program encompasses three prospective, international, single-arm studies evaluating the safety and efficacy of a 1-month (XIENCE 28 USA and Global) or 3-month (XIENCE 90) DAPT duration. The program enrolled HBR patients who had undergone successful XIENCE stent implantation for acute or chronic coronary syndrome (excluding ST-elevation ACS). Event-free subjects discontinued DAPT at 1 or 3 months post-PCI. The primary endpoint was the composite of all-cause death or myocardial infarction (MI), while the key secondary endpoint was Bleeding Academic Research Consortium (BARC) type 2–5 bleeding between 1 and 12 months post-PCI. Ischemic and bleeding events associated with 1-month versus 3-month DAPT were assessed according to clinical presentation using propensity-score (PS) adjustment. Results Out of 3,364 HBR patients (n=1,392 on 1-month DAPT and n=1,972 on 3-month DAPT), 1164 (34.6%) underwent PCI for NSTE-ACS. At 12 months, the risk of death or MI was similar between 1- and 3-month DAPT in patients with (adjHR 1.12, 95% CI 0.73–1.70) and without NSTE-ACS (adjHR 0.92, 95% CI 0.65–1.29; p-interaction = 0.33). Landmark analysis between 1 and 3 months post-PCI showed significant treatment effect modification according to clinical presentation (p-interaction = 0.03) with greater benefit of 1-month DAPT in stable patients. BARC 2–5 bleeding was consistently reduced in both NSTE-ACS (adjHR 0.58, 95% CI 0.38–0.90) and stable patients (adjHR 0.86, 95% CI 0.63–1.18; p-interaction = 0.15). Conclusions Among HBR patients undergoing PCI with an everolimus-eluting stent, 1-month compared with 3-month DAPT was associated with similar 1-year risk of ischemic events and reduced bleeding, irrespective of clinical presentation. Between 1 and 3 months post-PCI, however, stable patients seemed to derive greater net benefit from 1-month DAPT compared to those with NSTE-ACS. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Abbott

Cost-effectiveness of cholesterol-lowering drugs for secondary cardiovascular prevention in the UK: ezetimibe, evolocumab, and alirocumab

Abstract Background Despite statin treatment, patients with elevated low-density lipoprotein cholesterol (LDL-C) levels remain at high risk for acute cardiovascular events. Ezetimibe, evolocumab, and alirocumab were consequently developed to reduce the risk of recurrent ischemic events in patients with established cardiovascular diseases by 6%, 15%, and 15%, respectively. However, these novel treatments must demonstrate both clinical efficacy and cost-effectiveness to promote long-term adoption by patients, physicians, and insurers. Objective To assess the cost-effectiveness of statins in combination with ezetimibe, evolocumab, and alirocumab for secondary cardiovascular prevention from the perspective of England's National Health Service (NHS). Methods The incidence of major adverse cardiovascular events, including, myocardial infarction, stroke, angina, and coronary revascularization, was simulated with a Markov cohort model. The model was populated with transition probabilities and hazard ratios derived from cardiovascular outcome trials for statin combinations with ezetimibe (IMPROVE-IT), evolocumab (FOURIER), and alirocumab (ODYSSEY). Costs and utilities were retrieved from previous literature. Principle outcomes of interest were the incremental cost-effectiveness ratios (ICER) per quality-adjusted life year (QALY) gained in 2021 Great Britain Pounds (£). Univariate, scenario, willingness-to-pay, and probabilistic sensitivity analyses were conducted to assess the robustness of results. Results For secondary cardiovascular prevention, ezetimibe in combination with statins increased QALYs gained by 0.60 at cost reductions of −£2,529 (ICER: −4,231 £/QALY) per patients compared to statin monotherapy. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors provided incremental QALYs of 0.53 and 0.86 at costs of £45,279 and £46,375 for evolocumab (ICER: 75,283 £/QALY) and alirocumab (ICER: 40,708 £/QALY), respectively. At the NHS' willingness-to-pay threshold of 30,000 £/QALY, there is 100% probability for ezetimibe and 0% probability for PCSK9 inhibitors to be cost-effective in secondary prevention. Results remained robust under univariate, scenario, and probabilistic sensitivity analyses. Conclusions Ezetimibe is cost-effective for secondary cardiovascular prevention at an annual price of £346 in the UK. For PCSK9 inhibitors, discounts of −37% to −53% on alirocumab's (£4,412) and evolocumab's (£4,467) prices are necessary to achieve cost-effectiveness. Funding Acknowledgement Type of funding sources: None.

Lipoprotein(a) levels and risk of adverse events after myocardial infarction in patients with and without diabetes

Abstract Background There is a positive continuous association between Lipoprotein(a) (Lp[a]) levels and the risk of recurrent ischemic events in patients with recent myocardial infarction (MI). However, the prognostic significance of the association between high Lp(a) levels and diabetes has been poorly investigated after MI. Purpose The aim of this study was to evaluate the association of Lp(a) levels with the long-term risk of adverse events in post-MI patients, and to investigate whether diabetes may influence this association. Methods Consecutive MI patients who underwent urgent/emergent coronary angiography at our Institution from February 2013 to June 2019 were prospectively collected. Lp(a) serum concentrations was expressed for increasing range values (≤10, &amp;gt;10–30, &amp;gt;30–50, &amp;gt;50–70, and ≥70 mg/dL). The primary outcome was the recurrence of MI; the secondary outcome was all-cause death. The propensity score weighting technique was used to account for potential confounding between patients with and without diabetes. Results The study population consisted of 1018 post-MI patients (median age: 63 years; 76% males). Diabetes was reported in 280 patients (27.5%). The median value of Lp(a) was 10 mg/dL, and patients with diabetes showed significantly lower Lp(a) levels than patients without diabetes (p=0.025). At a median follow-up of 1121 days, the primary outcome was reported in 109 patients (10.7%), and the secondary outcome in 100 (9.8%). After propensity score weighting, there was a significant association between increasing Lp(a) range values and the primary outcome both in the overall population (p trend = 0.030) and in non-diabetic patients (p trend = 0.009), but not in diabetics. Conversely, no significant association with the risk of all-cause mortality across increasing Lp(a) categories both in the overall population and in the study groups according to the presence or not of diabetes was found. Compared with the lowest Lp(a) category, Lp(a) plasma levels &amp;gt;70 mg/dL were independently associated with the risk of recurrent MI (HR: 3.222; 95% CI, 1.225–8.478, p=0.018) and all-cause death (HR: 2.656; 95% CI, 1.009–6.991, p=0.048) in non-diabetic patients, but not in diabetics. Conclusions In this real-world post-MI population, Lp(a) serum levels were lower in diabetic than in non-diabetic patients. Increasing Lp(a) levels were significantly associated with the risk of recurrent MI, and very high Lp(a) serum concentration (&amp;gt;70 mg/dL) independently predicted recurrent MI and death in non-diabetic patients, but not in diabetics. These results reinforce the importance of routine assessment of Lp(a) levels after MI, particularly in patients without diabetes. Funding Acknowledgement Type of funding sources: None.

Comparison between ticagrelor and clopidogrel in high bleeding risk patients with acute coronary syndrome

Abstract Background Potent antiplatelet agents such as ticagrelor are associated with a lower risk of ischemic events than clopidogrel in patients with acute coronary syndrome (ACS). However, it is uncertain whether the benefits of more intensive anti-ischemic therapy outweigh the risks of major bleeding in individuals who have a high bleeding risk (HBR). This study aimed to assess treatment outcomes following dual antiplatelet therapy (DAPT) using either ticagrelor or clopidogrel in ACS patients with HBR. Methods All HBR patients enrolled in the SWEDEHEART registry who were discharged with DAPT using ticagrelor or clopidogrel following ACS between 2010 and 2017 were included in this study. Bleeding risk was assessed using the 4-item PRECISE-DAPT score, which consists of age, prior bleeding, haemoglobin concentration and creatinine clearance. HBR was defined as a PRECISE-DAPT score ≥25. Inverse-probability of treatment weighting was used to adjust for baseline differences between the treatment groups. The main analysis consisted of a doubly robust estimation of causal effect using Cox proportional hazards models. Data on major bleeding, recurrent myocardial infarction (MI), ischemic stroke and all-cause mortality was obtained from national registries, with 365 days of follow-up. Additional outcomes include major adverse cardiovascular events (MACE), a composite of MI, ischemic stroke and all-cause mortality, and net adverse clinical events (NACE), a composite of MACE and major bleeding. Results Of all ACS patients, 36% (n=25,042) had a PRECISE-DAPT score ≥25. Approximately half of the study participants were treated with ticagrelor (n=11,848). Ticagrelor reduced the risk of MI (hazard ratio [HR], 0.82 [95% CI 0.74–0.91]), ischemic stroke (HR, 0.73 [95% CI 0.60–0.88]) and MACE (HR, 0.90 [95% CI 0.84–0.97]), while also increasing the risk of major bleeding compared to clopidogrel (HR, 1.30 [95% CI 1.16–1.47]). We found no significant differences in all-cause mortality (HR 1.02 [95% CI 0.92–1.12]) and NACE (HR 0.98 [95% CI 0.92–1.05]). Conclusions Ticagrelor was associated with a lower risk of recurrent ischemic events, but a higher risk of major bleeding compared to clopidogrel. There were no significant differences in all-cause mortality and NACE between the treatment groups. These results suggest that more potent antiplatelet agents might not be superior to clopidogrel in ACS patients with HBR. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Stockholm county council

Balancing the Risks of Recurrent Ischaemic and Bleeding Events in a Stable Post ACS Population.

To better guide decisions regarding antithrombotic treatment in individual patients surviving 6 months following an acute coronary syndrome (ACS) by balancing between subsequent recurrent ischaemic and bleeding risk. Patients surviving 6 months following an ACS were followed in an Australian registry. Ischaemic (composite of cardiovascular death, myocardial infarction or stroke) and bleeding (≥BARC 2) events were collected. A dual binary outcome modelling strategy was used arriving at a common set of variables from which bleeding and ischaemic risk could be independently determined in individual patients. Patients in whom bleeding rates exceeded composite ischaemic event rates during the follow-up period were identified. The cohort comprised 5,905 patients in whom 215 experienced an ischaemic event and 49 a bleeding event. The single set of variables included in both ischaemic and bleeding models (C-statistics 0.71 and 0.72 respectively) included modified TIGRIS1 ischaemic score, mode of revascularisation, history of heart failure, anaemia, multivessel disease, readmission within 6 months of index ACS and age >75. In the majority, ischaemic events were more frequent than bleeding events. In higher risk patients post coronary artery bypass grafting (CABG), bleeding events were more frequent than recurrent ischaemic events. The risk of recurrent ischaemic events exceeds bleeding in most patients followed 6 to 24 months following an ACS. Post CABG patients with comorbidities have a higher risk of bleeding over this period during which time attention should be directed towards modifiable bleeding risk factors including requirement for dual antiplatelet therapy.

Natural history of carotid artery free-floating thrombus—A single center, consecutive cohort analysis

IntroductionCarotid free-floating thrombus (CFFT) is a rare cause of stroke and is thought to be associated with a high risk of recurrent cerebrovascular ischaemic events. The existing data on the natural history and optimal treatment modalities of CFFT is scanty and no clear recommendations exist.ObjectiveA retrospective analysis, single-center cohort of consecutive patients diagnosed with CFFT was conducted, investigating the risk for recurrent cerebrovascular ischaemic events.MethodsWe performed a single-center retrospective analysis including all patients presenting at our tertiary center between January 2005 and December 2020 with symptoms consistent with ischaemic stroke and/or transient ischaemic attack. Digital subtraction angiography (DSA), computed tomography angiography (CTA) or magnetic resonance angiography (MRA) were used to diagnose CFFT. In all included patients, CFFT was confirmed with a second imaging modality. CFFT was defined on imaging as a defect in contrast filling extending into the carotid lumen. We gathered information on vascular risk factors, diagnosis and follow-up methods, modality of treatment and neurological outcome. A survival analysis was performed, assessing the risk for recurrent cerebrovascular events.ResultsIn total, N = 62 patients presenting with symptomatic CFFT were included. Mean age was 68 years, 69% (43/62) of patients were male, 52% (32/62) current or previous smokers, 76% (47/62) suffered from arterial hypertension, 68% (42/62) from dyslipidaemia, and 31% (19/62) from diabetes mellitus. Overall, 71% (44/62) of patients received any kind of intervention [endovascular or surgical carotid thrombo-endartectomy (CEA)] at any time point during follow-up. Sixteen percent of patients (10/62) received intervention within 48 h after diagnosis of CFFT. The survival analysis and Kaplan-Meier model censoring patients at the time of intervention or last follow-up showed that the risk for any recurrent ischaemic stroke was 19.7% within the first 7 days and 27.4% within 3 months after diagnosis. No patients experienced a new ischaemic stroke beyond 11 days after diagnosis of CFTT (n = 17).ConclusionThe risk of recurrent ischaemic events in patients with CFFT is high, especially in the first week after diagnosis. Prospective studies are needed to further investigate the optimal management of these patients.