Impact of very low dose rivaroxaban in addition to dual antiplatelet therapy on endogenous fibrinolysis in acute coronary syndrome: The VaLiDate-R study.

BACKGROUND: Impaired endogenous fibrinolysis is adverse cardiovascular risk factor in acute coronary syndrome (ACS) patients. Addition of very low dose rivaroxaban (VLDR) to dual antiplatelet therapy (DAPT) reduces cardiovascular events but increases bleeding. OBJECTIVE: We aimed to assess whether addition of VLDR to DAPT can enhance endogenous fibrinolysis. METHODS: In a prospective, open-label trial, we assessed endogenous fibrinolysis in whole blood, in 549 patients with ACS using the Global Thrombosis Test (GTT) and Thromboelastography (TEG). Patients (n = 180) who demonstrated impaired endogenous fibrinolysis (lysis time [LT] >2000s with the GTT) were randomised 1:1:1 to (i) clopidogrel 75 mg daily; (ii) clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily; or (iii) ticagrelor 90 mg twice daily, for 30 days, in addition to aspirin. Fibrinolytic status was assessed at 0, 2, 4 and 8 weeks. The primary outcome was the change in LT from admission to week 4. We also measured thrombotic occlusion time (OT) at high shear, and rivaroxaban level. RESULTS: There was no difference between the groups with respect to LT or clot lysis with TEG, and no change in these parameters compared to baseline during study drug allocation. In the rivaroxaban plus clopidogrel group, OT was prolonged compared to the other groups, although rivaroxaban levels were low, suggesting non-compliance. CONCLUSION: Addition of rivaroxaban 2.5 mg twice daily to DAPT does not affect endogenous fibrinolysis of thrombus formed at either high or low shear. Further studies are needed to determine whether higher doses of rivaroxaban can favourably modulate fibrinolysis. CONDENSED ABSTRACT: Impaired endogenous fibrinolysis is a strong risk factor in ACS. We aimed to assess whether adding very low dose rivaroxaban (VLDR) to DAPT can enhance fibrinolysis. Fibrin and clot lysis were assessed in whole blood. ACS patients with impaired fibrinolysis were randomised 1:1:1 to clopidogrel 75 mg daily; clopidogrel 75 mg plus VLDR; or ticagrelor 90 mg twice daily, in addition to aspirin. At 30-days, there was no difference in lysis time between the groups, nor change from baseline. VLDR does not improve fibrinolysis at high or low shear. Further studies are needed to determine whether alternative antithrombotic regimens can enhance endogenous fibrinolysis.

Spontaneous reperfusion in STEMI: Its mechanisms and possible modulation.

Patients with transient ST-segment elevation myocardial infarction or spontaneous reperfusion, which occurs in approximately 20% of patients with ST-segment elevation myocardial infarction (STEMI), have smaller infarcts and more favorable clinical outcomes than patients without spontaneous reperfusion. Understanding the mechanisms underlying spontaneous reperfusion is therefore important since this may identify possible novel therapeutic targets to improve outcomes in patients with STEMI. In this review, we discuss some of the possible determinants of spontaneous reperfusion including pro-thrombotic profile, endogenous fibrinolytic status, lipoprotein(a) (Lp[a]), inflammatory markers, and neutrophil extracellular traps (NETs). Effective (rapid) endogenous fibrinolysis, as assessed in whole blood in vitro, using a point-of-care technique assessment of global thrombotic status, has been strongly linked to spontaneous reperfusion. Lp(a), which has a high degree of homology to plasminogen, may impair fibrinolysis through competitive inhibition of tissue plasminogen activator-mediated plasminogen activation as well as tissue plasminogen activator-mediated clot lysis and contribute to pathogenic clot properties by decreasing fibrin clot permeation. NETs appear to negatively modulate clot lysis by increasing thrombin fiber diameter and inhibiting plasmin-driven lysis of plasma clots. There are limited data that oral anticoagulation may modulate endogenous fibrinolysis but antiplatelet agents currently appear to have no impact. Phase III trials involving subcutaneous P2Y12 or glycoprotein IIb/IIIa inhibitors, oral factor XIa inhibitors, interleukin-6 inhibitors, and apolipoprotein(a) antisense oligonucleotides in patients with cardiovascular disease are ongoing. Future studies will be needed to determine the impact of these novel antithrombotic, anti-inflammatory, and lipid-lowering therapies on endogenous fibrinolysis and spontaneous reperfusion.

Measuring Thrombus Stability at High Shear, Together With Thrombus Formation and Endogenous Fibrinolysis: First Experience Using the Global Thrombosis Test 3 (GTT-3).

Thrombus formation in a severely stenosed artery is initiated by high shear activation of platelets, with soluble platelet agonists, such as ADP and thromboxane, playing only a secondary role in the growth and stability of the thrombus. Conventional platelet function tests, however, assess only the soluble agonist-dependent pathway of platelet aggregation. As the thrombus evolves, its stability and ability to withstand dislodgement by arterial flow will determine whether complete and persistent vessel occlusion will occur. The Global Thrombosis Test (GTT), an automated point-of-care technique, simulates the formation of thrombus in whole blood under high shear flow (shear rate >12 000 s-1) and measures the time for occlusive thrombus formation and spontaneous, endogenous thrombolysis/fibrinolysis. The latest GTT-3 model subjects the growing thrombus to upstream pressure, resembling that in a medium-sized artery, and provides an additional assessment of thrombus stability and fibrinolysis rate. It can be used in 3 programs, including a new "hypershear" mode, whereby repetitive cycles of pressure are applied to the growing thrombus, increasing shear rate to ∼22 000 s-1, such as that in patients on mechanical circulatory support. In addition to assessing the risk of arterial thrombosis, the GTT-3 could be used to assess the impact of antithrombotic medications on thrombus stability at high shear. Although current antiplatelet medications target the biochemical axis of platelet aggregation (soluble agonists) and also increase bleeding risk, novel shear-selective antiplatelet therapies may prevent thrombosis while preserving hemostasis. Future studies are needed to assess the usefulness of assessing thrombus stability on cardiovascular and pharmacological evaluation.

Biomarkers of Thrombotic Status Predict Spontaneous Reperfusion in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Spontaneous reperfusion, seen in ∼20% of patients with ST-segment elevation myocardial infarction (STEMI), manifests as normal epicardial flow in the infarct-related artery, with or without ST-segment resolution, before percutaneous coronary intervention (PCI). The drivers mediating this are unknown. OBJECTIVES: The authors sought to relate spontaneous reperfusion to the thrombotic profile. METHODS: In a prospective study, blood from STEMI patients (n = 801) was tested pre-PCI to assess in vitro, point-of-care, occlusion times (OT) and endogenous lysis times (LT). Spontaneous reperfusion was defined as infarct-related artery Thrombolysis In Myocardial Infarction flow grade 3 before PCI. Patients were followed for major cardiovascular events (death, myocardial infarction, or stroke). RESULTS: Spontaneous reperfusion was associated with a longer OT (435 seconds vs 366 seconds; P < 0.001) and a shorter LT (1,257 seconds vs 1,616 seconds; P < 0.001), lower troponin, and better left ventricular function. LT was superior to OT for predicting spontaneous reperfusion (area under the curve for LT: 0.707; 95% CI: 0.661-0.753; area under the curve for OT: 0.629; 95% CI: 0.581-0.677). Among patients with spontaneous reperfusion, those with complete, vs partial ST-segment resolution, had a longer OT (P = 0.002) and a shorter LT (P < 0.001). Spontaneous reperfusion was unrelated to clinical characteristics or pain-to-angiography times. Over 4 years, patients with spontaneous reperfusion experienced fewer major adverse cardiovascular events than those without (4.1% vs 10.6%; P = 0.013), especially in those with both spontaneous reperfusion and complete ST-segment resolution (1.5% vs 10.1%; P = 0.029). CONCLUSIONS: We demonstrate a novel hematological signature in STEMI patients with spontaneous reperfusion, namely, decreased platelet reactivity and faster endogenous fibrinolysis, relating to smaller infarcts and improved survival. This finding indicates a role for modulating thrombotic status early after STEMI onset, to facilitate spontaneous reperfusion and improve outcomes.

Crystal methamphetamine use and bacterial sexually transmitted infections (STIs) among gay, bisexual and other sexual minority men in Canada.

OBJECTIVE: While crystal methamphetamine use by gay, bisexual, and other men who have sex with men (GBM) is associated with increased risk for sexually transmitted infection (STI) transmission, less is understood about the causal pathways between crystal methamphetamine use and STIs. We examined whether the association between greater crystal methamphetamine risk and prevalent bacterial STI diagnosis among GBM was mediated by two types of attitudinal variables: attitudes toward condoms, and sexual escape motives, defined as the use of substances to escape self-awareness during sex, and by sexual behaviors. METHODS: We used computer-assisted self-interview questionnaires from 2449 sexually active GBM (18% living with HIV; median age = 33, interquartile range, 27-45) recruited via respondent-driven sampling in Vancouver, Toronto, and Montreal, Canada. Using the baseline data from the Engage cohort study, we fit a series of structural mediation models of the associations between greater crystal methamphetamine risk and bacterial STI (syphilis, gonorrhea, and chlamydia) diagnosis. We estimated indirect paths from greater crystal methamphetamine risk, attitudes toward condoms, sexual escape motives, and sexual risk behaviors, adjusting for self-reported demographic variables. RESULTS: In the mediated model, the direct association between greater crystal methamphetamine risk and bacterial STI diagnosis was non-significant; however, five indirect paths were significant. Greater crystal methamphetamine risk was associated with bacterial STIs via condom use attitudes and escape motives, which in turn were associated with number of male anal sex partners, condomless anal sex, and oral sex. DISCUSSION: Public health and counselling interventions for GBM who use crystal methamphetamine and who are at higher risk for STIs should target evidence-based causal paths that consider sexual attitudes and sexual practices.

Optimal Tests to Minimise Bleeding and Ischaemic Complications in Patients on Extracorporeal Membrane Oxygenation.

Patients supported with extracorporeal membrane oxygenation (ECMO) experience a very high frequency of bleeding and ischaemic complications, including stroke and systemic embolism. These patients require systemic anticoagulation, mainly with unfractionated heparin (UFH) to prevent clotting of the circuit and reduce the risk of arterial or venous thrombosis. Monitoring of UFH can be very challenging. While most centres routinely monitor the activated clotting time and activated partial thromboplastin time (aPTT) to assess UFH, measurement of anti-factor Xa (anti-Xa) level best correlates with heparin dose, and appears to be predictive of circuit thrombosis, although aPTT may be a better predictor of bleeding. Although monitoring of prothrombin time, platelet count and fibrinogen is routinely undertaken to assess haemostasis, there is no clear guidance available regarding the optimal test.Additional tests, including antithrombin level and thromboelastography, can be used for risk stratification of patients to try and predict the risks of thrombosis and bleeding. Each has their specific role, strengths and limitations. Increased thrombin generation may have a role in predicting thrombosis. Acquired von Willebrand syndrome is frequent with ECMO, contributing to bleeding risk and can be detected by assessing the von Willebrand factor activity-to-antigen ratio, while the platelet function analyser can be used in urgent situations to detect this, with a high negative predictive value. Tests of platelet aggregation can aid in the prediction of bleeding.To personalise management, a selection of complementary tests to collectively assess heparin-effect, coagulation, platelet function and platelet aggregation is proposed, to optimise clinical outcomes in these high-risk patients.

Determinants of Endogenous Fibrinolysis in Whole Blood Under High Shear in Patients With Myocardial Infarction.

Hypofibrinolysis is a recently-recognized risk factor for recurrent cardiovascular events in patients with ST-segment elevation myocardial infarction (STEMI), but the mechanistic determinants of this are not well understood. In patients with STEMI, we show that the effectiveness of endogenous fibrinolysis in whole blood is determined in part by fibrinogen level, high sensitivity C-reactive protein, and shear-induced platelet reactivity, the latter directly related to the speed of thrombin generation. Our findings strengthen the evidence for the role of cellular components and bidirectional crosstalk between coagulatory and inflammatory pathways as determinants of hypofibrinolysis.

Cultural contexts during a pandemic: a qualitative description of cultural factors that shape protective behaviours in the Chinese-Canadian community.

BACKGROUND: During the COVID-19 pandemic, there have been significant variations in the level of adoption of public health recommendations across international jurisdictions and between cultural groups. Such variations have contributed to the dissimilar levels of risks associated with this world-changing viral infection and have highlighted the potential role of culture in assigning meaning and importance to personal protective behaviours. The purpose of this study is to describe the cultural factors during the COVID-19 pandemic that shaped protective health behaviours in the Chinese-Canadian community, one of the largest Chinese diasporas outside of Asia. METHODS: A qualitative descriptive design was employed. Content analysis was used to analyze the data from semi-structured virtual interviews conducted with 83 adult Chinese-Canadian participants residing in a metropolitan area in the Province of Ontario, Canada. FINDINGS: The cultural factors of collectivism, information seeking behaviour, symbolism of masks, and previous experience with severe acute respiratory syndrome (SARS) emerged as themes driving the early adoption of personal protective behaviours within the Chinese-Canadian community during the first wave of COVID-19. These protective behaviours that emerged prior to the first nation-wide lockdown in Canada included physical distancing, mask use, and self-quarantine beyond what was required at the time. CONCLUSION: These findings have implications for the development of future public health interventions and campaigns targeting personal protective behaviours in this population and other ethnic minority populations with similar characteristics.

Fibrinolysis in Platelet Thrombi.

The extent and duration of occlusive thrombus formation following an arterial atherothrombotic plaque disruption may be determined by the effectiveness of endogenous fibrinolysis. The determinants of endogenous fibrinolysis are the subject of much research, and it is now broadly accepted that clot composition as well as the environment in which the thrombus was formed play a significant role. Thrombi with a high platelet content demonstrate significant resistance to fibrinolysis, and this may be attributable to an augmented ability for thrombin generation and the release of fibrinolysis inhibitors, resulting in a fibrin-dense, stable thrombus. Additional platelet activators may augment thrombin generation further, and in the case of coronary stenosis, high shear has been shown to strengthen the attachment of the thrombus to the vessel wall. Neutrophil extracellular traps contribute to fibrinolysis resistance. Additionally, platelet-mediated clot retraction, release of Factor XIII and resultant crosslinking with fibrinolysis inhibitors impart structural stability to the thrombus against dislodgment by flow. Further work is needed in this rapidly evolving field, and efforts to mimic the pathophysiological environment in vitro are essential to further elucidate the mechanism of fibrinolysis resistance and in providing models to assess the effects of pharmacotherapy.

Thrombotic complications in 2928 patients with COVID-19 treated in intensive care: a systematic review.

A prothrombotic state is reported with severe COVID-19 infection, which can manifest in venous and arterial thrombotic events. Coagulopathy is reflective of more severe disease and anticoagulant thromboprophylaxis is recommended in hospitalized patients. However, the prevalence of thrombosis on the intensive care unit (ICU) remains unclear, including whether this is sufficiently addressed by conventional anticoagulant thromboprophylaxis. We aimed to identify the rate of thrombotic complications in ICU-treated patients with COVID-19, to inform recommendations for diagnosis and management. A systematic review was conducted to assess the incidence of thrombotic complications in ICU-treated patients with COVID-19. Observational studies and registries reporting thrombotic complications in ICU-treated patients were included. Information extracted included patient demographics, use of thromboprophylaxis or anticoagulation, method of identifying thrombotic complications, and reported patient outcomes. In 28 studies including 2928 patients, thrombotic complications occurred in 34% of ICU-managed patients, with deep venous thrombosis reported in 16.1% and pulmonary embolism in 12.6% of patients, despite anticoagulant thromboprophylaxis, and were associated with high mortality. Studies adopting systematic screening for venous thrombosis with Duplex ultrasound reported a significantly higher incidence of venous thrombosis compared to those relying on clinical suspicion (56.3% vs. 11.0%, p < 0.001). Despite thromboprophylaxis, there is a very high incidence of thrombotic complications in patients with COVID-19 on the ICU. Systematic screening identifies many thrombotic complications that would be missed by relying on clinical suspicion and should be employed, with consideration given to increased dose anticoagulant thromboprophylaxis, whilst awaiting results of prospective trials of anticoagulation in this cohort.

Out-of-hospital cardiac arrest: A systematic review of current risk scores to predict survival.

IMPORTANCE: The arrest and the post-arrest period are an incredibly emotionally traumatic time for family and friends of the affected individual. There is a need to assess prognosis early in the patient pathway to offer objective, realistic and non-emotive information to the next-of-kin regarding the likelihood of survival. OBJECTIVE: To present a systematic review of the clinical risk scores available to assess patients on admission following out-of-hospital cardiac arrest (OHCA) which can predict in-hospital mortality. EVIDENCE REVIEW: A systematic search of online databases Embase, MEDLINE and Cochrane Central Register of Controlled Trials was conducted up until 20th November 2020. FINDINGS: Out of 1,817 initial articles, we identified a total of 28 scoring systems, with 11 of the scores predicting mortality following OHCA included in this review. The majority of the scores included arrest characteristics (initial rhythm and time to return of spontaneous circulation) as prognostic indicators. Out of these, the 3 most clinically-useful scores, namely those which are easy-to-use, comprise of commonly available parameters and measurements, and which have high predictive value are the OHCA, NULL-PLEASE, and rCAST scores, which appear to perform similarly. Of these, the NULL-PLEASE score is the easiest to calculate and has also been externally validated. CONCLUSIONS: Clinicians should be aware of these risk scores, which can be used to provide objective, nonemotive and reproducible information to the next-of-kin on the likely prognosis following OHCA. However, in isolation, these scores should not form the basis for clinical decision-making.

Endogenous fibrinolysis-Relevance to clinical thrombosis risk assessment.

The development of an obstructive luminal thrombus is pathological and considered a failure of endogenous fibrinolysis. The consequences may be fatal, or result in lasting downstream organ damage. Therefore, assessment of endogenous fibrinolytic status in an individual may identify those at risk of occlusive thrombus formation and provide prognostic information. Arterial thrombi are more platelet rich and more resistant to fibrinolysis than venous thrombi. Several recent studies using global tests of fibrinolysis in patients with acute coronary syndromes (ACS) have shown that despite dual antiplatelet therapy, patients with impaired fibrinolytic status have an increased risk of adverse cardiovascular events, compared with those with effective fibrinolytic function. Such data add significantly to the predictive value of established cardiovascular risk factors and conventional biomarkers. Most data reported have been obtained with the Global Thrombosis Test and the turbidimetric plasma clot lysis assay. A few small studies in patients with ischaemic stroke suggest a similar predictive role of fibrinolytic status assessment in these patients. Studies reporting an association between impaired fibrinolysis and future venous thrombotic events are limited, and in the form of case-control studies. Viscoelastic assays may have a role in the prediction of venous thromboembolic risk. Assays of fibrinolytic function should be used to obtain a more accurate risk of future thrombotic events, particularly in the setting of ACS. The availability of point-of-care tests helps facilitate this and should encourage future studies to assess personalised antithrombotic treatment combinations to optimise fibrinolytic status and reduce thrombosis risk.

Development of a novel risk score to predict mortality in patients admitted to hospital with COVID-19.

Patients hospitalised with COVID-19 have a high mortality. Identification of patients at increased risk of adverse outcome would be important, to allow closer observation and earlier medical intervention for those at risk, and to objectively guide prognosis for friends and family of affected individuals. We conducted a single-centre retrospective cohort study in all-comers with COVID-19 admitted to a large general hospital in the United Kingdom. Clinical characteristics and features on admission, including observations, haematological and biochemical characteristics, were used to develop a score to predict 30-day mortality, using multivariable logistic regression. We identified 316 patients, of whom 46% died within 30-days. We developed a mortality score incorporating age, sex, platelet count, international normalised ratio, and observations on admission including the Glasgow Coma Scale, respiratory rate and blood pressure. The score was highly predictive of 30-day mortality with an area under the receiver operating curve of 0.7933 (95% CI 0.745-0.841). The optimal cut-point was a score ≥ 4, which had a sensitivity of 78.36% and a specificity of 67.59%. Patients with a score ≥ 4 had an odds ratio of 7.6 for 30-day mortality compared to those with a score < 4 (95% CI 4.56-12.49, p < 0.001). This simple, easy-to-use risk score calculator for patients admitted to hospital with COVID-19 is a strong predictor of 30-day mortality. Whilst requiring further external validation, it has the potential to guide prognosis for family and friends, and to identify patients at increased risk, who may require closer observation and more intensive early intervention.

Usefulness of the NULL-PLEASE Score to Predict Survival in Out-of-Hospital Cardiac Arrest.

PURPOSE: Out-of-hospital cardiac arrest (OHCA) carries a very high mortality rate even after successful cardiopulmonary resuscitation. Currently, information given to relatives about prognosis following resuscitation is often emotive and subjective, and varies with clinician experience. We aimed to validate the NULL-PLEASE score to predict survival following OHCA. METHODS: A multicenter cohort study was conducted, with retrospective and prospective validation in consecutive unselected patients presenting with OHCA. The NULL-PLEASE score was calculated by attributing points to the following variables: Nonshockable initial rhythm, Unwitnessed arrest, Long low-flow period, Long no-flow period, pH <7.2, Lactate >7.0 mmol/L, End-stage renal failure, Age ≥85 years, Still resuscitation, and Extracardiac cause. The primary outcome was in-hospital death. RESULTS: We assessed 700 patients admitted with OHCA, of whom 47% survived to discharge. In 300 patients we performed a retrospective validation, followed by prospective validation in 400 patients. The NULL-PLEASE score was lower in patients who survived compared with those who died (0 [interquartile range 0-1] vs 4 [interquartile range 2-4], P < .0005) and strongly predictive of in-hospital death (C-statistic 0.874; 95% confidence interval, 0.848-0.899). Patients with a score ≥3 had a 24-fold increased risk of death (odds ratio 23.6; 95% confidence interval, 14.840-37.5; P < .0005) compared with those with lower scores. A score ≥3 has a 91% positive predictive value for in-hospital death, while a score <3 predicts a 71% chance of survival. CONCLUSION: The easy-to-use NULL-PLEASE score predicts in-hospital mortality with high specificity and can help clinicians explain the prognosis to relatives in an easy-to-understand, objective fashion, to realistically prepare them for the future.

MI with Non-obstructive Coronary Artery Presenting with STEMI: A Review of Incidence, Aetiology, Assessment and Treatment.

MI with non-obstructive coronary artery (MINOCA) is a condition previously thought to be benign that has recently been shown to have comparable mortality to that of acute coronary syndrome with obstructive coronary disease. The heterogeneity of the underlying aetiology makes the assessment, investigation and treatment of patients with MINOCA challenging. The majority of patients with MINOCA presenting with ST-segment elevation MI generally have an underlying coronary or myocardial cause, predominantly plaque disruption or myocarditis. In order to make the correct diagnosis, in addition to the cause of the presentation, a meticulous and methodical approach is required, with targeted investigations. Stratification of patients to guide investigations that are more likely to provide the diagnosis will allow the correct treatment to be initiated promptly. In this article, the authors review the contemporary incidence, aetiology, recommended assessment and treatment of patients with MINOCA presenting with ST-segment elevation MI.

Rationale and design of "Can Very Low Dose Rivaroxaban (VLDR) in addition to dual antiplatelet therapy improve thrombotic status in acute coronary syndrome (VaLiDate-R)" study : A randomised trial modulating endogenous fibrinolysis in patients with acute coronary syndrome.

Impaired endogenous fibrinolysis is novel biomarker that can identify patients with ACS at increased cardiovascular risk. The addition of Very Low Dose Rivaroxaban (VLDR) to dual antiplatelet therapy has been shown to reduce cardiovascular events but at a cost of increased bleeding and is therefore not suitable for all-comers. Targeted additional pharmacotherapy with VLDR to improve endogenous fibrinolysis may improve outcomes in high-risk patients, whilst avoiding unnecessary bleeding in low-risk individuals. The VaLiDate-R study (ClinicalTrials.gov Identifier: NCT03775746, EudraCT: 2018-003299-11) is an investigator-initiated, randomised, open-label, single centre trial comparing the effect of 3 antithrombotic regimens on endogenous fibrinolysis in 150 patients with ACS. Subjects whose screening blood test shows impaired fibrinolytic status (lysis time > 2000s), will be randomised to one of 3 treatment arms in a 1:1:1 ratio: clopidogrel 75 mg daily (Group 1); clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily (Group 2); ticagrelor 90 mg twice daily (Group 3), in addition to aspirin 75 mg daily. Rivaroxaban will be given for 30 days. Fibrinolytic status will be assessed during admission and at 2, 4 and 8 weeks. The primary outcome measure is the change in fibrinolysis time from admission to 4 weeks follow-up, using the Global Thrombosis Test. If VLDR can improve endogenous fibrinolysis in ACS, future large-scale studies would be required to assess whether targeted use of VLDR in patients with ACS and impaired fibrinolysis can translate into improved clinical outcomes, with reduction in major adverse cardiovascular events in this high-risk cohort.

Safety of FFR-guided revascularisation deferral in Anatomically prognostiC diseasE (FACE: CARDIOGROUP V STUDY): A prospective multicentre study.

BACKGROUND: FFR-guided coronary intervention is recommended for patients with intermediate stenoses. However, concerns exist with this approach in anatomically prognostic disease. METHODS: In this prospective, multicentre study, we consecutively enrolled patients found to have FFR negative lesions in anatomically significant sites: left main; proximal LAD; last remaining patent vessel; and multiple vessels with concomitant impaired left ventricular systolic function (EF < 40%). As per recommendation, revascularisation was deferred, and patients included into a registry. The primary endpoint was MACE (death, myocardial infarction and unplanned target lesion revascularization). Secondary endpoints were the above individual components. Subgroup analyses were performed for clinical presentation (stable vs. ACS), localization of lesion (ostial vs. non ostial) and renal function. RESULTS: The registry included 292 patients with 297 deferred stenoses. After 1-year, the primary endpoint occurred in 5% of patients, mainly driven by TLR (2.7%). Cardiovascular death occurred in 0.8% and AMI in 0.8%. During a follow-up of 22.2 ±â€¯11 months, MACE occurred in 11.6%. Cardiovascular death occurred in 1.8% and AMI in 2.1%. After multivariate analysis, impaired renal function (OR 1.99; CI 95% 1.74-5.41; p = 0.046) and ostial disease (OR 2.88; CI 95% 1.04-7.38; p = 0.041) were found to be predictors of MACE. Impaired renal function also predicted TLR (OR 2.43; CI 95% 1.17-5.02; p = 0.017). CONCLUSION: FFR-guided revascularisation deferral is safe in the majority of anatomically prognostic disease. However, further evaluation is required in the risk stratification of those patients with ostial disease and renal disease. Registered on ClinicalTrials, NCT02590926.

Unprotected Left Main Coronary Artery Disease: Outcomes of Treatment With Second-Generation Drug-Eluting Stents - Insight From the FAILS-2 Study.

OBJECTIVE: To evaluate the outcome of patients undergoing PCI for unprotected left main coronary artery (ULMCA) disease with different drug-eluting stent (DES) types. BACKGROUND: Published literature suggests that second-generation DES options have differing vascular responses and outcomes, but there is a paucity of data in real-life patients in the LM setting. METHODS: This is a retrospective, multicenter study, including patients treated with a second-generation DES for ULMCA disease between 2007 and 2015. The primary endpoint was target-lesion revascularization (TLR). Secondary endpoints were major adverse cardiac events, myocardial infarction (MI), and stent thrombosis (ST). RESULTS: A total of 1209 patients were enrolled; 840 patients (69.5%) received an everolimus-eluting stent (EES), 133 patients (11.0%) received a zotarolimus-eluting stent (ZES), and 236 patients (19.5%) received a biodegradable polymer, biolimus-eluting stent (BP-BES). During a mean follow-up of 722 ± 640 days, TLR occurred in 47 patients (3.8%). At univariate analysis, EES patients had a lower TLR rate (3.6% vs 4.5% in ZES vs 4.2% in BP-BES), which was statistically significant at multivariate analysis (hazard ratio, 0.50; 95% confidence interval, 0.27-0.93; P=.03). No differences in major adverse cardiac events, death, MI, or ST were observed between groups. CONCLUSION: The safety profile of the stents used was comparable over the follow-up period. However, EES patients had lower restenosis rates, with a reduced need for repeat PCI.