Antithrombotic Treatment Regimen Research Articles

Antithrombotic Therapy and Freedom From Bridging Stent Occlusion After Elective Branched Endovascular Repair: A Multicenter International Cohort Study.

Based on our study, no antithrombotic therapy is significantly associated with bridging stent occlusion, and no evidence of the superiority of other antithrombotic therapy exists. Nevertehless, due to the low number of bridging stent occlusions, this study can neither support nor reject the PRINCE2SS recommendations. Further studies with larger cohorts are needed to determine clear guideliness of the best antithrombotic treatment regimen after complex enfovascular aortic repair.

Preventing Lower Limb Graft Thrombosis after Infrainguinal Arterial Bypass Surgery with Antithrombotic Agents (PATENT Study): An International Expert Based Delphi Consensus.

(1) Background: High-level evidence on antithrombotic therapy after infrainguinal arterial bypass surgery in specific clinical scenarios is lacking. (2) Methods: A modified Delphi procedure was used to develop consensus statements. Experts voted on antithrombotic treatment regimens for three types of infrainguinal arterial bypass procedures: above-the-knee popliteal artery; below-the-knee popliteal artery; and distal, using vein, prosthetic, or biological grafts. The treatment regimens for these nine procedures were then voted on in three clinical scenarios: isolated PAOD, atrial fibrillation, and recent coronary intervention. (3) Results: The survey was conducted with 28 experts from 15 European countries, resulting in consensus statements on 25/27 scenarios. Experts recommended single antiplatelet therapy after above-the-knee popliteal artery bypasses regardless of the graft material used. For below-the-knee popliteal artery bypasses, experts suggested combining single antiplatelet therapy with low-dose rivaroxaban if the graft material used was autologous or biological. They did not recommend switching to triple therapy for patients on oral anticoagulants for atrial fibrillation or dual antiplatelet therapy in any scenario. (4) Conclusions: Great inconsistency in the antithrombotic therapy administered was found in this study. This consensus offers guidance for scenarios that are not covered in the current ESVS guidelines but must be interpreted within its limitations.

Thromboembolic Antiphospholipid Syndrome (APS): Efficacy and Safety of Different Anticoagulants-Results of the APSantiCO Registry.

Background: The particular challenge in dealing with patients with thromboembolic antiphospholipid syndrome (APS) is to establish an adequate therapy regime, as patients suffer from an increased risk of relapse despite antithrombotic treatment (ATT). Vitamin K antagonists (VKA) are the standard medication of choice. The current data on the use of direct oral anticoagulants (DOAC) in APS patients remain limited. Methods: The results of the retrospective APSantiCO registry are presented. In 80 patients with APS, the efficacy and safety of different ATT regimens were analyzed. Results: At the time of inclusion, 43.8% of patients were treated with VKA and 36.3% with DOAC. Medication regimes changed several times and 279 treatment phases were further analyzed with a total treatment length of 7529 months. The incidence of recurrent arterial thrombosis was significantly larger in the DOAC group compared with the VKA group (p < 0.001), while the incidence of recurrent venous thrombosis was comparable between both groups, as was the incidence of bleedings. Heavy menstrual bleeding was the most frequently observed bleeding complication. Conclusions: The data suggest that DOAC may be an alternative to VKA for APS patients with venous thromboembolism, while VKA should be used in APS-related arterial thrombosis.

Antithrombotic therapy to prevent cognitive decline in people with small vessel disease on neuroimaging but without dementia.

Cerebral small vessel disease is a progressivedisease of the brain'sdeep perforating blood vessels.It is usually diagnosed based on lesions seen on brain imaging. Cerebral small vessel disease is a common cause of stroke but can also cause a progressive cognitive decline. As antithrombotic therapy is anestablished treatment for stroke prevention, we sought to determinewhether antithrombotic therapy might also be effective in preventing cognitive decline in people with small vessel disease. To assess the effects of antithrombotic therapy for prevention of cognitive decline in people with small vessel disease on neuroimaging but without dementia. We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Review Group's Specialised Register, and the Cochrane Stroke Group's Specialised Register; the most recent search was on 21 July 2021. We also searched MEDLINE, Embase, four other databases and two trials registries. We searched the reference lists of the articles retrieved from these searches. As trials with a stroke focus may include relevant subgroup data, we complemented these searches with a focussed search of all antithrombotic titles in the Cochrane Stroke Group database. SELECTION CRITERIA: We included randomised controlled trials (RCT) of people with neuroimaging evidence of at least mild cerebral small vessel disease (defined here as white matter hyperintensities, lacunes of presumed vascular origin and subcortical infarcts) but with no evidence of dementia. The trials had to compareantithrombotic therapy of minimum 24 weeks' duration to no antithrombotic therapy (either placebo or treatment as usual), or comparedifferent antithrombotic treatment regimens. Antithrombotic therapy could include antiplatelet agents (as monotherapyor combination therapy), anticoagulants or a combination. Two review authors independently screened all the titlesidentified by the searches. We assessed full texts for eligibility for inclusion according to our prespecified selection criteria, extracted data to a proforma and assessed risk of bias using the Cochrane tool for RCTs. We evaluated the certainty of evidence using GRADE. Due to heterogeneity across included participants, interventions and outcomes of eligible trials, it was not possible to perform meta-analyses. We included threeRCTs (3384 participants). One study investigated the effect of antithrombotic therapy in participants not yet on antithrombotic therapy; two studies investigated the effect of additional antithrombotic therapy, one in a population already taking a single antithrombotic agent and one in a mixed population (participants on an antithrombotic drug and antithrombotic-naive participants). Intervention and follow-up durations varied from 24 weeks to four years. Jia 2016 was a placebo-controlled trial assessing 24 weeks of treatment with DL-3-n-butylphthalide (a compound with multimodal actions, including a putative antiplatelet effect) in 280 Chinese participants with vascular cognitive impairment caused by subcortical ischaemic small vessel disease, but without dementia. There was very low-certainty evidence for a small difference in cognitive test scores favouring treatment with DL-3-n-butylphthalide, as measured by the 12-item Alzheimer's Disease Assessment Scale-Cognitive subscale (adjusted mean difference -1.07, 95% confidence interval (CI) -2.02 to -0.12), but this difference may not be clinically relevant. There was also very low-certainty evidence for greater proportional improvement measured with the Clinician Interview-Based Impression of Change-Plus Caregiver Input (57% with DL-3-n-butylphthalide versus 42% with placebo; P = 0.01), but there was no difference in other measures of cognition (Mini-Mental State Examination and Clinical Dementia Rating) or function. There was no evidence of a difference in adverse events between treatment groups. The SILENCE RCT compared antithrombotic therapy (aspirin) and placebo during four years of treatment in 83 participants with 'silent brain infarcts' who were on no prior antithrombotic therapy. There was very low-certainty evidence for no difference between groups across various measures of cognition and function, rates of stroke or adverse events. The Secondary Prevention of Subcortical Stroke Study (SPS3) compared dual antiplatelet therapy (clopidogrel plus aspirin) to aspirin alone in 3020 participants with recent lacunar stroke. There was low-certainty evidence of no effect on cognitive outcomes as measured by the Cognitive Abilities Screening Instruments (CASI) assessed annually over five years. There was also low-certainty evidence of no difference in the annual incidence of mild cognitive decline between the two treatment groups (9.7% with dual antiplatelet therapy versus 9.9% with aspirin), or the annual stroke recurrence rate(2.5% with dual antiplatelet therapy versus 2.7% with aspirin). Bleeding risk may be higher with dual antiplatelet therapy (hazard ratio (HR) 2.15, 95% CI 1.49 to 3.11; low certainty evidence), but there may be no significant increase in intracerebral bleeding risk(HR 1.52, 95% CI 0.79 to 2.93; low-certainty evidence). None of the included trials assessed the incidence of new dementia. We found no convincing evidence to suggest any clinically relevant cognitive benefit of using antithrombotic therapy in addition tostandard treatment in people with cerebral small vessel disease but without dementia, but there may be an increased bleeding risk with this approach. There was marked heterogeneityacross the trials and the certainty of the evidence was generally poor.

Acute Ischemic Stroke, Depressed Left Ventricular Ejection Fraction, and Sinus Rhythm: Prevalence and Practice Patterns.

There are limited data about the epidemiology and secondary stroke prevention strategies used for patients with depressed left ventricular ejection fraction (LVEF) and sinus rhythm following an acute ischemic stroke (AIS). We sought to describe the prevalence of LVEF ≤40% and sinus rhythm among patients with AIS and antithrombotic treatment practice in a multi-center cohort from 2002 to 2018. This was a multi-center, retrospective cohort study comprised of patients with AIS hospitalized in the Greater Cincinnati Northern Kentucky Stroke Study and 4 academic, hospital-based cohorts in the United States. A 1-stage meta-analysis of proportions was undertaken to calculate a pooled prevalence. Univariate analyses and an adjusted multivariable logistic regression model were performed to identify demographic, clinical, and echocardiographic characteristics associated with being prescribed an anticoagulant upon AIS hospitalization discharge. Among 14 338 patients with AIS with documented LVEF during the stroke hospitalization, the weighted pooled prevalence of LVEF ≤40% and sinus rhythm was 5.0% (95% CI, 4.1-6.0%; I2, 84.4%). Of 524 patients with no cardiac thrombus and no prior indication for anticoagulant who survived postdischarge, 200 (38%) were discharged on anticoagulant, 289 (55%) were discharged on antiplatelet therapy only, and 35 (7%) on neither. There was heterogeneity by site in the proportion discharged with an anticoagulant (22% to 45%, P<0.0001). Cohort site and National Institutes of Health Stroke Severity scale >8 (odds ratio, 2.0 [95% CI, 1.1-3.8]) were significant, independent predictors of being discharged with an anticoagulant in an adjusted analysis. Nearly 5% of patients with AIS have a depressed LVEF and are in sinus rhythm. There is significant variation in the clinical practice of antithrombotic therapy prescription by site and stroke severity. Given this clinical equipoise, further study is needed to define optimal antithrombotic treatment regimens for secondary stroke prevention in this patient population.

Changes in antithrombotic treatment in patients with abdominal aortic aneurysmal disease and incident atrial fibrillation: a population-based case-crossover analyses

Abstract Background Abdominal aortic aneurysmal (AAA) disease is associated with a high risk of cardiovascular events, and prophylaxis with platelet-inhibitors are recommended at diagnosis. Incident atrial fibrillation (AF) changes that indication to oral anticoagulative (OAC) therapy. However, it is unknown to what extent the recommended change of indication is reflected in the actual antithrombotic treatment in clinical practice. Purpose To evaluate the antithrombotic therapy after an incident diagnosis of atrial fibrillation in patients with established AAA. Methods In this population-based case-crossover study, using nationwide Danish registries, we identified all patients registered with a diagnosis of AAA between 1997 and 2018, and a subsequent diagnosis of AF. The case-crossover analysis was performed to compare the within-subject antithrombotic therapy in 1-year time-periods before and after AF diagnosis in the study population. A blanking period of 30 days before AF-diagnosis was applied to avoid bias from potentially delayed hospital diagnosis of AF (Figure 1.1). We excluded patients with no eligible reference window due to recent cohort entry and patients with no AF-related indication for shift to OAC (CHA2DS2-VASc score of &amp;lt;1 in men and &amp;lt;2 in women). Odds ratios (OR) with 95% confidence intervals (CIs) comparing antithrombotic therapy before and after AF diagnosis was calculated using McNemars test for matched pair's data. Subgroup analyses of patients diagnosed with AAA between 2011 and 2018 were performed to evaluate changes after introduction of current antithrombotic treatment regimens and direct oral anticoagulants. Results A total of 3052 patients were included in the case-crossover analyses. Mean age was 77.8 years and 22.3% were females. Median time from AAA to AF diagnosis was 4.6 years (IQR; 2.6–7.8). Stroke risk in the study population was high with a median CHA2DS2-VASc score of 4 (IQR: 3–5). In the case-period after AF diagnosis, 1004 prescription claims of platelet-inhibitors were registered compared with 1461 claims in the control-period before AF diagnosis, corresponding to a matched OR of 0.31 (95% CI, 0.26–0.36) (Figure 1.2). Conversely, there were 1392 prescription claims for OAC in the case-period compared with 355 in the control-period, corresponding to an OR of 15.75 (95% CI, 12.38–20.31). When restricting the study-population to patients diagnosed with AAA during 2011–2018, the OR was 0.11 (95% CI, 0.07–0.16) for a prescription claim of platelet-inhibitors and 17.7 (95% CI, 11.22–29.17) for OAC before and after AF diagnosis (Figure 1.2). Conclusion In patients with established AAA and high risk of stroke, incident AF was associated with low likelihood of treatment with platelet-inhibitor and a high likelihood of OAC-treatment compared with before AF. This association was further strengthened in patients diagnosed after 2011. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The Obel Family Foundation, DenmarkThe Augustinus Foundation, DenmarkThe sponsors played no role in the study design; data collection, analysis, or interpretation; abstract writing; or in the decision to submit the abstract. Figure 1

Efficacy and safety of dual pathway inhibition in patients with cardiovascular disease

Abstract Background The use of low dose of direct oral anticoagulants (DOAC) in adjunct to antiplatelet therapy, known as dual pathway inhibition (DPI), has been tested as an antithrombotic treatment regimen for the prevention of ischemic events in patients with cardiovascular disease (CVD). Purpose The aim of this systematic review and meta-analysis is to determine the overall safety and efficacy of a DPI strategy in patients with CVD. Methods Randomized controlled trials (RCTs) comparing the use of a DOAC at a low dose (LD) regimen, defined as a dosage below that approved for stroke prevention, versus placebo among patients with CVD treated with single or dual antiplatelet therapy were included. Incidence Rate Ratios (IRRs) with 95% confidence Intervals (CIs) were used to overcome different follow-up durations among the included trials. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the primary safety endpoint was major bleeding. A pre- specified subgroup analysis was performed according to the different low dose DOAC regimens used in the DPI arm [LD versus very low dose (VLD)]. Number needed to treat (NNT) and number needed to harm (NNH) were also calculated. Results A total of 55,782 patients from 7 RCTs were included. Compared with placebo, a DPI strategy was associated with a significant reduction in MACE (IRR 0.85, 95% CI 0.78–0.91; NNT 86) and a significant increase of major bleeding (IRR 2.05, 95% CI 1.50–2.80; NNH 89). Moreover, there was a significant reduction of myocardial infarction (IRR 0.86, 95% CI 0.78–0.97; NNT 355) and a significant increase of all bleeding (IRR 1.82, 95% CI 1.49–2.22; NNH 23) with DPI compared to placebo. There were no differences between groups for the outcomes of CV death (IRR 0.90, 95% CI 0.79–1.03; NNT 784), intracranial hemorrhage (IRR 1.18, 95% CI 0.71–1.96; NNH 1810) and fatal bleeding (IRR 1.13, 95% CI 0.76–1.69; NNH 3170). There was a borderline non-significant reduction of all-cause death (IRR 0.92, 95% CI 0.80- 1.01; NNT 821), and stroke (IRR 0.73, 95% CI 0.53–1.01; NNT 315) favouring DPI (Figures 1 and 2). At subgroup analyses a DPI strategy with the use of VLD dose of DOAC (i.e. rivaroxaban 2.5 mg twice daily) mitigated the risk of bleeding without any trade-off in efficacy compared to LD of DOAC regimens and a meta-regression analysis showed a significant interaction between dual antiplatelet therapy use and the risk of major bleeding, intracranial hemorrhage and stroke. Conclusions In patients with CVD, the use of a LD of a DOAC in combination with antiplatelet therapy as part of a DPI regimen is effective in reducing ischemic events, at the expense of increased major and all bleeding but no increase of intracranial hemorrhage and fatal bleeding. A DPI strategy can be particularly advantageous with the use of a VLD of DOAC (i.e. rivaroxaban 2.5 mg twice daily) combined with a single antiplatelet agent among patients at high ischemic and low bleeding risk. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): D.C. declares that he has received consulting and speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, outside the present work. F.C declares that he has received consulting and speaker fees from Biotronic, Amgen, Astra Zeneca, Servier, Menarini, BMS, outside the present work. F.A. declares that she has received consulting and speaker fees from Amgen, Bayer, BMS-Pfizer and Daiichi Sankyo, outside the present work. D.J.A. declares that he has received consulting fees or honoraria from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company and has received payments for participation in review activities from CeloNova and St Jude Medical, outside the present work. D.J.A. also declares that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, Renal Guard Solutions and Scott R. MacKenzie Foundation. The remaining authors report no disclosures. Figure 1Figure 2

Bleeding avoidance strategies in percutaneous coronary intervention.

For many years, bleeding has been perceived as an unavoidable consequence of strategies aimed at reducing thrombotic complications in patients undergoing percutaneous coronary intervention (PCI). However, the paradigm has now shifted towards bleeding being recognized as a prognostically unfavourable event to the same extent as having a new or recurrent ischaemic or thrombotic complication. As such, in parallel with progress in device and drug development for PCI, there is clinical interest in developing strategies that maximize not only the efficacy but also the safety (for example, by minimizing bleeding) of any antithrombotic treatment or procedural aspect before, during or after PCI. In this Review, we discuss contemporary data and aspects of bleeding avoidance strategies in PCI, including risk stratification, timing of revascularization, pretreatment with antiplatelet agents, selection of vascular access, choice of coronary stents and antithrombotic treatment regimens.

Abstract S01-02: Optimizing treatment for COVID-19 using computational modeling: Implications for cancer patients

Abstract Emerging retrospective analyses show that cancer patients are more likely to develop severe COVID-19. The causes for these worse outcomes are unclear, but data suggest that cancer therapies, which can suppress the immune system, are not responsible for increased COVID-19 severity. An alternative hypothesis is that common molecular pathways are altered in cancer and COVID-19, resulting in worsened disease outcomes. Our previous work demonstrated that activated renin angiotensin signaling (RAS) modulates the tumor microenvironment, resulting in worse outcomes and therapy resistance. Inhibition of this pathway using angiotensin receptor blockers (ARBs) or angiotensin converting enzyme inhibitors (ACEIs) can improve the outcomes of cancer therapies. Similarly, there is great interest in understanding the implications of RAS in COVID-19 progression because a key component of this system, ACE2, is also the docking site for the SARS-CoV-2 virus. Indeed, multiple clinical trials are currently evaluating whether ARBs/ACEIs benefit or harm COVID-19 patients. To help guide administration of these drugs, we adapted our existing computational modeling framework of the cancer microenvironment using available data to simulate COVID-19 progression in patients. Using a systems biology approach, we mechanistically modeled the interaction of the RAS and coagulation pathways with COVID-19 infection. We further explored the efficacy of various antiviral, antithrombotic, and RAS-targeted treatment regimens to identify synergistic combinations as well as optimal schedules for therapy. The system is complex, given that viral binding of ACE2 interferes with its antiinflammatory signaling. When ACE2 is bound by the virus, its local activity decreases, leading to immune dysregulation and risk of coagulopathy, predictors of COVID-19 severity and mortality. To optimize combination treatments for cancer patients who contract COVID-19, multiple simulations were run by combining different therapeutics currently in clinical trials to predict their effects on viral load, thrombosis, oxygen saturation, and cytokine levels. These include ARBs, ACEIs, antiviral drugs, antithrombotic agents, and anti-inflammatory drugs (e.g., anti-IL6/6R). Our simulations predict that i) there is an optimal timing for treatment with antiviral drugs such as remdesivir, related to immune activation; ii) combinations of antiviral and antithrombotic drugs are able to prevent lung damage, increase blood oxygen levels, and inhibit thromboembolic events; and iii) RAS modulators can have a positive effect when added to the treatment regimen. Effective strategies for COVID-19 treatment identified by this in silico analysis will be further analyzed in combination with cancer therapeutics (e.g., immune checkpoint blockers, chemotherapy) to provide guidelines for optimal clinical management of both cancer and COVID-19. Citation Format: Chrysovalantis Voutouri, Mohammadreza Nikmaneshi, Melin Khandekar, Ankit B. Patel, Ashish Verma, Sayon Dutta, Triantafyllos Stylianopoulos, Lance L. Munn, Rakesh K. Jain. Optimizing treatment for COVID-19 using computational modeling: Implications for cancer patients [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr S01-02.

Renal arteriography with endovascular ultrasound for the management of renal infarction patients

BackgroundRenal infarction (RI) is a rare disease with poor prognosis. Appropriate secondary prevention treatment is essential and requires an exhaustive etiological assessment. We aimed to determine whether invasive endovascular explorations may improve the diagnostic process and change the secondary prevention treatment strategy in RI patients.MethodsWe report a retrospective observational study of 25 RI patients referred to Tours University Hospital between 2011 and 2018 for etiological investigation including renal arteriography and intravascular ultrasonography (IVUS). We sought for antithrombotic treatment regimen, vital status, bleeding and ischemic outcomes during the median follow-up of 59 months.ResultsInvasive explorations showed local arterial disease in 14 patients (56%). This led to a diagnosis or change in diagnosis in 9 patients (36%) and to a change in antithrombotic strategy in 56% of cases, with an increased prescription of antiplatelet therapy. No patient died, only two patients (8%) had persistent mild renal insufficiency. One IVUS complication was reported and treated without any significant long-term consequences.ConclusionInvasive endovascular investigations of RI may modify the secondary prevention treatment through a better assessment of the aetiology of RI. Multicentric randomized studies are necessary to advocate the hypothesis that invasive exploration of renal artery can improve long-term prognosis.

Determinants of preventable stroke—Ankara ACROSS stroke preventability study

BackgroundUnhealthy lifestyle and inadequate control of vascular risk factors are the major contributors of stroke burden. Failure in achieving the target levels in control of these factors, not only designate missed opportunities contributing to the preventability of an incident stroke, but also set the post-stroke treatment goals in a case wise basis. In this study, we analyzed pre-event clinical features that play a role in stroke preventability, and determined the cumulative burden of risk factors that necessitate optimization following the ischemic insult. MethodsInformation about the pre-stroke optimal control of seven major modifiable risk factors (Life's Simple 7: hypertension, diabetes mellitus, hyperlipidemia, smoking, obesity, diet, and physical activity) was prospectively collected in ischemic stroke patients admitted to three tertiary academic centers in Ankara. Stroke preventability was evaluated by the overall number of factors requiring optimization with patients ≥4 risk factor conditions categorized as those suffering from a preventable stroke. Bivariate and multivariate analyzes were performed to uncover predictors of stroke preventability. ResultsAmong 787 patients, 386 (49.0%) had ≥4 risk factor conditions requiring optimization. Preventable stroke was more common in younger patients, and patients with small artery occlusion. Multivariate analyses taking into account the pre-stroke antithrombotic treatment regimen, have highlighted age (OR: 0.99, 95%CI 0.98-1.00), female gender (1.59, 95%CI 1.17-2.16), coronary artery disease (1.54, 95%CI 1.10-2.14), small artery occlusion (1.90, 95%CI 1.13-3.18), and cardio-aortic embolism (0.53, 95%CI 0.35-0.82) as significant factors associated with preventability. ConclusionsApproximately half of the ischemic stroke patients have preventable stroke from the perspective of risk factor control. Extra care should be given to strategies directed to risk factor control and lifestyle interventions in certain high-risk groups for the prevention of future complications.

Echocardiographic features in antiphospholipid-negative Sneddon's syndrome and potential association with severity of neurological symptoms or recurrence of strokes: a longitudinal cohort study.

Sneddon's syndrome (SS) may be classified as antiphospholipid positive (aPL+) or negative (aPL- SS). An association between Libman-Sacks (LS) endocarditis and strokes has been described in aPL+ patients. To describe cardiac involvement in aPL- SS and assess the potential association between LS endocarditis and severity or recurrence of neurological symptoms. This longitudinal cohort study included aPL- SS patients followed in our departments between 1991 and June 2018. All patients underwent transthoracic 2D and Doppler echocardiography at diagnosis. Follow-up echocardiography was performed annually and the potential relationship between LS endocarditis development and neurovascular relapse as well as long-term cardiac worsening was prospectively assessed. We included 61 patients [52 women; median age 45 (range 24-60)]. For valvular involvement, 36 (59%) patients showed leaflet thickening; 18 (29.5%) had LS endocarditis at baseline. During a median follow-up of 72 months, LS endocarditis developed in eight (17.4%) patients, and 13 (28.3%) showed significant worsening of their cardiac status, including two who needed valvular replacement. After adjusting for baseline antithrombotic treatment regimen, neither the presence of LS endocarditis at baseline nor development during follow-up was associated with neurological relapse [hazard ratio (HR): 1.06, 95% confidence interval (CI): 0.33-4.74, P = 0.92] and [HR: 0.38, 95% CI: 0.02-1.89, P = 0.31], respectively. A long-term follow-up is needed to detect cardiac complications in aPL- SS. No change in neurological relapse was observed in patients presenting LS endocarditis occurrence during follow-up without any modification in antithrombotic treatment. Further research is necessary to assess the usefulness of treatment escalation in these patients.

P3469Effects of EDOXaban on the cellular and protein phase of coagulation in coronary artery disease patients on dual antiplatelet therapy with aspirin and clopidogrel: a randomized pharmacodynamic study

Abstract Background In patients on dual antiplatelet therapy (DAPT) also requiring oral anticoagulant therapy (OAC), withdrawal of aspirin therapy reduced the risk of bleeding complications without any apparent trade-off in efficacy. Purpose There is limited data on the pharmacodynamic (PD) effects the effects of high and low dose edoxaban regimens on platelet aggregation and clot kinetics in patients treated with DAPT as well as to assess the impact of discontinuation of aspirin therapy, which was the aim of our study. Methods In this prospective, randomized, open label PD investigation patients (n=75) with stable coronary artery disease on DAPT (aspirin plus clopidogrel) were randomized to DAPT plus high-dose edoxaban (60mg/od, Group A), DAPT plus low-dose edoxaban (30mg/od, Group B), or DAPT only (Group C) for 10±2 days (Phase I). Afterwards, Groups A and B interrupted aspirin and maintained single antiplatelet therapy (SAPT) with clopidogrel plus edoxaban for 10±2 days, while patients in Group C maintained DAPT (Phase II). Platelet aggregation and clot kinetics were assessed at baseline, end of Phase I, and end of Phase II using thrombelastography (TEG), light transmittance aggregometry (LTA) using arachidonic acid (AA), collagen (Coll), ADP and TRAP as agonists, VerifyNow P2Y12, and serum thromboxane B2 (TxB2) assessments. High platelet reactivity (HPR) was defined as P2Y12 reaction unit (PRU) &gt;208. Results Key PD findings are summarized in the Figure. Edoxaban prolonged in a dose-dependent manner speed of thrombin generation (TEG R). However, edoxaban did not impact (irrespective of dose) other markers of clot kinetics including the primary endpoint measure of TEG MA (Maximum Amplitude, a measure of clot strength). Although TEG MA was not affected by the intensity of antiplatelet therapy, showing consistent findings in patients treated with SAPT or DAPT, thrombin-mediated platelet reactivity by LTA-TRAP was significantly increased after aspirin withdrawal in patients treated with low-dose edoxaban, which was attenuated with the high-dose regimen. Although stopping aspirin therapy did not affect profiles of clot kinetics or markers of platelet reactivity specific to P2Y12 signaling (LTA-ADP and PRU), it was associated with an increase in markers sensitive to cyclooxygenase-1 (COX-1) blockade (LTA-AA, LTA-Coll, TxB2). Overall findings were consistent irrespective of HPR status at baseline. PD findings Conclusions Despite modulating thrombin generation, adjunctive edoxaban does not impact clot strength in DAPT-treated patients. Dropping aspirin on a background of OAC with edoxaban and P2Y12 inhibition with clopidogrel does not affect clot kinetics. However, profiles of platelet reactivity following withdrawal of aspirin therapy varies according to the intensity of OAC, which does not overcome COX-1 specific effects-induced by aspirin, suggesting that when considering a double antithrombotic treatment regimen, high-dose edoxaban should be used. Acknowledgement/Funding This work was supported by an investigator-initiated study grant funded by Daiichi Sankyo.

Role of oral anticoagulant therapy for secondary prevention in patients with stable atherothrombotic disease manifestations.

Coronary artery disease and peripheral arterial disease are strong predictors of risk for a future ischemic event. Despite the utilization of effective secondary prevention strategies, the prevalence of ischemic recurrences remains high, underscoring the need for effective secondary prevention antithrombotic treatment regimens. To date, most of the tested approaches have been with the use of antiplatelet therapies, used either individually or in combination. However, most recent findings support the potential role of oral anticoagulant therapy in addition to antiplatelet therapy to reduce the risk of ischemic recurrences. This approach has been tested in both acute and stable settings of patients with cardiovascular disease manifestations. The present manuscript provides an overview on the rationale and clinical trial updates on the role of oral anticoagulant therapy, in particular rivaroxaban used at the so-called vascular protection dose, in adjunct to antiplatelet therapy (i.e. aspirin), a strategy known as dual pathway inhibition, for secondary prevention of ischemic recurrences in patients with stable atherosclerotic disease manifestations.

The Impact of Antithrombotic Regimens on Clinical Outcomes After Endovascular Intervention and Bypass Surgery for Infrapopliteal Artery Disease.

Endovascular intervention and bypass surgery are the main options of treatments for infrapopliteal artery disease. Although post-intervention treatment with antiplatelet (AP) and/or anticoagulant (AC) drugs has reduced morbidity and mortality rates from cardiovascular complications; the ideal antithrombotic treatment regimen is unknown. The aim of this review was to compare the efficacy and safety of various anticoagulation and/or AP therapy regimens in patients undergoing below-knee endovascular treatment for infrapopliteal artery disease. We reviewed published literature in PubMed and Google Scholar, and Cochrane, evaluating efficacy and safety outcomes after antithrombotic treatment following endovascular intervention or bypass surgery in patients with infrapopliteal artery disease. We extracted relevant efficacy and safety data with related statistics from each study. We found that AP treatment should be administered to patients receiving endovascular therapy or bypass. We did not find superior effects for dual AP treatment (DAPT) over mono-AP therapy (MAPT) for endovascular intervention or bypass surgery with venous graft, suggesting that MAPT suffices for these groups. Also, aspirin + clopidogrel was effective over aspirin alone for prosthetic, but not venous graft, albeit higher non-severe bleeding incidences, suggesting a potential benefit of this regime for below-knee prosthetic graft. AP + AC yielded superior results compared to AP following endovascular procedure and bypass surgery, suggesting the potential benefit of this regime in the absence of contraindications. More prospective studies with large number of patients are warranted to identify the best treatment for infrapopliteal artery diseases.

Antithrombotic Therapy in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Undergoing Percutaneous Coronary Intervention: A North American Perspective-2018 Update.

The optimal antithrombotic treatment regimen for patients with atrial fibrillation undergoing percutaneous coronary intervention with stent implantation represents a challenge in clinical practice. In 2016, an updated opinion of selected experts from the United States and Canada on the treatment of patients with atrial fibrillation undergoing percutaneous coronary intervention was reported. After the 2016 North American consensus statement on the management of antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention, results of pivotal clinical trials assessing the type of oral anticoagulant agent and the duration of antiplatelet treatment have been published. On the basis of these results, this focused update on the antithrombotic management of patients with atrial fibrillation undergoing percutaneous coronary intervention recommends that a non-vitamin K antagonist oral anticoagulant be preferred over a vitamin K antagonist as the oral anticoagulant of choice. Moreover, a double-therapy regimen (oral anticoagulant plus single antiplatelet therapy with a P2Y12 inhibitor) by the time of hospital discharge should be considered for most patients, whereas extending the use of aspirin beyond hospital discharge (ie, triple therapy) should be considered only for selected patients at high ischemic/thrombotic and low bleeding risks and for a limited period of time. The present document provides a focused updated on the rationale for the new expert consensus-derived recommendations on the antithrombotic management of patients with atrial fibrillation treated with oral anticoagulation undergoing percutaneous coronary intervention.

The quest for safer antithrombotic treatment regimens in patients with coronary artery disease: new strategies and paradigm shifts

ABSTRACTIntroduction: Despite the undeniable benefits on reducing ischemic adverse events, antiplatelet regimens including dual antiplatelet therapy (DAPT) with aspirin and P2Y12 receptor inhibitors are associated with an increased risk of bleeding. The awareness of the unfavorable prognostic implications associated with bleeding complications have somewhat hampered the enthusiasm towards the use of more potent antiplatelet treatment regimens or prolonged use of DAPT. This awareness also has prompted a series of investigations geared towards the identification of antithrombotic treatment regimens which are efficacious at reducing ischemic recurrences while also safe in terms of bleeding risk profile.Areas covered: The present manuscript focuses on new approaches for improving the safety profile of antithrombotic treatment regimens, including most recent updates from clinical trials, as well as future perspectives in the field.Expert commentary: Results of ongoing trials testing new antithrombotic treatment regimens, including new drugs, new combinations, which may be used for different duration of time according to the individual’s risk of thrombotic and bleeding complications, may lead to paradigm shifts in secondary prevention of atherothrombotic events in patients with coronary artery disease.

Antithrombotic Therapy in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: A North American Perspective-2016 Update.

The optimal antithrombotic treatment regimen for patients with atrial fibrillation undergoing percutaneous coronary intervention with stent implantation is an emerging clinical problem. Currently, there is limited evidenced-based data on the optimal antithrombotic treatment regimen, including antiplatelet and anticoagulant therapies, for these high-risk patients with practice guidelines, thus, providing limited recommendations. Over the past years, expert consensus documents have provided guidance to clinicians on how to manage patients with atrial fibrillation undergoing percutaneous coronary intervention. Given the recent advancements in the field, the current document provides an updated opinion of selected North American experts from the United States and Canada on the treatment of patients with atrial fibrillation undergoing percutaneous coronary intervention. In particular, this document provides the current views on (1) embolic/stroke risk, (2) ischemic/thrombotic cardiac risk, and (3) bleeding risk, which are pivotal for discerning the choice of antithrombotic therapy. In addition, we describe the recent advances in pharmacology, stent designs, and clinical trials relevant to the field. Ultimately, we provide expert consensus-derived recommendations, using a pragmatic approach, on the management of patients with atrial fibrillation undergoing percutaneous coronary intervention.

Antithrombotic Therapy for Secondary Prevention in Patients With Diabetes Mellitus and Coronary Artery Disease.

Diabetes mellitus (DM) is a key risk factor for recurrent atherothrombotic events in patients with acute coronary syndrome (ACS) and in those undergoing percutaneous coronary intervention (PCI). The prothrombotic milieu that characterizes patients with DM underscores the importance of oral antithrombotic therapy for secondary prevention of recurrent events in these patients. Indeed, dual antiplatelet therapy (DAPT) with aspirin and the P2Y12inhibitor clopidogrel, which has represented the mainstay of treatment for many years, has significantly reduced the incidence of recurrent atherothrombotic events. However, recurrence rates in DM patients still remain high despite this treatment regimen, which may be partly related to inadequate platelet inhibition induced by standard DAPT with aspirin and clopidogrel. This underpins the need for more potent antithrombotic treatment regimens for secondary prevention of atherothrombotic events in DM patients following ACS or PCI. The development of antiplatelet therapies associated with more potent oral platelet P2Y12receptor inhibition, including prasugrel and ticagrelor, as well as platelet inhibitors blocking alternative pathways, such as thrombin-mediated platelet inhibition with vorapaxar, may represent potential treatment options in DM patients. Moreover, with the introduction of the target-specific oral anticoagulants, there has been a reappraisal of the use of anticoagulation in addition to antiplatelet therapy for secondary prevention in patients with ACS. This review provides an update on the recent advances and limitations of oral antithrombotic agents used for secondary prevention in DM patients following ACS or PCI.

Stroke and recurrent haemorrhage associated with antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation: nationwide cohort study

Study question What are the risks of all cause mortality, thromboembolism, major bleeding, and recurrent gastrointestinal bleeding associated with restarting antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation?...