Optimal Antithrombotic Regimen Research Articles

Antithrombotic Strategies in Atrial Fibrillation After ACS and/or PCI: A 4-Way Comparison From AUGUSTUS

BackgroundThe optimal antithrombotic regimen for patients with atrial fibrillation (AF) who had an acute coronary syndrome (ACS) or have undergone percutaneous coronary intervention (PCI) is not known. ObjectivesThe authors sought to determine which antithrombotic regimen best balances safety and efficacy. MethodsAUGUSTUS, a multicenter 2 × 2 factorial design randomized trial compared apixaban with vitamin K antagonist (VKA) and aspirin with placebo in patients with AF with recent ACS and/or PCI treated with a P2Y12 inhibitor. We conducted a 4-way analysis comparing safety and efficacy outcomes in the 4 randomized groups. The primary outcome was a composite of all-cause death, major or clinically relevant nonmajor bleeding, or hospitalization for cardiovascular causes over 6-month follow-up. Secondary outcomes included individual components of the primary endpoint. ResultsA total of 4,614 patients were enrolled. All patients were treated with a P2Y12 inhibitor. The primary endpoint occurred in 21.9% of patients randomized to apixaban plus placebo, 27.3% randomized to apixaban plus aspirin, 28.0% randomized to VKA plus placebo, and 33.3% randomized to VKA plus aspirin. Rates of major or clinically relevant nonmajor bleeding and hospitalization for cardiovascular causes were lower with apixaban and placebo compared with the other 3 antithrombotic strategies. There was no difference between the 4 randomized groups with respect to all-cause death. ConclusionsIn patients with AF and a recent ACS and/or PCI, an antithrombotic regimen that included a P2Y12 inhibitor and apixaban without aspirin resulted in a lower incidence of the composite of death, bleeding, or cardiovascular hospitalization than regimens including VKA, aspirin, or both. (An Open-label, 2 x 2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban vs. Vitamin K Antagonist and Aspirin vs. Aspirin Placebo in Patients with Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention; NCT02415400)

A real-world multicenter study on left atrial appendage occlusion: The Italian multi-device experience

BackgroundTranscatheter left atrial appendage occlusion (LAAO) has emerged as an alternative treatment for stroke prevention in patients with atrial fibrillation (AF) at high risk of thromboembolism, who cannot tolerate long-term oral anticoagulation (OAC). Questions persist regarding effectiveness and safety of this treatment and the optimal post-interventional antithrombotic regimen after LAAO. MethodsWe retrospectively gathered data from 428 patients who underwent percutaneous LAAO in 6 Italian high-volume centres, aimed at describing the real-world utilization, safety, and effectiveness of LAAO procedures, also assessing the clinical outcomes associated with different antithrombotic strategies. ResultsAmong the entire population, 20 (4.7 %) patients experienced a combination of pericardial effusion and periprocedural major bleeding: 8 (1.9 %) pericardial effusion, 1 (0.3 %) fatal bleeding, and 3 (0.7 %) non-fatal procedural major bleeding. Patients were discharged with different antithrombotic regimens: dual (DAPT) (27 %) or single (SAPT) (26 %) antiplatelet therapy, OAC (27 %), other antithrombotic regimens (14 %). Very few patients were not prescribed with antithrombotic drugs (6 %). At a medium 523 ± 58 days follow-up, 14 patients (3.3 %) experienced all-cause death, 6 patients (1.4 %) cardiovascular death, 3 patients (0.7 %) major bleeding, 10 patients (2.6 %) clinically relevant non-major bleeding, and 3 patients (0.7 %) ischemic stroke. At survival analysis, with DAPT as the reference group, OAC therapy was associated with better outcomes. ConclusionsOur findings confirm that LAAO is a safe procedure. Different individualized post-discharge antithrombotic regimens are now adopted, likely driven by the perceived thrombotic and hemorrhagic risk. The incidence of both ischemic and bleeding events tends to be low.

Eventos hemorrágicos tardíos en pacientes de TAVI anticoagulados con antagonistas de la vitamina K o anticoagulantes orales de acción directa

Introduction and objectivesThe optimal chronic antithrombotic regimen for patients with atrial fibrillation undergoing transcatheter aortic valve implantation (TAVI) remains uncertain. Our aim was to compare the incidence of late bleeding events between patients on direct oral anticoagulants (DOACs) and those on vitamin-K antagonists (VKA). MethodsThis single-center observational study included TAVI patients requiring oral anticoagulation at discharge between 2015 and 2021. The primary endpoint was any clinically significant bleeding event. Secondary endpoints were stroke, heart failure, and all-cause mortality. ResultsA total of 702 TAVI procedures were performed, with 297 patients requiring oral anticoagulation at discharge. Among them, 206 (69.4%) received VKA and 91 (30.6%) received DOAC. Baseline clinical, procedural and in-hospital characteristics did not significantly differ between groups, except for better renal function among DOAC patients. The median length of follow-up was 2.8 years. The risk of bleeding events was higher in patients receiving DOACs than in those receiving VKA (HR, 2.27; 95%CI, 1.21-4.26; incidence of 9.7 and 4.2 events per 100 patient-years of follow-up for DOAC and VKA patients, respectively). There were no statistically significant differences in the rates of stroke (HR, 1.28; 95%CI, 0.4-4.3), heart failure hospitalization (HR, 0.92; 95%CI, 0.46-1.86), or all-cause mortality (HR, 1.02; 95%CI, 0.68-1.55). ConclusionsIn older patients undergoing TAVI and receiving anticoagulant therapy for atrial fibrillation, the use of DOAC was associated with a higher risk of late bleeding events than VKA.

Antithrombotic Therapy after Percutaneous Left Atrial Appendage Closure: Evidence, Challenges and Future Directions.

Percutaneous left atrial appendage closure (LAAC) has been established in clinical practice as an attractive alternative to oral anticoagulation for preventing stroke in patients with atrial fibrillation and high bleeding risk. The devices approved in Europe and United States (US) for percutaneous LAAC contain metal and antithrombotic therapy is strongly recommended after their implantation to prevent apposition of thrombus on the atrial surface of the device during endothelialization. However, there is still uncertainty regarding the optimal antithrombotic drug regimen following device implantation in view of the incomplete understanding of the LAAC device healing process, the lack of randomized clinical trials comparing different antithrombotic agents after LAAC and the heterogeneous bleeding risk of patients undergoing LAAC. Thus, this review aims to evaluate the available evidence and the remaining challenges related to the post-LAAC antithrombotic regimens. Furthermore, common clinical scenarios associated with challenging management of antithrombotic therapy after LAAC and potential future directions, will be discussed.

Antithrombotic Management for Transcatheter Aortic Valve Implantation.

There have been significant changes in the optimal antithrombotic regimen post transcatheter aortic valve implantation (TAVI) after the results of major clinical trials in the past few years. Given the clinical importance of the optimal antithrombotic therapy post TAVI, we performed a narrative description of the major clinical trials behind the scientific evidence supporting these changes, as well the current guideline recommendations and knowledge gaps. We performed a narrative description of the major clinical trials behind the scientific evidence supporting these changes. We used PubMed as a major source to collect the major clinical trials including the following key words: "transcatheter aortic valve replacement", "transcatheter aortic valve implantation", "antithrombotic", "antiplatelet" and "anticoagulation". We selected the major clinical trials on this topic. This is not a systematic review or meta-analysis. We describe the results of the major clinical trials on antithrombotic therapy post TAVI: POPULAR-TAVI A, POPULAR-TAVI B, ENVISAGE-TAVI AF, GALILEO, ATLANTIS and ADAPT-TAVR trials. Based on the results of these trials, single antiplatelet therapy is recommended post TAVI in patients without concomitant indication for oral anticoagulation or dual antiplatelet therapy, especially in elderly patients. In younger patients, it is advised to evaluate the patient's bleeding and thrombotic risk, and dual antiplatelet therapy may be reasonable in patients with a high thrombotic risk and low bleeding risk. In patients with a concurrent indication for oral anticoagulation or dual antiplatelet therapy, it is recommended to continue oral anticoagulation or dual antiplatelet therapy post TAVI. In most patients without concomitant indication for oral anticoagulation, single antiplatelet therapy is recommended post TAVI.

Nationwide observational study of antithrombotic treatment strategies after coronary artery bypass graft surgery in patients with atrial fibrillation

Abstract Background Atrial fibrillation (AF) is common following coronary artery bypass graft surgery (CABG). Antiplatelet therapy (APT) is recommended after CABG to reduce graft failure. In the case of concomitant AF, this recommendation may instead include oral anticoagulation (OAC) guided by the CHA2DS2-VASc score and bleeding risk. Guidelines remain unclear on optimal antithrombotic treatment in AF patients after CABG. Purpose To assess comparative effectiveness and safety of different antithrombotic treatment strategies in AF patients after CABG. Methods In this nationwide observational study, we identified patients with AF in relation to isolated CABG surgery (before or ≤3 months after CABG) from January 2006 to January 2022 using national administrative registries. Patients alive and claiming a minimum of 1 antithrombotic prescription during the first 3 months after CABG were categorised in 1) APT alone, 2) OAC alone, and 3) OAC+APT. Incidence rates per 100 person-years were calculated for the effectiveness endpoint; a composite of all-cause mortality, stroke, and myocardial infarction, and its individual components, and for the safety endpoint; a composite of bleeding leading to hospitalisation. We also assessed the comparative effectiveness including its individual components and safety of APT and OAC+APT compared with OAC 3 to 12 months after CABG by multivariable Cox proportional-hazards models. Results We identified 33,763 patients who underwent CABG, of whom 6,008 (17.8%) patients had AF, were alive, and collected at least 1 antithrombotic drug ≤3 months after CABG. Temporal trends in the antithrombotic treatment strategies are illustrated in Figure 1. The mean age was 71 years, 18% were female, and 87% had a CHA2DS2-VASc score ≥2 for men and ≥3 for women. A total of 2,845 (47.3%) patients were treated with OAC+APT, 1,958 (32.6%) with APT alone, and 1,205 (20.1%) with OAC alone. Patients treated with APT more often had had a myocardial infarction and 87% had a CHA2DS2-VASc score ≥2 for men and ≥3 for women, whereas patients with OAC+APT more often had valve disease compared with OAC. The incidence rates per 100 patient-years (IR) of the effectiveness endpoint were 4.5 in patients with OAC+ACT, 4.8 with APT, and 4.9 with OAC. For the safety endpoint, the IR were 3.6 with OAC+ACT, 2.1 with APT, and 2.0 with OAC. No differences were found between treatment strategies for the effectiveness endpoint. Compared with patients with OAC, mortality was lower with OAC+APT (HR 0.66 [95% CI 0.45-0.98]) and APT (HR 0.53 [95% 0.34-0.84]), and bleeding risk was higher with OAC+APT (HR 1.69 [95% CI 1.08-2.64]) (Figure 2). Conclusion(s) Every third patient with AF were not treated with OAC after CABG. Compared with OAC alone, mortality was reduced in patients with OAC+APT and APT alone, and bleeding risk was higher in patients with OAC+APT. Future studies are warranted on optimal antithrombotic regimens in AF patients after CABG.Temporal trends in antithromboticsForest plot

Peripheral Artery Disease: Underappreciated Impact and Residual Cardiovascular Risk Despite Revascularization

This Commentary highlights the under-recognized prevalence and heavy burden of peripheral artery disease (PAD) and its important role as a harbinger of complications of atherosclerotic cardiovascular disease. Although increasing in prevalence globally, PAD is being further accelerated with diabetes, and patients with advanced PAD are at high risk for chronic limb-threatening ischemia. The need for (repeated) revascularization and amputation places a heavy social burden on patients and family, and a heavy financial burden on the health care system, exceeding the cost of coronary artery and cerebrovascular diseases. Clinical trial research in PAD will be enhanced by widely agreed-upon definitions of major adverse cardiovascular events and major adverse limb events. Antithrombotic and lipid-lowering therapies are recommended but underutilized, while the optimal peri-interventional antithrombotic regimen is still under debate. Additional antiinflammatory treatment is currently an unaddressed strategy in the management of patients with PAD, and there is a strong case for the evaluation of widely available antiinflammatory agents such as colchicine.

Optimal antiplatelet and antithrombotic regimen post-transcatheter aortic valve replacement.

There are limited data regarding optimal antiplatelet/antithrombotic therapy following transcatheter aortic valve replacement (TAVR). In this single-centre retrospective study including TAVR patients from 2012 to 2020, ischemic and bleeding outcomes were compared between antiplatelet (dual antiplatelet [DAPT] vs. single antiplatelet [SAPT]) and oral anticoagulation (OAC) groups using incidence rate, Kaplan-Meier and Cox proportional hazards analysis. Total 492 patients (mean age 79.7 ± 7.7 years, 53.7% males, 83.5% Caucasian) were included. There was higher incidence of 1-year death or ischemia with DAPT vs. SAPT (23.6 vs. 14.8 per 100 patient-years [PY], incidence rate ratio [IRR] 1.60, 95% confidence interval [CI] 0.97-2.68, p = .05), especially in those without coronary artery disease (23.9 vs. 10.7 per 100 PY, IRR 2.24, 95% CI 1.10-4.47, p = .017). There was significantly higher major bleeding in those on OAC vs. no OAC (15 vs. 8 per 100 PY, IRR 1.87, 95% CI 1.10-3.11, p = .016), especially late (>1-year) bleeding (10.2 vs. 3.6 per 100 PY, IRR 2.81, 95% CI 1.33-5.92, p = .004). In multivariate analysis, DAPT was an independent predictor of death or ischemia (adjusted hazard ratio [aHR] 1.41, 95% CI 1.01-1.96, p = .041). OAC was an independent predictor of major bleeding (aHR 2.32, 95% CI 1.31-4.13, p = .004). There is signal to harm with routine use of DAPT post-TAVR. There is higher incidence of late bleeding post-TAVR with OAC, suggesting potential role for alternate antithrombotic strategies.

Antithrombotic drugs for cardiovascular risk reduction in patients with lower limb peripheral arterial disease: protocol for a systematic review and network meta-analysis of randomised controlled trials

IntroductionThe optimal antithrombotic regimen to reduce the risk of vascular events in patients with peripheral arterial disease (PAD) is contentious. This systematic review and network meta-analysis (NMA) aims to define...

Rationale and design of the optimal antithrombotic treatment for acute coronary syndrome patients with concomitant atrial fibrillation and implanted with new-generation drug-eluting stent: OPtimal management of anTIthroMbotic Agents (OPTIMA)-4 trial.

About 5%-15% of acute coronary syndrome (ACS) patients undergoing stent implantation have concomitant atrial fibrillation and need both antiplatelet and anticoagulant therapies. The optimal antithrombotic regimen remains uncertain in this scenario. A multicenter randomized controlled trial (OPtimal management of anTIthroMbotic Agents [OPTIMA]-4) is designed to test the hypothesis that, for ACS patients with concomitant nonvalvular atrial fibrillation (NVAF) and having low-to-moderate risk of bleeding, clopidogrel is comparable in efficacy but superior in safety compared to ticagrelor while being used in combination with dabigatran after new-generation drug-eluting stent (DES) implantation. ACS patients who have low-to-moderate risk of bleeding (e.g., HAS-BLED score ≤ 2) and require anticoagulation therapy (CHA2 DS2 -VASc score ≥ 2) will be recruited after implantation of new-generation DES. A total of 1472 eligible patients will be randomly assigned to receive a 12-month dual antithrombotic treatment of either clopidogrel 75 mg daily or ticagrelor 90 mg twice daily in combination with dabigatran 110 mg twice daily. Participants will be followed upfor 12 months after randomization. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, unplanned revascularization, ischemic stroke, and systemic thromboembolism. The primary safety endpoint is set as major bleeding or clinically relevant nonmajor bleeding defined by the International Society of Thrombosis and Hemostasis. The enrollment and follow-up have been launched. The first enrollment occurred on March 12, 2018. The recruitment is anticipated to be completed before December 31, 2024. The OPTIMA-4 trial offers an opportunity to assess the optimal dual antithrombotic regimen in ACS patients with concomitant NVAF after the implantation of new-generation DES.

Antithrombotic treatment strategies in patients with established coronary atherosclerotic disease: 2022 joint clinical consensus statement of the European Association of Percutaneous Cardiovascular Interventions (EAPCI), Association for Acute CardioVascular Care (ACVC) and European Association of Preventive Cardiology (EAPC).

Multiple guidelines and consensus papers have addressed the role of antithrombotic strategies in patients with established coronary artery disease (CAD). Since evidence and terminology continue to evolve, the European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association for Acute Cardiovascular Care (ACVC) and European Association of Preventive Cardiology (EAPC) undertook a consensus initiative to guide clinicians to select the optimal antithrombotic regimen for each patient. The aim of this document is to provide an update for clinicians on best antithrombotic strategies in patients with established CAD, classifying each treatment option in relation to the number of antithrombotic drugs irrespective of whether the traditional mechanism of action is expected to mainly inhibit platelets or coagulation cascade. With the aim to reach comprehensiveness of available evidence, we systematically reviewed and performed meta-analyses by means of both direct and indirect comparisons to inform the present consensus document.

Optimal use of antithrombotic agents in ischemic stroke with atrial fibrillation and large artery atherosclerosis.

Optimal antithrombotic regimens to prevent recurrent stroke in patients with ischemic stroke due to atrial fibrillation (AF) and atherosclerotic large-vessel stenosis remain unknown. This study aimed to evaluate the effect of multiple antithrombotic therapies on outcomes at 1 year after ischemic stroke due to two or more causes. We identified 862 patients with ischemic stroke due to AF and large artery atherosclerosis from the linked data. These patients were categorized into three groups according to antithrombotic therapies at discharge: (1) antiplatelets, (2) oral anticoagulants (OAC), and (3) antiplatelets plus OAC. The study outcomes were recurrent ischemic stroke, composite outcomes for cardiovascular events, and major bleeding after 1 year. Inverse probability of treatment weighting (IPTW) was used to balance the three groups using propensity scores. Among 862 patients, 169 (19.6%) were treated with antiplatelets, 405 (47.0%) were treated with OAC, and 288 (33.4%) were treated with antiplatelets and OAC. After applying IPTW, only OAC had a significant beneficial effect on the 1-year composite outcome (hazard ratio (HR): 0.37, 95% confidence interval (CI): 0.23-0.60, p < 0.001) and death (HR: 0.35, 95% CI: (0.19-0.63), p < 0.001). The combination of antiplatelet agents and OAC group had an increased risk of major bleeding complications (HR: 5.27, 95% CI: (1.31-21.16), p = 0.019). However, there was no significant difference in 1-year recurrent stroke events among the three groups. This study demonstrated that OAC monotherapy was associated with lower risks of composite outcome and death in patients at 1 year after ischemic stroke due to AF and atherosclerotic stenosis. In addition, the combination of an antiplatelet and OAC had a high risk of major bleeding.

Physician Approaches to Antithrombotic Therapies for Recently Symptomatic Carotid Stenosis.

Whereas the beneficial effect of antiplatelet therapy for recurrent stroke prevention has been well established, uncertainties remain regarding the optimal antithrombotic regimen for recently symptomatic carotid stenosis. We sought to explore the approaches of stroke physicians to antithrombotic management of patients with symptomatic carotid stenosis. We employed a qualitative descriptive methodology to explore the decision-making approaches and opinions of physicians regarding antithrombotic regimens for symptomatic carotid stenosis. We conducted semi-structured interviews with a purposive sample of 22 stroke physicians (11 neurologists, 3 geriatricians, 5 interventional-neuroradiologists, and 3 neurosurgeons) from 16 centers on four continents to discuss symptomatic carotid stenosis management. We then conducted thematic analysis on the transcripts. Important themes revealed from our analysis included limitations of existing clinical trial evidence, competing surgeon versus neurologist/internist preferences, and the choice of antiplatelet therapy while awaiting revascularization. There was a greater concern for adverse events while using multiple antiplatelet agents (e.g., dual-antiplatelet therapy (DAPT)) in patients undergoing carotid endarterectomy compared to carotid artery stenting. Regional variations included more frequent use of single antiplatelet agents among European participants. Areas of uncertainty included antithrombotic management if already on an antiplatelet agent, implications of nonstenotic features of carotid disease, the role of newer antiplatelet agents or anticoagulants, platelet aggregation testing, and timing of DAPT. Our qualitative findings can help physicians critically examine the rationale underlying their own antithrombotic approaches to symptomatic carotid stenosis. Future clinical trials may wish to accommodate identified variations in practice patterns and areas of uncertainty to better inform clinical practice.

The Efficacy and Safety of Direct Oral Anticoagulants versus Standard of Care in Patients without an Indication of Anti-Coagulants after Transcatheter Aortic Valve Replacement: A Meta-Analysis of Randomized Controlled Trials.

Transcatheter aortic valve replacement (TAVR) is now considered the mainstay of aortic stenosis management; however, the optimal antithrombotic therapy in patent without indications for an oral anticoagulant (OAC) is yet to be identified. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of direct oral anticoagulant (DOAC) treatment versus the standard of care in patients without indications of OACs after TAVR. We synthesized randomized controlled trials (RCTs) from Web of Science, SCOPUS, EMBASE, PubMed, and Cochrane until 18 August 2022. We used the risk ratio (RR) for dichotomous outcomes with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID: CRD42022357027. Three RCTs with 2922 patients were identified. DOACs were significantly associated with higher incidence of all-cause mortality (RR: 1.68 with 95% CI [1.22, 2.30], p = 0.001), mortality due to non-cardiovascular causes (RR: 2.34 with 95% CI [1.36, 4.02], p = 0.002), and the composite outcome of death, myocardial infarction, or stroke (RR: 1.41 with 95% CI [1.13, 1.76], p = 0.002). However, DOACs were associated with decreased incidence of reduced leaflet motion (RLM) (RR: 0.19 with 95% CI [0.09, 0.41], p = 0.0001) and hypoattenuated leaflet thickening (HALT) (RR: 0.50 with 95% CI [0.36, 0.70], p = 0.0001). DOACs were effective to reduce RLM and HALT; however, the clinical effect of this is still controversial. DOACs were associated with worse efficacy and safety outcomes, including all-cause mortality. Further RCTs investigating the optimal antithrombotic regimen after TAVR.

Anticoagulation and/or Antiplatelet in Thrombotic Antiphospholipid Syndrome with Previous Arterial Thromboembolism: A Retrospective Cohort

Introduction: Thrombotic antiphospholipid syndrome (TAPS) is a prothrombotic autoimmune disease associated with a high risk of arterial thromboembolism (ATE). While direct oral anticoagulants (DOAC) are inferior treatment in TAPS with ATE, the optimal antithrombotic regimen of vitamin K antagonists (VKA) and/or antiplatelet therapy (AP) remains unclear. Objectives: To assess the effectiveness and safety of VKA (target (t) international normalized ratio (INR) 2-3), VKA (t INR 2-3) with AP (including dual AP therapy), VKA (t INR >3), VKA (t INR >3) with AP, and AP alone at preventing recurrent thrombotic events in TAPS patients with previous ATE. Methods: This retrospective cohort study included adult TAPS patients with previous ATE assessed at two academic tertiary care centers in Toronto, Canada between April 1, 2011 to April 1, 2021. Included patients met Sydney criteria for TAPS and had a history of ATE (ischemic stroke (IS), transient ischemic attack (TIA), myocardial infarction (MI), or systemic embolism (SE)). At participating centers, patients with a thrombotic history suspicious for TAPS were screened for lupus anticoagulant, anti-cardiolipin antibodies, and/or anti-beta-2-glycoprotein 1 antibodies (anti-B2GP1) at the discretion of the treating physician. Testing for anti-B2GP1 was only available as a send away test. We excluded patients with a known cardioembolic source for their ATE including atrial fibrillation, patent foramen ovale, mechanical heart valves, Libman-Sacks endocarditis, those with initial ATE associated with catastrophic antiphospholipid syndrome (CAPS), and those treated with DOAC. Outcomes included both thrombotic and bleeding events. Recurrent thrombosis included both ATE and VTE. ATE included IS, TIA, MI, or SE. Bleeding events were categorized as major bleeding (MB) or clinically relevant non-major bleeding (CRNMB) as defined by International Society on Thrombosis and Haemostasis criteria. Outcomes were assessed during the time the particular antithrombotic regimen was used. If a single patient had multiple antithrombotic regimens, they were included in multiple groups for the time they used that particular antithrombotic regimen, defined as antithrombotic trials. Outcomes were calculated as the number of events per 100 patient years by antithrombotic regimen with 95% confidence intervals (CI) using Poisson's exact test. Statistical calculations were performed using SPSS. Results: From an initial 891 patients with at least one positive antiphospholipid antibody test, 120 patients met criteria for TAPS and had a previous ATE. 62 patients were excluded for the following reasons: 47 for a cardio-embolic source of ATE, 5 for absence of any follow up, 7 for use of DOAC, and 3 for CAPS in the absence of any other ATE. After exclusions, 58 patients with a total of 89 antithrombotic trials were included in the analysis with a cumulative follow up of 248.4 years. The study population comprised of thirty-one (53.4%) women with a mean age of 51 (Standard Deviation (SD) 12.9) years at the start of their initial antithrombotic trial. Twenty-three (39.7%) patients were known to have systemic lupus erythematosus (SLE) whereas seven (12.1%) patients had non-SLE autoimmune disorders. Thirty-four (58.6%) patients had baseline hypertension. The baseline characteristics are summarized in table 1. Overall, there were a total of 7 ATE and 1 VTE recurrences with a thrombotic rate of 3.2 per 100 patient-years (95% CI 1.4 to 6.3). The recurrence rates in the VKA (t INR 2-3), VKA (t INR 2-3) with AP, VKA (t INR >3) with AP, and AP alone were 3.3 (95% CI 0.9 to 8.4), 2.6 (95% CI 0.3 to 9.3), 0 (95% CI 0 to 18.8), and 6.8 (0.8 to 24.4) per 100 patient-years respectively. There were a total of 10 MB events including 4 intracranial bleeding (ICB), 1 gastrointestinal bleeding, and 5 other types of MB. ICB occurred in 3 patients on VKA (t INR 2-3) and 1 on VKA (t INR 2-3) with AP. Outcomes are summarized in table 2. Conclusions: This retrospective cohort of 58 patients with TAPS and a previous ATE demonstrated a numerically higher risk of recurrent thrombosis with AP alone and a numerically higher risk of MB with the combination VKA and AP. Study limitations include the small sample size, risk of selection bias, and retrospective design. Larger, prospective studies are needed to confirm our observations. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Staphylococcus aureus increases platelet reactivity in patients with infective endocarditis

Thromboembolism is frequent in infective endocarditis (IE). However, the optimal antithrombotic regimen in IE is unknown. Staphylococcus aureus (SA) is the leading cause of IE. First studies emphasize increased platelet reactivity by SA. In this pilot study, we hypothesized that platelet reactivity is increased in patients with SA− IE, which could be abrogated by antiplatelet medication. We conducted a prospective, observatory, single-center cohort study in 114 patients with IE, with four cohorts: (1) SA coagulase positive IE without aspirin (ASA) medication, (2) coagulase negative IE without ASA, (3) SA coagulase positive IE with ASA, (4) coagulase negative IE with ASA. Platelet function was measured by Multiplate electrode aggregometry, blood clotting by ROTEM thromboelastometry. Bleeding events were assessed according to TIMI classification. In ASA-naïve patients, aggregation with ADP was increased with coag. pos. IE (coagulase negative: 39.47 ± 4.13 AUC vs. coagulase positive: 59.46 ± 8.19 AUC, p = 0.0219). This was abrogated with ASA medication (coagulase negative: 42.4 ± 4.67 AUC vs. coagulase positive: 45.11 ± 6.063 AUC p = 0.7824). Aspirin did not increase bleeding in SA positive patients. However, in SA negative patients with aspirin, red blood cell transfusions were enhanced. SA coagulase positive IE is associated with increased platelet reactivity. This could be abrogated by aspirin without increased bleeding risk. The results of this pilot study suggest that ASA might be beneficial in SA coagulase positive IE. This needs to be confirmed in clinical trials.

Five-Year Impacts of Antithrombotic Therapy Based on 10-Year Clinical Outcomes of Cypher™ Stent Implantation.

IntroductionFew researchers have investigated the optimal long-term antithrombotic therapy regimen, especially after first-generation drug-eluting stent (DES) use. This study aimed to evaluate the impact of mid-term antithrombotic therapy on long-term outcomes in patients treated with the first sirolimus-eluting coronary stent (Cypher™).MethodsBetween 2004 and 2009, 1021 patients underwent Cypher™ implantation at our institute; among them, 567 patients had available data on antithrombotic therapy at year 5. We assessed patients’ antithrombotic therapy at year 5 post Cypher™ implantation and examined their association with adverse events from year 5 to year 10 post Cypher™ implantation.ResultsPatients with dual-antiplatelet therapy (DAPT) at year 5 had significantly lower risk of stent thrombosis (ST) than those with single-antiplatelet therapy (SAPT) (hazard ratio [HR] 0.24, p = 0.034). The HR of major bleeding in DAPT, compared to SAPT, was high, but the difference was not significant (HR 1.72, p = 0.26). Risk of major bleeding was significantly higher in patients on oral anticoagulants (OAC) than in those in other groups (OAC/SAPT; HR 5.31, p = 0.0048, OAC/DAPT; HR 3.08, p = 0.022), without significant reduction in the risk of cardiovascular events.ConclusionsThe incidence of ST after Cypher™ implantation in patients with DAPT at year 5 was significantly lower than that in SAPT. However, the risk of bleeding was higher with DAPT than with SAPT. Moreover, the risk of major bleeding was significantly higher in patients on anticoagulant therapy than in other patients. New options for the use of antithrombotic drugs after percutaneous coronary intervention warrant further studies on the optimal antithrombotic therapy for first-generation DES.

Single Antiplatelet Therapy Versus Dual Antiplatelet Therapy After Transcatheter Aortic Valve Replacement: A Meta-analysis of Randomized Controlled Trials

INTRODUCTION: After transcatheter aortic valve replacement (TAVR), ischemic/embolic complications and bleeding remain important because it correlates with mortality. The optimal antithrombotic regimen after successful TAVR remains unclear. This study compared the efficacy and safety of single antiplatelet therapy (SAPT) versus dual antiplatelet therapy (DAPT) among post-TAVR patients. METHODS: Extensive search of PubMed, MEDLINE, Cochrane, and Ovid was done for articles published until November 20, 2020. Studies were limited to randomized controlled trials. Outcome measures include stroke, myocardial infarction (MI), all-cause mortality, and major bleeding. Two reviewers independently reviewed the studies. Results were gathered from published articles, journals, and clinical trials. Studies were critically appraised with regard to methods of minimizing bias. All four studies included received a quality scale for meta-analysis overall score of not less than B. Statistical analysis was done using Review Manager V5.4. RESULTS: Four randomized controlled trials with 1086 patients were included in this meta-analysis. Overall, the risk of stroke (odds ratio [OR], 0.94 [0.54–1.64]), MI (OR, 0.50 [0.18–1.40]), and overall mortality (OR, 1.01 [0.65–1.57]) did not differ significantly between DAPT and SAPT. There was increased risk of bleeding noted with DAPT, thus favoring SAPT (OR, 0.44 [0.30–0.65]). CONCLUSION: Among patients who underwent TAVR, DAPT compared with SAPT had similar rates of stroke, MI, and death. Because of lower rates of bleeding, we recommend using single antiplatelet therapy after TAVR. KEYWORDS: TAVR, TAVI, antiplatelet, single antiplatelet therapy, antithrombotic, DAPT

Consensus Document on Perioperative Antithrombotic Management: Part 1. A Review

The prevalence of ischemic heart disease is steadily growing as populations age. Antithrombotic treatment is a key therapeutic modality for the prevention of secondary cerebro-cardiovascular disease. Patients with acute coronary syndrome or who are undergoing percutaneous coronary intervention must be treated with dual antiplatelet therapy for a mandatory period. The optimal perioperative antithrombotic regimen remains debatable; antithrombotics can cause bleeding. Inadequate antithrombotic regimens are associated with perioperative ischemic events, but continuation of therapy may increase the risks of perioperative hemorrhagic complications (including mortality). Many guidelines on the perioperative management of antithrombotic agents have been established by academic societies. However, the existing guidelines do not cover all specialties, nor do they describe the thrombotic and hemorrhagic risks associated with various surgical interventions. Moreover, few practical recommendations on the modification of antithrombotic regimens in patients who require non-deferrable interventions/surgeries or procedures associated with a high risk of hemorrhage have appeared. Therefore, cardiologists, specialists performing invasive procedures, surgeons, dentists, and anesthesiologists have not come to a consensus on optimal perioperative antithrombotic regimens. The Korean Platelet-Thrombosis Research Group presented a positioning paper on perioperative antithrombotic management. We here discuss commonly encountered clinical scenarios and engage in evidence-based discussion to assist individualized, perioperative antithrombotic management in clinical practice.

In Search of the Optimal Antithrombotic Regimen for Intracerebral Hemorrhage Survivors with Atrial Fibrillation

Spontaneous intracerebral hemorrhage (ICH) constitutes 10-15% of all strokes, and is a significant cause of mortality and morbidity. Survivors of ICH, especially those with atrial fibrillation (AF), are at risk for both recurrent hemorrhagic and ischemic cerebrovascular events. A conundrum in the field of vascular neurology, neurosurgery, and cardiology has been the decision to initiate or resume versus withhold anticoagulation in survivors of ICH with AF. To initiate anticoagulation would decrease the risk of ischemic stroke but may increase the risk of hemorrhage. To withhold anticoagulation maintains a lower risk of hemorrhage but does not decrease the risk of ischemic stroke. In this narrative review, we discuss the evidence for and against the use of antithrombotics in ICH survivors with AF, focusing on recently completed and ongoing clinical trials.