Dual Antiplatelet Therapy Therapy Research Articles

Outcomes of dual antiplatelet therapy in combination with direct oral anticoagulants in patients with acute coronary syndrome: a meta-analysis

Abstract Background Recent data showed that the use of direct oral anticoagulants (DOAC) in addition to dual antiplatelet therapy (DAPT) is associated with reduced risk of adverse cardiovascular (CV) outcomes in patients with acute coronary syndrome (ACS) with or without percutaneous coronary intervention (PCI), but It has also been associated with increased risk of bleeding. The data differs among different studies, thus, the CV outcomes associated with use of DOAC therapy plus DAPT are not fully understood. We conducted a meta-analysis to explore the CV and bleeding outcomes of DOAC therapy plus DAPT vs DAPT with or without placebo in patients with ACS Methods We conducted a literature search of studies exploring the use of DAPT plus DOAC therapy with focusing on bleeding and CV outcomes including myocardial infarction (MI), stroke, stent thrombosis, limb thrombosis and VTE using Ovid, Scopus, PubMed, Medline, and EBSCO databases from January 2010 to March 2020. We used the following terms for the literature search: (Aspirin AND Clopidogrel OR Prasugrel OR Ticagrelor) AND (Apixaban OR Rivaroxaban OR Edoxaban OR Dabigatran OR Betrixaban). The efficacy outcome was a composite of CV death, MI and stroke, and the safety outcome was major bleeding. Results 4857 articles were included. Only RCTs and RCTs post-hoc analysis, were included (N=3). We found no significant heterogeneity and lower odds of the efficacy outcome in DOAC plus DAPT (experimental arm) compared to DAPT plus placebo (Control arm), which were unchanged in both the fixed and random effect models (Odds Ratio [OR] 0.87, 95% Confidence Interval [CI]: 0.78–0.97, I2=0%). We found no significant heterogeneity and higher odds of the safety outcome in DOAC plus DAPT (experimental arm) compared to DAPT plus placebo (Control arm) (OR fixed model 3.27, 95% CI: 2.28–4.70; OR random model 3.18, 95% CI: 2.21–4.57; I2=0%). Conclusion DOAC therapy plus DAPT in patients with ACS with or without PCI was associated with a lower rate of CV death, MI and stroke when compared to DAPT alone or with placebo and also associated with significant increase in major bleeding Funding Acknowledgement Type of funding sources: None.

Variability in Antithrombotic Therapy after Infrainguinal Lower Extremity Bypass

Antiplatelet monotherapy is recommended after infrainguinal lower extremity bypass (LEB). However, there is a paucity of high-quality data to guide therapy, and antiplatelet therapy is often prescribed in combination with anticoagulation. We therefore aimed to assess the variability in the use of antithrombotic therapy after infrainguinal LEB. The Vascular Quality Initiative dataset (2015-2021) was retrospectively reviewed to determine discharge patterns of antithrombotic therapy for all patients undergoing infrainguinal LEB. Monotherapy on discharge was defined as either single antiplatelet therapy (SAPT) or single anticoagulant (SAC). Combination therapy was dual antiplatelet therapy (DAPT), anticoagulant+antiplatelet (ACAP), or triple therapy. Hierarchical multivariable logistic regression with random effects for physician and center was used to identify predictors of combination therapy. Median odds ratios (MOR) were derived to quantify degree of variability in antithrombotic therapy. There were 29,507 patients undergoing infrainguinal LEB (monotherapy=10,634 vs. combination therapy=18,873). SAPT (90.6%) was the most common form of monotherapy, while DAPT (57.7%) and ACAP (34.6%) were the most common combination therapies. Patients undergoing LEB to popliteal targets were more likely to be prescribed monotherapy (SAC or SAPT) than to infra-popliteal targets (60.6% vs. 56.6%, P<0.001). Combination therapy (DAPT, ACAP, or triple therapy) was more often used in patients with tibial or plantar arteries as the bypass target. Patients undergoing bypass using autogenous vein were more likely to receive monotherapy compared with those receiving other conduits (64.8% vs. 52.9%, P<0.001), while patients with prosthetic grafts were more likely to receive combination therapy (37.9% vs. 28.2%, P<0.001). There were no significant differences in postoperative bleeding (P=0.491) or 30-day mortality (P=0.302) between the two groups. Prior peripheral vascular interventions (PVI) (odds ratio [OR]: 1.89, 95% confidence interval [CI]: 1.79-1.99), concomitant PVI (OR: 1.83, 95% CI: 1.66-2.02), prosthetic graft use (OR: 1.74, 95% CI: 1.64-1.85), prior percutaneous coronary intervention (OR: 1.53, 95% CI: 1.43-1.65), plantar distal target (OR: 1.46, 95% CI: 1.29-1.65), alternative conduits (OR: 1.39, 95% CI: 1.25-1.53), and tibial distal targets (OR: 1.36, 95% CI: 1.28-1.44) were independent predictors of combination therapy in a multivariable regression model. Upon adjusting for patient-level factors, there was significant physician-level (MOR: 1.65, 95% CI 1.61-1.67) and center-level (MOR: 1.64, 95% CI 1.57-1.69) variability in the selection of antithrombotic therapy. Significant physician- and center-level variability in the use of antithrombotic regimens after infrainguinal bypass reflects the paucity of available evidence to guide therapy. Pragmatic trials are needed to assess antithrombotic strategies and guide recommendations aimed at optimizing cardiovascular and graft-specific outcomes after LEB.

Comparative Effectiveness and Safety of Different Combinations of Antithrombotic Regimens in Atrial Fibrillation Patients With Stent Insertions.

This study aims to compare the risks of major adverse cardiac events (MACEs), including cardiovascular death, myocardial infarction, ischemic stroke and transient ischemic attack, and major bleeding across different antithrombotic regimens in Asian patients with atrial fibrillation (AF) with stent insertions. We conducted a retrospective cohort study using Taiwan's National Health Insurance Research Database and National Mortality Registry. A total of 10,208 patients with nonvalvular AF who had undergone percutaneous coronary intervention with stents for the first time in 2007-2017 were identified. Most patients (68.4%) were prescribed dual antiplatelet therapy (DAPT) at discharge. During follow-up, the use of anticoagulants increased, and double therapy (an antiplatelet plus an anticoagulant) was the most frequently prescribed therapy. The risks of MACEs were comparable in double therapy and had a similar risk of MACEs compared with DAPT (adjusted hazard ratio (aHR) 0.86, 95% confidence interval (CI) 0.67-1.11). Triple therapy (DAPT plus an anticoagulant) also had similar effectiveness to double therapy (aHR 1.23, 95% CI 0.84-1.80) or DAPT (aHR 1.06, 95% CI 0.77-1.45). However, triple therapy was associated with a nearly twofold higher major bleeding risk than DAPT and double therapy (aHR 1.97, 95% CI 1.31-2.94 and aHR 1.80, 95% CI 1.10-2.95, respectively). DAPT was the most frequently prescribed antithrombotic regimen at discharge for Asian patients with AF who had undergone stent insertions. DAPT and double and triple therapy had comparable effectiveness, but triple therapy had a significantly higher major bleeding risk than either DAPT or double therapy.

P203 CHALLENGES IN THE MANAGEMENT OF RECTUS MUSCLE HEMATOMA DURING TRIPLE ANTITHROMBOTIC THERAPY IN RECENT ANTERIOR STEMI COMPLICATED BY LEFT ENDOVENTRICULAR THROMBOSIS

Abstract A 69–year–old woman suffering from hypercholesterolemia, GERD, was admitted to our department for anterior ST elevation myocardial infarction and was treated with primary PCI and DES on the mid–distal LAD. Dual antiplatelet therapy (DAPT) with ticagrelor and cardioaspirin was started. The pre–discharge echocardiogram (echo) showed the presence of left ventricular thrombus (LVT) and anticoagulant therapy (enoxaparin and warfarin) was started. On the 9th day the patient complained abdominal pain with onset of chills and hyperthermia and was suspected an uro–septic fever. The day after a mass appeared on the right abdominal wall at the site of the enoxaparin injection and abdominal contrast CT showed a mass of inhomogeneous density, actively supplied by the inferior epigastric artery and its terminal branches, indicative of hematoma of the abdominal rectus muscle. Anticoagulant therapy was suspended. Interventional radiologists in consideration of clinical stability and stable Hb value and the absence of the signs of active arterial bleeding on CT have not indicated an urgent endovascular treatment and DAPT with clopidogrel and cardioaspirin was continued. After V days, echo showed persistent pedunculated and mobile LVT and aspirin was therefore suspended and anticoagulant therapy was reintroduced with fondaparinux 2.5 mg daily. After two days, considering the stability of hematoma dimensions and the Hb values but the persistence of the extremely floating LVT, fondaparinux was increased at dose of 5 mg daily. In the following days, echo showed LVT reworking until its complete disappearance. On the 32th day blood test showed significant reduction in Hb values and a contrast CT showed an increase in size of the hematoma and resumption of micro bleeding. Fondaparinux was stopped and the patient was transferred to the interventional radiology center. Angiography highlights point–like spreads of extravascular contrast from branches of the inferior epigastric artery and branches of the external circumflex iliac artery. Embolization was performed. After a close monitoring of the hemoglobin values and of the echo which showed no LVT and recovery of LV function, in consideration of her thrombotic and hemorragic risks, she was discharged with DAPT with clopidogrel and low dose of aspirin. Abdominal wall hematoma may be a rare complication of subcutaneous enoxaparin therapy especially in STEMI patients undergoing also a DAPT therapy.

Utilization of Drug-Coated Balloons for the Treatment of Coronary Lesions in the Elderly Population.

Introduction: The use of drug-coated balloons (DCBs) has become more prevalent in the past few years for the treatment of in-stent restenosis (ISR) and de novo lesions. The absence of foreign polymer implantations potentially shortens the duration of dual anti-platelet therapy (DAPT), which can be beneficial for the elderly population. We aimed to investigate the safety and efficacy of the use of DCBs for the treatment of coronary lesions in elderly patients as compared to the younger population. Materials and methods: A database of 446 consecutive patients who underwent a procedure of DCB inflation in our institution was divided into two groups, below 70 years old and above 80 years old. We compared and analyzed the endpoints of total major adverse cardiovascular events (MACE), cardiovascular (CV) death, and all-cause mortality in both groups. Results: The difference in MACE between the two age groups was non-significant (p = 0.225); the difference in cardiovascular death was also non-significant (p = 0.086). All-cause mortality was significantly different (p < 0.0001) and can be attributed to the age of the patients. Conclusion: The utilization of DCBs for the treatment of coronary lesions may be as safe and effective for the elderly population as for the younger population and may allow a shorter period of DAPT therapy, which can lower the risk of bleeding.

How Do Lipoprotein(a) Concentrations Affect Clinical Outcomes for Patients With Stable Coronary Artery Disease Who Underwent Different Dual Antiplatelet Therapy After Percutaneous Coronary Intervention?

BackgroundLp(a) (lipoprotein[a]) plays an important role in predicting cardiovascular events in patients with coronary artery disease through its proatherogenic and prothrombotic effects. We hypothesized that prolonged dual antiplatelet therapy (DAPT) might be beneficial for patients undergoing percutaneous coronary intervention who had elevated Lp(a) levels. This study aimed to evaluate the effect of Lp(a) on the efficacy and safety of prolonged DAPT versus shortened DAPT in stable patients with coronary artery disease who were treated with a drug‐eluting stent.Methods and ResultsWe selected 3201 stable patients with CAD from the prospective Fuwai Percutaneous Coronary Intervention Registry, of which 2124 patients had Lp(a) ≤30 mg/dL, and 1077 patients had Lp(a) >30 mg/dL. Patients were divided into 4 groups according to Lp(a) levels and the duration of DAPT therapy (≤1 year versus >1 year). The primary end point was major adverse cardiovascular and cerebrovascular event, defined as a composite of all‐cause death, myocardial infarction, or stroke. The median follow‐up time was 2.5 years. Among patients with elevated Lp(a) levels, DAPT >1 year presented lower risk of major adverse cardiovascular and cerebrovascular event and definite/probable stent thrombosis compared with DAPT ≤1 year. In contrast, in patients with normal Lp(a) levels, the risks of major adverse cardiovascular and cerebrovascular event and definite/probable stent thrombosis were not significantly different between the DAPT >1 year and DAPT ≤1 year groups. Prolonged DAPT had 2.4‐times higher risk of clinically relevant bleeding than shortened DAPT in patients with normal Lp(a) levels, although without statistical difference.ConclusionsIn stable patients with coronary artery disease, who underwent percutaneous coronary intervention with a drug‐eluting stent, prolonged DAPT was associated with reduced risk of cardiovascular events among those with elevated Lp(a) levels, whereas it did not show statistically significant evidence of benefit for reducing ischemic events and tended to increase clinically relevant bleeding among those with normal Lp(a) levels.

Prognosis impact of ticagrelor vs clopidogrel based DAPT discontinuation after acute coronary syndrome. Insights from the multicenter CREA ARIAM Andalucia registry

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): The study project was financially supported by a non-conditional grant by Astrazeneca. Background/Introduction Premature cessation of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) has been associated with increased risk of major adverse cardiovascular events (MACE) Purpose To assess the relationship between premature DAPT discontinuation versus therapy continuation and outcomes in ACS patients discharged on ticagrelor or clopidogrel. Methods Prospective, observational, multicentre all-comers registry of ACS patients who were intended to receive 12-month DAPT with ticagrelor or clopidogrel. Adherence was defined by the medication possession ratio metric (MPA, proportion of days of medication supply within a time interval). Categories for DAPT cessation included: physician-recommended discontinuation, brief interruption (invasive procedures), or disruption due to non-compliance or because of bleeding. Fully-adjusted Cox models with time-varying covariates to account for informative censoring, were used to examine the effect of DAPT cessation on MACE (a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, definite stent thrombosis, or target-lesion revascularization). Moderation analysis was also performed to assess for potential exposure-adherence interaction. Results Among 2070 patients included (mean age 63 years, 73% men), 150 (7.3%) prematurely discontinued DAPT, median (IQR) 214 (101-236) days. Significantly more clopidogrel than ticagrelor users discontinued medication (9.5% vs 5%, respectively; P = .001), though timing of cessation was similar in both groups. At 1 year, MPR was slightly higher, but not significantly different, in the clopidogrel group than in the ticagrelor group (70±30 vs 64±29; P = .06). Overall, physician-guided discontinuation and bleeding were the main reasons for DAPT cessation. These were observed with a similar rate in both groups, while non-compliant disruption was more common among ticagrelor- than clopidogrel-treated patients (8% vs 2%, respectively; P for trend .04). After adjustments, DAPT cessation was associated with significantly increased risk of MACE (adjusted HR 2.94; 95% CI 1.82 – 4.74; P &amp;lt; .0001), regardless of the P2Y12 inhibitor (P interaction = 0.665). Non-compliance related cessation resulted in higher risk of MACE (HR 6.04, 95%CI 2.15 – 16.95; P = .001). Conclusion(s) Overall, approximately 7% of patients discontinued DAPT. Early cessation of either ticagrelor- or clopidogrel-based DAPT portended to a near 3-fold increased risk of MACE. Disruption due to non-compliance resulted in higher risk for ischemic events. These data warrant efforts to focus on patient education in subgroups at high risk of non-compliance.

Use and outcomes of dual antiplatelet therapy for acute coronary syndrome in patients with chronic kidney disease: insights from the Canadian Observational Antiplatelet Study (COAPT).

Chronic kidney disease (CKD) increases the risk of adverse outcomes in acute coronary syndrome (ACS). The optimal regimen of dual antiplatelet therapy (DAPT) post-percutaneous coronary intervention (PCI) in CKD poses a challenge due to the increased bleeding and clotting tendencies, particularly since patients with CKD were underrepresented in randomized controlled trials. We examined the practice patterns of DAPT prescription stratified by the presence of CKD. The multicentre prospective Canadian Observational Antiplatelet Study (COAPT) enrolled patients with ACS between December 2011 and May 2013. The present study is a subgroup analysis comparing type and duration of DAPT and associated outcomes among patients with and without CKD (eGFR < 60ml/min/1.73m2, calculated by CKD-EPI). Patients with CKD (275/1921, 14.3%) were prescribed prasugrel/ticagrelor less (18.5% vs 25.8%, p = 0.01) and had a shorter duration of DAPT therapy versus patients without CKD (median 382 vs 402days, p = 0.003). CKD was associated with major adverse cardiovascular events (MACE) at 12months (p < 0.001) but not bleeding when compared to patients without CKD. CKD was associated with MACE in both patients on prasugrel/ticagrelor (p = 0.017) and those on clopidogrel (p < 0.001) (p for heterogeneity = 0.70). CKD was associated with increased bleeding only among patients receiving prasugrel/ticagrelor (p = 0.007), but not among those receiving clopidogrel (p = 0.64) (p for heterogeneity = 0.036). Patients with CKD had a shorter DAPT duration and were less frequently prescribed potent P2Y12 inhibitors than patients without CKD. Overall, compared with patients without CKD, patients with CKD had higher rates of MACE and similar bleeding rates. However, among those prescribed more potent P2Y12 inhibitors, CKD was associated with more bleeding than those without CKD. Further studies are needed to better define the benefit/risk evaluation, and establish a more tailored and evidence-based DAPT regimen for this high-risk patient group.

Individualizing Dual Antiplatelet Therapy (DAPT) Duration Based on Bleeding Risk, Ischemic Risk, or Both: An Analysis From the DAPT Study

BackgroundGuidelines recommend individualization of dual antiplatelet therapy (DAPT) duration. Whether to guide decisions based on bleeding risk, ischemic risk or a combination is not known. AimsTo compare a bleeding prediction model, an ischemic prediction model, and the DAPT score in guiding DAPT duration. Methods11,648 patients in the DAPT Study were categorized into higher and lower risk using a bleeding model, an ischemic model, and the DAPT score. Effect of 30 vs. 12 months of DAPT on bleeding events, ischemic events, and the combination (net-adverse clinical events [NACE]) was assessed. ResultsAmong patients stratified with the bleeding model, 30 vs. 12 months of DAPT resulted in similar ischemic and bleeding event rates. With the ischemic model, however, higher risk patients had a greater reduction in ischemic events with extended duration of DAPT (difference in risk differences [DRD]: −2.6%, 95% CI: −3.9 to −1.3%; p < 0.01), and a smaller increase in bleeding (DRD: −1.0%, 95% CI: −2.1–0.0%; p = 0.04). Similarly, high DAPT score patients had a greater reduction in ischemic events with extended DAPT duration (DRD: −2.4%, 95%: CI: −3.6 to −1.1%; p < 0.01) and a smaller increase in bleeding (DRD: −1.2%, 95%: CI: −2.2–0.0%; p = 0.02). Although NACE was similar for bleeding risk groups, NACE was significantly reduced with extended DAPT in the higher ischemic risk and high DAPT score groups. ConclusionsIn this low-bleeding risk population, stratifying patients based on predicted ischemic risk and the DAPT score best discerned benefit versus harm of extended DAPT duration on ischemic events, bleeding events, and NACE. Condensed abstractDuration of dual antiplatelet therapy (DAPT) should be guided by an individualized risk assessment. Bleeding risk tools have emerged to identify patients at high bleeding risk for whom truncated DAPT therapy may be safest. In a lower bleeding risk population, however, whether DAPT duration should be guided by bleeding risk, ischemic risk, or a combination is unknown.In this analysis, implementation of a score based on ischemic risk prediction and the DAPT score (a combination of ischemic and bleeding risk) best predicted ischemic events, bleeding events, and net-adverse clinical events (NACE).

Dual Antiplatelet Versus Single Antiplatelet in Post– Transcatheter Aortic Valve Implantation/Transcatheter Aortic Valve Replacement for Stroke Prevention: A Systematic Review and Meta-analysis

BACKGROUND: There is ambiguity on antiplatelet therapy for post–transcatheter aortic valve replacement (TAVR) patients for stroke prevention, but dual antiplatelet therapy (DAPT) is routinely started despite lack of data on effectiveness and bleeding safety of DAPT versus single antiplatelet therapy (SAPT). This study aims to determine the effectiveness of DAPT versus SAPT in stroke prevention and assess bleeding safety. METHODS: A systematic search was done for randomized clinical trials involving DAPT and SAPT in patients who underwent TAVR. The primary outcome was stroke after 1 year of either DAPT and SAPT and life-threatening bleeding. Secondary end points included all-cause mortality. Trials were identified through systematic searches on the following databases (November 2019): Cochrane, MEDLINE, and Google Scholar and ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform. Risk ratio was used for dichotomous outcomes. Heterogeneity among the studies for the meta-analysis was detected using a χ2 test (0.01 level of significance). Risk-of-bias assessment was done. RESULTS: There is a lower incidence of stroke in patients on DAPT, but with a higher incidence of life-threatening bleeding and major bleeding. There is also a lower incidence of all-cause mortality in SAPT. The statistical power of this meta-analysis is low due to small population size. CONCLUSION: Single antiplatelet therapy is comparable to DAPT in preventing stroke with the added benefit of a lower incidence of life-threatening and major bleeding and a lower incidence of all-cause mortality. KEYWORDS: antiplatelet therapy, bleeding, dual antiplatelet therapy, single antiplatelet therapy, mortality, myocardial infarction, stroke, transcatheter aortic valve replacement, transcatheter aortic valve implantation

Abstract 11190: Impact of the Use of Platelet Function Testing to Guide P2Y12 Inhibitor Usage After Percutaneous Coronary Intervention (PCI): Results of a Large Real-World Experience

Background: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor remains standard treatment for patients undergoing PCI, and clopidogrel remains the most used agent. Many patients (pts) are genetically resistant to clopidogrel and may not receive its full benefit. However, the use of platelet function testing to provide individualized management of P2Y12 inhibitor therapy remains controversial. Therefore, we analyzed the impact of the use of platelet function testing after PCI in a large real-world experience. Methods: We searched Intermountain Healthcare medical records for pts who underwent PCI followed by DAPT. We compared 1-year outcomes (MACE=death, MI, stroke; and repeat revascularization and major bleeding) in those who did, or did not, receive P2Y12 platelet function testing within 90 days. Cox hazard regression analysis was used to determine multivariable hazard ratios. Results: A total of 11,561 pts were included, of which 650 (5.6%) received P2Y12 platelet function testing. Baseline demographics, discharge P2Y12 inhibitor and outcomes are shown in the Table. Conclusion: In this real-world analysis of patients undergoing PCI, a small proportion of the patients received P2Y12 platelet function testing. Platelet function testing was associated with increased utilization of prasugrel or ticagrelor and a statistically lower incidence of 1-year MACE (10.8% vs. 12.4%, adjusted odds ratio = 0.69, p=0.03), with a very low incidence of major bleeding. Further investigation regarding the potential benefits of individualized management of DAPT therapy through P2Y12 platelet function testing may be justified.

USE AND OUTCOME OF DUAL ANTIPLATELET THERAPY FOR ACUTE CORONARY SYNDROME IN PATIENTS WITH CHRONIC KIDNEY DISEASE: INSIGHTS FROM THE CANADIAN OBSERVATIONAL ANTIPLATELET STUDY (COAPT), A MULTICENTRE PROSPECTIVE COHORT STUDY

<h3>BACKGROUND</h3> Chronic kidney disease (CKD) increases the risk of adverse outcomes in acute coronary syndrome (ACS). The optimal regimen of dual antiplatelet therapy (DAPT) post percutaneous coronary intervention (PCI) is challenging due to both increased bleeding and thrombotic risks in patients with CKD, particularly since these patients were under-represented in randomized controlled trials. We examined the patterns of DAPT use in ACS patients post PCI stratified by presence of CKD. <h3>METHODS AND RESULTS</h3> The multi-centre prospective Canadian Observational Antiplatelet Study (COAPT) enrolled patients with an ACS diagnosis from 43 hospitals between December 2011-May 2013. The present study is a subgroup analysis comparing type and duration of DAPT, and associated outcomes among patients with and without CKD defined as eGFR < 60 ml/min/1.73m2 (calculated by CKD-EPI). COAPT enrolled 1921 patients (mean age: 61; 21.4% female) with a median eGFR of 85 ml/min/1.73 m2 (25th and 75th percentiles [69, 97]). Of those, 275 (14.3%) had CKD. CKD patients were older, more likely to be female and have comorbidities including previous ACS, heart failure, hypertension, cerebrovascular disease, atrial fibrillation and gastrointestinal bleeding. Patients with CKD were less frequently prescribed the more potent P2Y12 inhibitors prasugrel/ticagrelor (18.5% vs 25.8%, p=0.01) and had a shorter duration of DAPT therapy than patients without CKD (median 382 vs 402 days, p=0.003). CKD was associated with major adverse cardiovascular events (MACE) at 12 months (p < 0.001) but not bleeding when compared to patients without CKD (figure 1). CKD was associated with MACE in both patients on prasugrel/ticagrelor (p=0.017) and those on clopidogrel (p < 0.001) (p for heterogeneity=0.70). CKD was associated with increased bleeding only among patients receiving prasugrel/ticagrelor (p=0.007), but not among those receiving clopidogrel (p=0.64) (p for heterogeneity=0.036). Patients with CKD were more frequently considered to have an ongoing indication for DAPT therapy during follow-up. Discontinuation of DAPT was more likely in patients with CKD due to the need for an oral anticoagulant. <h3>CONCLUSION</h3> Patients with CKD had a shorter DAPT duration and were less frequently prescribed potent P2Y12 inhibitors than patients without CKD. Overall, compared with patients without CKD, patients with CKD had higher rates of MACE and similar bleeding rates. However, among those prescribed more potent P2Y12 inhibitors, CKD was associated with more bleeding than those without CKD. Further studies are needed to better define the benefit/risk ratio, and establish a more tailored and evidence-based DAPT regimen for this high-risk patient group.

The impact of J-CTO score on in-stent chronic total occlusion percutaneous coronary intervention.

The purpose of this study was to investigate the impact of J-CTO (Multicenter Chronic Total Occlusion Registry of Japan) score on in-stent chronic total occlusion (IS-CTO) percutaneous coronary intervention (PCI). A retrospective data collection was conducted on 474 patients undergoing a difficult IS-CTO PCI from January 2015 to December 2018. The primary endpoint (major adverse cardiovascular events [MACE]) consisted of target-vessel myocardial infarction (MI), cardiac death or ischemia-driven target-vessel revascularisation (TVR) at follow-up. The cut-off points were estimated by the Youden index. The overall procedural success rate was 77.6%. On multivariable analysis, factors including proximal bending (beta coefficient [β] = 3.465), tortuosity (β=3.064), stent under expansion (β=3.109) and poor distal landing zone (β=1.959) were associated with technical failure via antegrade approach but not the J-CTO score (OR = 0.632; 95% CI [0.352-1.134]; P=.124). After a median follow-up of 30months (interquartile range: 17-42months), multivariable analysis revealed that receiving >18months of dual antiplatelet therapy (DAPT) was an independent predictor of decreased risk of MACE (HR: 2.690; 95% CI: 1.346-5.347; P=.005). But the J-CTO score was not an independent predictor of MACE (HR: 1.018; 95% CI: 0.728-1.424; P=.917). J-CTO score system is not a helpful tool to predict the technical success of difficult IS-CTO PCI via antegrade approach, nor does it correlate with long-term outcomes in patients undergoing IS-CTO PCI. Nevertheless, factors associated with technical failure include proximal bending of ≥30 degrees, under expansion of ≥10mm, moderate or severe tortuosity (bending) ≥20 and poor distal target. Long-term DAPT therapy contributes significantly to decreased MACE.

Rivaroxaban versus Vitamin K Antagonists (warfarin) based on the triple therapy for left ventricular thrombus after ST-Elevation myocardial infarction.

Left ventricular thrombus (LVT) can complicate ST-Elevation myocardial infarction (STEMI) and is associated with poor outcomes. Conventional triple anticoagulation [Vitamin K Antagonists (VKA) plus dual-antiplatelet therapy (DAPT)] is the first-line therapy for LVT after STEMI. In patients with LVT following STEMI, contemporary data of triple therapy with rivaroxaban are lacking. We conducted a retrospective cohort study involving 1335 STEMI patients who underwent primary percutaneous coronary intervention (PCI). Among patients who developed LVT after STEMI, we observed differences in efficacy between rivaroxaban plus DAPT therapy and VKA plus DAPT. The time of LVT resolution was also evaluated, as well as net clinical adverse events, and rates of bleeding events. In 1335 patients with STEMI, a total of 77 (5.7%) developed LVT over the follow-up period (median 25.0months). Of the patients diagnosed with LVT, 31 patients were started on triple therapy with VKA, 33 patients on triple therapy with rivaroxaban. There was a consistent similarity in LVT resolution with rivaroxaban application compared to VKA application during the follow-up period [HR (log-rank test) 1.57(95% CI 0.89-2.77), p = 0.096; Adjusted HR 1.70(95% CI 0.90-3.22), p = 0.104]. Triple therapy with rivaroxaban showed quicker resolution than with VKA (6months: p = 0.049; 12months: p = 0.044; 18months: p = 0.045). Similar risks of ISTH bleeding were not significantly different between the 2 groups [VKA 9.7% vs Rivaroxaban 6.1%, Adjusted HR 0.48 (95% CI 0.73-3.20); p = 0.444)]. Fewer net adverse clinical events (NACE) were observed in the rivaroxaban group [VKA 58.1% vs Rivaroxaban 24.2%; HR (log-rank test) 0.31(95% CI 0.14-0.68), p = 0.003; Adjusted HR 0.23(95% CI 0.09-0.57), p = 0.001]. In the observational study, triple therapy with rivaroxaban has similar and quicker LVT resolution in patients with LVT after STEMI, compared with triple therapy with VKA, and perhaps was associated with a better clinical benefit. Larger sample sizes and randomized controlled trials are needed to confirm this observation.

Procedural outcomes in patients with dual versus single antiplatelet therapy prior to transcatheter aortic valve replacement

The impact of uninterrupted dual antiplatelet therapy (DAPT) on bleeding events among patients undergoing transcatheter aortic valve replacement (TAVR) has not been well studied. We conducted an analysis of 529 patients who underwent transfemoral TAVR in our centre and were receiving either DAPT or single antiplatelet therapy (SAPT) prior to the procedure. Accordingly, patients were grouped into a DAPT or SAPT group. Following current guidelines, patients in the SAPT group were switched to DAPT for 90 days after the procedure. The primary endpoint of our analysis was the incidence of bleeding events at 30 days according to the VARC-2 classification system. Any VARC-2 bleeding complications were found in 153 patients (28.9%), while major/life-threatening or disabling bleeding events occurred in 60 patients (11.3%). Our study revealed no significant difference between the DAPT vs. SAPT group regarding periprocedural bleeding complications. Based on multivariable analyses, major bleeding (HR 4.59, 95% CI 1.64–12.83, p = 0.004) and life-threatening/disabling bleeding (HR 8.66, 95% CI 3.31–22.65, p < 0.001) events were significantly associated with mortality at 90 days after TAVR. Both pre-existing DAPT and SAPT showed a comparable safety profile regarding periprocedural bleeding complications and mortality at 90 days. Thus, DAPT can be safely continued in patients undergoing transfemoral TAVR.

Meta-Analysis of Usefulness of Antiplatelet Therapy in Ischemic Stroke or Transient Ischemic Attack

The efficacy of early administration of dual antiplatelet therapy (DAPT) for secondary prevention after acute ischemic stroke or transient ischemic attack (TIA) is uncertain. This systematic review and meta-analysis compares the safety and efficacy of early administration (<24 hours) of DAPT (using either clopidogrel or ticagrelor with aspirin) versus single antiplatelet therapy (SAPT; aspirin alone) in acute non-cardioembolic ischemic stroke or TIA, incorporating data from large randomized controlled trials. Published trials fulfilling our criteria were identified from an electronic search of MEDLINE, with key words including: "clopidogrel or ticagrelor", "aspirin", "ischemic stroke", "transient ischemic attack", and "randomized controlled trial". Included were 3 randomized controlled trials of 21,067 patients assessing early administration (<24 hours from symptom onset) of DAPT versus SAPT in non-cardioembolic acute ischemic stroke or TIA. Our efficacy outcomes were ischemic stroke and all-cause mortality. Our safety outcome was severe bleeding. We performed a meta-analysis to pool results with a hierarchical Bayesian random-effects model. Dual antiplatelet therapy significantly reduced the risk of ischemic stroke (hazard ratio [HR], 0.73; 95% credible interval [CrI]: 0.54, 0.97), while increasing the risk of severe bleeding (HR, 2.48; 95% CrI: 1.07, 5.26). There was a non-significant numerical trend toward increased mortality with DAPT (HR, 1.29; 95% CrI: 0.73, 2.23). These observations were robust under the sensitivity analysis. In the present systematic review and meta-analysis of randomized controlled trials, DAPT reduced the risk of ischemic stroke at the cost of an increase in severe bleeding. Additional trials examining the ideal timing of DAPT administration are needed to thoroughly investigate the role, if any, of routine DAPT in patients with non-cardioembolic ischemic stroke or high-risk TIA.

Percutaneous dilatational tracheotomy in high-risk ICU patients

Abstract Funding Acknowledgements Type of funding sources: None. Background Percutaneous dilatational tracheotomy (PDT) has become an established procedure in cardiac intensive care units (ICU). However, the safety of this method has been under debate given the growing number of critically ill patients with high bleeding risk receiving anticoagulation, dual antiplatelet therapy (DAPT) or even a combination of both, i.e. triple therapy. There is a need for critical evaluation of these safety concerns. This is the first and largest international, multicenter study on PDT to date including such a high proportion of patients on antithrombotic therapy investigating whether PDT in high-risk ICU patients is associated with elevated procedural complications and analysing risk factors for bleeding occurring during and after PDT. Methods PDT interventions conducted in ICUs at 12 European sites between January 2016 and October 2019 were retrospectively analysed for procedural complications. For subgroup analyses, patient stratification into clinically relevant risk groups based on anticoagulation and antiplatelet treatment regimens was performed. Procedure-related complications for each risk group were analysed until hospital discharge. Additionally, predictors of bleeding occurrence were analysed by uni- and multivariable regression models. Results In total, 671 patients receiving PDT according to Ciaglia’s technique with accompanying bronchoscopy were included. Patients were stratified into seven clinically relevant antithrombotic treatment groups. Within the whole cohort, 74 (11%) bleedings were reported to be procedure-related, none of which required surgical intervention. In almost all cases bleedings were associated with skin bleedings from the entry site and could easily be treated with minimally invasive stitching. Subgroup analysis showed no increase in the rate of procedure-related complications in patients with elevated body mass index. In a multivariable regression model bleeding occurrence during and after PDT was independently associated with platelet count (Odds ratio [OR] 0.73, 95% confidence interval [95% CI] [0.56, 0.92], p = 0.009), chronic kidney disease (OR 1.75, 95% CI [1.01, 3.03], p = 0.047) and previous stroke (OR 2.13, 95% CI [1.1, 3.97], p = 0.02). Neither PTT (OR 1.01, 95% CI [0.99, 1.02], p = 0.32), nor DAPT (OR 1.11, 95% CI [0.56, 2.04], p = 0.75) nor triple therapy (OR 0.93, 95% CI [0.49, 1.66], p = 0.82) were associated with bleeding risk. Conclusion In this international, multicenter study bronchoscopy-guided PDT was a safe and low-complication airway management option, even in a cohort of high risk for bleeding on cardiovascular ICUs. Platelet count, chronic kidney disease and previous stroke were identified as independent risk factors of bleeding during and after PDT whereas DAPT and triple therapy had no influence on bleeding events.

Impact of extended dual antiplatelet therapy on long-term prognosis in patients with acute coronary syndrome complicated with anemia: A sub-analysis of the real-world OPT-CAD study.

To evaluate the impact of extended dual antiplatelet therapy (DAPT) beyond 12 months on long-term prognosis in acute coronary syndrome (ACS) patients complicated with anemia undergoing percutaneous coronary intervention (PCI). Anemia is frequent among ACS patients and is associated with increased risk of adverse clinical outcomes. A total of 6,953 patients were enrolled from the Optimal anti Platelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD) study. A landmark analysis comparing extended DAPT versus single antiplatelet therapy (SAPT) at 12-24 months were performed in anemia patients without premature discontinuation of DAPT before 9months and major clinical adverse events within 12 months. The primary outcome was major adverse cardiovascular and cerebrovascular events (MACCE), defined as a composite of all-cause death, myocardial infarction, and stroke. Patients with anemia (n=1,728) had higher rates of MACCE, all-cause mortality, and BARC type 2, 3, 5 bleeding (p < .05) compared to those without anemia (n=5,225). Anemia patients received extended DAPT (n=1,010) were associated with a lower risk of stroke (0.3% vs. 1.8%; HR, 0.14; 95% CI, 0.03-0.71; p=.018) compared to those received SAPT (n=342). The rates of MACCE and all revascularization were lower in patients with extended DAPT, but the differences were not statistically significant. Risk of all-cause mortality and bleeding were comparable between the two groups. Extended DAPT beyond 12 months may reduce the incidence of stroke without increasing the risk of bleeding in anemic ACS patients who tolerate 12-month DAPT.

Abstract 12787: Meta-analysis of Dual Antiplatelet Theraphyversus Single Antiplatelet Theraphyafter Transcatheter Aortic Valve Implatation: A Popular Forecast

Background: Despite improving experience and techniques, ischemic and bleeding complications after transcatheter aortic valve implantation (TAVI) remain prevalent and affect survival. Recent guidelines recommend dual antiplatelet therapy (DAPT) in the initial period after TAVI. Explorative studies have suggested DAPT is associated with higher rate of major bleeding without a decrease in thromboembolic complications. Purpose: To compare DAPT (aspirin plus clopidogrel) versus single antiplatelet therapy (SAPT) (as aspirin) alone as antithrombotic treatment following TAVI for the prevention of cerebrovascular events, bleeding events and all-cause death. Methods: We systematically searched PubMed, Embase and Cochrane databases, in April 2020, for both interventional or observational studies comparing DAPT with (SAPT) following TAVI. Random-effects and meta-analysis for DAPT and SAPT were performed. Results: Nine studies were included (six registry-based or unrandomized studies and three randomized clinical trials) providing a total of 19389 patients, and 631 pooled stroke or transient ischemic attack. There was no statistically difference between DAPT and SAPT for the prevention of cerebrovascular events after TAVI (pooled OR 1.04 [0.85, 1.26], P=0.04, I 2 = 0%). Similarly, there was a similar rate of all-cause mortality (pooled OR 1.07 [0.81, 1.42], P=0.33, I 2 = 50%). Furthermore, the rate of major bleeding or life-threatening events was significantly higher for the DAPT compared with SAPT group (pooled OR 1.46 [1.19, 1.78], P&lt;0.01, I 2 = 79%), although with a considerable amount of heterogeneity between studies in the magnitude of effect. Conclusions: Our pooled data suggests that after TAVI, the clinical benefit of DAPT compared to SAPT is questionable. The POPular-TAVI trial Cohort A is expected to clarify this research question during 2020.

The 2020 breakthroughs in early secondary prevention: dual antiplatelet therapy versus single antiplatelet therapy.

Single antiplatelet therapy represents an established treatment in secondary prevention of ischemic strokes and transient ischemic attacks (TIAs). In contrast with coronary artery disease, the use of dual antiplatelet therapy (DAPT) for secondary prevention in patients with acute cerebral ischemia (ACI) remains under debate. In this narrative review, we present and analyse the most recent findings concerning the potential efficacy and safety of DAPT therapy after ischemic strokes or TIA. Following the publication of the three (CHANCE, POINT and THALES) large, randomized-controlled, clinical trials (RCTs) that showed efficacy of early DAPT for the secondary prevention after minor AIS or TIA, short-term DAPT use is becoming the most prevalent choice of treatment. Notably, DAPT is even more popular after AIS attributed to large artery atherosclerosis given randomized data from small RCTs supporting the use of DAPT in patients with extracranial or intracranial atherosclerosis and microembolization detected by transcranial Doppler. Recent subanalysis of data from the randomized trials aim to identify specific patient subgroups, which are determined by genetic, imaging or clinical characteristics, and for whom DAPT appears to be more beneficial. The potential role of different antiplatelet agents (aspirin, clopidogrel, ticagrelor) is also discussed. DAPT has recently proven its efficacy for the early secondary prevention of AIS patients with minor stroke severity and high-risk TIA patients. However, the length of DAPT is still controversial, as well as the individualized selection of AIS or TIA patients with the lower risk of bleeding and with the greater benefit in prevention of ischemic cerebrovascular and cardiovascular events.