Dual Antiplatelet Therapy Group Research Articles

Abstract 9424: Single versus Dual Antiplatelet Therapy for Stroke Prevention Following Left Atrial Appendage Occlusion in Patients With High Bleeding Risk

Introduction: The optimal antiplatelet therapy following Left atrial appendage occlusion (LAAO) in atrial fibrillation patients who are not candidates for long-term oral anticoagulation therapy (OAC) is subject to debate. Hypothesis: Is single antiplatelet therapy (SAPT) safe and effective when compared to dual antiplatelet therapy (DAPT) in patients with high bleeding risk? Methods: We conducted a comprehensive search for all studies that compared the use of SAPT with DAPT following LAAO for patients in whom OAC is deemed highly risky or contraindicated. The outcomes of our study were device-related thrombosis (DRT), stroke and systemic embolization (SSE), and major bleeding (MB). The risk ratio (RR) with 95% confidence intervals (CIs) are presented as summary statistics and were calculated using a random-effects model. Results: A total of 15 observational studies with 3231 patients (SAPT, n=1036; DAPT, n=2195; 64.5% men; median follow-up duration 12 months; mean age 74.7±8.5 years; CHA2DS2-VASc score 4.3±1.6; HASBLED score 3.2±1.2) were included. For DRT, data were available from 10 studies (2910 patients); there was no difference between SAPT and DAPT groups (2.6% vs. 2.3%; RR: 1.41; 95%CI: 0.77-2.59; P=0.26; I 2 :0%). For SSE (8 studies, 959 patients); although numerically more events were observed in the SAPT group, there was no statistical difference between the two groups in the pooled analysis (2.9% vs. 1.5%; RR: 5.43; 95%CI: 0.74-39.81; P=0.1; I 2 :78%). Finally, for MB (8 studies, 1818 patients); although numerically more events were observed in the DAPT group, there was no statistical difference between the two arms (2.3% vs. 3.2%; RR: 1.90; 95%CI: 0.46-7.87; P=0.37; I 2 :72%). Conclusions: Our study showed comparable safety and efficacy profiles for SAPT and DAPT after LAAO. Adequately powered randomized studies determining the optimal antithrombotic therapy in the first weeks after LAAO are warranted in patients at high risk for bleeding.

Abstract 9672: Antiplatelet Therapy and Covid-19 Outcomes in Patients With Stable Coronary Artery Disease

Introduction: Severe COVID-19 can cause acute respiratory distress syndrome (ARDS), with pulmonary pathology composed of platelet microthrombi. Antiplatelet agents have been investigated as a treatment in ARDS, but without clear evidence of benefit. The decision on antiplatelet use in patients with COVID-19 and coronary artery disease (CAD) is key. Hypothesis: We assessed the hypothesis that increased use of antiplatelet therapy was associated with no worse clinical outcomes in COVID-19 among adults with stable CAD. Methods: We performed a retrospective cohort study of patients who presented with COVID-19 to two New York City hospitals from March 3 to May 15, 2020. Patients were separated into groups based on antiplatelet use, including no outpatient antiplatelet use, monotherapy, and dual antiplatelet therapy (DAPT). Outcomes and complications were compared among the groups, using propensity scoring with inverse probability of treatment weighting. Results: This study included 315 patients with stable CAD and COVID-19. Patients on no outpatient antiplatelet therapy were significantly older and more likely to be taking anticoagulation, while patients on DAPT had the highest rates of diabetes and chronic kidney disease. The most prescribed antiplatelet in the cohort was aspirin (72.1%) followed by clopidogrel (22.5%). There was no difference in COVID-19 admission mortality between the DAPT and monotherapy groups (DAPT 27.9%, monotherapy 27.2%, p=NS). Patients on DAPT had decreased rates of venous thromboembolism compared to monotherapy (DAPT 0.0%, monotherapy 6.4%, p=0.01), and bleeding rates were similar. The rate of home monotherapy continuation in hospital was 79.9%, with the most common reasons for discontinuation being hemorrhage, anemia, and thrombocytopenia. No outpatient antiplatelet use was a high-risk group, with the highest rates of intensive care admissions, intubations and mortality. Conclusions: In conclusion, we found no difference in COVID-19 outcomes for CAD patients on DAPT compared to those on monotherapy. There were decreased clotting complications in patients on more antiplatelet therapy, while bleeding rates were similar. No outpatient antiplatelet use was found to be a high-risk group in COVID-19.

Abstract 13859: Efficacy and Safety of Ticagrelor Monotherapy versus Dual Antiplatelet Therapy After Percutaneous Coronary Intervention With Drug Eluting Stent in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Introduction: Dual AntiplateletTherapy(DAPT) with aspirinanda P2Y12inhibitoris the currentstandardofcareforthe preventionofthromboticeventsinpatientsundergoingpercutaneouscoronaryintervention(PCI). Type2Diabetes Mellitus (DM) patientsare a subgroupofpopulationwith higher risk ofbleedinganddevelopmentofthromboticeventsafter PCI. There is currentlylimited data onthe efficacy andsafety ofTicagrelormonotherapyinterms of bleeding and thrombotic event risk aftera short-course DAPT among DM patients undergoing PCI. Methods: A comprehensiveandrelevantsearch ofrandomizedcontrolledtrials (RCT) was conducted.Outcomemeasures formajorbleeding,myocardialinfarctionandall-cause mortalitywere extracted andanalyzedusingarandom effects model via Review Manager V5.3. Results: A totalofthree RCTs, with 7482subjects were analyzed.There were nosignificantdifferencesinmajorbleeding(p=0.26)andmyocardialinfarction(p=0.66)eventsbetweenthe TicagrelorandDAPT groups.However,there was a higher rate ofall-cause mortalityinthe DAPT group,which was statistically significant(RR 0.76[95%CI:0.59-0.98], p=0.03). Figure 1 Forestplotcomparison: Ticagrelor Monotherapyversus DAPT onBleedingRisk usingthe BleedingAcademic Research Consortium (BARC) 3 to 5 Figure 2 Forest plot comparison: Ticagrelor Monotherapyversus DAPT onAll Cause Mortality Figure 3 Forest plot comparison:Ticagrelor Monotherapyversus DAPT on Myocardial Infarction Conclusion: TicagrelormonotherapyandDAPT have similar rates ofmajorbleedingandmyocardialinfarctionamongDM patientsundergoingPCI with DES after initialshort-courseDAPT. However, DAPT strategy had a higherincidenceofall-cause mortality, which suggests that Ticagrelormonotherapymay be a preferableantiplateletstrategyin DM patients undergoing PCI.

P2Y12 Inhibitors Exacerbate Low-dose Aspirin-induced Small Bowel Injury in Dual Antiplatelet Therapy.

Objective Antithrombotic drugs are being used increasingly frequently to prevent cardiovascular diseases. Few studies have evaluated small bowel mucosal injury induced by dual antiplatelet therapy (DAPT). The aim of the present study was to evaluate small bowel mucosal injury induced by DAPT compared with other antithrombotics using video capsule endoscopy (VCE). Methods The study included chronic users of antithrombotics who underwent VCE for obscure gastrointestinal bleeding between January 2007 and July 2018. We evaluated the instances of small bowel injury classified into erosions and ulcers. Results Overall, 183 patients (114 men and 69 women; mean age, 73.6 years old) were enrolled, and the study groups comprised 49 patients taking low-dose aspirin (LDA) only, 50 taking anticoagulants only, 37 being treated with DAPT, 33 on combined LDA and anticoagulants, and 14 taking P2Y12 inhibitors. Small bowel erosions and ulcers were most frequently observed in the DAPT group, with frequencies of 78.4% and 37.8%, respectively. Exacerbating factors of small bowel ulcers were DAPT [odds ratio (OR) 3.0, 95% confidence interval (CI) 1.2-7.7] and age over 80 years old (OR 2.4, 95% CI 1.1-5.4). Conclusion P2Y12 inhibitors seem to exacerbate LDA-induced small bowel injury. Preventive strategies for small bowel injury induced by LDA, especially DAPT, are urgently required.

Early argatroban and antiplatelet combination therapy in acute non-lacunar single subcortical infarct associated with mild intracranial atherosclerosis

BackgroundPatients with acute non-lacunar single subcortical infarct (SSI) associated with mild intracranial atherosclerosis (ICAS) have a relatively high incidence of early neurological deterioration (END), resulting in unfavorable functional outcomes. Whether the early administration of argatroban and aspirin or clopidogrel within 6–12 h after symptom onset is effective and safe in these patients is unknown.MethodsA review of the stroke database of Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University and Qingdao Center Hospital, Qingdao University Medical College in China was undertaken from May 2017 to January 2020 to identify all patients with non-lacunar SSI caused by ICAS within 6–12 h of symptom onset based on MRI screening. Patients were divided into two groups, one comprising those who received argatroban and mono antiplatelet therapy with aspirin or clopidogrel on admission (argatroban group), and the other those who received dual antiplatelet therapy (DAPT) with aspirin and clopidogrel during hospitalization (DAPT group). The primary outcome was recovery by 90 days after stroke based on a modified Rankin scale (mRS) score (0 to 1). The secondary outcome was END incidence within 120 h of admission. Safety outcomes were intracranial hemorrhage (ICH) and major extracranial bleeding. The probability of clinical benefit (mRS score 0–1 at 90 days) was estimated using multivariable logistic regression analysis.ResultsA total of 304 acute non-lacunar SSI associated with mild ICAS patients were analyzed. At 90 days, 101 (74.2%) patients in the argatroban group and 80 (47.6%) in the DAPT group had an mRS score that improved from 0 to 1 (P < 0.001). The relative risk (95% credible interval) for an mRS score improving from 0 to 1 in the argatroban group was 1.50 (1.05–2.70). END occurred in 10 (7.3%) patients in the argatroban group compared with 37 (22.0%) in the DAPT group (P < 0.001). No patients experienced symptomatic hemorrhagic transformation.ConclusionsEarly combined administration of argatroban and an antiplatelet agent (aspirin or clopidogrel) may be beneficial for patients with non-lacunar SSI associated with mild ICAS identified by MRI screening and may attenuate progressive neurological deficits.Trial registrationOur study is a retrospectively registered trial.

Antithrombotic strategy and its relationship with outcomes in patients with atrial fibrillation and chronic coronary syndrome.

This study aimed to explore antithrombotic strategy and its relationship with outcomes in patients with atrial fibrillation (AF) at high risk for stroke and chronic coronary syndrome (CCS) in real-world clinical practice. Patients with AF at high risk for stroke complicated with CCS from China Atrial Fibrillation Registry (CAFR) were enrolled. The patients were divided into non-antithrombotic (Non-AT) group, oral anticoagulants (OAC) group, antiplatelet therapy (APT) group (aspirin or clopidogrel), and dual antiplatelet therapy (DAPT) group (aspirin + clopidogrel) according to their antithrombotic strategies at baseline. The patients with OAC + single antiplatelet drug (14 cases) and OAC + dual antiplatelet therapy (7 cases) were excluded for the small sample size. The primary effectiveness outcome was the composite outcome of coronary events, thromboembolism, and all-cause mortality. The primary safety outcome was major bleeding events. From 2011 to 2018, 25,512 patients were included in the CARF study, 769 patients with AF at high risk for stroke and CCS were enrolled in this study. After a follow-up of 47.4 ± 25.3months, the incidences of primary effectiveness outcome were 44.6%, 25.7%, 43.6%, and 29.1% in the four groups, respectively (P < 0.001). The incidences of primary effectiveness and all-cause mortality were both significantly lower in the OAC group than in the Non-AT group, (25.7% vs. 44.6%, HR 0.53, 95% CI 0.39-0.73, P < 0.001) and (14.6% vs. 38.5%, HR 0.36, 95%CI 0.25-0.52, P < 0.001). In multivariate analysis, age (HR 1.03, 95%CI 1.01-1.05, P = 0.015), heart failure (HR 1.67, 95%CI 1.20-2.33, P = 0.002) and OAC (HR 0.66, 95%CI 0.47-0.91, P = 0.012) were independent factors for the composite outcome. There was no significant difference in major bleeding events between the four groups. OAC monotherapy significantly reduced the primary effectiveness composite outcome and all-cause mortality in the patients with AF at high risk for stroke complicated with CCS. However, there was no significant difference in major bleeding among the different antithrombotic strategies.Trial Registration www.chictr.org.cn (No. ChiCTR-OCH-13003729).

Effects of single versus dual antiplatelet therapy on the adverse events after transcatheter aortic valve implantation: A meta-analysis.

Dual antiplatelet therapy (DAPT) was currently recommended for transcatheter aortic valve implantation (TAVI) postoperative management in clinical application. However, POPular‐TAVI trial showed DAPT increased the incidence of adverse events compared to single antiplatelet therapy (SAPT). Herein, we performed a meta‐analysis to investigate the effect of SAPT versus DAPT on the adverse events after TAVI. Eleven studies were available from PubMed, Embase, Cochrane Library, and Web of Science from inception to April 1, 2021. The pooled effect size was presented as relative risk (RR) with 95% confidence intervals (CIs). The sensitivity analysis was used to assess the stability of analysis results, and Begg's test was applied to evaluate the publication bias. The Cochran Q test and the I 2 statistic were used to evaluate the heterogeneity, and the source of heterogeneity was explored by meta‐regression. A total of 4804 patients were obtained, with 2257 in SAPT group and 2547 in DAPT group. Compared to the DAPT, SAPT was associated with the decreased risk of all‐cause bleeding (RR: 0.51, 95% CI: 0.44–0.61), major bleeding (RR: 0.53, 95% CI: 0.32–0.86), and minor bleeding (RR: 0.58, 95% CI: 0.34–0.98). There were no significant differences in mortality and myocardial infarction events, stroke events, and acute kidney injury between the two groups. SAPT was superior to DAPT in decreasing all‐cause bleeding, major bleeding, and minor bleeding, suggesting that SAPT could be preferentially recommended for TAVI postoperative management in most patients without another indication for DAPT and oral anticoagulation.

Evaluation of management strategies in patients with coronary ectasia: a retrospective cohort study

Abstract Background/Introduction Since patients with coronary ectasia have an increased risk of developing myocardial infarction and cardiovascular death, these patients could benefit from a more intensive treatment. Unfortunately, the evidence regarding outcomes with different management strategies is limited, especially with direct oral anticoagulants (DOAC). Purpose To compare clinical outcomes in patients with coronary ectasia based on the selected/chosen treatment strategy. Methods We conducted a retrospective cohort study in patients diagnosed with coronary artery ectasia. They were divided into 3 different groups based on the treatment they received at discharge and we evaluated the main cardiovascular outcomes at one-year follow-up. Results Between 2016 and 2019, 7,579 angiographies were performed, in which 510 patients with coronary ectasia were found (prevalence of 6.72%). Of these patients, 43.9% (n=224) had the diagnosis of STEMI, 21% NSTEMI (n=107), 5.1% unstable angina (n=26), 18.6% chronic stable angina (n=95) and other 11.4% (n=58). The angiographic distribution of the lesions was as follows: left main coronary artery 25.1%, Left descending coronary artery 62.7%, circumflex artery 52.1%, right coronary artery 79.2%. It was possible to obtain the follow-up of 363 patients (71.2%) because 25 died during their hospitalization and data of 122 were not available at the time of analysis. Three groups were formed based on the treatment: (1) Dual Antiplatelet Therapy (DAPT) in 47% (n=174); (2) DAPT + Vitamin K Antagonist (VKA) in 8.5% (n=31); (3) DAPT + DOAC in 6.6% (n=24). The overall MACE rate at 1-year of follow-up was 6.6% (n=15): 11 patients in the DAPT group (6.3%), 1 patient in the DAPT + VKA group (3.2%), and 3 patients in the DAPT + DOAC group (12.5%). During this period, 3 patients died from cardiovascular causes, all of them in the DAPT group. Myocardial infarction occurred in 12 patients, 8 in the DAPT group (4.2%), 1 in the DAPT + VKA group (3.2%) and 3 in the DAPT + DOAC group (12.5%). Stroke occurred in 2 patients: 1 patient in the DAPT group (0.5%) and 1 patient in the DAPT + DOAC group, 4.1% None of these findings were statistically significant. One-year occurrence of bleeding events was also evaluated: 23 patients presented a bleeding event, 14 in the DAPT group (8%), 7 in the DAPT + VKA group (22.5%) and 2 in the DAPT + DOAC group (8.3%); p=0.010. Conclusion(s) Our findings suggest that there is no statistically significant difference in the incidence of thrombotic complications, when comparing the treatment options. Patients using the combination of DAPT+VKA have a higher incidence of bleeding. Funding Acknowledgement Type of funding sources: None.

Dual antithrombotic therapy on early clinical outcomes in patients with atrial fibrillation after percutaneous coronary intervention: a nationwide study in the era of NOAC

Abstract Background/Introduction Recent evidence has confirmed low bleeding risk with double antithrombotic therapy, combining oral anticoagulant (OAC) and single platelet inhibitor, in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). Among the Asian AF population, most of the patients received dual antiplatelet therapy (DAPT) without OACs, even after the introduction of non-vitamin K oral anticoagulants (NOACs). Purpose The current nationwide study assessed 3-month ischemic and bleeding risks of DAPT in comparison to triple antithrombotic therapy among the Korean AF population undergoing PCI. Methods We analyzed the claims records of 11,039 patients (mean age 70 years, 66.3% male, and mean CHA2DS2-VASc score 3.2) between 2013 to 2018. Patients were categorized into triple therapy group with vitamin K antagonists (VKAs-TT), or NOACs (NOACs-TT), and DAPT group according to the antithrombotic therapy after PCI. 3-month risks of ischemic stroke, non-fatal myocardial infarction, any in-hospital death, and major bleeding were compared between groups after baseline adjustment using inverse probability weighting. Results A total of 1,786, 1,997, and 7,256 patients were allocated to the VKAs-TT, NOACs-TT, and DAPT groups. The DAPT group had a higher prevalence of prior MI and coronary revascularization, but had lower thromboembolic and bleeding risks than the triple antithrombotic therapy groups (mean CHA2DS2-VASc score 3.8, 4.1, and 3.5; and mean HAS-BLED score 3.3, 3.4, and 3.1 for VKAs-TT, NOACs-TT, and DAPT groups, respectively). The NOACs-TT group was associated with a lower risk of ischemic stroke (hazard ratio [HR] 0.38, 95% confidence interval [CI] 0.20–0.70) and any in-hospital death (HR 0.70, 95% CI 0.49–0.98) compared with the VKAs-TT group. The DAPT group showed a lower risk of ischemic stroke (HR 0.41, 95% CI 0.27–0.63) and major bleeding (HR 0.55, 95% CI 0.37–0.84) than the VKAs-TT group, especially in patients without prior OAC treatment. The DAPT group showed a comparable ischemic risk against the NOACs-TT group, although the risk of major bleeding was lower in the DAPT group, especially among old age (HR 0.47, 95% CI 0.29–0.78) or OACs-naive patients (HR 0.50, 95% CI 0.29–0.86). Conclusion Among the Asian AF population, using short-term DAPT for 3-month after PCI was associated with a lower risk of bleeding without increasing ischemic risk compared to triple antithrombotic therapy with OAC. This may be a therapeutic option in very high bleeding risk patients who have had complex PCI necessitating focus on DAPT in the initial 3 month period. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): This study was supported by grant no 3020200200 from the Seoul National University Hospital Research Fund, by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health &amp; Welfare, Republic of Korea, the Ministry of Food and Drug Safety) (Project Number: 202013B14), and by the Korea National Research Foundation funded by the Ministry of Education, Science and Technology (grant 2020R1F1A106740). Figure 1Figure 2

Dual-Antiplatelet Therapy May Not Be Associated With an Increased Risk of In-hospital Bleeding in Patients With Moderate or Severe Ischemic Stroke.

Background and Purpose: Dual antiplatelet therapy (DAPT), compared to single antiplatelet therapy (SAPT), lowers the risk of stroke or death early after TIA and minor ischemic stroke. Prior trials excluded moderate to severe strokes, due to a potential increased risk of bleeding. We aimed to compare in-hospital bleeding rates in SAPT and DAPT patients with moderate or severe stroke (defined by NIHSS ≥4).Methods: We performed a retrospective cohort study of ischemic stroke over a 2-year period with admission NIHSS ≥4. The primary outcome was symptomatic intracranial hemorrhage (ICH) with any change in NIHSS. Secondary outcomes included systemic bleeding and major bleeding, a composite of serious systemic bleeding and symptomatic ICH. We performed analyses stratified by stroke severity (NIHSS 4–7 vs. 8+) and by preceding use of tPA and/or thrombectomy. Univariate followed by multivariate logistic regression evaluated whether DAPT was independently associated with bleeding.Results: Of 377 patients who met our inclusion criteria, 148 received DAPT (39%). Symptomatic ICH was less common with DAPT compared to SAPT (0.7 vs. 6.4%, p < 0.01), as was the composite of major bleeding (2.1 vs. 7.6%, p = 0.03). Symptomatic ICH was numerically less frequent in the DAPT group, but not statistically significant, when stratified by stroke severity (NIHSS 4–7: 0 vs. 5.9%, p = 0.06; NIHSS 8+: 1.5 vs. 6.6%, p = 0.18) and by treatment with tPA and/or thrombectomy (Yes: 2.6 vs. 9.1%, p = 0.30; No: 0 vs. 2.9%, p = 0.25). DAPT was not associated with major bleeding in either the univariate or the multivariate regression.Conclusions: In this single center cohort, symptomatic ICH and the composite of serious systemic bleeding and symptomatic ICH was rare in patients on DAPT. Relative to single antiplatelet therapy DAPT was not associated with an increased risk of in-hospital bleeding in patients with moderate and severe ischemic stroke.

Treatment Pattern of Antithrombotic Therapy over Time after Percutaneous Coronary Intervention in Patients with Atrial Fibrillation in Real-World Practice in Korea.

We examined antithrombotic treatment patterns with clinical characteristics and therapy changes over time in patients with atrial fibrillation (AF) after percutaneous coronary intervention (PCI). Using the Health Insurance Review and Assessment service claims database (01JAN2007-30NOV2016) in Korea, we included adult patients with AF and PCI: (1) who underwent PCI with stenting between 01JAN2008 and 30NOV2016; (2) with ≥1 claim for AF (ICD code: I48) (3) with antithrombotics 1 day prior to or at the date of PCI; and (4) with CHADS2-VASc of ≥2. In this study, 7749 patients with AF who underwent PCI, triple therapy, dual therapy, dual antiplatelet therapy (DAPT), and single antiplatelet therapy were prescribed to 24.6%, 3.4%, 60.8%, and 11.0%, respectively. In the triple therapy group, 23.1% persisted with triple therapy for 12 months, whereas the remaining patients switched to a different therapy. In the entire cohort and several subgroups, the median treatment duration of triple therapy was 55–87 days. DAPT use for 12 months was the most common treatment pattern (62.6%) in the DAPT group (median treatment duration, 324–345 days). A significant discrepancy exists between the current guidelines and real-world practice regarding antithrombotic treatment with PCI for patients with AF. Appropriate use of anticoagulants should be emphasized.

Does preoperative dual antiplatelet therapy affect bleeding and mortality after total arch repair for acute type A dissection?

Data are scarce and mixed regarding the impact of preoperative dual antiplatelet therapy (DAPT) on the surgical outcomes of acute type A aortic dissection (ATAAD). We seek to evaluate the impact of DAPT on bleeding-related events and early- and mid-term mortality after total arch replacement and frozen elephant trunk in such patients. This study comprised 48 ATAAD patients on preoperative DAPT and 418 without DAPT (the whole series, i.e. unmatched cohort), from which 45 matched pairs were selected by propensity score (matched cohort). Bleeding-related events (reoperation for bleeding, bleeding of ≥1500 ml within the first 12 h postoperatively or transfusion of ≥10 units of red blood cell or use of recombinant activated factor VII), operative mortality and mid-term survival were compared in the unmatched and matched cohorts. The impact of preoperative DAPT was evaluated with multivariable analysis. In the unmatched cohort, bleeding of ≥1500 ml/12 h postoperatively was more common in the DAPT group (18.8% vs 8.4%, P = 0.020); operative mortality was 9.7%, which did not differ with DAPT (12.5% vs 9.3%, P = 0.48). Nor did bleeding-related events (54.2% vs 43.5%, P = 0.16) differ significantly between 2 groups. In the matched cohort, neither were drainage of ≥1500 ml/12 h (20% vs 6.7%, P = 0.063) and bleeding-related events (53.3% vs 42.2%, P = 0.30), nor operative mortality (13.8 vs 8.9%, P = 0.50) and mid-term survival (79.3% vs 76.4%, P = 0.93) significantly different between 2 groups. DAPT was not identified as a predictor for operative mortality [odd ratio (OR) 0.97, 95% confidence interval (CI) 0.31-3.08; P = 0.96; adjusted OR 1.28, 95% CI 0.22-7.20; P = 0.78] and bleeding-related events (OR 1.50, 95% CI 0.76-2.95; P = 0.24; adjusted OR 2.03, 95% CI 0.80-3.66; P = 0.14). In patients with ATAAD undergoing total arch replacement and frozen elephant trunk, although preoperative DAPT led to more postoperative bleeding, it did not increase bleeding-related events nor operative mortality nor mid-term death. The results of this study imply that for patients with ATAAD, emergency surgical repair, even if as extensive as total arch repair, should not be contraindicated or delayed simply because of ongoing DAPT.

Dual Antiplatelet Therapy Using Cilostazol With Aspirin or Clopidogrel: Subanalysis of the CSPS.com Trial.

Although dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduces the recurrence of ischemic stroke while significantly increasing the bleeding events compared with monotherapy, the CSPS.com trial (Cilostazol Stroke Prevention Study combination) showed that DAPT using cilostazol was more effective without the bleeding risk. In the CSPS.com trial, aspirin or clopidogrel was used as the underlying antiplatelet drug. The effectiveness and safety of each combination were examined and clarified. In the CSPS.com trial, a multicenter, open-label, randomized controlled study, patients with high-risk, noncardioembolic ischemic stroke 8 to 180 days after onset treated with aspirin or clopidogrel alone at the discretion of the physician in charge were recruited. Patients were randomly assigned to receive either monotherapy or DAPT using cilostazol and followed for 0.5 to 3.5 years. The primary efficacy outcome was first recurrence of ischemic stroke. The safety outcome was severe or life-threatening bleeding. The analysis was based on the underlying antiplatelet agents. A total of 763 patients taking aspirin and 1116 taking clopidogrel were included in the intention-to-treat analysis. Although the clopidogrel group had more risk factors than the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the 2 groups. In the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the DAPT group and the aspirin-monotherapy group. In the clopidogrel group, the primary end point occurred at a rate of 2.31 per 100 patient-years in the DAPT group and 5.19 per 100 patient-years in the clopidogrel-monotherapy group (hazard ratio, 0.447 [95% CI, 0.258–0.774]). Safety outcome did not differ significantly between groups (0.51 per 100 patient-years versus 0.71 per 100 patient-years, respectively; hazard ratio, 0.730 [95% CI, 0.206–2.588]). The combination of cilostazol and clopidogrel significantly reduced the recurrence of ischemic stroke without increasing the bleeding risk in noncardioembolic, high-risk patients. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000012180.

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.

Molecular and metabolic characteristics of changes in the platelet sensitivity to antiplatelet therapy in patients with coronary artery disease before and after coronary artery bypass grafting

Aim. To study the production of reactive oxygen species (ROS) by platelets in patients with coronary artery disease (CAD) before and after coronary artery bypass grafting (CABG), depending on their sensitivity to acetylsalicylic acid (ASA) as a part of ASA monotherapy and dual antiplatelet therapy (DAPT) (ASA+clopidogrel).Material and methods. The study included 104 patients with CAD (ASA monotherapy, 64 patients; DAPT, 40 patients). From day 1 after CABG, they took 100 mg a day of enteric-coated ASA. In the DAPT group, clopidogrel was prescribed for 2-3 days after CABG. All measurements were performed before surgery, on the 1st day and days 8-10 after surgery. Control group consisted of 36 healthy donors. Resistance to ASA was determined at a level of optical platelet aggregation with arachidonic acid &gt;20% at least at one observation point. The spontaneous and ADP-induced chemiluminescence (CL) of platelets with luminol and lucigenin was assessed according to the following parameters: time to maximum intensity (Tmax), maximum intensity (Imax), area (S) under the CL curve, and the ratio of ADP-induced CL S to spontaneous CL S.Results. Throughout the study, 71 patients with CAD were sensitive to ASA (sASA) (ASA monotherapy, 46 patients; DAPT, 25 patients), three patients — resistant (rASA) (ASA monotherapy, 1; DAPT, 2). Sensitivity of other 30 patients (ASA monotherapy, 17; DAPT, 13) changed in different follow-up periods. Compared to the control group, sASA patients had increased values of platelet CL parameters throughout the study, while in the rASA group (ASA monotherapy), Tmax was higher before CABG, and in the rASA group (ASA therapy+clopidogrel), Imax and S were higher on the first day after CABG, while Imax — on days 8-10 after CABG. Compared to sASA, the values of S and Imax before CABG, Imax after CABG, as well as Imax and S on the days 8-10 after CABG in rASA (ASA monotherapy) were significantly lower, while in rASA (ASA therapy+clopidogrel), only the Tmax values were lower on the 8-10 days after CABG.Conclusion. In patients with CAD, depending on the sensitivity to ASA and antiplatelet therapy after CABG, the metabolic activity of platelets in terms of ROS production differs. In sASA patients, ROS synthesis is higher than in healthy individuals, while, in rASA patients (ASA monotherapy), platelets produce ROS levels lower than in sASA. CABG surgery and the addition of clopidogrel to ASA therapy leads to increased ROS production in rASA patients in the postoperative period.

Impact of preprocedural coronary flow grade on duration of dual antiplatelet therapy in acute myocardial infarction

We investigated the impact of pre-percutaneous coronary intervention (pre-PCI) thrombolysis in myocardial infarction (TIMI) flow grade (pre-TIMI) on 3-month (3-mo) and 12-mo of dual antiplatelet therapy (DAPT) in patients with acute myocardial infarction (AMI). This was a post hoc analysis of the TICO trial. A total of 2083 patients with AMI (pre-TIMI 0/1: n = 1143; pre-TIMI 2/3: n = 940) were evaluated. The primary outcome was the occurrence of net adverse clinical events (NACE), defined as a composite of TIMI major bleeding and major adverse cardiac and cerebrovascular events (MACCE) within 12-mo following PCI. The secondary outcomes were the occurrence of the individual components of TIMI bleedings and MACCE. In the pre-TIMI 0/1 group, the primary and second outcomes were not significantly different between the 3-mo and 12-mo DAPT groups. However, in the pre-TIMI 2/3 group, the occurrences of TIMI minor (adjusted hazard ratio [aHR]: 0.294; p = 0.016) and major or minor bleeding (aHR: 0.483; p = 0.014) on intention-to-treat analysis were significantly higher in the 12-mo than in the 3-mo DAPT group. The occurrence of MACCE was similar between the two groups. A higher bleeding tendency in 12-mo DAPT compared with 3-mo DAPT was more obvious in the pre-TIMI 2/3 group than in the pre-TIMI 0/1 group.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02494895.

Effects of Prolonged Dual Antiplatelet Therapy in ST-Segment Elevation vs. Non-ST-Segment Elevation Myocardial Infarction.

The benefits and risks of prolonged dual antiplatelet therapy (DAPT) have not been studied extensively across a broad spectrum of acute coronary syndromes. In this study we investigated whether treatment effects of prolonged DAPT were consistent in patients presenting with ST-segment elevation myocardial infarction (STEMI) vs. non-STEMI (NSTEMI). As a post hoc analysis of the SMART-DATE trial, effects of ≥12 vs. 6 months DAPT were compared among 1,023 patients presenting with STEMI and 853 NSTEMI patients. The primary outcome was a composite of recurrent myocardial infarction (MI) or stent thrombosis at 18 months after the index procedure. Compared with the 6-month DAPT group, the rate of the composite endpoint was significantly lower in the ≥12-month DAPT group (1.2% vs. 3.8%; hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.12-0.77; P=0.012). The treatment effect of ≥12- vs. 6-month DAPT on the composite endpoint was consistent among NSTEMI patients (0.2% vs. 1.2%, respectively; HR 0.20, 95% CI 0.02-1.70; P=0.140; Pinteraction=0.718). In addition, ≥12-month DAPT increased Bleeding Academic Research Consortium (BARC) Type 2-5 bleeding among both STEMI (4.4% vs. 2.0%; HR 2.18, 95% CI 1.03-4.60; P=0.041) and NSTEMI (5.1% vs. 2.2%; HR 2.37, 95% CI 1.08-5.17; P=0.031; Pinteraction=0.885) patients. Compared with 6-month DAPT, ≥12-month DAPT reduced recurrent MI or stent thrombosis regardless of the type of MI at presentation.

Impact of dual antiplatelet therapy after lower extremity revascularization for chronic limb-threatening ischemia

ObjectiveThe optimal antiplatelet regimen after lower extremity revascularization in patients with chronic limb-threatening ischemia (CLTI) is unknown because current recommendations are based on extrapolation of data from trials in coronary artery disease and stroke. MethodsWe identified all patients undergoing an elective lower extremity revascularization for CLTI in the Vascular Quality Initiative registry discharged on a mono antiplatelet agent (MAPT) or dual antiplatelet therapy (DAPT). ResultsFrom 2003 to 2018, 50,890 patients underwent revascularization procedures for CLTI, and were discharged on MAPT or DAPT. Of these, 33,781 patients underwent endovascular therapy (EVT), and 17,109 patients underwent open surgery (OS) procedures. The rate of major amputation at 30 days in the target limb in the EVT group was 0.3% and 0.4% in the OS group (P = .22). On Kaplan-Meier analyses, patients on MAPT at discharge had a higher risk of 1-year major amputation compared with DAPT after EVT but not after OS procedures. Patients on MAPT had lower overall survival and amputation-free survival at 30 days and 1 year compared with DAPT after both EVT and OS. At 1 year, the MAPT group was at higher risk for target lesion reintervention after EVT compared with the DAPT group (15.9% vs 13%; P = .0012). There was no significant difference in thrombosis at 1 year between the MAPT and DAPT groups either after EVT (3.9% vs 3.7%; P = .3048) or OS (3.1% vs 3.2%; P = .2893). On Cox regression analysis, DAPT was associated with improved survival but not major amputation after both EVT and OS. ConclusionsIn patients with CLTI, DAPT at the time of discharge has a positive impact on amputation-free survival and overall survival after both EVT and OS as well as target lesion reintervention after EVT. DAPT was not associated with a positive impact on major amputation after either EVT or OS.

Long-term dual antiplatelet-induced intestinal injury resulting in translocation of intestinal bacteria into blood circulation increased the incidence of adverse events after PCI in patients with coronary artery disease

Background and aimsThe present study aimed to investigate the efficacy and safety of long-term (>18 months) dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). MethodsA total of 3205 coronary artery disease (CAD) patients after PCI from CORFCHD-PCI, a retrospective cohort study (Identifier: ChiCTR-ORC-16010153), were divided into two groups: monotherapy of aspirin or clopidogrel group (SAPT group, n = 2188 and DAPT group, n = 1017) according to whether to discontinue DAPT 18 months after PCI. After propensity matching analysis (PSM), we included 1017 patients in the DAPT group and 1017 patients in the SAPT group. All the patients were followed-up for at least 18 months and the longest follow-up time is 120 months. The primary endpoint was the incidence of major adverse cardiac events (MACEs). The secondary endpoints were the incidence of major adverse cardiovascular and cerebrovascular events (MACEEs) and bleeding events. We also selected 178 patients for detection of claudin-3 and intestinal fatty acid-binding protein and 58 patients for 16s RNA sequencing of whole blood. ResultsThe incidences of MACEs (13.9% vs. 9.0%, p = 0.001) and MACCEs (16.3% vs.10.0%, p < 0.001) were significantly increased in the DAPT group compared to the SAPT group. We also found DAPT increased the bleeding events compared to SAPT (4.6% vs. 2.9%, p = 0.048). Multivariate Cox regression analyses showed that in the DAPT group, cumulative risk of MACCEs increased 1.797 times (HR = 1.797, 95%CI: 1.429–2.226, p < 0.001), MACEs increased 1.737 times (HR = 1.737, 95%CI: 1.360–2.218, p < 0.001) and the bleeding events increased 2.129 times (HR = 2.129, 95%CI: 1.388–3.266, p = 0.001) compared to the SAPT group. We also found the plasma concentrations of claudin-3 and intestinal fatty acid-binding protein (I-FABP) were significantly higher in patients in the DAPT group compared with patients in the SAPT group (both p < 0.001). Correspondingly, the abundance of blood intestinal bacteria in the DAPT group was significantly increased compared to that in the SAPT group (p < 0.001). Furthermore, high-throughput metabolomics analysis suggested that serum level of ceramide (d18:1/16:0) and Neu5Ac was significantly increased in the DAPT group compared to the SAPT group (both p < 0.001). ConclusionsThe present study suggests that long-term dual antiplatelet therapy longer than 18 months significantly increases the incidence of both ischemic events and bleeding events after PCI. This preliminary study also indicates that long-term DAPT causes intestinal injury, which induces translocation of intestinal bacteria into the bloodstream.

Assessing the Efficacy and Safety of Tirofiban in Combination With Dual-antiplatelet Therapy in Progressive Ischemic Stroke Patients.

This study assessed the efficacy and safety of tirofiban in combination with dual-antiplatelet therapy (DAPT) in progressive ischemic stroke. One hundred and four patients equally divided into a tirofiban group or DAPT group were enrolled from June 2018 to December 2019. Efficacy outcomes included National Institutes of Health Stroke Scale score for 14 days, and modified Rankin scale (mRs) scores as excellent (mRs 0-1) or favorable (mRs 0-2) measured 90 days after stroke. At 14 days, the tirofiban group had a lower National Institutes of Health Stroke Scale score compared with the DAPT group (F = 14.959, P = 0.000). The mRS scores of the 2 groups at 90 days after treatment were significantly different from those before treatment. At 90 days, excellent favorable functional outcome (mRS ≤ 2) was achieved in 33 of 52 (63.43%) patients in the tirofiban group compared with 25 of 52 (48.08%) patients in the DAPT group. The incidence of bleeding was 5.77% in the tirofiban group, compared with 0% in DAPT group. Intravenous (IV) tirofiban alone or combined with DAPT was shown to be safe and effectively improved clinical outcome in progressive ischemic stroke patients. IV tirofiban was shown to be superior to the DAPT regimen.