Short-term (1-3 months) versus standard (12 months) dual antiplatelet therapy following new-generation drug-eluting stent implantation: A meta-analysis of randomized controlled trials.

BACKGROUND: Patients undergoing percutaneous coronary intervention mainly receive antiplatelet therapy. However, limited data are available regarding the optimal dual antiplatelet therapy (DAPT) following the implantation of new-generation drug-eluting stent (DES). OBJECTIVE: This study aimed to compare the clinical outcomes of short-term (1-3 months) DAPT and standard (12 months) DAPT after the implantation of a new-generation of DES. METHODS: We systematically searched PubMed, The Cochrane Library Database, Embase for trials that compared short-term (1-3 months) and standard DAPT after the implantation of next-generation DES were retrieved from all published studies in English until December 31, 2021. The primary endpoint was major bleeding. The secondary endpoints included all-cause mortality, cardiac death, myocardial infarction, stroke, stent thrombosis, and all bleeding. RESULTS: This study included a total of 7 randomized controlled trials, comprising 28,344 subjects. Regarding primary endpoints, short-term DAPT exhibited a significantly lower incidence of major bleeding compared with standard DAPT [relative risk (RR): 0.66, 95% confidence interval (CI): (0.54, 0.81), P < .0001]. For secondary endpoints, there were significant differences between short-term and standard DAPT in all bleeding [RR: 0.59, 95% CI: (0.50, 0.69), P < .00001]. However, no significant differences were identified in all-cause mortality [RR: 0.96, 95% CI: (0.77, 1.18), P = .27], myocardial infarction [RR: 0.98, 95% CI: (0.82, 1.18), P = .86], cardiac death [RR: 0.83, 95% CI: (0.63, 1.10), P = .20], stroke [RR: 1.08, 95% CI: (0.79, 1.47), P = .63], cerebrovascular [RR: 1.08, 95% CI: (0.79, 1.47), P = .63], and stent thrombosis [RR: 1.13, 95% CI: (0.80, 1.57), P = .49] between the 2 groups. CONCLUSION: In patients undergoing implantation of a new-generation of DES, short-term (1-3 months) DAPT exhibited no inferiority compared with standard (12 months) DAPT in terms of all-cause mortality, cardiac death, myocardial infarction, stroke, and definite or probable stent thrombosis compared with standard (12 months) DAPT. However, short-term DAPT appeared superior to standard DAPT in terms of major bleeding and all bleeding.

De-escalation to ticagrelor monotherapy versus 12 months of dual antiplatelet therapy in patients with and without acute coronary syndromes: a systematic review and individual patient-level meta-analysis of randomised trials.

BACKGROUND: Dual antiplatelet therapy (DAPT) for 12 months is the standard of care after coronary stenting in patients with acute coronary syndrome (ACS). The aim of this individual patient-level meta-analysis was to summarise the evidence comparing DAPT de-escalation to ticagrelor monotherapy versus continuing DAPT for 12 months after coronary drug-eluting stent implantation. METHODS: A systematic review and individual patient data (IPD)-level meta-analysis of randomised trials with centrally adjudicated endpoints was performed to evaluate the comparative efficacy and safety of ticagrelor monotherapy (90 mg twice a day) after short-term DAPT (from 2 weeks to 3 months) versus 12-month DAPT in patients undergoing percutaneous coronary intervention with a coronary drug-eluting stent. Randomised trials comparing P2Y12 inhibitor monotherapy with DAPT after coronary revascularisation were searched in Ovid MEDLINE, Embase, and two websites (www.tctmd.com and www.escardio.org) from database inception up to May 20, 2024. Trials that included patients with an indication for long-term oral anticoagulants were excluded. The risk of bias was assessed using the revised Cochrane risk-of-bias tool. The principal investigators of the eligible trials provided IPD by means of an anonymised electronic dataset. The three ranked coprimary endpoints were major adverse cardiovascular or cerebrovascular events (MACCE; a composite of all-cause death, myocardial infarction, or stroke) tested for non-inferiority in the per-protocol population; and Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding and all-cause death tested for superiority in the intention-to-treat population. All outcomes are reported as Kaplan-Meier estimates. The non-inferiority was tested using a one-sided α of 0·025 with the prespecified non-inferiority margin of 1·15 (hazard ratio [HR] scale), followed by the ranked superiority testing at a two-sided α of 0·05. This study is registered with PROSPERO (CRD42024506083). FINDINGS: A total of 8361 unique citations were screened, of which 610 records were considered potentially eligible during the screening of titles and abstracts. Of these, six trials that randomly assigned patients to ticagrelor monotherapy or DAPT were identified. De-escalation took place a median of 78 days (IQR 31-92) after intervention, with a median duration of treatment of 334 days (329-365). Among 23 256 patients in the per-protocol population, MACCE occurred in 297 (Kaplan-Meier estimate 2·8%) with ticagrelor monotherapy and 332 (Kaplan-Meier estimate 3·2%) with DAPT (HR 0·91 [95% CI 0·78-1·07]; p=0·0039 for non-inferiority; τ2<0·0001). Among 24 407 patients in the intention-to-treat population, the risks of BARC 3 or 5 bleeding (Kaplan-Meier estimate 0·9% vs 2·1%; HR 0·43 [95% CI 0·34-0·54]; p<0·0001 for superiority; τ2=0·079) and all-cause death (Kaplan-Meier estimate 0·9% vs 1·2%; 0·76 [0·59-0·98]; p=0·034 for superiority; τ2<0·0001) were lower with ticagrelor monotherapy. Trial sequential analysis showed strong evidence of non-inferiority for MACCE and superiority for bleeding among the overall and ACS populations (the z-curve crossed the monitoring boundaries or the required information size without crossing the futility boundaries or approaching the null). The treatment effects were heterogeneous by sex for MACCE (p interaction=0·041) and all-cause death (p interaction=0·050), indicating a possible benefit in women with ticagrelor monotherapy, and by clinical presentation for bleeding (p interaction=0·022), indicating a benefit in ACS with ticagrelor monotherapy. INTERPRETATION: Our study found robust evidence that, compared with 12 months of DAPT, de-escalation to ticagrelor monotherapy does not increase ischaemic risk and reduces the risk of major bleeding, especially in patients with ACS. Ticagrelor monotherapy might also be associated with a mortality benefit, particularly among women, which warrants further investigation. FUNDING: Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale.

Antiplatelet Therapy in Patients Requiring Oral Anticoagulation and Undergoing Percutaneous Coronary Intervention.

Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is fundamental in all patients undergoing percutaneous coronary intervention (PCI) to prevent coronary thrombosis. In patients with atrial fibrillation (AF), an oral anticoagulant gives protection against ischemic stroke or systemic embolism. AF-PCI patients are at high bleeding risk and decision-making regarding the optimal antithrombotic therapy remains challenging. Dual antithrombotic therapy (DAT) has been shown to reduce bleeding events but at the cost of a higher risk of stent thrombosis. Further studies are needed to clarify the optimal duration of triple antithrombotic therapy (TAT) or DAT and the role of more potent antiplatelet drugs.

Antithrombotic Therapy in Patients with Chronic Coronary Syndromes.

The antithrombotic management of chronic coronary syndrome (CCS) involves a 6-month course of dual antiplatelet therapy (DAPT), followed by chronic aspirin therapy. In patients with a baseline indication for anticoagulation, a variable duration of triple antithrombotic therapy is administered, followed by dual antithrombotic therapy until the sixth month post-percutaneous coronary intervention (PCI), and ultimately a transition to chronic anticoagulation. However, advancements in stent technology reducing the risk of stent thrombosis and a growing focus on the impact of bleeding on prognosis have prompted the development of new therapeutic strategies. These strategies aim to enhance protection against ischemic events in the initial stages after PCI while mitigating the risk of bleeding in the long term. This article delineates the therapeutic strategies outlined in European and American guidelines for CCS management, with special attention to investigational strategies.

Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry - Informing optimal antiplatelet strategies.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is indicated after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Approximately 30% of the US population has a CYP2C19 no-function allele that reduces the effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI. We have shown improved outcomes with the integration of CYP2C19 genotyping into clinical care to guide the selection of prasugrel or ticagrelor in CYP2C19 no-function allele carriers. However, the influence of patient-specific demographic, clinical, and other genetic factors on outcomes with genotype-guided DAPT has not been defined. In addition, the impact of genotype-guided de-escalation from prasugrel or ticagrelor to clopidogrel in patients without a CYP2C19 no-function allele has not been investigated in a diverse, real-world clinical setting. The Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry is a multicenter US registry of patients who underwent PCI and clinical CYP2C19 testing. The registry is enrolling a diverse population, assessing atherothrombotic and bleeding events over 12 months, collecting DNA samples, and conducting platelet function testing in a subset of patients. The registry aims to define the influence of African ancestry and other patient-specific factors on clinical outcomes with CYP2C19-guided DAPT, evaluate the safety and effectiveness of CYP2C19-guided DAPT de-escalation following PCI in a real-world setting, and identify additional genetic influences of clopidogrel response after PCI, with the ultimate goal of establishing optimal strategies for individualized antiplatelet therapy that improves outcomes in a diverse, real-world population.

After PCI in older adults, DAPT for 3 vs. 6 or 12 mo reduces bleeding without increasing NACE or MACE.

SOURCE CITATION: Park DY, Hu JR, Jamil Y, et al. Shorter dual antiplatelet therapy for older adults after percutaneous coronary intervention: a systematic review and network meta-analysis. JAMA Netw Open. 2024;7:e244000. 38546647.

After PCI and 1 mo of DAPT for ACS, ticagrelor alone vs. continued DAPT for 11 mo reduced bleeding without increasing MACCE.

SOURCE CITATION: Ge Z, Kan J, Gao X, et al; ULTIMATE-DAPT investigators. Ticagrelor alone versus ticagrelor plus aspirin from month 1 to month 12 after percutaneous coronary intervention in patients with acute coronary syndromes (ULTIMATE-DAPT): a randomised, placebo-controlled, double-blind clinical trial. Lancet. 2024;403:1866-1878. 38599220.

Anticoagulation Alone vs Anticoagulation Plus Aspirin or DAPT Following Left Atrial Appendage Occlusion.

BACKGROUND: The prevalence of and outcomes associated with different antithrombotic strategies after left atrial appendage occlusion (LAAO) are not well described. OBJECTIVES: This study sought to evaluate patterns of antithrombotic medication strategies at discharge following LAAO with the Watchman FLX device in real-world practice and to compare the risk of adverse events among the different antithrombotic regimens. METHODS: The authors evaluated patients in the NCDR (National Cardiovascular Data Registry) LAAO Registry who underwent LAAO with the second-generation LAA closure device between 2020 and 2022. They grouped patients by mutually exclusive discharge antithrombotic strategies and compared the rates of adverse events at 45 days and 6 months using multivariable Cox proportional hazards regression. RESULTS: Among 53,878 patients undergoing successful LAAO with the second-generation LAA closure device, the most common antithrombotic discharge regimens were direct oral anticoagulant (DOAC) plus aspirin (48.3%), DOAC alone (22.6%), dual antiplatelet therapy (8.1%), warfarin plus aspirin (7.7%), and DOAC plus P2Y12 inhibitor (4.9%). In multivariate analysis, DOAC alone had a lower rate of major adverse events and major bleeding at 45 days of follow-up compared with DOAC plus aspirin (major adverse events: HR: 0.78; 95% CI: 0.68-0.91; major bleeding: HR: 0.69; 95% CI: 0.60-0.80). These differences persisted at 6 months. Warfarin without aspirin also showed lower rates of major bleeding at both time points. No differences were seen in stroke/transient ischemic attack or device-related thrombus. CONCLUSIONS: In real-world U.S. practice, discharge on DOAC alone or warfarin alone was associated with a lower rate of adverse events compared with DOAC plus aspirin.

Thrombus aspiration is associated with improved platelet inhibition rate following dual antiplatelet therapy in acute myocardial infarction patients.

BACKGROUND: It is well-established that thrombus aspiration during primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) indicates a higher thrombus burden and necessitates more intensive antithrombotic therapy. The bidirectional association between adverse events in AMI patients and platelet reactivity is typically observed during dual antiplatelet therapy (DAPT). OBJECTIVE: To investigate platelet reactivity after DAPT in AMI patients with thrombus aspiration performed during PCI. METHODS: In this retrospective study, we examined 269 consecutive AMI patients who underwent PCI and recorded their demographic, clinical and laboratory data. The platelet reactivity was measured with thromboelastogram (TEM). RESULTS: Ultimately, 208 patients were included in this study and divided into a Thrombus Aspiration group (N = 97) and a PCI Alone group (N = 111) based on whether thrombus aspiration was performed or not. The adenosine diphosphate (ADP)-induced platelet inhibition rate in the Thrombus Aspiration group was higher than that in the PCI Alone group (P < 0.001). Furthermore, multivariate linear regression analysis revealed that the ADP-induced platelet inhibition rate was independently associated with leukocyte count, thrombus aspiration and the combination of aspirin and ticagrelor as DAPT after adjusting for potential covariates in all AMI patients. CONCLUSION: In conclusion, clinicians should exercise heightened attention towards the bleeding risk among patients undergoing PCI concomitant with Thrombus Aspiration postoperatively.

Clopidogrel Versus Aspirin as Monotherapy Following Dual Antiplatelet Therapy in Patients With Acute Coronary Syndrome Receiving a Drug-Eluting Stent: A Systematic Literature Review and Meta-Analysis.

OBJECTIVE: This study aimed to evaluate the comparative effectiveness and safety of clopidogrel versus aspirin as monotherapy following adequate dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS). METHODS: MEDLINE, Embase, and CENTRAL were searched from database inception to September 1, 2023. Randomized controlled trials (RCTs) and observational studies evaluating the effectiveness or safety of clopidogrel versus aspirin as monotherapy following DAPT in patients with ACS who received a drug-eluting stent were included. Random-effects meta-analyses were conducted to compare risks of major adverse cardiovascular events (MACE) and clinically relevant bleeding. RESULTS: Of 6242 abstracts identified, three unique studies were included: one RCT and two retrospective cohort studies. Studies included a total of 7081 post-percutaneous coronary intervention ACS patients, 4260 of whom received aspirin monotherapy and 2821 received clopidogrel monotherapy. Studies included variable proportions of patients with ST-elevation myocardial infarction (STEMI), non-STEMI, and unstable angina. From the meta-analysis, clopidogrel was associated with a 28% reduction in the risk of MACE compared with aspirin (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.54, 0.98), with no significant difference in clinically relevant bleeding (HR: 0.92; 95% CI: 0.68, 1.24). CONCLUSION: Despite the paucity of published evidence on the effectiveness and safety of clopidogrel versus aspirin in patients with ACS post-drug-eluting stent implantation, this meta-analysis suggests that clopidogrel versus aspirin may result in a lower risk of MACE, with a similar risk of major bleeding. The present results are hypothesis-generating and further large RCTs comparing antiplatelet monotherapy options in ACS patients are warranted.

Combining Intravenous Thrombolysis and Dual Antiplatelet Treatment in Patients With Minor Ischemic Stroke: A Propensity Matched Analysis of the READAPT Study Cohort.

BACKGROUND: The optimal treatment for acute minor ischemic stroke is still undefined. and options include dual antiplatelet treatment (DAPT), intravenous thrombolysis (IVT), or their combination. We aimed to investigate benefits and risks of combining IVT and DAPT versus DAPT alone in patients with MIS. METHODS AND RESULTS: This is a prespecified propensity score-matched analysis from a prospective multicentric real-world study (READAPT [Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or Transient Ischemic Attack]). We included patients with MIS (National Institutes of Health Stroke Scale score at admission ≤5), without prestroke disability (modified Rankin scale [mRS] score ≤2). The primary outcomes were 90-day mRS score of 0 to 2 and ordinal mRS distribution. The secondary outcomes included 90-day risk of stroke and other vascular events and 24-hour early neurological improvement or deterioration (≥2-point National Institutes of Health Stroke Scale score decrease or increase from the baseline, respectively). From 1373 patients with MIS, 240 patients treated with IVT plus DAPT were matched with 427 patients treated with DAPT alone. At 90 days, IVT plus DAPT versus DAPT alone showed similar frequency of mRS 0 to 2 (risk difference, 2.3% [95% CI -2.0% to 6.7%]; P=0.295; risk ratio, 1.03 [95% CI 0.98-1.08]; P=0.312) but more favorable ordinal mRS scores distribution (odds ratio, 0.57 [95% CI 0.41-0.79]; P<0.001). Compared with patients treated with DAPT alone, those combining IVT and DAPT had higher 24-hour early neurological improvement (risk difference, 20.9% [95% CI 13.1%-28.6%]; risk ratio, 1.59 [95% CI 1.34-1.89]; both P<0.001) and lower 90-day risk of stroke and other vascular events (hazard ratio, 0.27 [95% CI 0.08-0.90]; P=0.034). There were no differences in safety outcomes. CONCLUSIONS: According to findings from this observational study, patients with MIS may benefit in terms of better functional outcome and lower risk of recurrent events from combining IVT and DAPT versus DAPT alone without safety concerns. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05476081.

A comparison of simplified or conventional antithrombotic regimens after left atrial appendage closure in patients at high bleeding risk: the PLATEBRISK study.

BACKGROUND: Antithrombotic treatment (ATT) post-left atrial appendage occlusion (LAAO) remains controversial. Furthermore, most of the patients undergoing LAAO are at a very high bleeding risk. AIMS: This study aimed to compare a simplified versus conventional ATT after LAAO in very high bleeding risk patients. METHODS: This is a multicentre, retrospective study including very high bleeding risk patients, according to the Bleeding Academic Research Consortium (BARC) definition, who underwent LAAO. These included patients at >4% risk of BARC 3 to 5 bleeding or >1% risk of intracranial bleeding after the procedure. Two groups were established based on the discharge ATT. The simplified group included single antiplatelet treatment or no treatment, and the conventional group comprised dual antiplatelet treatment or anticoagulation (combined or not with antiplatelet therapy). RESULTS: A total of 1,135 patients were included. The mean CHA2DS2-VASc and HAS-BLED scores were 4.5±1.5 and 3.7±1.0, respectively. There were no differences in the composite endpoint (death, stroke, transient ischaemic attack, device-related thrombus or major bleeding) between the 2 groups (hazard ratio [HR] 0.81, 95% confidence interval [CI]: 0.59-1.11; p=0.188). Although the rate of major bleeding during the first year was numerically lower in the simplified group, it did not reach statistical significance (HR 0.67, 95% CI: 0.41-1.10; p=0.104). Nonetheless, patients with previous major bleeding presented a significantly lower rate of major bleeding when using the simplified treatment (HR 0.61, 95% CI: 0.36-0.99; p=0.049). CONCLUSIONS: In patients with very high bleeding risk, a simplified ATT after LAAO seems to be as effective as conventional protocols. Furthermore, patients with a history of major bleeding experienced a lower risk of major bleeding with the simplified ATT.

Cost-effectiveness of platelet function testing in dual antiplatelet therapy decision-making after intracranial aneurysm treatment with flow diversion.

Dual antiplatelet therapy (DAPT) use is the standard of practice after flow diversion (FD) for intracranial aneurysms (IAs). Yet, no consensus exists in the literature regarding the optimal regimen. Certain institutions utilize various platelet function testing (PFT) to assess patient responsiveness to DAPT. Clopidogrel is the most commonly prescribed drug during DAPT; however, up to 52% of patients can be non-responders, justifying PFT use. Additionally, prices vary significantly among antiplatelet drugs, often further complicated by insurance restrictions. We aimed to determine the most cost-effective strategy for deciding DAPT regimens for patients after IA treatment. A decision tree with Monte Carlo simulations was performed to simulate patients undergoing various three-month postoperative DAPT regimens. Patients were either universally administered aspirin alongside clopidogrel, ticagrelor, or prasugrel without PFT, or administered one of the former thienopyridine medications based on platelet reactivity unit (PRU) results after clopidogrel. Input data for the model were extracted from the current literature, and the willingness-to-pay threshold (WTP) was defined as $100,000 per QALY as per standard practice in the US. The baseline comparison was with universal clopidogrel DAPT without any PFT. Probabilistic and deterministic sensitivity analyses were performed to evaluate the robustness of the model. Utilizing PFT and switching clopidogrel to prasugrel if resistance is documented was the most cost-effective regimen compared to universal clopidogrel, with a base-case incremental cost-effectiveness ratio (ICER) of $-35,255 (cost $2,336.67, effectiveness 0.85). Performing PFT and switching clopidogrel to ticagrelor (ICER $-4,671; cost $2,995.06, effectiveness 0.84), universal prasugrel (ICER $5,553; cost $3,097.30, effectiveness 0.84), or universal ticagrelor (ICER $75,969; cost $3,801.36, effectiveness 0.84) were all more cost-effective than treating patients with universal clopidogrel (cost $3,041.77, effectiveness 0.83). These conclusions remain robust in probabilistic and deterministic sensitivity analyses. The most cost-effective strategy guiding DAPT after FD for IAs is to perform PFTs and switch clopidogrel to prasugrel if resistance is documented, alongside aspirin. The cost of PFT is strongly justified and recommended when deciding patient-specific DAPT regimens.

Demystifying the Contemporary Role of 12-Month Dual Antiplatelet Therapy After Acute Coronary Syndrome.

For almost two decades, 12-month dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) has been the only class I recommendation on DAPT in American and European guidelines, which has resulted in 12-month durations of DAPT therapy being the most frequently implemented in ACS patients undergoing percutaneous coronary intervention (PCI) across the globe. Twelve-month DAPT was initially grounded in the results of the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial, which, by design, studied DAPT versus no DAPT rather than the optimal DAPT duration. The average DAPT duration in this study was 9 months, not 12 months. Subsequent ACS studies, which were not designed to assess DAPT duration, rather its composition (aspirin with prasugrel or ticagrelor compared with clopidogrel) were further interpreted as supportive evidence for 12-month DAPT duration. In these studies, the median DAPT duration was 9 or 15 months for ticagrelor and prasugrel, respectively. Several subsequent studies questioned the 12-month regimen and suggested that DAPT duration should either be fewer than 12 months in patients at high bleeding risk or more than 12 months in patients at high ischemic risk who can safely tolerate the treatment. Bleeding, rather than ischemic risk assessment, has emerged as a treatment modifier for maximizing the net clinical benefit of DAPT, due to excessive bleeding and no clear benefit of prolonged treatment regimens in high bleeding risk patients. Multiple DAPT de-escalation treatment strategies, including switching from prasugrel or ticagrelor to clopidogrel, reducing the dose of prasugrel or ticagrelor, and shortening DAPT duration while maintaining monotherapy with ticagrelor, have been consistently shown to reduce bleeding without increasing fatal or nonfatal cardiovascular or cerebral ischemic risks compared with 12-month DAPT. However, 12-month DAPT remains the only class-I DAPT recommendation for patients with ACS despite the lack of prospectively established evidence, leading to unnecessary and potentially harmful overtreatment in many patients. It is time for clinical practice and guideline recommendations to be updated to reflect the totality of the evidence regarding the optimal DAPT duration in ACS.

Effects of dual antiplatelet therapy (DAPT) compared to single antiplatelet therapy (SAPT) in patients with traumatic brain injury.

Japan is one of the world's most aging societies and the number of elderly patients taking antithrombotic drugs is increasing. In recent years, dual antiplatelet therapy (DAPT), in which two antiplatelet drugs are administered, has become common in anticipation of its high therapeutic efficacy. However, there are concerns about increased bleeding complications in use of DAPT. Therefore, the goal of this study was to investigate the effects of DAPT in patients with traumatic brain injury (TBI). A prospective, multicenter, observational study was conducted from December 2019 to May 2021 to examine the effects of antithrombotic drugs and reversal drugs in 721 elderly patients with TBI. In the current study, the effect of DAPT on TBI was examined in a secondary analysis. Among the registered patients, 132 patients taking antiplatelet drugs only were divided into those treated with single antiplatelet therapy (SAPT) (n=106) and those treated with DAPT (n=26) prior to TBI. Glasgow Coma Scale (GCS) on admission, pupillary findings, course during hospitalization, and outcome were compared in the two groups. A similar analysis was performed in patients with a mild GCS of 13-15 (n=95) and a moderate to severe GCS of 3-12 (n=37) on admission. The DAPT group had significantly more males (67.0 % vs. 96.2 %), a higher severity of illness on admission, and a higher frequency of brain herniation findings on head CT (21.7 % vs. 46.2 %), resulting in significantly higher mortality (12.3 % vs. 30.8 %). The only significant factor for mortality was severity on admission. The rate of DAPT was significantly higher in patients with a moderate to severe GCS on admission, and DAPT was the only significant factor related to severity on admission. These findings suggest that the severity of injury on admission influences the outcome six months after injury, and that patients with more severe TBI on admission are more likely to have been treated with DAPT compared to SAPT.

Post-procedural Anticoagulation With Unfractionated Heparin in Acute Coronary Syndrome: Insight from the STOPDAPT-3 Trial.

The current guidelines for acute coronary syndrome (ACS) discourage the use of anticoagulation after percutaneous coronary intervention (PCI) without specific indications, although the recommendation is not well supported by evidence. In this post hoc analysis of the ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-3 (STOPDAPT-3) trial, 30-day outcomes were compared between the 2 groups with and without post-PCI heparin administration among patients with ACS who did not receive mechanical support devices. The co-primary end points were the bleeding end point, defined as the Bleeding Academic Research Consortium type 3 or 5 bleeding, and the cardiovascular end point, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke. Among 4,088 patients with ACS, 2,339 patients (57.2%) received post-PCI heparin. The proportion of patients receiving post-PCI heparin was higher among those with ST-elevation myocardial infarction compared with others (72.3% and 38.8%, p <0.001), and among patients with intraprocedural adverse angiographic findings compared with those without (67.6% and 47.5%, p <0.001). Post-PCI heparin compared with no post-PCI heparin was associated with a significantly increased risk of the bleeding end point (4.75% and 2.52%, adjusted hazard ratio 1.69, 95% confidence interval 1.15 to 2.46, p = 0.007) and a numerically increased risk of the cardiovascular end point (3.16% and 1.72%, adjusted hazard ratio 1.56, 95% confidence interval 0.98 to 2.46, p = 0.06). Higher hourly dose or total doses of heparin were also associated with higher incidence of both bleeding and cardiovascular events within 30 days. In conclusion, post-PCI anticoagulation with unfractionated heparin was frequently implemented in patients with ACS. Post-PCI heparin use was associated with harm in terms of increased bleeding without the benefit of reducing cardiovascular events. Trial identifier: STOPDAPT-3 ClinicalTrials.gov number, NCT04609111.

Aspirin-Free Strategy for Percutaneous Coronary Intervention in Patients With Oral Anticoagulation: Prespecified Subgroup Analysis From the STOPDAPT-3 Trial.

BACKGROUND: The effects of aspirin-free strategy on bleeding and cardiovascular events in patients undergoing percutaneous coronary intervention with oral anticoagulation (OAC) have not been fully elucidated. METHODS AND RESULTS: We conducted the prespecified subgroup analysis based on the use of OAC, including vitamin K antagonist and direct oral anticoagulants, within 7 days before percutaneous coronary intervention in the STOPDAPT-3 (Short and Optimal Duration of Dual Antiplatelet Therapy-3) trial, which randomly compared prasugrel monotherapy (2984 patients) to dual antiplatelet therapy (DAPT) with prasugrel and aspirin (2982 patients) in patients with acute coronary syndrome or high bleeding risk. The coprimary end points were major bleeding events (Bleeding Academic Research Consortium types 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month. Among 5966 study patients, there were 530 patients (8.9%) with OAC (no aspirin: N=248, and DAPT: N=282) and 5436 patients (91.1%) without OAC (no aspirin: N=2736, and DAPT: N=2700). Regardless of the use of OAC, the effects of no aspirin compared with DAPT were not significant for the bleeding end point (OAC: 4.45% and 4.27%, hazard ratio [HR], 1.04 [95% CI, 0.46-2.35]; no-OAC: 4.47% and 4.75%, HR, 0.94 [95% CI, 0.73-1.20]; P for interaction=0.82), and for the cardiovascular end point (OAC: 4.84% and 3.20%, HR, 1.53 [95% CI, 0.64-3.62]; no-OAC: 4.06% and 3.74%, HR, 1.09 [95% CI 0.83-1.42]; P for interaction =0.46). CONCLUSIONS: The no-aspirin strategy compared with the DAPT strategy failed to reduce major bleeding events irrespective of the use of OAC. There was a numerical excess risk of the no-aspirin strategy relative to the DAPT strategy for cardiovascular events in patients with OAC.

Early Nonprocedural Bleeding After Left Atrial Appendage Occlusion.

BACKGROUND: Patients treated with left atrial appendage occlusion (LAAO) are at high bleeding risk. Intensive antithrombotic treatment is recommended after the procedure to prevent device-related thrombosis. OBJECTIVES: This study sought to evaluate the incidence, consequences, and predictors of early nonprocedural bleeding after LAAO. METHODS: This was a multicenter study including 1,649 patients undergoing LAAO in 9 centers. Early nonprocedural bleeding was defined as bleeding unrelated to the procedure occurring within 3 months after device implantation. The severity of bleeding was defined by the Valve Academic Research Consortium-2 classification. A sensitivity analysis was performed at 45 days. RESULTS: A total of 121 (7.3%) patients experienced early nonprocedural bleeding events, and 69 (57.0%) were classified as major bleeding (4.2% of patients). Independent predictors of early nonprocedural bleeding were dual antiplatelet therapy (DAPT) at discharge (adjusted HR [aHR]: 1.61; 95% CI: 1.12-2.33; P = 0.01), prior gastrointestinal bleeding (aHR: 2.15; 95% CI: 1.38-3.35; P < 0.001), and multiple locations of prior bleeding (aHR: 2.33; 95% CI: 1.34-4.05; P < 0.001). DAPT at discharge was predictive of both all and major nonprocedural bleeding at 3 months and 45 days. After a median follow-up of 2.3 years (Q1-Q3: 1.1-4.1 years), early nonprocedural bleeding was independently associated with an increased risk of all-cause death (aHR: 1.53; 95% CI: 1.15-2.06; P < 0.001). This heightened mortality risk was similar at 45 days. CONCLUSIONS: Early nonprocedural bleeding after LAAO occurred in ∼7% of patients within 3 months, with more than one-half being classified as major bleeding. Regardless of severity, early nonprocedural bleeding was associated with increased mortality. DAPT at discharge determined an increased risk of early nonprocedural bleeding after LAAO. These results emphasize the importance of bleeding risk for determining antithrombotic strategies after LAAO.