Pharmacogenetics of Antiplatelet Therapy.

Antiplatelet therapy is used in the treatment of patients with acute coronary syndromes, stroke, and those undergoing percutaneous coronary intervention. Clopidogrel is the most widely used antiplatelet P2Y12 inhibitor in clinical practice. Genetic variation in CYP2C19 may influence its enzymatic activity, resulting in individuals who are carriers of loss-of-function CYP2C19 alleles and thus have reduced active clopidogrel metabolites, high on-treatment platelet reactivity, and increased ischemic risk. Prospective studies have examined the utility of CYP2C19 genetic testing to guide antiplatelet therapy, and more recently published meta-analyses suggest that pharmacogenetics represents a key treatment strategy to individualize antiplatelet therapy. Rapid genetic tests, including bedside genotyping platforms that are validated and have high reproducibility, are available to guide selection of P2Y12 inhibitors in clinical practice. The aim of this review is to provide an overview of the background and rationale for the role of a guided antiplatelet approach to enhance patient care.

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.

Ticagrelor monotherapy for acute coronary syndrome: an individual patient data meta-analysis of TICO and T-PASS trials.

BACKGROUND AND AIMS: In patients with acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is recommended for 12 months after drug-eluting stent (DES) implantation. Monotherapy with a potent P2Y12 inhibitor after short-term DAPT is an attractive option to better balance the risks of ischaemia and bleeding. Therefore, this study evaluated the efficacy and safety of ticagrelor monotherapy after short-term DAPT, especially in patients with ACS. METHODS: Electronic databases were searched from inception to 11 November 2023, and for the primary analysis, individual patient data were pooled from the relevant randomized clinical trials comparing ticagrelor monotherapy after short-term (≤3 months) DAPT with ticagrelor-based 12-month DAPT, exclusively in ACS patients undergoing DES implantation. The co-primary endpoints were ischaemic endpoint (composite of all-cause death, myocardial infarction, or stroke) and bleeding endpoint [Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding] at 1 year. RESULTS: Individual patient data from two randomized clinical trials including 5906 ACS patients were analysed. At 1 year, the primary ischaemic endpoint did not differ between the ticagrelor monotherapy and ticagrelor-based DAPT groups [1.9% vs. 2.5%; adjusted hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.56-1.13; P = .194]. The incidence of the primary bleeding endpoint was lower in the ticagrelor monotherapy group (2.4% vs. 4.5%; adjusted HR 0.54; 95% CI 0.40-0.72; P < .001). The results were consistent in a secondary aggregate data meta-analysis including the ACS subgroup of additional randomized clinical trials which enrolled patients with ACS as well as chronic coronary syndrome. CONCLUSIONS: In ACS patients undergoing DES implantation, ticagrelor monotherapy after short-term DAPT was associated with less major bleeding without a concomitant increase in ischaemic events compared with ticagrelor-based 12-month DAPT. STUDY REGISTRATION: PROSPERO (ID: CRD42023476470).

Aspirin-free antiplatelet strategies after percutaneous coronary interventions.

Dual antiplatelet therapy (DAPT) with aspirin and a platelet P2Y12 receptor inhibitor is the standard antithrombotic treatment after percutaneous coronary interventions (PCI). Several trials have challenged guideline-recommended DAPT after PCI by testing the relative clinical effect of an aspirin-free antiplatelet approach-consisting of P2Y12 inhibitor monotherapy after a short course (mostly 1-3 months) of DAPT-among patients undergoing PCI without a concomitant indication for oral anticoagulation (OAC). Overall, these studies have shown P2Y12 inhibitor monotherapy after short DAPT to be associated with a significant reduction in the risk of bleeding without an increase in thrombotic or ischaemic events compared with continued DAPT. Moreover, the effects of the P2Y12 inhibitor monotherapy without prior DAPT or following a very short course of DAPT after PCI are being investigated in emerging studies, of which one has recently reported unfavourable efficacy results associated with the aspirin-free approach compared with conventional DAPT. Finally, P2Y12 inhibitor alone has been compared with aspirin alone as chronic therapy after DAPT discontinuation, thus challenging the historical role of aspirin as a standard of care for secondary prevention following PCI. A thorough understanding of study designs, populations, treatments, results, and limitations of trials testing P2Y12 inhibitor monotherapy vs. DAPT or vs. aspirin is required to consider adopting this treatment in clinical practice. This review addresses the use of aspirin-free antiplatelet strategies among patients undergoing PCI without a concomitant indication for OAC, providing an overview of clinical evidence, guideline indications, practical implications, ongoing issues, and future perspectives.

Coronary bypass surgery for multivessel disease after percutaneous coronary intervention in acute coronary syndromes: why, for whom, how early?

Multivessel coronary artery disease is present in ∼50% of patients with acute coronary syndrome and, compared with single-vessel disease, entails a higher risk of new ischaemic events and a worse prognosis. Randomized controlled trials have shown the superiority of 'complete revascularization' over culprit lesion-only treatment. Trials, however, only included patients treated with percutaneous coronary intervention (PCI), and evidence regarding complete revascularization with coronary artery bypass graft (CABG) surgery after culprit lesion-only PCI ('hybrid revascularization') is lacking. The CABG after PCI is an open, non-negligible therapeutic option, for patients with non-culprit left main and/or left anterior descending coronary artery disease where evidence in chronic coronary syndrome patients points in several cases to a preference of CABG over PCI. This valuable but poorly studied 'PCI first-CABG later' option presents, however, relevant challenges, mostly in the need of interrupting post-stenting dual antiplatelet therapy (DAPT) for surgery to prevent excess bleeding. Depending on patients' clinical characteristics and coronary anatomical features, either deferring surgery after a safe interruption of DAPT or bridging DAPT interruption with intravenous short-acting antithrombotic agents appears to be a suitable option. Off-pump minimally invasive surgical revascularization, associated with less operative bleeding than open-chest surgery, may be an adjunctive strategy when revascularization cannot be safely deferred and DAPT is not interrupted. Here, the rationale, patient selection, optimal timing, and adjunctive strategies are reviewed for an ideal approach to hybrid revascularization in post-acute coronary syndrome patients to support physicians' choices in a case-by-case patient-tailored approach.

2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease." METHODS: A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE: This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Real-world performance of indobufen versus aspirin after percutaneous coronary intervention: insights from the ASPIRATION registry.

BACKGROUND: Indobufen is widely used in patients with aspirin intolerance in East Asia. The OPTION trial launched by our cardiac center examined the performance of indobufen based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, the vast majority of patients with acute coronary syndrome (ACS) and aspirin intolerance were excluded. We aimed to explore this question in a real-world population. METHODS: Patients enrolled in the ASPIRATION registry were grouped according to the DAPT strategy that they received after PCI. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. Propensity score matching (PSM) was adopted for confounder adjustment. RESULTS: A total of 7135 patients were reviewed. After one-year follow-up, the indobufen group was associated with the same risk of MACCE versus the aspirin group after PSM (6.5% vs. 6.5%, hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.65 to 1.52, P = 0.978). However, BARC type 2, 3, or 5 bleeding was significantly reduced (3.0% vs. 11.9%, HR = 0.24, 95% CI = 0.15 to 0.40, P < 0.001). These results were generally consistent across different subgroups including aspirin intolerance, except that indobufen appeared to increase the risk of MACCE in patients with ACS. CONCLUSIONS: Indobufen shared the same risk of MACCE but a lower risk of bleeding after PCI versus aspirin from a real-world perspective. Due to the observational nature of the current analysis, future studies are still warranted to further evaluate the efficacy of indobufen based DAPT, especially in patients with ACS. TRIAL REGISTRATION: Chinese Clinical Trial Register ( https://www.chictr.org.cn ); Number: ChiCTR2300067274.

Effects of Body Mass Index and Body Weight on Plasma Concentration of Ticagrelor and Platelet Aggregation Rate in Patients with Unstable Angina in a Chinese Han Population.

Background: The aim of this study was to investigate the impact of body mass index (BMI) and body weight on the concentrations of ticagrelor and the ticagrelor metabolite, AR-C124910XX, as well as the platelet aggregation rate (PAR) in a Chinese Han population with unstable angina (UA). Specifically, it focused on these parameters following the administration of dual antiplatelet therapy (DAPT) comprising aspirin and ticagrelor. Methods: A total of 105 patients with UA were included in the study. Measurement of the platelet aggregation rate induced by adenosine diphosphate (PAR-ADP) was performed before, as well as 3 and 30 days after DAPT treatment. The plasma concentrations of ticagrelor and AR-C124910XX were detected at 3 and 30 days after DAPT treatment. We conducted correlation analyses to assess the effects of BMI and body weight on the concentrations of ticagrelor and AR-C124910XX, on PAR-ADP, and on the inhibition of platelet aggregation induced by adenosine diphosphate (IPA-ADP) at both 3 and 30 days after DAPT treatment. Results: The BMI and body weight were positively correlated with baseline PAR-ADP (r = 0.205, p = 0.007; r = 0.122, p = 0.022). The PAR-ADP at 3 and 30 days after DAPT treatment were significantly lower than at baseline (61.56% ± 10.62%, 8.02% ± 7.52%, 12.90% ± 7.42%, p < 0.001). There was a negative correlation between body weight and the concentrations of ticagrelor and AR-C124910XX at 3 days following DAPT treatment (r = -0.276, p < 0.001; r = -0.337, p < 0.001). Additionally, BMI showed a similar negative correlation with the concentrations of ticagrelor and AR-C124910XX (r = -0.173, p = 0.009; r = -0.207, p = 0.002). At 30 days after treatment, both body weight and BMI were negatively correlated with ticagrelor (r = -0.256, p < 0.001; r = -0.162, p = 0.015) and its metabolite (r = -0.352, p < 0.001; r = -0.202, p = 0.002). Body weight was positively correlated with PAR-ADP (r = 0.171, p = 0.010) and negatively correlated with IPA-ADP (r = -0.163, p = 0.015) at 30 days after treatment. Similarly, BMI was positively correlated with PAR-ADP (r = 0.217, p = 0.001) and negatively correlated with IPA-ADP (r = -0.211, p = 0.001) at the same time point. Conclusions: BMI and body weight are key factors influencing the pharmacokinetics and pharmacodynamics of ticagrelor in Chinese Han patients with UA following DAPT treatment that includes ticagrelor. Both BMI and body weight were positively correlated with PAR-ADP at baseline and 30 days after DAPT treatment. Clinical Trial Registration: ChiCTR2100044938, https://www.chictr.org.cn/.

Comparison of thrombogenicity in different types of drug-eluting stents during transition from DAPT to SAPT.

BACKGROUND: During the transition from dual antiplatelet therapy (DAPT) to single antiplatelet therapy (SAPT), previous studies have raised concerns about a rebound effect. We compared platelet and inflammatory cell adhesion on different types of stents in the setting of clopidogrel presence and withdrawal. METHODS: In Experiment 1, three pigs were administered with DAPT, that is, clopidogrel and acetylsalicylic acid (ASA), for 7 days. Each animal underwent an extracorporeal carotid arteriovenous shunt model implanted with fluoropolymer-coated everolimus-eluting stent (FP-EES), biodegradable-polymer sirolimus-eluting stent (BP-SES), and biodegradable-polymer everolimus-eluting stents (BP-EES). In Experiment 2, two pigs were administered DAPT, clopidogrel was then withdrawn at day 7, and SAPT with ASA was continued for next 21 days. Then flow-loop experiments with the drawn blood from each time point were performed for FP-EES, BioLinx-polymer zotarolimus-eluting stents (BL-ZES), and BP-EES. The rebound effect was defined as the statistical increase of inflammation and platelet adhesion assessed with immunohistochemistry on the stent-strut level basis from baseline to day-14 or 28. RESULTS: Both experiments showed platelet adhesion value was highest in BP-EES, while the least in FP-EES during DAPT therapy. There was no increase in platelet or inflammatory cell adhesion above baseline values (i.e., no therapy) due to the cessation of clopidogrel on the stent-strut level. Monocyte adhesion was the least for FP-EES with the same trend observed for neutrophil adhesion. CONCLUSIONS: No evidence of rebound effect was seen after the transition from DAPT to SAPT. FP-EES demonstrated the most favorable antithrombotic and anti-inflammatory profile regardless of the different experimental designs.

One-Month Dual Antiplatelet Therapy Followed by P2Y12 Inhibitor Monotherapy After Biodegradable Polymer Drug-Eluting Stent Implantation　- The REIWA Region-Wide Registry.

BACKGROUND: The safety and feasibility of using 1-month dual antiplatelet therapy (DAPT) followed by P2Y12inhibitor monotherapy for patients after percutaneous coronary intervention (PCI) with thin-strut biodegradable polymer drug-eluting stents (BP-DES) in daily clinical practice remain uncertain. METHODS AND RESULTS: The REIWA region-wide registry is a prospective study conducted in 1 PCI center and 9 local hospitals in northern Japan. A total of 1,202 patients who successfully underwent final PCI using BP-DES (Synergy: n=400; Ultimaster: n=401; Orsiro: n=401), were enrolled in the registry, and received 1-month DAPT followed by P2Y12inhibitor (prasugrel 3.75 mg/day or clopidogrel 75 mg/day) monotherapy. The primary endpoint was a composite of cardiovascular and bleeding events at 12 months, including cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST), ischemic or hemorrhagic stroke, and Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding. Based on the results of a previous study, we set the performance goal at 5.0%. Over the 1-year follow-up, the primary endpoint occurred in 3.08% of patients, which was lower than the predefined performance goal (Pnon-inferiority<0.0001). Notably, definite ST occurred in only 1 patient (0.08%) within 1 year (at 258 days). No differences were observed in the primary endpoint between stent types. CONCLUSIONS: The REIWA region-wide registry suggests that 1-month DAPT followed by P2Y12inhibitor monotherapy is safe and feasible for Japanese patients with BP-DES.

Randomized evaluation of 5-month Ticagrelor monotherapy after 1-month dual-antiplatelet therapy in patients with acute coronary syndrome treated with drug-coated balloons: REC-CAGEFREE II trial rationale and design.

BACKGROUND: Patients treated with drug-coated balloons (DCB) have the theoretical advantage of adopting a low-intensity antiplatelet regimen due to the absence of struts and polymers. Nevertheless, the optimal antiplatelet strategy for patients undergoing DCB-only treatment remains a topic of debate and has not been investigated in randomized trials. METHODS: The REC-CAGEFREE II is an investigator-initiated, prospective, open-label, multi-center, randomized, non-inferiority trial aimed to enroll 1908 patients from ≥ 40 interventional cardiology centers in China to evaluate the non-inferiority of an antiplatelet regimen consisting of Aspirin plus Ticagrelor for one month, followed by five months Ticagrelor monotherapy, and then Aspirin monotherapy for six months (Experimental group) compared to the conventional treatment of Aspirin plus Ticagrelor for 12 months (Reference group) in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) using paclitaxel-coated balloons (DCB) exclusively. Participants will be randomly assigned to the Experimental or Reference group in a 1:1 ratio. The randomization will be stratified based on the center and the type of lesion being treated (De novo or in-stent restenosis). The primary endpoint is net adverse clinical events (NACE) within 12 months of PCI, which includes the composite of all-cause death, any stroke, any myocardial infarction, any revascularization and Bleeding Academic Research Consortium (BARC) defined type 3 or 5 bleeding. The secondary endpoint, any ischemic and bleeding event, which includes all-cause death, any stroke, MI, BARC-defined type 3 bleeding, any revascularization, and BARC-defined type 2 bleeding events, will be treated as having hierarchical clinical importance in the above order and analyzed using the win ratio method. DISCUSSION: The ongoing REC-CAGEFREE II trial aims to assess the efficacy and safety of a low-intensity antiplatelet approach among ACS patients with DCB. If non-inferiority is shown, the novel antiplatelet approach could provide an alternative treatment for ACS patients with DCB. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04971356.

Ticagrelor monotherapy after a short course of dual antiplatelet therapy with ticagrelor plus aspirin following percutaneous coronary intervention in patients with versus without diabetes mellitus: a meta-analysis of randomized trials.

BACKGROUND: Cardiovascular disease (CVD) is one among the major causes of mortality all round the globe. Several anti-platelet regimens have been proposed following percutaneous coronary intervention (PCI). In this analysis, we aimed to show the adverse clinical outcomes associated with ticagrelor monotherapy after a short course of dual antiplatelet therapy (DAPT) with ticagrelor and aspirin following PCI in patients with versus without diabetes mellitus (DM). METHODS: Electronic databases were searched by four authors from September to November 2023. Cardiovascular outcomes and bleeding events were the endpoints of this analysis. Revman 5.4 software was used to conduct this meta-analysis. Risk ratio (RR) and 95% confidence intervals (CI) were used to represent the results which were generated. RESULTS: Three studies with a total number of 22,574 participants enrolled from years 2013 to 2019 were included in this analysis. Results of this analysis showed that DM was associated with significantly higher risks of major adverse cardiovascular events (RR: 1.73, 95% CI: 1.49 - 2.00; P = 0.00001), all-cause mortality (RR: 2.15, 95% CI: 1.73 - 2.66; P = 0.00001), cardiac death (RR: 2.82, 95% CI: 1.42 - 5.60; P = 0.003), stroke (RR: 1.78, 95% CI: 1.16 - 2.74; P = 0.009), myocardial infarction (RR: 1.63, 95% CI: 1.17 - 2.26; P = 0.004) and stent thrombosis (RR: 1.74, 95% CI: 1.03 - 2.94; P = 0.04) when compared to patients without DM. However, thrombolysis in myocardial infarction (TIMI) defined minor and major bleedings, bleeding defined according to the academic research consortium (BARC) type 3c (RR: 1.31, 95% CI: 0.14 - 11.90; P = 0.81) and BARC type 2, 3 or 5 (RR: 1.17, 95% CI: 0.85 - 1.62; P = 0.34) were not significantly different. CONCLUSION: In patients who were treated with ticagrelor monotherapy after a short course of DAPT with ticagrelor and aspirin, DM was an independent risk factor for the significantly increased adverse cardiovascular outcomes. However, TIMI and BARC defined bleeding events were not significantly different in patients with versus without DM.

Low-dose prasugrel versus standard-dose ticagrelor in east Asian patients with acute coronary syndrome.

Low-dose prasugrel demonstrated a similar effectiveness profile to clopidogrel in East Asian ACS patients, but its comparison with another new-generation potent P2Y12 inhibitor, ticagrelor, remains unclear. To compare the effectiveness and safety of low-dose prasugrel against those of standard-dose ticagrelor in East Asian patients with ACS. This retrospective cohort study used Taiwan's National Health and Welfare Database. This study included ACS patients who underwent percutaneous coronary intervention and, at discharge between January 1, 2018 and December 31, 2020, were prescribed with low-dose prasugrel plus aspirin or standard-dose ticagrelor plus aspirin. Stabilized inverse probability of treatment weighting was used to balance the covariates across these two groups. The primary effectiveness outcome was a composite of acute myocardial infarction, ischemic stroke, and cardiovascular death; the secondary effectiveness outcome was each of the individual components of the primary outcome, transient ischemic attack, and repeat revascularization. The primary safety outcome was a composite of intracranial hemorrhage and gastrointestinal bleeding, and the two secondary safety outcomes were intracranial hemorrhage and gastrointestinal bleeding. A total of 24,807 patients were included in this study. Among them, 1,493 were low-dose prasugrel users and 23,314 were standard-dose ticagrelor users. No significant differences were found in primary effectiveness [HR: 0.97 (0.74-1.28)] or primary safety outcomes [HR: 1.22 (0.73-2.01)] between the two study groups. For East Asian patients with ACS, low-dose prasugrel provides comparable effectiveness without increasing bleeding risk compared to standard-dose ticagrelor. Low-dose prasugrel may be an appropriate alternative for East Asian populations.

Outcomes of patients with cerebral microbleeds undergoing percutaneous coronary intervention and dual antiplatelet therapy.

INTRODUCTION: Cerebral microbleeds (CMBs) on brain magnetic resonance imaging (MRI) are predictive of intracerebral hemorrhage (ICH). However, the risk of ICH in patients with CMBs who undergo percutaneous coronary intervention (PCI) while receiving dual antiplatelet therapy (DAPT) is unclear. MATERIALS AND METHODS: We conducted a study on 329 consecutive patients with coronary artery disease who underwent PCI and were evaluated using a 3T MRI scanner. Based on T2*-weighted imaging, patients were classified into three groups: no CMBs, < 5 CMBs, or ≥ 5 CMBs. We determined the occurrence of ICH during follow-up. RESULTS: At least 1 CMB was found in 109 (33%) patients. The mean number of CMBs per patient was 2.9 ± 3.6. Among the 109 patients with CMBs, 16 (15%) had ≥ 5 CMBs. Coronary stent implantation was performed in 321 patients (98%). DAPT was prescribed for 325 patients (99%). During a mean follow-up period of 2.3 years (interquartile range, 1.9-2.5 years), ICH occurred in one patient (1.1%) with four CMBs. There were no significant differences in the incidence of ICH (0% vs. 1.1% vs. 0%; p = 0.28). However, the rate of DAPT at 6 months of follow-up was significantly lower in patients with ≥ 5 CMBs than in patients with no CMBs or < 5 CMBs (89% vs. 91% vs. 66%, p = 0.026). Furthermore, there were no significant differences in systemic blood pressure during follow-up (123 ± 16 vs. 125 ± 16 vs. 118 ± 11 mmHg; p = 0.40). CONCLUSION: Although a substantial number of patients who underwent PCI had cerebral microbleeds, at approximately two years of follow-up, intracerebral hemorrhage was very rare in our study population.

Safety and efficacy of stent-assisted coil embolization with periprocedural dual antiplatelet therapy for the treatment of acutely ruptured intracranial aneurysms.

PURPOSE: Despite growing evidence for the effectiveness of stent-assisted coil embolization (SAC) in treating acutely ruptured aneurysms, the safety of stent placement in acute phase remains controversial because of concerns for stent-induced thromboembolism and hemorrhagic events attributable to the necessity of antiplatelet therapy. Therefore, we investigated the safety and efficacy of SAC with periprocedural dual antiplatelet therapy (DAPT) compared with the coiling-only technique to determine whether it is a promising treatment strategy for ruptured aneurysms. METHODS: We retrospectively evaluated 203 enrolled patients with acutely ruptured aneurysms, categorizing them into two groups: SAC and coiling-only groups. Comparative analyses between the two groups regarding angiographic results, clinical outcomes, and procedure-related complications were performed. A subgroup analysis of procedural complications was conducted on patients who did not receive chronic antithrombotic medications to alleviate their influence before hospitalization. RESULTS: 130 (64.0%) patients were treated using the coiling-only technique, whereas 73 (36.0%) underwent SAC. There was a trend to a higher complete obliteration rate (p = 0.061) and significantly lower recanalization rate (p = 0.030) at angiographic follow-up in the SAC group compared to the coiling-only group. Postprocedural cerebral infarction occurred less frequently in the SAC group (8.2%) than in the coiling-only group (17.7%), showing a significant difference (p = 0.044). Although the ventriculostomy-related hemorrhage rate was significantly higher in the SAC group than in the coiling-only group (26.2% vs. 9.3%, p = 0.031), the incidence of symptomatic ventriculostomy-related hemorrhage was comparable. Subgroup analysis excluding patients receiving chronic antithrombotic medications showed similar results. CONCLUSION: SAC with periprocedural DAPT could be a safe and effective treatment strategy for acutely ruptured aneurysms. Moreover, it might have a protective effect on postprocedural cerebral infarction without increasing the risk of symptomatic hemorrhagic complications.

Flow diversion of ruptured intracranial aneurysms: a single-center study with a standardized antithrombotic treatment protocol.

BACKGROUND: The use of antithrombotic medication following acute flow diversion for a ruptured intracranial aneurysm (IA) is challenging with no current guidelines. We investigated the incidence of treatment-related complications and patient outcomes after flow diversion for a ruptured IA before and after the implementation of a standardized antithrombotic medication protocol. METHODS: We conducted a single-center retrospective study including consecutive patients treated for acutely ruptured IAs with flow diversion during 2015-2023. We divided the patients into two groups: those treated before the implementation of the protocol (pre-protocol) and those treated after the implementation of the protocol (post-protocol). The primary outcomes were hemorrhagic and ischemic complications. A secondary outcome was clinical outcome using the modified Ranking Scale (mRS). RESULTS: Totally 39 patients with 40 ruptured IAs were treated with flow diversion (69% pre-protocol, 31% post-protocol). The patient mean age was 55 years, 62% were female, 63% of aneurysms were in the posterior circulation, 92% of aneurysms were non-saccular, and 44% were in poor grade on admission. Treatment differences included the use of glycoprotein IIb/IIIa inhibitors (pre-group 48% vs. post-group 100%), and the use of early dual antiplatelets (pre-group 44% vs. 92% post-group). The incidence of ischemic complications was 37% and 42% and the incidence of hemorrhagic complications was 30% and 33% in the pre- and post-groups, respectively, with no between-group differences. There were three (11%) aneurysm re-ruptures in the pre-group and none in the post-group. There were no differences in mortality or mRS 0-2 between the groups at 6 months. CONCLUSION: We found no major differences in the incidence of ischemic or hemorrhagic complications after the implementation of a standardized antithrombotic protocol for acute flow diversion for ruptured IAs. There is an urgent need for more evidence-based guidelines to optimize antithrombotic treatment after flow diversion in the setting of subarachnoid hemorrhage.

Multicenter Comparison of the Safety and Efficacy of Clopidogrel Versus Ticagrelor for Neuroendovascular Stents.

BACKGROUND: Dual antiplatelet therapy (DAPT) is commonly employed for neuroendovascular stenting due to the significant risk of thromboembolism. Clopidogrel and aspirin are most often selected as initial DAPTs; however, there is limited literature available to support guidance of DAPT in this setting. The objective of this study was to evaluate safety and efficacy in patients whose final regimen included either DAPT with aspirin and clopidogrel (DAPT-C) or DAPT with aspirin and ticagrelor (DAPT-T). METHODS: This was a multicenter, retrospective cohort of patients who underwent neuroendovascular stenting and received DAPT between July 1, 2017, and October 31, 2020. Study participants were allocated into groups based on discharge DAPT regimen. The primary outcome was incidence of stent thrombosis at 3-6 months on DAPT-C versus DAPT-T, as defined by the presence of thrombus on imaging or new onset stroke. Secondary outcomes included major and minor bleeding and death within 3-6 months after the procedure. RESULTS: Five hundred and seventy patients were screened across 12 sites. Of those, 486 were included (DAPT-C n = 360, DAPT-T n = 126). There was no difference in the primary outcome of stent thrombosis between the DAPT-C and DAPT-T groups (8% vs. 8%, p = 0.97) and no difference in any of the secondary safety outcomes. CONCLUSIONS: Using DAPT-C or DAPT-T regimens in a broad population of neuroendovascular stenting procedures appears to have similar safety and efficacy profiles. Further prospective evaluation is warranted to streamline the practice of DAPT selection and monitoring to determine the impact on clinical outcomes.

Dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk: a meta-analysis of randomized trials.

AIMS: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) is still debated. The current study, using the totality of existing evidence, evaluated the impact of an abbreviated DAPT regimen in HBR patients. METHODS AND RESULTS: A systematic review and meta-analysis was performed to search randomized clinical trials comparing abbreviated [i.e. very-short (1 month) or short (3 months)] with standard (≥6 months) DAPT in HBR patients without indication for oral anticoagulation. A total of 11 trials, including 9006 HBR patients, were included. Abbreviated DAPT reduced major or clinically relevant non-major bleeding [risk ratio (RR): 0.76, 95% confidence interval (CI): 0.61-0.94; I2 = 28%], major bleeding (RR: 0.80, 95% CI: 0.64-0.99, I2 = 0%), and cardiovascular mortality (RR: 0.79, 95% CI: 0.65-0.95, I2 = 0%) compared with standard DAPT. No difference in all-cause mortality, major adverse cardiovascular events, myocardial infarction, or stent thrombosis was observed. Results were consistent, irrespective of HBR definition and clinical presentation. CONCLUSION: In HBR patients undergoing PCI, a 1- or 3-month abbreviated DAPT regimen was associated with lower bleeding and cardiovascular mortality, without increasing ischaemic events, compared with a ≥6-month DAPT regimen. STUDY REGISTRATION: PROSPERO registration number CRD42021284004.

Dual antiplatelet therapy is associated with favorable outcome in acute minor stroke with an onset-to-door time beyond 24 h.

BACKGROUND/PURPOSE: In patients with noncardioembolic acute minor ischemic stroke (AMIS), dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel within 24 h after stroke onset was more effective than aspirin alone. This study investigated the efficacy and safety of DAPT in AMIS patients with an onset-to-door time (OTDT) of more than 24 h. METHODS: This was a retrospective analysis of a prospective stroke registry from 2015 to 2021. Patients with AMIS and an OTDT within seven days were classified into the Early (≤24 h) and Late groups (>24 h) according to the time of antiplatelet administration after stroke onset. RESULTS: In total, 691 patients were identified. Of these, 446 (64.5%) and 245 (35.5%) patients were classified into the Early and Late groups, respectively. The rates of recurrent infarction and symptomatic intracranial hemorrhage at 90 days were similar between the single antiplatelet therapy (SAPT) and DAPT subgroups in both the Early and Late groups. More patients in the DAPT subgroup had a favorable outcome (modified Rankin scale of 0-1) at 90 days in both Early (84.2% versus 75.0%, p = 0.016) and Late (88.2% versus 76.9%, p = 0.040) groups. DAPT was independently associated with a favorable outcome in both the Early (odds ratio, 1.95; 95% CI, 1.15-3.32; p = 0.013) and Late (odds ratio, 2.72; 95% CI, 1.14-6.48; p = 0.024) groups. CONCLUSION: In patients with AMIS and an OTDT of more than 24 h, DAPT was associated with a favorable outcome at 90 days.

One year clinical outcome of dual anti-platelet therapy with the Novel Ticagrelor plus Aspirin versus Clopidogrel plus Aspirin for Endovascular Intervention of patients with Intracranial Aneurysm: A meta-analysis.

BACKGROUND: The use of stents to treat un-ruptured intracranial aneurysms was first approved in the year 2002 in the United States as a Humanitarian Device Exemption. Antiplatelet therapy is mandatory following stent placement. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel has been the first line agents for the prevention of thromboembolic events following neuro-endovascular procedures. However, clopidogrel hypo-responsiveness has often been observed. In this analysis, we aimed to systematically compare one year clinical outcome of DAPT with the Novel Ticagrelor plus Aspirin versus Clopidogrel plus Aspirin for Endovascular Intervention of patients with Intracranial Aneurysm. METHODS: Online electronic databases were searched from June 2023 till July 2023 for relevant studies which compared DAPT with ticagrelor or clopidogrel for endovascular intervention in patients with intracranial aneurysm. The endpoints which were analyzed were classified into thromboembolic and hemorrhagic events. A fixed and a random effect statistical model were used during data analysis respectively. Risk ratio (RR) with 95 % confidence interval (CI) was used to represent the data following analysis. RESULTS: Five studies with a total number of 893 participants were included in this analysis. Three hundred and fifty eight (358) participants were assigned to the ticagrelor group whereas 535 participants were assigned to clopidogrel group. Participants' enrollment period ranged from the year 2009 to 2019. Our results showed that during a mean follow-up time period of one year, DAPT with ticagrelor was associated with significantly lower thromboembolic events with RR: 0.33, 95 % CI: 0.16 - 0.68; P = 0.003. In addition, at one year, DAPT with ticagrelor was not associated with any increase in hemorrhagic events (RR: 0.66, 95 % CI: 0.29 - 1.50; P = 0.32) when compared to DAPT with clopidogrel. CONCLUSION: At one year, DAPT with ticagrelor was associated with significantly lower thromboembolic events without any increase in hemorrhagic events when compared to clopidogrel associated DAPT for endovascular intervention of patients with intracranial aneurysm. However, even though ticagrelor-associated DAPT use appeared to be more effective and safe, this hypothesis should only be confirmed in larger upcoming trials.