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.

2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease" provides recommendations to guide clinicians in the treatment of patients with lower extremity peripheral artery disease across its multiple clinical presentation subsets (ie, asymptomatic, chronic symptomatic, chronic limb-threatening ischemia, and acute limb ischemia). METHODS: A comprehensive literature search was conducted from October 2020 to June 2022, encompassing studies, reviews, and other evidence conducted on human subjects that was published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through May 2023 during the peer review process, were also considered by the writing committee and added to the evidence tables where appropriate. STRUCTURE: Recommendations from the "2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with peripheral artery disease have been developed.

Anticoagulation for post-operative atrial fibrillation after isolated coronary artery bypass grafting: a meta-analysis.

BACKGROUND AND AIMS: This study aimed to evaluate clinical outcomes in patients developing post-operative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) and characterize variations in oral anticoagulation (OAC) use, benefits, and complications. METHODS: A systematic search identified studies on new-onset POAF after CABG and OAC initiation. Outcomes included risks of thromboembolic events, bleeding, and mortality. Furthermore, a meta-analysis was conducted on these outcomes, stratified by the use or non-use of OAC. RESULTS: The identified studies were all non-randomized. Among 1 698 307 CABG patients, POAF incidence ranged from 7.9% to 37.6%. Of all POAF patients, 15.5% received OAC. Within 30 days, thromboembolic events occurred at rates of 1.0% (POAF: 0.3%; non-POAF: 0.8%) with 2.0% mortality (POAF: 1.0%; non-POAF: 0.5%). Bleeding rates were 1.1% for POAF patients and 2.7% for non-POAF patients. Over a median of 4.6 years, POAF patients had 1.73 thromboembolic events, 3.39 mortality, and 2.00 bleeding events per 100 person-years; non-POAF patients had 1.14, 2.19, and 1.60, respectively. No significant differences in thromboembolic risks [effect size -0.11 (-0.36 to 0.13)] and mortality [effect size -0.07 (-0.21 to 0.07)] were observed between OAC users and non-users. However, OAC use was associated with higher bleeding risk [effect size 0.32 (0.06-0.58)]. CONCLUSIONS: In multiple timeframes following CABG, the incidence of complications in patients who develop POAF is low. The use of OAC in patients with POAF after CABG is associated with increased bleeding risk.

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).

Low-dose aspirin for the prevention of atherosclerotic cardiovascular disease.

During the past 30 years, several developments have occurred in the antiplatelet field, including the role of aspirin in primary prevention of atherosclerotic cardiovascular disease. There have been several attempts to develop antiplatelet drugs more effective and safer than aspirin and a shift in emphasis from efficacy to safety, advocating aspirin-free antiplatelet regimens after percutaneous coronary intervention. Evidence supporting a chemopreventive effect of low-dose aspirin against colorectal (and other digestive tract) cancer has also strengthened. The aim of this article is to revisit the role of aspirin in the prevention of atherothrombosis across the cardiovascular risk continuum, in view of developments in the antiplatelet field. The review will offer a clinical perspective on aspirin's mechanism of action, pharmacokinetics, and pharmacodynamics. This will be followed by a detailed discussion of its clinical efficacy and safety.

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.

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.

Single versus dual antiplatelet therapy following percutaneous left atrial appendage closure-A systematic review and meta-analysis.

BACKGROUND: In the last few years, percutaneous LAA occlusion (LAAO) has become a plausible alternative in atrial fibrillation (AF) patients with contraindications to anticoagulation therapy. Nevertheless, the optimal antiplatelet strategy following percutaneous LAAO remains to be defined. METHODS: Studies comparing single antiplatelet therapy (SAPT) versus dual antiplatelet therapy (DAPT) following LAAO were systematically searched and screened. The outcomes of interest were ischemic stroke, device-related thrombus (DRT) and major bleeding. A random-effect meta-analysis was performed comparing outcomes in both groups. The moderator effect of baseline characteristics on outcomes was evaluated by univariate meta-regression analyses. RESULTS: Sixteen observational studies with 3255 patients treated with antiplatelet therapy (SAPT, n = 1033; DAPT, n = 2222) after LAAO were included. Mean age was 74.5 ± 8.3 years, mean CHA2DS2-VASc and HAS-BLED scores were 4.3 ± 1.5 and 3.2 ± 1.0, respectively. At a weighted mean follow-up of 12.7 months, the occurrence of stroke (RR 1.33; 95% CI 0.64-2.77; p =.44), DRT (RR 1.52; 95% CI 0.90-2.58; p =.12), and the composite of stroke and DRT (RR 1.26; 95% CI 0.67-2.37; p =.47) did not differ significantly between SAPT and DAPT groups. The rate of major bleedings was also not different between groups (RR 1.41; 95% CI 0.64-3.12; p =.39). CONCLUSIONS: Among AF patients at high bleeding risk undergoing percutaneous LAAO, a post-procedural minimalistic antiplatelet strategy with SAPT did not significantly differ from DAPT regimens regarding the rate of stroke, DRT and major bleeding.

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.

Cost-effectiveness analysis of CYP2C19 genotype-guided antiplatelet therapy for patients with acute minor ischemic stroke and high-risk transient ischemic attack in China.

AIMS: The study aimed to estimate the cost-effectiveness of CYP2C19 genotype-guided antiplatelet therapy using cilostazol and ticagrelor as an alternative to clopidogrel, compared to conventional antiplatelet therapy with clopidogrel and aspirin. METHODS: A 90-day decision tree and 30-year Markov model were employed to assess the costs and quality-adjusted life years (QALYs) of personalized antiplatelet therapy for patients with minor ischemic stroke and high-risk transient ischemic attack, compared to conventional antiplatelet therapy in the Chinese healthcare system. The primary outcome was the incremental cost-effectiveness ratio (ICER). The data sources included clinical trials, published literature, official documents and local prices. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to confirm the robustness of the findings. RESULTS: The base-case analysis indicated that the CYP2C19 genotype-guided antiplatelet strategy was cost-effective, and cilostazol group and ticagrelor group yielded an ICER of 3327.40 US dollars (USD)/QALY and 3426.92 USD/QALY, respectively, which were less than threshold. The one-way sensitivity analysis showed the results were robust, where the most sensitive parameter was the disability distribution in the modified Rankin scale 3-5. The probabilistic analysis showed that the CYP2C19 genotype-guided antiplatelet therapy with either cilostazol or ticagrelor was 100% cost-effective under the willingness-to-pay threshold. CONCLUSIONS: CYP2C19 genotype-guided antiplatelet therapy using cilostazol and ticagrelor as an alternative to clopidogrel appeared to be more cost-effective than conventional antiplatelet therapy for acute minor ischemic stroke and high-risk transient ischemic attack patients over 30 years in China.

Smokers with Elevated Glycated Albumin Could Not Benefit from Dual Antiplatelet Therapy after Minor Stroke or Transient Ischemic Attack.

INTRODUCTION: The aim of this study was to investigate the impact of smoking on dual antiplatelet therapy in patients with minor stroke or transient ischemic attack (TIA) under different glycated albumin (GA) levels. METHODS: We analyzed data from the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial. A subgroup of 3,044 patients with baseline GA levels was included and categorized by smoking status and GA levels. The primary efficacy outcome was a new stroke within 90 days. The safety outcome was any bleeding event at 90 days. The interaction of smoking status with antiplatelet therapy was calculated by Cox proportional hazards regression model. RESULTS: In patients with GA levels ≤15.5%, the proportion of smokers was 37.7% (719/1,908), while in patients with GA levels >15.5%, it was 51.6% (586/1,136). During the 3-month follow-up period, 299 (9.9%) patients had a new stroke occurrence. In patients with elevated GA levels, both smokers and nonsmokers could not benefit from dual antiplatelet therapy (smokers, adjusted hazard ratio [HR] 0.70, 95% confidence interval [CI]: 0.42-1.17; nonsmokers, adjusted HR 0.82, 95% CI: 0.57-1.18). In patients with normal GA levels, dual antiplatelet therapy reduced the risk of stroke recurrence in smokers by 72% (adjusted HR 0.28, 95% CI: 0.14-0.56) and in nonsmokers by 53% (adjusted HR 0.47, 95% CI: 0.26-0.86). However, whether the GA level was elevated or normal, there was no significant interaction between smoking status and antiplatelet therapy. CONCLUSIONS: Smokers with elevated GA levels could not benefit from dual antiplatelet therapy after minor stroke or TIA.

Anticoagulation and Antiplatelet Regimen in Cardiac Transplant. Clinical Characteristics, Outcomes, and Blood Product Transfusion.

BACKGROUND: We aimed to evaluate the characteristics, clinical outcomes, and blood product transfusion (BPT) rates of patients undergoing cardiac transplant (CT) while receiving uninterrupted anticoagulation and antiplatelet therapy. METHODS: A retrospective, single-center, and observational study of adult patients who underwent CT was performed. Patients were classified into four groups: (1) patients without anticoagulation or antiplatelet therapy (control), (2) patients on antiplatelet therapy (AP), (3) patients on vitamin K antagonists (AVKs), and (4) patients on dabigatran (dabigatran). The primary endpoints were reoperation due to bleeding and perioperative BPT rates (packed red blood cells (PRBC), fresh frozen plasma, platelets). Secondary outcomes assessed included morbidity and mortality-related events. RESULTS: Of the 55 patients included, 6 (11%) received no therapy (control), 8 (15%) received antiplatelet therapy, 15 (27%) were on AVKs, and 26 (47%) were on dabigatran. There were no significant differences in the need for reoperation or other secondary morbidity-associated events. During surgery patients on dabigatran showed lower transfusion rates of PRBC (control 100%, AP 100%, AVKs 73%, dabigatran 50%, p = 0.011) and platelets (control 100%, AP 100%, AVKs 100%, dabigatran 69%, p = 0.019). The total intraoperative number of BPT was also the lowest in the dabigatran group (control 5.5 units, AP 5 units, AVKs 6 units, dabigatran 3 units; p = 0.038); receiving significantly less PRBC (control 2.5 units, AP 3 units, AVKs 2 units, dabigatran 0.5 units; p = 0.011). A Poisson multivariate analysis showed that only treatment on dabigatran reduces PRBC requirements during surgery, with an expected reduction of 64.5% (95% CI: 32.4%-81.4%). CONCLUSIONS: In patients listed for CT requiring anticoagulation due to nonvalvular atrial fibrillation, the use of dabigatran and its reversal with idarucizumab significantly reduces intraoperative BPT demand.

Adherence and Persistence to Antiplatelet Therapy in Lower Extremity Peripheral Arterial Disease: A Danish Population Based Cohort Study.

OBJECTIVE: Adherence to antiplatelet therapy is recommended but unexplored in patients with symptomatic lower extremity peripheral arterial disease (PAD). Therefore, this study aimed to determine adherence and persistence to antiplatelet therapy in patients with PAD, defined as intermittent claudication and chronic limb threatening ischaemia. DESIGN: Population based nationwide cohort study. METHODS: This study included all Danish citizens aged ≥ 40 years with a first inpatient or outpatient diagnosis of symptomatic PAD between 2010 - 2017, and who had at least one prescription claim for aspirin and/or clopidogrel within 90 days after diagnosis. Adherence was determined by the proportion of days covered (PDC) during the first year after diagnosis. Persistence was defined as no treatment gap ≥ 30 days between prescription renewals over three year follow up. RESULTS: A total of 39 687 patients were eligible for inclusion, of whom 23 279 (58.7%) claimed a prescription for aspirin and/or clopidogrel within 90 days of diagnosis. Among these, 12 898 (55.4%) were prevalent users, while the remainder comprised new users who initiated the therapy after the index PAD diagnosis. The mean PDC was 74.5% (SD 35.0%) for prevalent users and 60.5% (SD 30.5%) for new users. Adherence increased with age and number of concomitant drugs. The overall one year cumulative incidence treatment discontinuation was 13.0% (95% CI 12.5 - 13.4%) overall, 17.2% (CI 16.6 - 17.9%) for prevalent users, and 7.9% (CI 7.4 - 8.4%) for new users. At three year follow up, the cumulative incidence of discontinuation was 31.5% (CI 30.9 - 32.2%) overall, 44.6% (CI 43.7 - 45.4%) for prevalent users, and 14.6% (CI 13.9 - 15.3) for new users. CONCLUSION: Less than 60% of patients with newly diagnosed symptomatic PAD claimed a prescription for antiplatelet therapy within 90 days of diagnosis, and both adherence and persistence were moderate during the first year after diagnosis. These findings underscore the importance of efforts to improve the initiation and continuation of antiplatelet therapy in patients with PAD.

Risk factors and management of gastrointestinal bleeding in patients with or without antiplatelet and anticoagulation therapy: a multicenter real-world prospective study.

BACKGROUND: Antiplatelet and anticoagulation drugs complicate acute gastrointestinal bleeding (GIB) patients. Limited data about the risk factors and patient management has been presented. This study explored the association between previous antiplatelet or anticoagulant drug usage and clinical outcomes in GIB patients to improve awareness further and optimize treatment. METHODS: We conducted a multicenter, non-interventional, real-world prospective study in 106 hospitals in 23 provinces in China. GIB patients confirmed in the emergency department were included and were grouped according to previous drug histories. Univariate analysis, multivariate logistic regression, and multivariate stratification models were performed separately to investigate the associations. RESULTS: A total of 2299 patients (57.23 ± 17.21 years old, 68.3% male) were included, of whom 20.1% and 2.9% received antiplatelet and anticoagulation therapy, respectively. The all-cause 28-day mortality rates in patients without antiplatelet or anticoagulants, patients undergoing antiplatelet treatment, and patients with anticoagulation therapy were 2.8%, 4.6%, and 10.5%, respectively. After adjusting for confounding factors, both antiplatelet [odd ratio (OR), 2.92; 95% confidence interval (CI), 1.48-5.76; p = 0.002] and anticoagulation therapy (OR, 8.87; 95% CI, 3.02-26.02; p < 0.001) were associated with higher 28-day mortality. In the subgroup analysis, blood transfusion, especially red blood cell transfusion, in patients undergoing antiplatelet and anticoagulation therapy was associated with a decreased death risk. CONCLUSION: We confirmed an association between concurrent antiplatelet or anticoagulation therapy in GIB patients and elevated 28-day mortality. Blood transfusions could improve poor outcomes in such patients.

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.

Short-term antiplatelet versus anticoagulant therapy after left atrial appendage closure: a systematic review and meta-analysis.

This meta-analysis compared the efficacy and safety of different antithrombotic regimens after left atrial appendage closure (LAAC). PubMed, Embase, Medline, Cochrane Library databases were systematically searched from their inception to March 2023. Patients were divided into short-term oral anticoagulation (OAC) group and antiplatelet therapy (APT) group. The incidence of events were performed using RevMan 5.4. The events including device-related thrombus (DRT), ischemic stroke/systemic embolization (SE), major bleeding, any bleeding, any major adverse event and all-cause mortality. Subgroup analysis were based on OAC alone or OAC plus single antiplatelet therapy (SAPT) in OAC group. Oral anticoagulants include warfarin and direct oral anticoagulant (DOAC). Fourteen studies with 35,166 patients were included. We found that the incidence of DRT (OR = 0.49, 95% CI 0.36-0.66, P＜0.0001) and all-cause mortality (OR = 0.71, 95% CI 0.57-0.89, P = 0.002) were significantly lower in OAC group than APT group. However, there was no statistical differences in the incidence rates of ischemic stroke/SE (OR = 0.77, 95% CI 0.49-1.20, P = 0.25), major bleeding (OR = 0.84, 95% CI 0.55-1.27, P = 0.84), any bleeding (OR = 0.83, 95% CI 0.56-1.22, P = 0.34) and any major adverse event (OR = 0.56, 95% CI 0.30-1.03, P = 0.06) in the two groups. Subgroup analysis found that the incidence of DRT, all-cause mortality and any major adverse event in OAC monotherapy were lower than that in APT group (P＜0.05), but not statistically different from other outcome. The incidence of DRT, all-cause mortality, any major adverse event and any bleeding in DOAC were significantly better than APT group (P＜0.05). While warfarin only has better incidence of DRT than APT (P＜0.05), there was no statistical difference between the two groups in other outcome (P＞0.05). The incidence of DRT was significantly lower than APT group (P＜0.05), major bleeding were higher, and the rest of the outcome did not show any statistically significant differences(P＞0.05) when OAC plus SAPT. Based on the existing data, short-term OAC may be favored over APT for patients who undergo LAAC. DOAC monotherapy may be favored over warfarin monotherapy or OAC plus APT, when selecting anticoagulant therapies.

Impact of hemodialysis on efficacies of the antiplatelet agents in coronary artery disease patients complicated with end-stage renal disease.

It is controversial whether hemodialysis affects the efficacy of the antiplatelet agents. We aimed to investigate the impact of hemodialysis on efficacies of the antiplatelet agents in coronary artery disease (CAD) patients complicated with end-stage renal disease (ESRD). 86 CAD patients complicated with ESRD requiring hemodialysis were consecutively enrolled. After 5-day treatment with aspirin and clopidogrel or ticagrelor, the platelet aggregations induced by arachidonic acid (PLAA) or adenosine diphosphate (PLADP), and the P2Y12 reaction unit (PRU) were measured before and after hemodialysis. The propensity matching score method was adopted to generate a control group with normal renal function from 2439 CAD patients. In patients taking aspirin, the PLAA remained unchanged after hemodialysis. In patients taking clopidogrel, the PLADP (37.26 ± 17.04 vs. 31.77 ± 16.09, p = 0.029) and corresponding clopidogrel resistance (CR) rate (23 [48.9%] vs. 14 [29.8%], p = 0.022) significantly decreased after hemodialysis, though PRU remained unchanged. Subgroup analysis indicated that PLADP significantly decreased while using polysulfone membrane (36.8 ± 17.9 vs. 31.1 ± 14.5, p = 0.024). In patients taking ticagrelor, PLADP, and PRU remained unchanged after hemodialysis. ESRD patients had higher incidences of aspirin resistance (AR) and CR compared to those with normal renal function (AR: 16.1% vs. 0%, p = 0.001; CR: 48.4% vs. 24.8%, p = 0.024). Hemodialysis does not have negative effect on the efficacies of aspirin, clopidogrel and ticagrelor in ESRD patients with CAD. ESRD patients have higher incidences of AR and CR compared with those with normal renal function.Trial registration ClinicalTrials.gov Identifier: NCT03330223, first registered January 4, 2018.