BACKGROUND: We conducted a post hoc analysis of the ATAMIS (Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke) trial to investigate whether the priority of clopidogrel plus aspirin to aspirin alone was consistent between patients with and without stroke pathogenesis of large-artery atherosclerosis (LAA).
RESULTS: Patients with stroke classification randomized to a clopidogrel-plus-aspirin group and aspirin-alone group in a modified intention-to-treat analysis set of ATAMIS were classified into LAA and non-LAA subtypes. The primary outcome was early neurologic deterioration at 7 days, defined as a >2-point increase in National Institutes of Health Stroke Scale score compared with baseline, and safety outcomes were bleeding events and intracranial hemorrhage. We compared treatment effects in each stroke subtype and investigated the interaction. Among 2910 patients, 225 were assigned into the LAA subtype (119 in the clopidogrel-plus-aspirin group and 106 in the aspirin-alone group) and 2685 into the non-LAA subtype (1380 in the clopidogrel-plus-aspirin group and 1305 in the aspirin-alone group). Median age was 66 years, and 35% were women. A lower proportion of early neurologic deterioration was found to be associated with dual antiplatelet therapy in the LAA subtype (adjusted risk difference, -10.4% [95% CI, -16.2% to -4.7%]; P=0.001) but not in the non-LAA subtype (adjusted risk difference, -1.4% [95% CI, -2.6% to 0.1%]; P=0.06). No significant interaction was found (P=0.11).
CONCLUSIONS: Compared with the non-LAA subtype, patients with stroke of the LAA subtype may get more benefit from dual antiplatelet therapy with clopidogrel plus aspirin with respect to early neurologic deterioration at 7 days.
BACKGROUND: URL: clinicaltrials.gov; UnIque identifier: NCT02869009.

Early mechanical reperfusion, primarily via percutaneous coronary intervention, combined with timely antithrombotic drug administration, constitutes the main approach for managing acute coronary syndrome (ACS). Clinicians have access to a variety of antithrombotic agents, necessitating careful selection to balance reducing thrombotic events against increased bleeding risks. This review offers a comprehensive update on current antithrombotic therapy in ACS, emphasizing the need for individualized treatment strategies.

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.

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BACKGROUND: CYP2C19 genotype-guided de-escalation from ticagrelor or prasugrel to clopidogrel may optimize the balance between ischemic and bleeding risk in patients with acute coronary syndrome (ACS).
OBJECTIVE: This study sought to compare bleeding and ischemic event rates in genotyped patients vs standard care.
METHODS: Since 2015, ACS patients in the multicenter FORCE-ACS (Future Optimal Research and Care Evaluation in Patients with Acute Coronary Syndrome) registry received standard dual antiplatelet therapy (DAPT). Since 2021, genotype-guided P2Y12 inhibitor de-escalation was recommended at a single center, switching noncarriers of the loss-of-function allele CYP2C19∗3 or CYP2C19∗2 from ticagrelor or prasugrel to clopidogrel, whereas loss-of-function carriers remained on ticagrelor or prasugrel. The primary ischemic endpoint, a composite of cardiovascular mortality, myocardial infarction, or stroke, and the primary bleeding endpoint, Bleeding Academic Research Consortium 2, 3, or 5 bleeding, were compared between a genotyped cohort and a cohort treated with standard DAPT after 1 year.
RESULTS: Among 5,321 enrolled ACS patients, 406 underwent genotyping compared with 4,915 nongenotyped ACS patients on standard DAPT. In the genotyped cohort, 65.3% (n = 265) were noncarriers, 88.7% (n = 235) of whom were switched to clopidogrel. The primary ischemic endpoint occurred in 5.2% (n = 21) of patients in the genotyped cohort compared to 6.9% (n = 337) in the standard care cohort (adjusted HR: 0.82; 95% CI: 0.53-1.28). The primary bleeding rate was significantly lower in the genotyped cohort compared to the standard care cohort (4.7% vs 9.8%; adjusted HR: 0.47; 95% CI: 0.30-0.76).
CONCLUSIONS: The implementation of a CYP2C19 genotype-guided P2Y12 inhibitor de-escalation strategy in a real-world ACS population resulted in lower bleeding rates without an increase in ischemic events compared to a standard DAPT regimen.

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).
CONCLUSIONS: 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.

Objectives: Secondary prevention is crucial for reducing morbidity and mortality in patients following acute myocardial infraction (MI). However, adherence to cardiac rehabilitation (CR) and pharmacotherapy remains suboptimal despite strong guideline recommendations. This study investigated the adherence to CR, dual antiplatelet therapy (DAPT), and statins following acute MI and evaluated their impact on patient outcomes from a nationwide perspective in Austria. Methods: In this national observational study, all patients diagnosed with acute MI, defined as STEMI or NSTEMI, between April 2011 and August 2015 in Austria were included. Patient characteristics and comorbidities were derived from the Austrian national health insurance system using ICD-10 codes. Adherence to CR, high-intensity statins, and DAPT was assessed based on health insurance records and pharmacy prescription submissions. Cox Regression hazard analysis was used to explore the impact of non-adherence to CR on mortality. Results: Among 16,518 acute MI patients, only 13.4% adhered to the recommended CR programs, which was associated with a significantly lower risk of mortality (adjusted hazard ratio [HR] 0.73; 95% CI: 0.54-0.98; p = 0.036). In contrast, 66.4% of 23,240 patients did not comply with high-intensity statin therapy, correlating with an increased mortality risk (adjusted HR 1.16; 95% CI: 1.06-1.25; p < 0.001). Furthermore, among 22,331 patients analyzed for DAPT adherence, only 29.3% followed the guidelines, yet this adherence was linked to a 21% reduction in mortality over the observation period (adjusted HR 0.79; 95% CI: 0.72-0.88; p < 0.001). Conclusions: This nationwide study reveals alarmingly low adherence to CR and secondary preventive medications among acute MI patients, which is significantly linked to higher mortality rates. Enhanced efforts to promote awareness and adherence are crucial, involving structured referrals and personalized follow-ups to improve patient outcomes. Addressing these gaps through comprehensive healthcare strategies could substantially enhance cardiovascular health.

Despite significant goals achieved in diagnosis and treatment in recent decades, coronary artery disease (CAD) remains a high mortality entity and continues to pose substantial challenges to healthcare systems globally. After the latest guidelines, novel data have emerged and have not been yet considered for routine practice. The scope of this review is to go beyond the guidelines, providing insights into the most recent clinical updates in CAD, focusing on non-invasive diagnostic techniques, risk stratification, medical management and interventional therapies in the acute and stable scenarios. Highlighting and synthesizing the latest developments in these areas, this review aims to contribute to the understanding and management of CAD helping healthcare providers worldwide.

BACKGROUND: Drug coated balloons (DCB) are potentially less thrombogenic than drug eluting stents (DES).
OBJECTIVE: To explore the safety and the feasibility of single antiplatelet therapy in percutaneous coronary intervention with sirolimus-coated balloons.
METHODS: The All-comers Sirolimus-coated Balloon European Registry (EASTBOURNE) is a prospective investigator-driven registry assessing the performance of a novel sirolimus-coated balloon (SCB) in a real-world population. This prespecified post hoc analysis aimed at comparing the outcome in patients prescribed either single antiplatelet therapy (SAPT) or dual antiplatelet therapy (DAPT); choice of antiplatelet agent and duration of the regimen were at operator\'s discretion in both groups. Primary endpoint was target lesion revascularization (TLR) at 12 months. Secondary endpoints were bleeding grade 3-5 according to The Bleeding Academic Research Consortium (BARC) criteria and major adverse cardiovascular events (MACE) at 12 months follow-up.
RESULTS: Among 2123 patients enrolled in the study between September 2016 and November 2020, 113 patients (5.8 %) received SAPT while 1826 patients (94.1 %) received DAPT after SCB. The majority of the patients underwent DCB PCI for de novo lesions (n = 1091, 56.3 %) while 848 patients (47.7 %) had DCB revascularization for in-stent restenosis. No cases of TLR occurred in the SAPT group within one month after the index procedure, and no acute occlusive events were recorded during follow up in patients taking a single antiplatelet agent. Moreover, no differences in terms of TLR were observed between SAPT vs DAPT regimens nor in case of de novo treatment with an overall rate of TLR at 12 months of 7.7 % for SAPT and 5.6 % for DAPT (p = 0.6). The cumulative rate of MACE at 12 months was not different between SAPT and DAPT regimens (n = 12 [11.2 %] vs. n = 162 [8.9 %], p = 0.4), and results were consistent in the de novo and in-stent restenosis groups.
CONCLUSIONS: Our post hoc analysis of the EASTBOURNE registry suggests that the use of single antiplatelet agent after sirolimus-DCB PCI for both de novo or in-stent restenosis lesions is safe and effective and can help to contain the risk of bleeding in a selected population.
CONCLUSIONS: The manuscript aims to explore the feasibility of a single antiplatelet regimen following angioplasty using drug coated balloon with sirolimus. Among 2123 patients treated with sirolimus coated balloon (SCB), 113 patients (5.8 %) received a single antiplatelet therapy (SAPT) while 1826 patients (94.1 %) received dual antiplatelet therapy DAPT. No cases of target lesion revascularization occurred in the SAPT group within one month after the index procedure, and no acute occlusive events were recorded during follow up in patients taking a single antiplatelet agent. The cumulative rate of major adverse cardiovascular events at 12 months was not different between SAPT and DAPT regimens and results were consistent in the de novo and in-stent restenosis groups.

UNASSIGNED: A modified antiplatelet therapy approach after percutaneous coronary intervention (PCI), specifically reducing dual antiplatelet therapy (DAPT) duration and transitioning to P2Y12 inhibitor monotherapy, may offer advantages in terms of bleeding risk reduction. However, the impact of initiating aspirin-free P2Y12 inhibitor monotherapy immediately after PCI is not yet fully understood.
UNASSIGNED: We systematically searched the PubMed and Embase databases until January 2024 for studies that examined the use of P2Y12 inhibitor monotherapy as a treatment approach without initial DAPT following PCI.
UNASSIGNED: Four single-arm pilot prospective studies and 1 randomized controlled trial were included. In acute coronary syndrome patients with P2Y12 monotherapy following aspirin withdrawal immediately after PCI, the occurrence rates of the primary ischemic and bleeding endpoint were 2.91 % (8 out of 275 patients) and 1.09 % (3 out of 275 patients) respectively, whereas both the incidence rates of the primary ischemic and bleeding endpoints were 0.25 % (1 out of 407 patients) in individuals with stable coronary artery disease. In the STOPDAPT-3 trial comparing the effect of aspirin-free prasugrel monotherapy with standard DAPT after PCI, no differences were found in the primary ischemic or bleeding endpoints and most secondary outcomes (death, stroke, and myocardial infarction). However, there was an increased risk of coronary revascularization and stent thrombosis in the no-aspirin group.
UNASSIGNED: Single-arm studies suggest the safety and feasibility of aspirin-free P2Y12 inhibitor monotherapy without initial DAPT after PCI in selected patients with acute coronary syndrome or stable coronary artery disease. However, the safety and efficacy of this aspirin-free approach compared with standard DAPT strategies following PCI still require further investigation.