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BACKGROUND: Recent clinical trials established the benefit of dual antiplatelet therapy with aspirin and clopidogrel (DAPT-AC) in early-presenting patients with minor ischemic stroke. However, the impact of these trials over time on the use and outcomes of DAPT-AC among the patients with nonminor or late-presenting stroke who do not meet the eligibility criteria of these trials has not been delineated. METHODS AND RESULTS: In a multicenter stroke registry, this study examined yearly changes from April 2008 to August 2022 in DAPT-AC use for stroke patients ineligible for CHANCE/POINT (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events/Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) clinical trials due to National Institutes of Health Stroke Scale >4 or late arrival beyond 24 hours of onset. A total of 32 118 patients (age, 68.1±13.1 years; male, 58.5%) with National Institutes of Health Stroke Scale of 4 (interquartile range, 1-7) were analyzed. In 2008, DAPT-AC was used in 33.0%, other antiplatelets in 62.7%, and no antiplatelet in 4.3%. The frequency of DAPT-AC was relatively unchanged through 2013, when the CHANCE trial was published, and then increased steadily, reaching 78% in 2022, while other antiplatelets decreased to 17.8% in 2022 (Ptrend

Background The optimal treatment for acute minor ischemic stroke is still undefined. and options include dual antiplatelet treatment (DAPT), intravenous thrombolysis (IVT), or their combination. We aimed to investigate benefits and risks of combining IVT and DAPT versus DAPT alone in patients with MIS. Methods and Results This is a prespecified propensity score‐matched analysis from a prospective multicentric real‐world study (READAPT [Real‐Life Study on Short‐Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or Transient Ischemic Attack]). We included patients with MIS (National Institutes of Health Stroke Scale score at admission ≤5), without prestroke disability (modified Rankin scale [mRS] score ≤2). The primary outcomes were 90‐day mRS score of 0 to 2 and ordinal mRS distribution. The secondary outcomes included 90‐day risk of stroke and other vascular events and 24‐hour early neurological improvement or deterioration (≥2‐point National Institutes of Health Stroke Scale score decrease or increase from the baseline, respectively). From 1373 patients with MIS, 240 patients treated with IVT plus DAPT were matched with 427 patients treated with DAPT alone. At 90 days, IVT plus DAPT versus DAPT alone showed similar frequency of mRS 0 to 2 (risk difference, 2.3% [95% CI −2.0% to 6.7%]; P=0.295; risk ratio, 1.03 [95% CI 0.98–1.08]; P=0.312) but more favorable ordinal mRS scores distribution (odds ratio, 0.57 [95% CI 0.41–0.79]; P

Background Recent clinical trials established the benefit of dual antiplatelet therapy with aspirin and clopidogrel (DAPT‐AC) in early‐presenting patients with minor ischemic stroke. However, the impact of these trials over time on the use and outcomes of DAPT‐AC among the patients with nonminor or late‐presenting stroke who do not meet the eligibility criteria of these trials has not been delineated. Methods and Results In a multicenter stroke registry, this study examined yearly changes from April 2008 to August 2022 in DAPT‐AC use for stroke patients ineligible for CHANCE/POINT (Clopidogrel in High‐Risk Patients with Acute Nondisabling Cerebrovascular Events/Platelet‐Oriented Inhibition in New TIA and Minor Ischemic Stroke) clinical trials due to National Institutes of Health Stroke Scale >4 or late arrival beyond 24 hours of onset. A total of 32 118 patients (age, 68.1±13.1 years; male, 58.5%) with National Institutes of Health Stroke Scale of 4 (interquartile range, 1–7) were analyzed. In 2008, DAPT‐AC was used in 33.0%, other antiplatelets in 62.7%, and no antiplatelet in 4.3%. The frequency of DAPT‐AC was relatively unchanged through 2013, when the CHANCE trial was published, and then increased steadily, reaching 78% in 2022, while other antiplatelets decreased to 17.8% in 2022 (Ptrend

Background: The outcomes of minor ischemic stroke resulting from small artery occlusion (SAO-MIS) have not yet been characterized after dual antiplatelet treatment (DAPT) has become the standard of care. We provided updated figures on the short-term prognosis of SAO-MIS treated with early short-term DAPT and compared the outcomes of SAO-MIS versus non-SAO-MIS patients., Methods: This is a prespecified sub-analysis from a prospective multicentric real-world study (READAPT, NCT05476081) including patients with minor (NIHSS≤5) non-cardioembolic ischemic stroke treated with DAPT. The primary outcome was a composite of 90-day symptomatic ischemic stroke or major cardiovascular events. Secondary outcomes were the 90-day ordinal distribution of modified Rankin Scale (mRS) scores, 90-day excellent functional outcome (mRS of 0 to 1), and 24-h early neurological deterioration (END). Safety outcomes were 90-day intracerebral hemorrhage, moderate-to-severe and any bleedings. All outcomes were compared between SAO-MIS and non-SAO-MIS patients., Results: We included 678 MIS, of whom 253 (37.3 %) were SAO-related. At 90 days, 3 patients with SAO-MIS had primary outcome (1.2 % [95 % CI 0.2 %-3.5 %]), which were all SAO-related ischemic strokes. For the secondary outcomes, most SAO-MIS patients (n = 191, 75.5 %) had 90-day excellent functional outcome and 12 had 24-h END (4.7 % [95 % CI 2.5 %-8.3 %]). Referring to safety outcomes, 90-day intracerebral hemorrhage occurred only in one patient with SAO-MIS (0.4 % [95 % CI 0.0 %- 2.2 %]). Compared to non-SAO-MIS, the 90-day risk of recurrent vascular events was significantly lower among SAO-MIS (aHR 0.24 [95 % CI 0.08-0.68]; p = 0.007), while there were not significant differences in other secondary outcomes, nor in the risk of safety events., Conclusions: Our findings show overall favorable short-term prognosis after SAO-MIS treated with DAPT. Future studies should investigate factors associated with residual stroke risk and long-term outcomes of SAO-MIS., Competing Interests: Declaration of competing interest Andrea Zini reports compensation from Angels Initiative, Boehringer-Ingelheim, Daiichi Sankyo for consultant services; from Angels Initiative, Boehringer-Ingelheim, CSL Behring for speaking honoraria or other education services; from Daiichi Sankyo for meeting; from Bayer, and Astra Zeneca for participation on a Data Safety, Monitoring Board or Advisory Board; and he is member of ESO guidelines, ISA-AII guidelines, and IRETAS steering committee. Raffaele Ornello reports grants from Novartis and Allergan; compensation from Teva Pharmaceutical Industries, Eli Lilly and Company, and Novartis for other services; and travel support from Teva Pharmaceutical Industries. Simona Sacco reports compensation from Novartis, NovoNordisk, Allergan, AstraZeneca, Pfizer Canada, Inc., Eli Lilly and Company, Teva Pharmaceutical Industries, H. Lundbeck A/S, and Abbott Canada for consultant services; employment by University of L'Aquila; and compensation from Novartis for other services. Maurizio Paciaroni reports compensation from Daiichi Sankyo Company, Bristol Myers Squibb, Bayer, and Pfizer Canada, Inc., for consultant services. Danilo Toni reports compensation from Alexion, Astra Zeneca, Medtronic, and Pfizer for consultant services and participation on a Data Safety, Monitoring Board or Advisory Board. The other authors report no conflicts., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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

Zhong-Guo Fan,1 Wen-Ling Zhang,2 Bing Xu,1 Jun Ji,1 Nai-Liang Tian,3 Sheng-Hu He1 1Department of Cardiology, Subei People’s Hospital of Jiangsu Province, Yangzhou University, Yangzhou, Jiangsu, China; 2Department of Geriatric Gastroenterology, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China; 3Department of Cardiology, Nanjing First Hospital, Nanjing Heart Center, Nanjing Medical University, Nanjing, Jiangsu, China Background: The efficacy and safety of ticagrelor following percutaneous coronary intervention for patients with acute coronary syndrome remains unclear. This study sought to evaluate clinical outcomes of ticagrelor as part of dual-antiplatelet treatment for these patients. Methods: PubMed, MEDLINE, Embase, and other Internet sources were searched for eligible citations. The primary end point was major adverse cardiovascular and cerebrovascular events, consisting of cardiovascular death, myocardial infarction, and stroke. The secondary end point was the occurrence of definite/probable stent thrombosis (ST). The risk of bleeding was chosen to be the safety end point. Results: Eleven clinical trials – six randomized trials and five observational trials – were finally analyzed. A tendency toward reduction in the risk of major adverse cardiovascular and cerebrovascular events was observed only with respect to ticagrelor (OR 0.83, 95% CI 0.66–1.03; P=0.091), which might have resulted from the lower risk of cardiovascular death (OR 0.78, 95% CI 0.68–0.89; P

Cardiovascular diseases are responsible for the majority of deaths in the developed countries as well as in the Czech Republic. Pharmacotherapy after PCI in patients with chronic CAD must be tailored to the individual patient with respect to patient characteristics (age, history of MI, presence of other risk factors, etc.), coronary involvement and systolic function of the left ventricle (single versus multivessel disease, completeness of revascularization, preserved or depressed left ventricular systolic function), and with respect to the percutaneous procedure itself (number of stents, bare versus drug-eluting stents, bifurcation stenosis, left main PCI, etc.). The goal of the treatment is pain relief and improvement of the patient’s outcome. [ABSTRACT FROM AUTHOR]

Aims Guidelines differ in their recommendations on therapy to prevent gastrointestinal bleeding for patients treated with dual antiplatelet treatment (DAPT). We sought to investigate the effectiveness of proton pump inhibitors (PPIs) to prevent upper gastrointestinal (UGI) bleeding in patients using DAPT following myocardial infarction (MI) in relation to current European Society of Cardiology guidelines recommendations. Methods and results We linked Danish nationwide registries to identify patients taking DAPT 7 days following hospital discharge for an acute MI, and excluded individuals on anticoagulation therapy. We used multiple Cox regression modelling, to compute average risk of UGI bleeding in relation to PPI use. The associated treatment efficacy was compared based on guideline risk assessment. We studied 46 301 patients on DAPT after MI. Only 35% of patients at higher risk of UGI bleeding received recommended treatment with a PPI based on the guideline criteria. The 1--year risk of UGI bleeding was 1.0% [95% confidence interval (CI) 0.9–1.1%] and 1.7% (CI 1.5–2.0%) for high-risk patients. Overall PPI compared with no therapy, was associated with a risk ratio for UGI bleeding of 0.62 (CI 0.48–0.77) corresponding to an absolute risk difference of 0.44% (CI 0.39–0.48%). Proton pump inhibitor therapy was associated with a similar absolute risk difference [0.47% (CI 0.43–0.51%)] for high-risk patients. Conclusion Proton pump inhibitor therapy is used less than suggested by guidelines in patients treated with DAPT following MI and was generally associated with reduced risk of UGI bleeding. Considering the overall low risk of bleeding, more focus should be on identifying patients benefiting the most from PPI therapy. View large Download slide View large Download slide [ABSTRACT FROM AUTHOR]

Nowadays, elderly people represent a growing population segment with a well known increased risk of both ischemic and bleeding events. Current acute coronary syndrome guidelines, strongly recommend dual antiplatelet therapy (DAPT) with few specific references for aged patients due to lack of evidence. Patients aged = 75 years are misrepresented in the classic derivation trials cohorts. Strategies to reduce the bleeding risk in this group of patients are urgently needed for the daily clinical practice. Identify the specific age related bleeding risk factors and the importance of an integral geriatric assessment remains challenging. Some of the available in-hospital and out-hospital bleeding risk scores have shown a lower to moderate predictive ability in older patients and no specific tools are developed in elderly population. The importance of an appropriate vascular access choice, type and duration of antiplatelet drugs is crucial to reduce the bleeding risk. Increase radial approaches and short DAPT duration leads to reduce hemorrhages. One interesting subgroup of patients is those who need chronic anticoagulation therapy after percutaneous coronary intervention, due to their very high risk of bleeding. New alternatives as dual therapy with oral anticoagulation and only one antiplatlet drug should be considered. In current review, we evaluate the available evidence about bleeding risk in elderly. [ABSTRACT FROM AUTHOR]

Zhong-Guo Fan,1,* Guo-Bin Ding,2,* Xiao-Bo Li,1,3 Xiao-Fei Gao,1,3 Ya-Li Gao,1 Nai-Liang Tian1,3 1Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 2Department of Cardiology, Taixing People’s Hospital, Yangzhou University, Taizhou, 3Department of Cardiology, Nanjing Heart Center, Nanjing, People’s Republic of China *These authors contributed equally to this work Background: The optimal antiplatelet regimen after in-coronary intervention among patients presenting with complex coronary artery lesions or acute coronary syndrome (ACS) has remained unclear. This study sought to evaluate the clinical outcomes of triple antiplatelet treatment (TAPT) (cilostazol added to aspirin plus clopidogrel) in these patients.Methods: The PubMed, EMBASE, MEDLINE, and other Internet sources were searched for relevant articles. The primary end point was major adverse cardiac events (MACE), including all-cause mortality, myocardial infarction, and target vessel revascularization. The incidence of definite/probable stent thrombosis and bleeding were analyzed as the safety end points.Results: Eleven clinical trials involving 9,553 patients were analyzed. The risk of MACE was significantly decreased following TAPT after stent implantation in the ACS subgroup (odds ratio [OR]: 0.72; 95% confidence interval [CI]: 0.61–0.85; P

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Purpose: Coronary angiography provides no details on underlying pathology in acute coronary syndromes (ACS). Optical coherence tomography (OCT) can visualize coronary atherosclerosis, thrombus formation, and plaque rupture in patients with myocardial infarction (MI) where coronary angiography is unclear.Materials and Methods: We present a case series containing six young patients with ACS, four of them due to non-obstructive thrombus, in whom the operators refrained from stent implantation despite an identifiable culprit lesion with OCT-validated thrombus formation.Results: The median age was 31.5 years. In four of these six patients, no invasive intervention was performed while the remaining two patients underwent thrombus aspiration and balloon angioplasty without stent implantation. Four patients were examined at the primary evaluation and all patients were examined by OCT between 3-5 days after initial examination. This short-term follow-up with OCT showed non-obstructive thrombus formation in all patients with varying degrees of thrombus resolution. No adverse cardiac events were reported after a median follow up of 5.5 months.Conclusions: OCT can visualize thrombus formation in young ACS patients with non-obstructive thrombus or following thrombus reduction by aspiration and balloon dilatation. These patients seems safely treated with a conservative medical approach rather than with stent implantation. [ABSTRACT FROM AUTHOR]

Objectives: New dual antiplatelet therapies (DAPTs) have been introduced in clinical practice for patients with acute coronary syndrome (ACS). This nationwide study investigated DAPT patterns over time and patient characteristics associated with the various treatments in a population with ACS. Design: This observational cohort study linked morbidity, mortality and medication data from Swedish national registries. Results: Overall, 91% (104 012 patients) of all patients admitted to the hospital with an ACS (2009-2013) were alive after discharge and included in this study. Compared with 2009, in 2013 patients investigated with angiography increased by 10%, patients revascularized with percutaneous coronary intervention (PCI) increased by 11% and patients prescribed DAPT increased by 8%. Mean DAPT duration increased from 225 to 298 days in patients investigated with angiography, and from 155 to 208 days in patients who were not investigated with angiography. Furthermore, in patients undergoing angiography a treatment switch from clopidogrel to ticagrelor was observed. DAPT with prasugrel was used to a low extent. Approximately 10% of patients initiated on prasugrel or ticagrelor switched to clopidogrel during the first year of treatment. Conclusion: During the study more patients underwent angiography and PCI. There was an increase in the proportion of ACS patients receiving DAPT, as well as longer duration of DAPT in line with ESC guidelines. Among DAPT-treated patients, ticagrelor has emerged as the preferred P2Y12 antagonist in patients undergoing angiography, whereas clopidogrel tended to be prescribed to patients treated non-invasively. [ABSTRACT FROM AUTHOR]

Background Duration of dual antiplatelet therapy (DAPT) following drug-eluting stents (DES) remains controversial and is a topic of ongoing research. Methods Direct and adjusted indirect comparisons of all the recent randomized control trials (RCTs) were performed to evaluate the safety of short-term versus long-term DAPT following DES. Results 8 RCTs were identified and 7 (16,318 subjects) were included. 4 groups of 3 vs 12 months, 6 vs 12 months, 6 vs 24 months and 12 vs 24 months of DAPT were used for direct comparison. There was no significant difference in stent thrombosis, myocardial infarction (MI), stroke and revascularization, cardiovascular and all-cause mortality between the different durations in all 4 groups. Pooling trials of 3-6 months of DAPT against 12 months, we found a significant reduction in the risk of total bleeding (RR 0.61, 95% CI 0.43-0.87). Adjusted indirect comparison between 3 vs 6 months, 3 vs 24 months and 6 vs 24 month duration of DAPT showed no significant differences in risk of death or MI, or revascularization between 3 or 6 months and 24 months. However, 24 months of DAPT was associated with significantly more bleeding than 3 or 6 months. Conclusions 3 to 6 months of DAPT following second generation DES and above is safe with no increased risk of thrombotic complications and mortality, and lower bleeding risk. However a tailored approach may be more appropriate for high-risk patients. [ABSTRACT FROM AUTHOR]

Background Dual antiplatelet therapy with clopidogrel and aspirin reduces the presence and number of microembolic signals in patients with large artery disease. However, whether it is effective in patients with intracranial disease alone remains uncertain. We performed a subgroup analysis of the The CLopidogrel plus Aspirin for Infarction Reduction ( CLAIR in acute stroke or transient ischemic attack patients with large artery stenosis and microembolic signals) study of only patients with intracranial occlusive disease, excluding those with extra cranial disease. Methods CLAIR was a randomized-controlled, open-label, multicenter clinical trial with blinded outcome evaluation, which recruited patients with symptoms of ischemic stroke or transient ischemic attack within seven-days of onset, with large artery stenosis verified by transcranial Doppler and carotid ultrasound, and with microembolic signals detected by transcranial Doppler recording. All patients were randomized to receive clopidogrel plus aspirin daily for seven-days (dual treatment), or aspirin alone for seven-days (monotherapy). Repeated transcranial Doppler recordings for microembolic signals were made on day one, two, and seven. This subgroup study only analyzed the patients with purely intracranial large artery disease and excluded those with extra cranial stenosis. Results There were 70 patients recruited with purely intracranial stenosis, 34 in the dual treatment group and 36 in the monotherapy group. The proportion of the patients with positive emboli at day seven in the dual treatment group was significantly lower than that in the monotherapy group (relative risk reduction 56·5%, 95% confidence interval 2·5-80·6; P = 0·029). The number of emboli in the dual treatment group decreased significantly at day two ( P = 0·043) and day seven ( P = 0·018) compared with the monotherapy group. After adjustment for the number of emboli at day one, the effect of dual treatment was still significant for the reduction of presence (relative risk reduction 56·0%; 95% confidence interval 5·4−79·6; P = 0·036) and number (adjusted mean difference −0·9; 95% confidence interval −1·5 to −0·3; P = 0·004) of positive emboli at day seven. Conclusions Dual treatment with clopidogrel and aspirin for seven-days is more effective than aspirin alone to reduce microembolic signals in patients with intracranial arterial stenosis. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The effects of intracoronary injection of mononuclear bone marrow cells (mBMC) on haemostasis are not clarified. The aim of the present substudy of the autologous stem cell transplantation in acute myocardial infarction (ASTAMI) trial was to investigate the influence of intracoronary injection of mBMC on selected circulating prothrombotic markers. Materials and methods: One hundred patients with ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) on the left descending coronary artery were randomized to receive mBMC (Tx) (median 6days after the STEMI) or to a control group. Fasting blood samples were drawn the day before Tx (day-1, 4–5days after the STEMI), and 1day, 3days, 2–3weeks and 3months after Tx. Results: No significant differences in changes between the groups were observed from day-1 to any later time points in the levels of TF (tissue factor), F1+2 (prothrombin fragment 1+2), D-dimer, ETP (endogenous thrombin potential), PAI-1 (plasminogen activator inhibitor 1) or tissue plasminogen activator. However, TF and F1+2 decreased from day-1 to the subsequent time points in both groups, except from a small increase of TF at 3months in the control group. In both groups, D-dimer and ETP decreased from day-1 to 2–3weeks and 3months, whereas PAI-1 increased to 2–3weeks and 3months. Conclusions: Intracoronary injection of mBMC did not influence on prothrombotic markers in patients with STEMI. Reduction in several prothrombotic markers from day-1 to 2–3weeks and 3months could be demonstrated in both groups indicating decreased hypercoagulability. This is a substudy of the ASTAMI trial which is registered at www.clinicaltrials.gov, NCT 00199823. [Copyright &y& Elsevier]

Copyright of Der Kardiologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The authors present a fatal case of late thrombosis of paclitaxel-eluting stent implanted in the left main stem occurring 6 months after the procedure and 3 weeks after the cessation of clopidogrel. An autopsy has shown the lack of endothelization of deployed stent. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effect of polymorphisms affecting the clopidogrel metabolism (CYP3A4 IVS10+12G/A and CYP2C19∗2) and the P2Y12 receptor (P2Y12 T744C) on modulating platelet function in acute coronary syndrome patients on dual antiplatelet treatment.Residual platelet reactivity (RPR) phenomenon on antiplatelet therapy requires clarification. P2Y12 T744C, CYP3A4 IVS10+12G/A and, in healthy individuals only, CYP2C19∗2 polymorphisms have been investigated; however, the influence on platelet reactivity in a large population of high-risk vascular patients on dual antiplatelet treatment has not yet been elucidated.A total of 1419 acute coronary syndrome patients on dual antiplatelet treatment were studied. Platelet function was evaluated by platelet-rich plasma aggregation. Electronic nanochips and restriction-fragment length polymorphism were used for analysis of polymorphisms.Only CYP2C19∗2, out of the three investigated polymorphisms, is associated with higher platelet reactivity. Carriers of the ∗2 allele had significantly higher platelet aggregation values after arachidonic acid (AA; P=0.043), 2 μmol/l adenosine 5′ diphosphate (ADP; P<0.0001) and 10 μmol/l ADP (P=0.001) stimuli. The genotype distribution of CYP2C19∗2 polymorphism significantly differed between patients with and without RPR, as evaluated by 10-μmol/l ADP-induced platelet aggregation (P=0.002) and by AA-induced platelet aggregation (P=0.045). At the multivariate linear regression analysis, the CYP2C19∗2 polymorphism remained a significant and independent risk factor for dual antiplatelet treatment variability.This study demonstrates, for the first time, that the ∗2 CYP2C19 allele is associated with higher platelet aggregability and RPR in high-risk vascular patients on dual antiplatelet treatment. These findings can have a significant impact on the future design of pharmacogenetic antiaggregant strategies for high-risk vascular patients on dual antiplatelet treatment. [ABSTRACT FROM AUTHOR]

Coexistence of atrial fibrillation and ischaemic heart disease is very common and patients affected by these conditions are exposed to both a high ischaemic and haemorrhagic risk. The choice of an appropriate combination of anticoagulant therapy with single or dual antiplatelet treatment is indeed one of the most relevant and contemporary challenges in clinical practice. Several studies and meta-analyses pointed out that 1 year after an acute coronary syndrome or percutaneous revascularization, the use of the sole anticoagulant therapy is not associated with increased risk of major cardiovascular events, whereas there is a substantial reduction of clinical significant bleeding events, as compared to patients treated also with antiplatelet medications. However, there are no clear-cut data regarding the possibility to implement this strategy in each patient, regardless the cardiovascular risk class. Furthermore, for patients requiring a combined anticoagulant and antiplatelet treatment, the available data seem to favour an association of direct anticoagulant and inhibitors of P2Y12, rather than regimens including aspirin. These data are derived mainly from observational studies, with all their limitations. The use of aspirin could be beneficial in patients with significant comorbidities, such as diabetes mellitus, or with severe peripheral atherosclerotic disease, involving the carotids and other large arteries., (Published on behalf of the European Society of Cardiology. © The Author(s) 2020.)

Aims: In PEGASUS-TIMI 54, ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15-16% in stable patients with a prior myocardial infarction (MI) 1-3 years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60 mg b.i.d. initiated up to 2 years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment., Methods and Results: Of the 21 162 patients enrolled in PEGASUS-TIMI 54, 10 779 patients were included in the primary analysis for this study, randomized to ticagrelor 60 mg (n = 5388) or matching placebo (n = 5391). The cumulative proportions of patients with events at 36 months were calculated by the Kaplan-Meier (KM) method. The composite of CV death, MI, or stroke occurred less frequently in the ticagrelor group (7.9% KM rate vs. 9.6%), hazard ratio (HR) 0.80 [95% confidence interval (CI) 0.70-0.91; P = 0.001]. Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (0.67-0.96; P = 0.018). Thrombolysis in myocardial infarction major bleeding was more frequent in the ticagrelor group 2.5% vs. 1.1%; HR 2.36 (1.65-3.39; P < 0.001). The corresponding HR for fatal or intracranial bleeding was 1.17 (0.68-2.01; P = 0.58)., Conclusion: In PEGASUS-TIMI 54, treatment with ticagrelor 60 mg as recommended in the EU label, was associated with a relative risk reduction of 20% in CV death, MI, or stroke. Thrombolysis in myocardial infarction major bleeding was increased, but fatal or intracranial bleeding was similar to placebo. There appears to be a favourable benefit-risk ratio for long-term ticagrelor 60 mg in this population., Clinical Trial Registration: http://www.clinicaltrials.gov NCT01225562., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Endovascular interventions in patients with peripheral artery disease (PAD) have been significantly developed and improved in the last decade. However, guideline recommendations for the treatment in postprocedural period still vary significantly, ranging from the use of aspirin alone to the use of conventional dual antiplatelet treatment (DAPT) clopidogrel with aspirin for one to three months followed by continued long-term aspirin use. Treatment recommendations focus on platelet aggregation, and do not include the role of coagulation cascade in thrombus formation.1,2 Loss of patency after endovascular treatment remains high, ranging from 17 to 40% in patients on dual antiplatelet therapy. Endovascular treatment can also result in catheter-induced damage to the endothelium, exposing tissue factor-rich subendothelium to the blood stream and creating a thrombogenic environment wherein platelets and coagulation factors are activated. That means that with DAPT we do not protect the endothelium or lesion surface i.e. activation of coagulation cascade. At the moment there are several ongoing trials (up to approx. 200 patients) with postprocedural combination of anticoagulant (NOACs) and aspirin treatment for one to three months followed by aspirin. Risk of bleeding according to ISTH (International Society on Thrombosis and Hemostasis) criteria was as follows: non-major bleeding and all bleedings were higher with NOACs and aspirin than with clopidogrel and aspirin, though major bleeding was lower. Further on, in PAD patients, six months composite endpoint event rates showed that NOACs was more favorable treatment than clopidogrel in all cases of restenosis, with or without target lesion revascularization, ischemic complications including amputation and/or major adverse cardiac events. It was also more favorable treatment for all different characteristics of patients such as: gender, lesion length, age and region. Despite significantly increasing number of PAD endovascular procedures still remains dilemma due to postprocedural protection of endothelium and lesion surface. NOACs and aspirin combination is a new promising approach. [ABSTRACT FROM AUTHOR]

Dual antiplatelet therapy (DAPT) has represented for decades the cornerstone of treatment for the prevention of ischemic complications, including stent thrombosis, in patients undergoing percutaneous coronary intervention (PCI). Despite the evolution in stent technologies, which has allowed the reduction in the minimum required duration of DAPT, the optimal duration of DAPT to ensure the best safety and efficacy still remains largely debated. Indeed, the results from investigations regarding the optimal DAPT duration based on stent type is limited. Overall, DAPT duration should be defined as a minimal period needed to prevent the vulnerable phase of having stent thrombosis, which may indeed be more stent specific, from that required for secondary prevention of ischemic complications, which may depend on the general risk profile of the patient. The present manuscript is an overview on the optimal duration of DAPT after stent implantation, providing an overview on the evolution of stent technology over the past decades and how this has impacted considerations on DAPT duration as well providing future perspectives in the field., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Dual antiplatelet treatment (DAPT) is a cornerstone of maintenance medication of patients following elective percutaneous coronary interventions or an acute coronary syndrome (ACS), e. g. ST elevation myocardial infarction, non-ST elevation myocardial infarction and unstable angina. In recent years the inclusion of P2Y 12 inhibition in addition to low-dose acetylsalicylic acid has been intensively debated. Following the introduction of the modern generation of drug-eluting stents for elective coronary interventions, the duration of the necessary DAPT has been clearly reduced. In patients with ACS the question arises when treatment with one of the more potent P2Y 12 inhibitors, such as prasugrel and ticagrelor should be used instead of clopidogrel. A potential extension of DAPT beyond 12 months can be considered in high-risk patients after implantation of bioresorbable vascular scaffolds and following myocardial infarction. A special focus is on those patients who have already been treated with oral anticoagulants for stroke prevention in atrial fibrillation and require additional platelet inhibition following coronary stenting. This article summarizes and assesses the major recommendations given in the Focused Update DAPT 2017 of the European Society of Cardiology (ESC). In particular the recommendations address strategies to reduce an increased risk of bleeding based on clinical predictors.

Current percutaneous coronary intervention guidelines recommend dual antiplatelets (aspirin 100 mg + clopidogrel 75 mg daily) for at least 12 mo following drug-eluting stent (DES) implantation if patients are not at high risk of bleeding. Several reports have tried to shorten the dual antiplatelet therapy to 3-6 mo, especially following next-generation DES implantation, for cost-effectiveness. However, the clinical results are inconsistent and the data regarding next-generation DESs limited. In this report, recently published important pivotal reports regarding the optimal duration of dual antiplatelets following DES implantation are summarized.

Background: Dual antiplatelet therapy with clopidogrel and aspirin reduces the presence and number of microembolic signals in patients with large artery disease. However, whether it is effective in patients with intracranial disease alone remains uncertain. We performed a subgroup analysis of the The CLopidogrel plus Aspirin for Infarction Reduction (CLAIR in acute stroke or transient ischemic attack patients with large artery stenosis and microembolic signals) study of only patients with intracranial occlusive disease, excluding those with extra cranial disease., Methods: CLAIR was a randomized-controlled, open-label, multicenter clinical trial with blinded outcome evaluation, which recruited patients with symptoms of ischemic stroke or transient ischemic attack within seven-days of onset, with large artery stenosis verified by transcranial Doppler and carotid ultrasound, and with microembolic signals detected by transcranial Doppler recording. All patients were randomized to receive clopidogrel plus aspirin daily for seven-days (dual treatment), or aspirin alone for seven-days (monotherapy). Repeated transcranial Doppler recordings for microembolic signals were made on day one, two, and seven. This subgroup study only analyzed the patients with purely intracranial large artery disease and excluded those with extra cranial stenosis., Results: There were 70 patients recruited with purely intracranial stenosis, 34 in the dual treatment group and 36 in the monotherapy group. The proportion of the patients with positive emboli at day seven in the dual treatment group was significantly lower than that in the monotherapy group (relative risk reduction 56·5%, 95% confidence interval 2·5-80·6; P = 0·029). The number of emboli in the dual treatment group decreased significantly at day two (P = 0·043) and day seven (P = 0·018) compared with the monotherapy group. After adjustment for the number of emboli at day one, the effect of dual treatment was still significant for the reduction of presence (relative risk reduction 56·0%; 95% confidence interval 5·4-79·6; P = 0·036) and number (adjusted mean difference -0·9; 95% confidence interval -1·5 to -0·3; P = 0·004) of positive emboli at day seven., Conclusions: Dual treatment with clopidogrel and aspirin for seven-days is more effective than aspirin alone to reduce microembolic signals in patients with intracranial arterial stenosis., (© 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.)