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Antiplatelet therapy is one of the cornerstones in the acute treatment of patients with ST-elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PCI). However, hemodynamic changes and delayed intestinal absorption of P2Y12 inhibitors leads to a delay in the onset of antiplatelet effects resulting in a gap of platelet inhibition. Several strategies have been proposed to bridge this gap, such as pre-hospital administration of antiplatelet therapy, higher loading doses of P2Y12 inhibitors, crushing or chewing tablets, subcutaneous or intravenous administration of platelet inhibitors, or use of pain relievers alternative to opioids that do not delay intestinal absorption of oral platelet inhibitors. These strategies may improve platelet inhibition with the goal of optimizing clinical outcomes in the acute phase of STEMI. In this review we present current and future insights for bridging the gap in platelet inhibition in STEMI patients undergoing primary PCI. (c) 2020 Published by Elsevier B.V.Superscript/Subscript Available

Background The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with second-generation drug eluting stents (DESs) is unclear. Because prolonged DAPT is associated with higher bleeding risk and health care costs, establishing optimal DAPT duration is of paramount importance. No other randomized controlled trials have evaluated the safety of shorter DAPT duration in ST-elevation myocardial infarction (STEMI) patients treated with second-generation DESs and latest P2Y12 platelet receptor inhibitors. Hypothesis Six months of DAPT after Resolute Integrity stent implantation in STEMI patients is not inferior to 12 months of DAPT in clinical outcomes. Study design The Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation In ST-elevation Myocardial Infarction (DAPT-STEMI) trial is a randomized, multicenter, international, open-label trial designed to examine the safety (noninferiority) of 6-month DAPT after Resolute Integrity stent implantation in STEMI patients compared with 12-month DAPT. Event-free patients on DAPT at 6month will be randomized (1:1 fashion) between single (aspirin only) versus DAPT for an additional 6 months and followed until 2 years after primary percutaneous coronary intervention. The primary end point is a patient-oriented composite endpoint of all-cause mortality, any myocardial infarction, any revascularization, stroke, and major bleeding (net adverse clinical events [NACE]) at 18 months after randomization. To achieve a power of 85% for a noninferiority limit of 1.66, a total of 1100 enrolled patients are required. Summary The DAPT-STEMI trial aims to assess in STEMI patients treated with second-generation DESs whether discontinuation of DAPT after 6 months of event-free survival is noninferior to routine 12-month DAPT.

Background Peripheral artery disease is considered to be a manifestation of systemic atherosclerosis with associated adverse cardiovascular and limb events. Data from previous trials have suggested that patients receiving clopidogrel monotherapy had a lower risk of cardiovascular events than those receiving aspirin. We wanted to compare clopidogrel with ticagrelor, a potent antiplatelet agent, in patients with peripheral artery disease. Methods In this double-blind, event-driven trial, we randomly assigned 13,885 patients with symptomatic peripheral artery disease to receive monotherapy with ticagrelor (90 mg twice daily) or clopidogrel (75 mg once daily). Patients were eligible if they had an ankle-brachial index (ABI) of 0.80 or less or had undergone previous revascularization of the lower limbs. The primary efficacy end point was a composite of adjudicated cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding. The median follow-up was 30 months. Results The median age of the patients was 66 years, and 72% were men; 43% were enrolled on the basis of the ABI and 57% on the basis of previous revascularization. The mean baseline ABI in all patients was 0.71, 76.6% of the patients had claudication, and 4.6% had critical limb ischemia. The primary efficacy end point occurred in 751 of 6930 patients (10.8%) receiving ticagrelor and in 740 of 6955 (10.6%) receiving clopidogrel (hazard ratio, 1.02; 95% confidence interval [CI], 0.92 to 1.13; P=0.65). In each group, acute limb ischemia occurred in 1.7% of the patients (hazard ratio, 1.03; 95% CI, 0.79 to 1.33; P=0.85) and major bleeding in 1.6% (hazard ratio, 1.10; 95% CI, 0.84 to 1.43; P=0.49). Conclusions In patients with symptomatic peripheral artery disease, ticagrelor was not shown to be superior to clopidogrel for the reduction of cardiovascular events. Major bleeding occurred at similar rates among the patients in the two trial groups. (Funded by AstraZeneca; EUCLID ClinicalTrials.gov number, NCT01732822 .).

OBJECTIVES: The study sought to evaluate the presence of a clinically relevant rebound phenomenon after dual antiplatelet therapy (DAPT) discontinuation in randomized trials. BACKGROUND: It is currently unknown whether clopidogrel discontinuation after short-term DAPT is associated with an early hazard of ischemic events. METHODS: The authors performed an individual participant data analysis and aggregate meta-analysis. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), defined as the composite of cardiac death, myocardial infarction (MI), or stroke. RESULTS: The study included 11,473 PCI patients with individual participant data from 6 randomized trials comparing short-term DAPT (3 or 6 months) versus long-term DAPT (12 months or more). During the first 90 days following clopidogrel discontinuation, there was no significant increase in the risk of MACCE between patients randomized to short-term DAPT compared with long-term DAPT (hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 0.71 to 1.98; p = 0.52; absolute risk difference 0.10%; 95% CI: -0.16% to 0.36%). The risk of MI or stent thrombosis was similar among patients randomized to short-term DAPT versus long-term DAPT (HR: 0.93; 95% CI: 0.46 to 1.90; p = 0.85). In the aggregate data meta-analysis of 11 trials including 38,919 patients, a higher risk of early MACCE was observed after long-term (≥12 months) DAPT duration (HR: 2.28; 95% CI: 1.69 to 3.09; p < 0.001) but not short-term (

Objectives The aim of this study was to examine the frequency and clinical impact of different cessation patterns of dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention with drug-eluting stents among patients with and those without diabetes mellitus (DM). Background Early DAPT suspension after percutaneous coronary intervention increases the risk for major adverse cardiac events. However, temporal variability in risk and relation to DAPT cessation patterns among patients with DM remain unclear. Methods Using data from the PARIS (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients) registry, 1,430 patients with DM (34%) and 2,777 without DM (66%) treated with drug-eluting stents were identified. DAPT cessation modes were classified as temporary interruption (

Purpose of Review: This review aims to summarize and discuss safety and effectiveness of the long-term use of ticagrelor in patients with coronary artery disease (CAD). Recent Findings: Ticagrelor is an orally administered, direct, and reversible inhibitor of the P2Y12-platelet receptor. Long-term use of ticagrelor in patients with previous myocardial infarction (MI) has been investigated in the PEGASUS-TIMI-54 trial. Overall, 21,162 patients with a spontaneous MI 1 to 3 years before randomization were randomly assigned to ticagrelor 90 mg bid, ticagrelor 60 mg bid, or placebo. Compared with placebo, both doses of ticagrelor showed that they were capable of significantly reducing the primary efficacy endpoint, although with a significant increase in TIMI major bleeding. Intracranial hemorrhage or fatal bleeding did not differ across groups. Summary: These findings establish clear benefit of DAPT extension with ticagrelor beyond 1 year of treatment, which comes with a tradeoff of clinically meaningful bleeding. Altogether, current evidence suggests that the duration of DAPT remains a patient-by-patient decision based on thrombotic and bleeding risk profiles.

OBJECTIVES: In the present study, we aimed to deterimine the dose-related effects of ticagrelor, the first reversible inhibitor of the P2Y(12) receptor, found in smooth muscle cells as well as platelets, during neointimal hyperplasia in a rabbit carotid anastomosis model. METHODS: This study was an experimental, prospective, randomized controlled study including 20 New Zealand white female rabbits (6-months old; weighing 2300 +/- 300 g). Under general anaesthesia, the rabbits underwent transection of the right carotid artery and subsequent anastomosis of both ends. The study animals were divided into the following 4 groups: T1 (ticagrelor 5 mg/kg, orally, daily), T2 (ticagrelor 10 mg/kg, orally, daily), T3 (ticagrelor 20 mg/kg, orally, daily) and control (no ticagrelor treatment). The single oral doses were administered in phosphate-buffered saline. The control group received sterile phosphate-buffered saline (2 ml/kg/day, orally) for 3 weeks postoperatively. At the end of the study, the animals were killed, and the anastomosed segment of the right carotid artery and part of the left carotid artery were excised from each animal. Antibodies against transforming growth factor-beta were used in staining of arterial sections, which was followed by histomorphological and immunohistochemical studies. RESULTS: The median intimal thickness (2.0 +/- 0.14 m left vs 73.4 +/- 35.8 m anastomosed right arteries; P

Aspirin represents the sine qua non for antiplatelet pharmacotherapy in patients with cardiovascular diseases because of its well-established role in secondary prevention and its widespread availability and affordability. Historical studies, conducted in an era that bears little resemblance to contemporary clinical practice, demonstrated large reductions in thrombotic risk when aspirin was compared with placebo, thus forming the evidence base promulgated in practice guidelines and recommendations. P2Y 12 inhibitors have mostly been studied in addition to aspirin; dual-antiplatelet therapy proved superiority compared with aspirin monotherapy for the prevention of ischemic events, despite increased bleeding risks. An alternative approach currently under investigation includes evaluation of single-antiplatelet therapy with P2Y 12 inhibitors alone versus dual-antiplatelet therapy after acute coronary syndromes or coronary stent implantation. As the availability of more effective antiplatelet agents increases, it is time to revisit the existing and long-standing paradigm supporting aspirin use for secondary prevention of atherothrombotic events. Ongoing trials will provide new evidence whether the less-is-more strategy is justified.

Background High platelet reactivity (HPR) to clopidogrel is associated with an increased risk of ischaemic complications during and after coronary interventions and concerns up to 50% of patients undergoing PCI. Aim of the study The aim of the study was to identify patients with HPR to clopidogrel using bedside clinical information obtained in the Stent Thrombosis In Belgium (STIB) trial. Methods Data on platelet reactivity using the VerifyNow (R) point-of-care assay were obtained in 844 patients undergoing PCI for stable coronary artery disease 12 to 24 hours after a 600-mg loading dose of clopidogrel was given. Demographic, clinical and baseline routine biological tests were obtained and compared with P2Y12 reaction units (PRU). Patients with PRU >230 (HPR) were considered as non-responders to clopidogrel. Results HPR was observed in 424/844 pts. Age, weight, body mass index (BMI), HPR to aspirin, diabetes, renal failure (MDRD 28 kg/m(2) and presence of diabetes were equally associated to predict HPR and can be added to derive a simple score to predict clopidogrel resistance. Although 38.5% of patients without a single clinical predictor still have HPR, 2/3 patients with 2 or 3 risk factors are resistant to clopidogrel. Conclusions STIB HPR score allows identification of patients with a high probability of resistance to clopidogrel based on diabetes, Hb 28 kg/m(2). This bedside clinical test could be useful for the identification of patients in whom another P2Y12 inhibitor should be recommended before and after PCI.