Average daily ischemic versus bleeding risk in patients with ACS undergoing PCI: Insights from the BleeMACS and RENAMI registries.

BACKGROUND: The risk of recurrent ischemia and bleeding after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) may vary during the first year of follow-up according to clinical presentation, and medical and interventional strategies. METHODS: BleeMACS and RENAMI are 2 multicenter registries enrolling patients with ACS treated with PCI and clopidogrel, prasugrel, or ticagrelor. The average daily ischemic and bleeding risks (ADIR and ADBR) in the first year after PCI were the primary end points. The difference between ADBR and ADIR was calculated to estimate the potential excess of bleeding/ischemic events in a given period or specific subgroup. RESULTS: A total of 19,826 patients were included. Overall, in the first year after PCI, the ADBR was 0.008085%, whereas ADIR was 0.008017% (P = .886). In the first 2 weeks ADIR was higher than ADBR (P = .013), especially in patients with ST-segment elevation myocardial infarction or incomplete revascularization. ADIR continued to be, albeit non-significantly, greater than ADBR up to the third month, whereas ADBR became higher, although not significantly, afterward. Patients with incomplete revascularization had an excess in ischemic risk (P = .003), whereas non-ST-segment elevation ACS patients and those on ticagrelor had an excess of bleeding (P = .012 and P = .022, respectively). CONCLUSIONS: In unselected ACS patients, ADIR and ADBR occurred at similar rates within 1 year after PCI. ADIR was greater than ADBR in the first 2 weeks, especially in ST-segment elevation myocardial infarction patients and those with incomplete revascularization. In the first year, ADIR was higher than ADBR in patients with incomplete revascularization, whereas ADBR was higher in non-ST-segment elevation ACS patients and in those discharged on ticagrelor.

Contemporary Antithrombotic Treatment in Patients with Non-valvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: Rationale and Design of the Greek AntiPlatElet Atrial Fibrillation (GRAPE-AF) Registry.

BACKGROUND: Approximately 5 to 7% of patients undergoing percutaneous coronary intervention (PCI) for the treatment of coronary artery disease require chronic oral anticoagulation (OAC) on top of aspirin and a P2Y12 receptor antagonist, mainly due to non-valvular atrial fibrillation (AF). The advent of non-vitamin K antagonist oral anticoagulants (NOACs) increased treatment options, while there is cumulative evidence that dual combination of a NOAC and a P2Y12 receptor antagonist attenuates risk of bleeding, compared to traditional triple therapy, consisting of a vitamin K antagonist (VKA), aspirin, and a P2Y12 receptor antagonist, without significantly compromising efficacy. STUDY DESIGN: Greek AntiPlatElet Atrial Fibrillation (GRAPE-AF, NCT 03362788) is an observational, nationwide study of non-valvular AF patients undergoing PCI, planning to enroll over 1-year period > 500 participants in 25 tertiary and non-tertiary PCI centers in Greece. Key data to be collected pre-discharge include demographics, detailed past medical history, and antithrombotic and concomitant treatment. Patients will be followed up at 1, 6, and 12 months post hospital discharge. Αt each follow-up visit, data on antithrombotic treatment, ischemic, bleeding, and adverse events will be collected. Study's primary endpoint is clinically significant bleeding (Bleeding Academic Research Consortium, BARC ≥ 2) at 12 months, between VKAs and NOACs-treated patients, analyzed using Cox proportional hazards models, by an intention-to-treat principle. An independent endpoint committee will adjudicate all clinical events. CONCLUSIONS: This study aims at providing "real-world" information on current antithrombotic treatment patterns and clinical outcome of patients with non-valvular AF undergoing PCI.

Platelet reactivity in sepsis syndrome: results from the PRESS study.

Platelet activation mediates systemic inflammatory response during infection. However, data on platelet reactivity (PR) varies among different settings. We assessed PR along different stages of sepsis and tried to predict for determinants of its variance. In parallel, we evaluated it as an early bedside diagnostic biomarker. This was an observational prospective cohort study. Incoming patients were assorted to distinct groups of uncomplicated infection, sepsis, and severe sepsis/septic shock. A control group of healthy volunteers was used as comparison. PR was assessed using the bedside point-of-care VerifyNow assay, in P2Y12 reaction units (PRU) alongside with levels of major inflammatory markers and whole blood parameters. A total of 101 patients and 27 healthy volunteers were enrolled. PR significantly and reversibly increases during sepsis compared to uncomplicated infection and healthy controls (244 ± 66.7 vs 187.33 ± 60.98, p < 0.001 and 192.17 ± 47.51, p < 0.001, respectively). In severe sepsis, PR did not significantly differ compared to other groups. Sepsis stage uniquely accounts for 15.5% of PR in a linear regression prediction model accounting for 30% of the variance of PR (F = 8.836, p < 0.001). PRU >253 had specificity of 91.2% and sensitivity of 40.8% in discriminating septic from non-septic patients. The addition of PRU to SOFA and qSOFA scores significantly increased their c-statistic (AUC SOFA + PRU, 0.867 vs SOFA, 0.824, p < 0.003 and AUC qSOFA + PRU, 0.842 vs qSOFA, 0.739, p < 0.001), making them comparable (AUC SOFA + PRU vs qSOFA + PRU, p = 0.4). PR significantly and reversibly increases early in sepsis, but seems to exhaust while disease progresses. Bedside assessment of PR can provide robust discriminative accuracy in the early diagnosis of septic patients.

Contemporary Antiplatelet Treatment in Acute Coronary Syndrome Patients with Impaired Renal Function Undergoing Percutaneous Coronary Intervention.

OBJECTIVES: To assess the clinical impact of impaired renal function (IRF), in "real-world" acute coronary syndrome (ACS) patients, receiving clopidogrel, prasugrel, or ticagrelor. METHODS: This was a prospective, observational, multicenter, cohort study of ACS patients undergoing percutaneous coronary interventions (PCI) with IRF (creatinine clearance <60 mL/min by Cockroft-Gault equation), who were recruited into the Greek Antiplatelet Registry (GRAPE). Patients were followed-up until 1 year for major adverse cardiovascular events (MACE; a composite of death, nonfatal myocardial infarction, urgent revascularization, and stroke) and BARC (Bleeding Academic Research Consortium) bleeding. RESULTS: Out of 2,047 registered patients, there were 344 (16.8%) with IRF. At the 1-year follow-up, MACE occurred in 18.6 and 6.2% of those patients with and without IRF, respectively: adjusted hazard ratio (HR) = 2.13 (95% confidence interval, CI 1.16-3.91), p = 0.02. IRF patients were also at higher risk of death and BARC type ≥2 and ≥3 bleeding: adjusted HR = 3.55 (95% CI 1.73-7.27), p = 0.001; HR = 2.75 (95% CI 1.13-6.68), p = 0.03; and HR = 6.02 (95% CI 2.30-15.77), p < 0.001, respectively. Combined MACE and BARC type ≥2 bleeding occurred in 34.0 and 14.0% of those with and without IRF, respectively: adjusted HR = 2.65 (95% CI 1.36-5.16), p = 0.004. At discharge, clopidogrel was more frequently prescribed in IRF patients (61.0 vs. 33.1%, p < 0.001). CONCLUSIONS: Real-world ACS patients with IRF subjected to PCI demonstrate higher thrombotic and bleeding risks than patients with normal renal function.

Dyspnea in patients treated with P2Y12 receptor antagonists: insights from the GReek AntiPlatElet (GRAPE) registry.

In 'real life' acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) and receiving contemporary antiplatelet treatment, data on dyspnea occurrence and impact on persistence with treatment are scarce. In a prospective, multicenter, cohort study, ACS patients undergoing PCI were recruited into the GReekAntiPlatElet (GRAPE) registry. During 1-year follow up, overall, 249/1989 (12.5%) patients reported dyspnea, more frequently at 1-month and decreasing thereafter. Multivariate analysis showed that ticagrelor administration (n = 738) at discharge was associated with the occurrence of dyspnea: Odds ratio 2.46 (95% confidence interval, CI, 1.87-3.25), p < 0.001. Older age, lower hematocrit, and prior bleeding event were also associated with dyspnea reports. Persistence, switching, and cessation rates were 68.3%, 20.9%, and 10.8% vs 76.7%, 12.5%, and 10.9% among patients reporting dyspnea compared with those who did not, p for trend = 0.002. In conclusion, in ACS patients undergoing PCI and treated with a P2Y12 receptor antagonist, dyspnea occurs commonly, particularly when ticagrelor is administered. Non-persistence with antiplatelet agents at discharge is more frequently observed among dyspnea-reporters.

Factors Affecting Platelet Reactivity 2 Hours After P2Y12 Receptor Antagonist Loading in Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction - Impact of Pain-to-Loading Time.

BACKGROUND: Delay in the onset of antiplatelet action occurs in patients with ST-elevation myocardial infarction (STEMI) and is likely due to disturbed absorption. We hypothesized that patients presenting relatively late after the onset of symptoms would have faster antiplatelet action. METHODS AND RESULTS: We analyzed patient-level data from 5 studies of 207 P2Y12 receptor antagonist-naïve patients with STEMI undergoing primary percutaneous coronary intervention (PCI). All patients had available platelet reactivity (PR) assessment with the VerifyNow assay (in P2Y12 reaction units; PRU) prior to and 2 h after loading. High PR (HPR) was defined as ≥ 208 PRU. Pain-to-antiplatelet loading time independently predicted PR at 2 h after loading: every 1-h increase in pain-to-antiplatelet loading time produced a 7% decrease in PR (P=0.001). Pretreatment PR, body mass index, morphine and novel P2Y12 receptor antagonist also affected PR 2 h after loading. Novel P2Y12 receptor antagonist use and per hour increase in pain-to-antiplatelet loading time were independently associated with lower probability for HPR with an OR (95% CI) of 0.145 (0.095-0.220) and 0.776 (0.689-0.873), P<0.001 for both (C-statistic, 0.752; 95% CI: 0.685-0.819). CONCLUSIONS: In STEMI patients undergoing primary PCI, pain-to-antiplatelet loading interval is a newly described factor affecting PR shortly after P2Y12 receptor antagonist loading, according to patient-level data pooled analysis.

Ticagrelor vs clopidogrel followed by ticagrelor re-loading in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: A randomized, pharmacodynamic comparison.

Among patients allocated to ticagrelor in the primary percutaneous coronary intervention (PCI) cohort of Platelet Inhibition and Patient Outcomes (PLATO) trial, 40.7% had received pre-randomization 600 mg of clopidogrel. This scenario is frequently employed in real-world practice. In a prospective, three-center, single-blind, parallel design study, 74 P2Y12 inhibitor-naive patients undergoing primary PCI were randomized (Hour 0) to ticagrelor 180 mg loading dose (LD) vs clopidogrel 600 mg LD followed after 2 h by ticagrelor 180 mg re-LD. Platelet reactivity (VerifyNow, in PRU) was assessed at Hour 0, 2, 4, 6, and 24. The primary comparison was non-inferiority of ticagrelor to clopidogrel followed by ticagrelor re-LD regarding platelet reactivity at 24 h using a prespecified margin of <35 PRU for the upper bound of the one-sided 97.5% confidence interval (CI). Ticagrelor was proven non-inferior to clopidogrel followed by ticagrelor re-LD with a difference between arms of 13.5 PRU (28.8 upper 97.5% CI), p = 0.001. At Hour 2, platelet reactivity was lower in ticagrelor only vs clopidogrel followed by ticagrelor re-LD groups with least square estimate mean difference (95% CI) -105.7 (-140.6 to -70.8), p < 0.001, without significant difference thereafter. In conclusion, in patients undergoing primary PCI, a strategy of ticagrelor LD only was proven non-inferior to clopidogrel LD followed by ticagrelor re-LD, in terms of antiplatelet efficacy at 24 h post-randomization and provided an earlier onset of platelet inhibition.

Diabetes mellitus and platelet reactivity in patients under prasugrel or ticagrelor treatment: an observational study.

BACKGROUND: The influence of diabetes mellitus (DM) on platelet reactivity (PR) in prasugrel or ticagrelor treated patients is not well studied. METHODS: In an observational study involving 777 patients with acute coronary syndrome undergoing percutaneous coronary intervention treated by either prasugrel 10 mg od (n = 315) or ticagrelor 90 mg bid (n = 462), platelet function was assessed using the VerifyNow P2Y12 function assay (in PRU) at one month post intrvention. RESULTS: In the overall population, ticagrelor and insulin-treated DM affected PR, with a decrease in log by 0.88 (corresponding to a 58 % decrease in PR) compared to prasugrel-treated patients (p < 0.001), and an increase in log by 0.26 (corresponding to a 30 % increase in PR) compared to non-diabetic patients (p = 0.01), respectively. PR in prasugrel-treated patients differed significantly by DM status: 70.0 (36.3-113.0) in non-diabetic vs 69.0 (44.5-115.3) in non insulin-treated diabetic vs 122.0 (69.0-161.0) in insulin-treated diabetic patients, p for trend = 0.01. No differences were observed in ticagrelor-treated patients. By multivariate analysis, in prasugrel-treated patients insulin-treated DM was the only factor predicting PR, with log of PR increased by 0.42 (corresponding to a 52 % increase in PR) compared to non-diabetic patients (p = 0.001). No factor was found to affect PR in ticagrelor-treated patients. CONCLUSIONS: Patients with insulin-treated DM treated with prasugrel post PCI have higher PR, than patients without DM or non insulin-treated diabetic patients treated with this drug. Ticagrelor treated patients have overall lower PR than patients on prasugrel, independent of DM status or insulin treatment. TRIAL REGISTRATION: Clinical Trials Gov. NCT01774955.

Ticagrelor versus high dose clopidogrel in ST-segment elevation myocardial infarction patients with high platelet reactivity post fibrinolysis.

Limited data are available on high platelet reactivity (HPR) rate early post fibrinolysis, while no effective way to overcome it has been proposed. In this context, we aimed to compare ticagrelor versus high dose clopidogrel in patients with ST-segment elevation myocardial infarction (STEMI) who exhibit HPR post fibrinolysis. In a prospective, randomized, parallel design, 3-center study, 56 STEMI patients, out of 83 (67.5 %) screened, who presented with HPR (PRU ≥ 208 by VerifyNow) 3-48 h post fibrinolysis and prior to coronary angiography were allocated to ticagrelor 180 mg loading dose (LD)/90 mg bid maintenance dose (MD) or clopidogrel 600 mg LD/150 mg MD. Platelet reactivity was assessed at randomization (Hour 0), at Hour 2, Hour 24 and pre-discharge. The primary endpoint of platelet reactivity (in PRU) at Hour 2 was significantly lower for ticagrelor compared to clopidogrel with a least square mean difference (95 % confidence interval) of -141.7 (-173.4 to -109.9), p < 0.001. HPR rates at Hour 2 and 24 were significantly lower for ticagrelor versus clopidogrel (14.3 vs. 82.1 %, p < 0.001 and 0 vs. 25.0 %, p = 0.01 respectively), though not significantly different pre-discharge. In-hospital Bleeding Academic Research Consortium type ≥2 bleeding occurred in 1 and 2 clopidogrel and ticagrelor-treated patients, respectively. In STEMI patients, post fibrinolysis HPR is common. Ticagrelor treats HPR more effectively compared to high dose clopidogrel therapy. Although antiplatelet regimens tested in this study were well tolerated, this finding should be considered only exploratory.

Platelet reactivity during ticagrelor maintenance therapy: a patient-level data meta-analysis.

BACKGROUND: Factors associated with platelet reactivity (PR) during ticagrelor maintenance dose (MD) are not well defined. We aimed to examine factors that influence levels of PR during chronic ticagrelor therapy. METHODS: We performed individual participant data meta-analysis of 445 patients from 8 studies who had PR assessment with the VerifyNow P2Y12 assay (Accumetrics, Inc, San Diego, CA) while on ticagrelor 90 mg twice a day MD for at least 14 days. RESULTS: Distribution of PR during ticagrelor MD was highly skewed toward lower values. No case of high PR (≥230 P2Y12 reaction units [PRU]) was observed. Age and body mass index (BMI) positively affected PR, with every increase in decade and 5 units of BMI resulting in 7.9% and 4.1% increase in PR, respectively. Current smoking status negatively affected PR with 13.7% decrease in PR in current smokers, compared with nonsmokers. Low PR (LPR) was defined as the lowest quartile of PR values (<10 PRU). In multivariate analysis, diabetes mellitus and age >70 years were independently associated with lower probability for LPR with a relative risk (95% CIs) of 0.570 (0.361-0.899) and 0.554 (0.325-0.944), P = .016 and P = .030, respectively. CONCLUSIONS: Age, BMI, and current smoking status affect PR during ticagrelor MD. Diabetes mellitus and age >70 years were found to be associated with lower probability for LPR. Further research is required to assess the clinical implications of these findings in ticagrelor-treated patients.

In-hospital switching of oral P2Y12 inhibitor treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention: prevalence, predictors and short-term outcome.

BACKGROUND: P2Y12 inhibitor switching has appeared in clinical practice as a consequence of prasugrel and ticagrelor availability, apart from clopidogrel, for use in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS: In the context of the GReek AntiPlatelet REgistry (GRAPE) we assessed the prevalence, predictive factors and short-term outcome of in-hospital P2Y12 inhibitor switching in 1794 ACS patients undergoing PCI. RESULTS: Switching occurred in 636 (35.5%) patients of which in the form of clopidogrel to a novel agent, novel agent to clopidogrel and between prasugrel and ticagrelor in 574 (90.4%), 34 (5.3%) and 27 (4.3%) patients, respectively. Presentation to non PCI-capable hospital, bivalirudin use, age ≥75 years (inverse predictor), and regional trends emerged as predictive factors of switching to a novel agent. At combined in-hospital and one-month follow-up, propensity matched pairs analysis showed no differences in major adverse cardiovascular (MACE) or bleeding events between switching from clopidogrel to a novel agent vs novel agent constant administration. More Bleeding Academic Research Consortium type 1, type 2 and any type events and fewer MACE were seen when switching from clopidogrel to a novel agent vs only clopidogrel administration (23.7%, 3.8%, 30.6%, 1.2% vs 8.9%, 1.2%, 12.0%, 3.8% with P < .001, P = .03, P < .001 and P = .03 respectively). CONCLUSIONS: In a real-life experience with contemporary antiplatelet treatment in ACS patients undergoing PCI, in-hospital switching represents common clinical practice. Clinical factors and regional practice differences seem to affect this strategy's choice, while switching to a novel agent may be associated with higher risk of bleeding.

Contraindications/special warnings and precautions for use of contemporary oral antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: The prevalence of contraindications/special warnings and precautions (CON/SWP) for clopidogrel, prasugrel and ticagrelor use is not adequately studied and might affect P2Y12 inhibitor choice in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: In the context of the GReek AntiPlatelet rEgistry (GRAPE) a detailed recording of CON/SWP for use of clopidogrel, prasugrel and ticagrelor was done for 1,280 consecutive, moderate-high-risk ACS patients undergoing PCI. At least 1 CON for use of clopidogrel, prasugrel and ticagrelor was present in 5 (0.4%), 49 (3.8%) and 12 patients (0.9%), respectively. Prevalence of at least 1 CON/SWP to clopidogrel (45.8%) was less frequent compared to prasugrel (49.1%) or ticagrelor (49.1%; P=0.02 and P=0.04, respectively), while 34% of patients had at least 1 CON/SWP to all the 3 P2Y12 inhibitors. At discharge, 482 (38.6%), 301 (24.1%) and 464 patients (37.2%) received clopidogrel, prasugrel and ticagrelor, respectively. Age ≥75 years, co-medication related to increased bleeding risk, and history of asthma/chronic obstructive pulmonary disease favored clopidogrel vs. prasugrel or ticagrelor use as discharge medication, while geographic region also affected this choice (C-statistic, 0.81; 95% CI: 0.78-0.83). CONCLUSIONS: In patients with ACS undergoing PCI the prevalence of CON to antiplatelet agents is low, whereas that of SWP is high. Certain SWP, along with regional trends may affect the choice of newer P2Y12 inhibitors vs. clopidogrel.

Pharmacodynamic effect of prasugrel 5 mg vs clopidogrel 150 mg in elderly patients with high on-clopidogrel platelet reactivity.

BACKGROUND: Elderly patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) frequently exhibit high platelet reactivity (HPR) while on clopidogrel. In the elderly cohort, either prasugrel is not recommended or, if used, halving of the dose has been suggested. We aimed to test the hypothesis that in elderly patients exhibiting HPR after standard treatment with clopidogrel, prasugrel-reduced dose (5 mg) could be more effective than high-dose (150 mg) clopidogrel. METHODS: Consecutive elderly (≥75 years old) patients with ACS undergoing PCI and loaded with clopidogrel were considered for platelet reactivity (PR) assessment at 24 hours after PCI with the VerifyNow assay (Accumetrics Inc, San Diego, CA), measured in P2Y12 reaction units (PRU). Of 63 screened patients, 30 (47.6%) were found with HPR (defined as PRU ≥230) and 27 of them participated in a prospective, randomized, single-center, single-blind, investigator-initiated, crossover study of platelet inhibition by prasugrel 5 mg/d vs clopidogrel 150 mg/d, with a 15-day treatment period. RESULTS: The primary end point of PR at the end of the 2 study periods was lower in patients receiving low-dose prasugrel than those receiving high-dose clopidogrel (least squares estimates 190.8 [95% CI 161.5-220.1] and 240.8 [95% CI 211.0-270.6], respectively; P = .008). The secondary end point of HPR rate at the end of treatment periods was lower for prasugrel (8/24; 33.3%) compared with clopidogrel (16/24; 66.7%), P = .02. CONCLUSIONS: In elderly patients with ACS undergoing PCI and exhibiting HPR after standard clopidogrel treatment, prasugrel 5 mg/d is significantly more efficacious than clopidogrel 150 mg/d in reducing PR and HPR rate.

Resistance to high-maintenance dose of prasugrel treated by ticagrelor: a case report.

We describe a case of a 34-year-old woman with chronic renal failure under haemodialysis. The patient exhibited high on-treatment platelet reactivity to gradually stronger thienopyridine regimens, including standard and high maintenance doses of prasugrel. Platelet function was monitored by VerifyNow assay and genotyping for various single-nucleotide polymorphisms was performed. Treatment with ticagrelor 180 mg/day was effective in reducing the platelet reactivity.

First-line treatment patterns and lipid target levels attainment in very high cardiovascular risk outpatients.

OBJECTIVES: Previous studies have demonstrated gaps in achievement of low-density lipoprotein-cholesterol (LDL-C) goals among patients at very high cardiovascular risk. We aimed to investigate lipid treatment patterns, rates and predictors of lipid targets attainment, in such outpatients in an urban area of Greece. METHODS: This was a prospective observational study, conducted in 19 outpatient clinics of Western Greece. We recruited patients with established cardiovascular disease (CVD) and/or diabetes mellitus (DM), previously (at least 3 months before baseline assessment) untreated with any lipid lowering medication. Lipid profile assessment was performed at baseline (prior to lipid-lowering treatment initiation) and at follow-up. Lipid lowering treatment choice was at physicians' discretion and was kept constant until follow-up. RESULTS: We recruited 712 patients with a mean age 61.4 ± 10.4 years, 68.0% males, 43.0% with DM, 64.7% with prior coronary artery disease-CAD. In total, 237/712 (33.3%) of prescribed regimens were of high or very high LDL-C lowering efficacy and out of them 113/237 (47.7%) comprised a combination of statin and ezetimibe. At follow-up the primary target of LDL-C < 70 mg/dL (1.8 mmol/L) was achieved in 71(10.0%) patients. The secondary target of non-HDL-C < 100 mg/dL (2.6 mmol/L) in the subgroup of patients with DM or increased triglycerides levels (>150 mg/dl or 1.7 mmol/L) was achieved in 45(11.6%) of patients. In multivariate logistic regression analysis (AUC = 0.71, 95% CIs 0.65-0.77, p < 0.001) male gender, smoking, baseline LDL-C and very high potency LDL-C lowering regimen emerged as independent predictors of LDL-C goal attainment (OR = 1.88, 95% CIs 1.03-3.44, p = 0.04, OR = 0.57, 95% CIs 0.33-0.96, p = 0.04, OR = 0.98, 95% CIs 0.98-0.99, p < 0.001 and OR = 2.21, 95% CIs 1.15-4.24, p = 0.02 respectively). CONCLUSIONS: First-line management of dyslipidemia among very-high cardiovascular risk outpatients in Western Greece is unsatisfactory, with the majority of treated individuals failing to attain the LDL-C and non-HDL-C targets. This finding points out the need for intensification of statin treatment in such patients.

Antithrombotic Strategy in Secondary Prevention for High-Risk Patients with Previous Acute Coronary Syndrome: Overlap between the PEGASUS Eligibility and the COMPASS Eligibility in a Large Multicenter Registry.

BACKGROUND: Patients with previous acute coronary syndrome (ACS) are at high risk of recurrent adverse cardiovascular events. Recently, prolonged dual antiplatelet therapy (DAPT) and oral anticoagulation therapy (OAT) have been shown to reduce recurrent ischemic events to the expense of an increase in bleeding events. The number of patients potentially eligible for these therapies in real life remains to be determined. METHODS: Among ACS patients from five registries and one randomized controlled trial, we assessed the proportion of patients eligible for the PEGASUS strategy only and the proportion of patients eligible for the COMPASS strategy only, and set out the proportion of patients with an overlap between the strategies. FINDINGS: Among the 10,048 evaluable patients, we found that 5373 (53.4%) were eligible for the PEGASUS strategy and 3841 (38.2%) were eligible for the COMPASS strategy, with a group of 3444 (34.4%) overlapping between the two strategies. The number of patients eligible for the PEGASUS strategy only was 1929 (19.2%) and the number eligible for the COMPASS strategy only was 397 (4.0%); 4278 (42.6%) were eligible for neither a PEGASUS strategy nor a COMPASS strategy. INTERPRETATION: In a large cohort of ACS patients, one in three patients was eligible for either a prolonged DAPT with ticagrelor 60 mg and low-dose aspirin or a dual pathway inhibition approach with rivaroxaban 2.5 mg and low-dose aspirin.

Predictors of high on-treatment platelet reactivity early after clopidogrel loading in ST-elevation myocardial infarction.

BACKGROUND: Given that platelet inhibition is crucial when ST-elevation myocardial infarction (STEMI) patients undergo primary PCI (PPCI), the identification of factors associated with early high on-treatment platelet reactivity may be important. METHODS AND RESULTS: Consecutive STEMI patients admitted for PPCI were considered for platelet reactivity assessment 2 h after loading with 600 mg clopidogrel using the VerifyNow point-of-care P2Y12 assay. A cut-off of ≥235 P2Y12 reaction units indicated high on-treatment platelet reactivity. Out of 92 STEMI patients, 63 (68.5%) were found to have high on-treatment platelet reactivity. Patients with high on-treatment platelet reactivity had received upstream clopidogrel loading and pantoprazol more frequently, had lower admission hemoglobin and tended to have an impaired renal function compared to those with an adequate response to clopidogrel. On multivariate analysis, upstream clopidogrel loading and creatinine clearance <60 ml/min were independently associated with higher risk for high on-treatment platelet reactivity (relative risk [RR]=1.55, 95% confidence interval [CI]: 1.11-2.17, P=0.01; RR=1.31, 95% CI: 1.008-1.71, P=0.04, respectively). CONCLUSIONS: In patients with STEMI undergoing PPCI, use of upstream clopidogrel and impaired renal function independently predict high on-treatment platelet reactivity assessed as early as 2h following 600 mg of clopidogrel loading dose on point-of-care P2Y12 function assay.

Prasugrel overcomes high on-clopidogrel platelet reactivity in chronic coronary artery disease patients more effectively than high dose (150 mg) clopidogrel.

BACKGROUND: High on-treatment platelet reactivity (HTPR) is present in a substantial percentage of patients on chronic clopidogrel treatment and may have prognostic implications. Strategies to optimize platelet inhibition in such patients are not clear. METHODS: We performed a prospective, single-center, single-blinded, investigator-initiated randomized, crossover study of platelet inhibition by prasugrel 10 mg/day versus high-dose 150 mg/day clopidogrel, with a 14 day treatment period, in 31 patients with HTPR (out of 99 screened, 31.3%) while on chronic (≥ 12 months) treatment with clopidogrel. All patients had stable coronary artery disease and 87.1% of them had a prior percutaneous coronary intervention. Platelet reactivity (PR) was assessed by the VerifyNow assay measured in platelet reactivity units (PRU). RESULTS: The primary end point of PR at the end of the two treatment periods was lower in patients receiving prasugrel compared with high dose clopidogrel ( least squares estimate 148.1, 95% CI 127.1-169.2 and 219.8, 95% CI 198.6-240.9 respectively, P < .001). The secondary end point of HTPR rate was lower for prasugrel compared with clopidogrel, 11.5% vs 46.3%, P = .003. CONCLUSIONS: Prasugrel appears more effective than double clopidogrel in inhibiting PR in patients with HTPR following chronic clopidogrel treatment.

Mechanisms of non-fatal stent-related myocardial infarction late following coronary stenting with drug-eluting stents and bare metal stents. Insights from optical coherence tomography.

BACKGROUND: A prospective observational study using optical coherence tomography (OCT) of patients with myocardial infarction (MI), late following drug-eluting (DES) or bare metal stent (BMS) implantation, when the stented segment was considered culprit. METHODS AND RESULTS: Seventeen patients (58.9±8.3 years; 7 DES, 10 BMS) with MI at 50 (3-180) months post-stenting. Patients with BMS sustained a MI later than patients with DES (95 (3-180) vs. 8 (3-62) months, P=0.01]; 5 (71.4%) of the DES patients demonstrated binary angiographic restenosis, in contrast to 8 (80%) with BMS (P=1.0). DES had significantly less thickness of the neointimal hyperplasia compared with BMS (0.08±0.04 vs. 0.36±0.2mm, P=0.003). None of the DES was totally covered with neointimal tissue. The overall percentage of uncovered and malapposed struts (ANCOVA), was significantly higher in DES than BMS (1.96, 95% confidence interval (CI) 1.5-2.4 vs. 0.25, 95%CI 0.1-0.6, P<0.001, and 0.66, 95%CI 0.29-1.03 vs. 0.11, 95%CI 0.19-0.4, P=0.03, respectively). OCT features of atherosclerosis (lipid, neovascularization, or calcification) and possible neointimal rupture were found only in patients with BMS. Thrombus detection was not different between the 2 groups. CONCLUSIONS: Stent-related, non-fatal, late acute MI following stent implantation occurs later in patients with a BMS compared with those with a DES, and the mechanism includes delayed healing (mainly DES), and neointimal hyperplasia with atherosclerotic transformation and subsequent rupture (mainly BMS).

Prevalence of contraindications and conditions for precaution for prasugrel administration in a real world acute coronary syndrome population.

The prevalence of prasugrel contraindications and specific conditions requiring precaution for its use in a real world acute coronary syndrome (ACS) population is not known. We performed a prospective descriptive study in 1016 consecutive moderate to high risk ACS patients. In 646 patients (63.6%) subjected to percutaneous coronary intervention, analysis of absolute contraindications (history of stroke/transient ischemic attack or active bleeding), relative contraindications and specific conditions (age ≥ 75 years and/or weight < 60 kg) for prasugrel theoretical administration was performed. In 242 (37.5%) patients there was at least one absolute or relative contraindication or specific condition requiring attention for its use. Overall, 23.1% of patients in our cohort had a prior stroke/transient ischemic attack and/or specific condition to be considered for prasugrel administration. Specifically, the prevalence of stroke/TIA was 3.6%, the prevalence of patients ≥75 years 20% and the prevalence of patients weighing <60 kg 2.2%. Among patients ≥75 years old, 63 (9.8%) had diabetes mellitus or previous myocardial infarction, consisting a high risk subgroup that might benefit from prasugrel administration. In a real world ACS population a relatively high proportion of patients have a potential contraindication for prasugrel administration or necessitate special attention for its use.