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.

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.

Antiplatelet treatment in diabetic patients with acute coronary syndrome undergoing percutaneous coronary intervention: a GReek AntiPlatElet registry substudy.

BACKGROUND AND AIMS: We compared the clinical outcome of diabetic versus nondiabetic patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in the GReek AntiPlatElet (GRAPE) registry. PATIENTS AND METHODS: GRAPE is a prospective observational study, focusing on contemporary antiplatelet use in moderate-risk to high-risk ACS patients receiving PCI. Major adverse cardiovascular events (MACE), (composite of death, nonfatal myocardial infarction, urgent revascularization, and stroke) and bleeding events (Bleeding Academic Research Consortium definition) at 1 year of follow-up were analyzed using propensity score adjustment. A subanalysis according to diabetes mellitus (DM) status was performed. RESULTS: Out of 2047 registered patients, 469 (22.9%) were diabetic. Complete 1-year follow-up was available in 95.1% of patients. MACE occurred in 12.2 and 7.2% of those patients with and without DM, respectively [adjusted hazard ratio (HR), 95% confidence interval (CI)=1.27 (0.89-1.79), P=0.2]. Observed BARC type ≥3 bleeding risk was not higher in diabetic patients: adjusted HR (95% CI)=1.20 (0.79-1.84). In the subgroup of clopidogrel-treated patients (N=238), MACE rate was significantly higher in diabetic compared with nondiabetic cohort [13.4 vs. 9%, adjusted HR (95% CI)=1.68 (1.07-2.64), P=0.03]. In the subgroup of ticagrelor-treated or prasugrel-treated patients (N=228), MACE rate did not differ significantly between diabetic and nondiabetic patients: 9.6 versus 5%, adjusted HR (95% CI)=1.35 (0.77-2.37), P=0.38. CONCLUSION: In 'real-life' ACS undergoing PCI, diabetic patients have higher - although not significantly - MACE rate and no difference in bleeding events. This difference in MACE was significant among clopidogrel-treated patients, whereas when newer antiplatelet agents were used the negative impact of DM on ischemic events was eliminated.

Gender-related differences in antiplatelet treatment patterns and outcome: Insights from the GReekAntiPlatElet Registry.

AIMS: Data on the clinical impact of gender in "real-life" patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), receiving clopidogrel, prasugrel, or ticagrelor are limited. We aimed to investigate sex-based differences in clinical outcome of those patients. METHODS: In a prospective, observational, multicenter, cohort study, 2047 patients were recruited into the GReekAntiPlatElet (GRAPE) Registry and were followed up until 1 year for major adverse cardiovascular events (MACE, composite of death, nonfatal myocardial infarction, urgent revascularization, and stroke) and bleeding events (Bleeding Academic Research Consortium [BARC] classification). RESULTS: Women (n=360, 17.6%) were more frequently administered clopidogrel (rather than novel P2Y12 receptor antagonists) at PCI hospital and at discharge. MACE occurred in 9.2% and 8.1% of women and men, respectively and did not differ significantly by gender. Rate of observed bleeding BARC any type was 57.2% and 44.4% in women and men, respectively. Following adjustment, only differences in BARC any type and BARC type 1 events remained significant, with higher rates observed between women: hazard ratio (95% confidence interval) 1.51 (1.23-1.85) and 1.58 (1.27-1.96), respectively, P<.001 for both. CONCLUSIONS: In a contemporary "real-life" cohort of patients with ACS treated with PCI and focusing on antiplatelet treatment 1-year ischemic outcome does not differ by gender, while women do present more frequently not actionable bleeding events.

Carotid plaque composition in stable and unstable coronary artery disease.

BACKGROUND: Several pieces of evidence suggest that formation of complex atheromatous plaques may be influenced not only by local but also by systemic factors. METHODS: Twenty-five patients (16 men/9 women, age 63 +/- 10 years) with stable coronary artery disease (sCAD) and 61 (41 men/20 women, age 66 +/- 16 years) with acute coronary syndromes (ACSs) underwent carotid ultrasonography within 2 days of cardiac catheterization. Complex coronary plaques were associated with intraluminal filling defect consistent with thrombus, ulceration, or irregularity. Complex carotid plaques had one or more of the following features: (a) ulceration, (b) irregular surface, (c) mobile thrombi on plaque surface, (d) predominant echolucency, and (e) heterogeneity with intraplaque echolucent areas. RESULTS: Carotid intimamedia thickness and luminal diameter were not significantly different between patients with sCAD and those with ACS (0.95 +/- 0.22 vs 1.0 +/- 0.15 mm [P = .23] and 6.1 +/- 0.89 vs 6.20 +/- 0.77 mm [P = .60], respectively), whereas the interadventitial diameter was slightly greater in the latter (7.93 +/- 1.05 vs 8.40 +/- 0.97 mm, P = .0496). Both complex coronary plaques and complex carotid plaques were more common in patients with ACS than in those with sCAD (n = 52 [85.2%] vs n = 6 [24%] [P < .0001] and n = 38 [62.3%] vs n = 5 [20%] [P = .0009], respectively). The odds of having complex carotid plaques were increased > 6-fold in patients with ACS compared with those with sCAD (OR 6.61, 95% CI 2.24-19.32). CONCLUSIONS: Complex coronary plaques are associated with complex carotid plaques and the high prevalence of both plaque types in patients with ACS is indicative of a systemic process contributing to complex plaque formation and instability.

Prognostic significance of coronary artery calcium in asymptomatic subjects with usual cardiovascular risk.

BACKGROUND: Coronary calcium detected noninvasively is an attractive way to diagnose atherosclerosis before the development of symptoms. This study examines the prognostic value of coronary calcium in asymptomatic subjects with usual cardiovascular risk. METHODS AND RESULTS: In 425 asymptomatic subjects, 229 men (aged 45.1 +/- 14 years) and 196 women (aged 42.7 +/- 13 years), coronary calcium presence was studied by digital cinefluoroscopy. The majority (76%) had no or at most one risk factor. Subjects were followed up for 58.4 +/- 12.7 months for cardiac events. Coronary calcium was present in 76 of 425 (17.9%) subjects. Cardiac events were observed in 21 subjects: 2 cardiac deaths, 7 acute myocardial infarctions, 3 coronary artery bypass grafts, 3 coronary angioplasty procedures, 3 events of unstable angina, and 10 events of stable angina pectoris. Survival curve analysis showed significant differences in all the studied end points between subjects with and those without calcium. Coronary calcium was an independent predictor of all events (3.6-fold increase, P <.008), cardiac death/myocardial infarction/revascularization (13.9-fold increase, P <.02), and stable angina (7.4-fold increase, P <.007). However, calcium did not independently predict cardiac death/myocardial infarction or acute coronary syndromes. CONCLUSIONS: Coronary calcium in asymptomatic subjects with usual cardiovascular risk adds significant incremental information to risk factors information for the development of symptomatic coronary artery disease.

Bivalirudin use and one-month outcome in the context of contemporary antiplatelet treatment: insights from the Greek Antiplatelet Registry.

AIMS: Little is known about the use of bivalirudin in "real life". In the context of contemporary antiplatelet treatment, we aimed to assess bivalirudin treatment patterns and short-term (one-month) outcome. METHODS: Greek Antiplatelet Registry (GRAPE) is a prospective, observational, multicenter cohort study of consecutive, moderate-to-high-risk acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI). We assessed bivalirudin treatment patterns and predictive factors for its use. Combined in-hospital and one-month major adverse cardiovascular events (MACE, including death, myocardial infarction, urgent revascularization, and stroke), and bleeding events according to Bleeding Academic Research Consortium (BARC) criteria were analyzed after propensity matching. RESULTS: Of 2047 registered patients, 480 (23.4%) were treated with bivalirudin. Multivariate analysis (C statistic 0.77, 0.75-0.80 95% CIs, P < 0.001) revealed as factors favoring bivalirudin use primary PCI, radial arterial access, presentation with positive biomarkers and use of novel P2Y12 inhibitor, whereas IIb/IIIa inhibitor administration did not. Regional trends also affected bivalirudin's choice. In 370 propensity-matched pairs of patients who received or not bivalirudin, MACE, BARC type 1, 2 and 3 did not differ between groups: 4.1%, 21.9%, 3.2%, 3.5% and 5.1%, 18.9%, 2.7%, 4.3%, respectively, P = nonsignificant for all. CONCLUSIONS: In a "real life", contemporary antiplatelet treatment registry, clinical, laboratory and logistic factors affect bivalirudin's choice, while there are no differences in one-month outcome between bivalirudin-treated and non-bivalirudin-treated patients.

Implementation of contemporary oral antiplatelet treatment guidelines in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a report from the GReek AntiPlatelet rEgistry (GRAPE).

BACKGROUND: Few data exist about the implementation of contemporary oral antiplatelet treatment guidelines in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS: GReek AntiPlatelet rEgistry (GRAPE), initiated on January 2012, is a prospective, observational, multicenter cohort study focusing on contemporary use of P2Y12 inhibitors. In 1434 patients we evaluated appropriateness of P2Y12 selection initially and at discharge by applying an eligibility-assessing algorithm based on P2Y12 inhibitors' contraindications/specific warnings and precautions. RESULTS: Appropriate, less preferable and inappropriate P2Y12 inhibitor selections were made initially in 45.8%, 47.2% and 6.6% and at discharge in 64.1%, 29.2% and 6.6% of patients, respectively. The selection of clopidogrel was most commonly less preferable, both initially (69.7%) and at discharge (75.6%). Appropriate selection of newer agents was high initially (79.2%-82.8%), with further increase as selection at discharge (89.4%-89.8%). Inappropriate selection of the newer agents was 17.2%-20.8% initially, decreasing to 10.2%-10.6% at discharge. Conditions and co-medications related to increased bleeding risk, presentation with ST elevation myocardial infarction and the absence of reperfusion within the first 24h were the most powerful predictors of appropriate P2Y12 selection initially, whereas age ≥75 years, conditions and co-medications related to increased bleeding risk and regional trends mostly affected appropriate P2Y12 selection at discharge. CONCLUSIONS: In GRAPE, adherence with the recently released guidelines on oral antiplatelet therapy was satisfactory. Clopidogrel was most commonly used as a less preferable selection, while prasugrel or ticagrelor selection was mostly appropriate. Certain factors may predict initial and at discharge guideline implementation. Clinical Trial Registration-clinicaltrials.gov Identifier: NCT01774955 http://clinicaltrials.gov/.

Cardiac mortality in {beta}-thalassemia major: resting but not dobutamine stress echocardiography predicts mortality among initially cardiac disease-free patients in a prospective 12-year study.

AIMS: Cardiac death remains the principal cause of mortality in beta-thalassemia major (beta-TM). Echocardiography may provide additional information, incremental to haematological profile, both for guiding chelation therapy and to assess prognosis. METHODS AND RESULTS: Between 1993 and 1995, 36 patients with beta-TM and normal cardiac function and 25 normal volunteers underwent evaluation using resting and dobutamine stress echocardiography (DSE). Dobutamine stress echocardiography was performed at baseline and repeated after 2 years. The primary endpoint was cardiac mortality. During a 12-year observation period, seven patients (19%) died from heart failure. All seven deaths occurred among the cohort of 12 patients with median ferritin concentrations >or= 2800 ng/mg. In addition, a resting left ventricular ejection fraction (LVEF) < 60% was also associated with increased late mortality. In multivariate analysis, increased serum ferritin levels and reduced LVEF but not DSE or other haematological variables were independent survival determinants. CONCLUSION: Resting LVEF provides prognostic information that is additional to ferritin levels among patients with beta-TM.

Echocardiographic assessment of left atrial ejection force and kinetic energy in chronic heart failure.

BACKGROUND: There is limited information regarding left atrial (LA) systolic adaptation to chronic heart failure (HF) in humans. Therefore, the aim of our study was to determine the LA ejection force (LAEF) and kinetic energy in patients with HF. METHODS AND RESULTS: 58 HF patients (63.8% in NYHA II) and 48 controls were studied. LA volumes were echocardiographically determined using the biplane area-length method. LA systolic function was assessed with the: (a) active emptying volume (ACTEV) and fraction (ACTEF), (b) ejection force (kdynes/m2), calculated with Manning's method [LAEF = 0.5 * rho * mitral orifice area * A2; rho: blood density, Alpha: late transmitral flow velocity] and a modification incorporating parameters of LA function [LAEFm = 0.5 * rho * LA volume at onset of atrial systole * ACTEF * A2/VTl A], and (c) kinetic energy [LA-ke (kdynes.cm/m2) = 0.5 * rho * ACTEV * A2]. LA maximal volume and ACTEV were lower (42.9 +/- 14.4 vs. 59.7 +/- 14.7 cm3, P < 0.0001; 10.9 +/- 3.3 vs. 13 +/- 3.3 cm3, P = 0.0001, respectively), whereas ACTEF (%) was higher (36.3 +/- 7 vs. 29.3 +/- 7.6 cm3, P < 0.0001) in controls than HF. LAEF, LAEFm, and LA-ke were lower in controls than HF (7.68 +/- 5.1 vs. 10.16 +/- 3.7 kdynes/m2, P = 0.006; 3.63 +/- 2.05 vs. 5.02 +/- 1.74 kdynes/m2, P = 0.0004; 2.41 +/- 1.91 vs. 3.99 +/- 2.1 kdynes.cm/m2, P < 0.0004, respectively). CONCLUSION: Despite the decreased LA systolic shortening, overall LA systolic performance is augmented in chronic HF due to LA dilation.

Left atrial remodeling in patients younger than 70 years with diastolic and systolic heart failure.

OBJECTIVE: We sought to determine left atrial (LA) volume and systolic function (LA remodeling) in younger (<70 years) patients with systolic and diastolic heart failure (HF). METHODS: In all, 32 patients with diastolic HF (left ventricular [LV] ejection fraction > or = 0.50), 26 patients with systolic HF (LV ejection fraction < 0.50), and 48 control subjects were studied. LAlpha volume (cm(3)/m(2)) was echocardiographically determined at mitral valve opening (maximal), mitral valve closure (minimal), and atrial systole (electrocardiographic Rho wave) using the biplane area-length method. The LA active emptying fraction (%) and ejection force (kdyne/m(2)) served as indices of LA systolic function. RESULTS: LA maximal volume was greater in systolic HF than diastolic HF and in the latter greater than control (68.6 +/- 13.8 vs 52 +/- 11.6 vs 42.9 +/- 14.4, respectively, P < .0001). Active emptying fraction was similar between diastolic HF and control, and greater than systolic HF (31.5 +/- 8.1 vs 36.3 +/- 7 vs 26.6 +/- 6.2, respectively, P < .0001), whereas LA ejection force was similar in diastolic and systolic HF and greater than control (5.05 +/- 1.3 vs 4.98 +/- 2.17 vs 3.63 +/- 2.05, respectively, P = .001). Vmax was related to body surface area, brain natriuretic peptide, and LV mass in diastolic HF (multiple R2 = 0.74) and to diastolic blood pressure, LV mass, and early to late transmitral flow velocity ratio in systolic HF (multiple R2 = 0.96). CONCLUSIONS: LA remodeling is more severe in systolic HF than diastolic HF and governed by different mechanisms. This may be of significant clinical relevance regarding the morbidity and mortality of these two conditions.